Adolescent and Childhood Diseases

Adolescent and Childhood Diseases

A custom publication of the Disease Control Priorities Project

©2006 The International Bank for Reconstruction and Development / The World Bank 1818 H Street NW Washington DC 20433 Telephone: 202-473-1000 Internet: www.worldbank.org E-mail: [email protected] All rights reserved The findings, interpretations, and conclusions expressed herein do not necessarily reflect the views of the Executive Directors of The World Bank or the governments they represent, The World Health Organization, or the Fogarty International Center, U.S. National Institutes of Health. The World Bank, the World Health Organization, and the Fogarty International Center, U.S. National Institutes of Health do not guarantee the accuracy of the data included herein. The boundaries, colors, denominations, and other information shown on any map do not imply any judgment on the part of The World Bank, the World Health Organization, or the Fogarty International Center, U.S. National Institutes of Health concerning the legal status of any territory or the endorsement or acceptance of such boundaries. Rights and Permissions The material in this work is copyrighted. Copying and/or transmitting portions or all of this work without permission other than for non-commercial, educational and scholarly purposes may be a violation of applicable law. The International Bank for Reconstruction and Development / The World Bank encourages dissemination of its work and will normally grant permission to reproduce portions of the work promptly. For permission to reproduce, photocopy or reprint other than for non-commercial, educational and scholarly purposes, please send a request with complete information to the Copyright Clearance Center Inc., 222 Rosewood Drive, Danvers, MA 01923, USA; telephone: 978-7508400; fax: 978-750-4470; Internet: www.copyright.com. All other queries on rights and licenses, including subsidiary rights, should be addressed to the Office of the Publisher, The World Bank, 1818 H Street NW, Washington, DC 20433, USA; fax: 202-522-2422; e-mail: [email protected]. The chapters in this publication were originally published in the following two books, and any citations should include the complete information provided: 1) Dean T. Jamison, Joel G. Breman, Anthony R. Measham, George Alleyne, Mariam Claeson, David B. Evans, Prabhat Jha, Anne Mills, and Philip Musgrove, eds. 2006. Disease Control Priorities in Developing Countries, 2nd ed. New York: Oxford University Press. 2) Alan D. Lopez, Colin D. Mathers, Majid Ezzati, Dean T. Jamison, and Christopher J. L. Murray, eds. 2006. Global Burden of Disease and Risk Factors. New York: Oxford University Press.

Contents

1

Improving the Health of Populations: Lessons of Experience .........................................................................................

1

Disease Control Priorities in Developing Countries Carol Ann Medlin, Mushtaque Chowdhury, Dean Jamison, and others

2

Millennium Development Goals for Health: What Will It Take to Accelerate Progress? ...............................................

17

Disease Control Priorities in Developing Countries Adam Wagstaff, Mariam Claeson, Robert M. Hecht, and others

3

Diarrheal Diseases ............................................................................................................................................................

31

Disease Control Priorities in Developing Countries Gerald T. Keusch, Olivier Fontaine, Alok Bhargava, and others

4

Vaccine-Preventable Diseases ..........................................................................................................................................

49

Disease Control Priorities in Developing Countries Logan Brenzel, Lara J. Wolfson, Julia Fox-Rushby, and others

5

Helminth Infections: Soil-Transmitted Helminth Infections and Schistosomiasis ..........................................................

73

Disease Control Priorities in Developing Countries Peter J. Hotez, Donald A. P. Bundy, Kathleen Beegle, Simon Brooker, Lesley Drake, Nilanthi de Silva, Antonio Montresor, Dirk Engels, Matthew Jukes, Lester Chitsulo, Jeffrey Chow, Ramanan Laxminarayan, Catherine Michaud, Jeff Bethony, Rodrigo Correa-Oliveira, Xiao Shuhua, Alan Fenwick, and Lorenzo Savioli

6

Acute Respiratory Infections in Children ........................................................................................................................

89

Disease Control Priorities in Developing Countries Eric A. F. Simoes, Thomas Cherian, Jeffrey Chow, Sonbol A. Shahid-Salles, Ramanan Laxminarayan, and T. Jacob John

7

Newborn Survival ............................................................................................................................................................

105

Disease Control Priorities in Developing Countries Joy E. Lawn, Jelka Zupan, Geneviève Begkoyian, and Rudolf Knippenberg

8

Stunting, Wasting, and Micronutrient Deficiency Disorders ...........................................................................................

125

Disease Control Priorities in Developing Countries Laura E. Caulfield, Stephanie A. Richard, Juan A. Rivera, Philip Musgrove, and Robert E. Black

9

Oral and Craniofacial Diseases and Disorders .................................................................................................................

143

Disease Control Priorities in Developing Countries Douglas Bratthall, Poul Erik Petersen, Jayanthi Ramanathan Stjernswärd, and others

10

Unintentional Injuries ......................................................................................................................................................

157

Disease Control Priorities in Developing Countries Robyn Norton, Adnan A. Hyder, David Bishai, and Margie Peden

11

Learning and Developmental Disabilities ........................................................................................................................

175

Disease Control Priorities in Developing Countries Maureen S. Durkin, Helen Schneider, Vikram S. Pathania, Karin B. Nelson, Geoffrey C. Solarsh, Nicole Bellows, Richard M. Scheffler, and Karen J. Hofman

12

Community Health and Nutrition Programs ....................................................................................................................

195

Global Burden of Disease and Risk Factors John B. Mason, David Sanders, Philip Musgrove, Soekirman, and Rae Galloway

13

Adolescent Health Programs ............................................................................................................................................

217

Disease Control Priorities in Developing Countries Elizabeth Lule, James E. Rosen, Susheela Singh, and others

14

Control and Eradication ...................................................................................................................................................

235

Disease Control Priorities in Developing Countries Mark Miller, Scott Barrett, and D. A. Henderson

15

Integrated Management of the Sick Child ........................................................................................................................

249

Global Burden of Disease and Risk Factors Cesar G. Victora, Taghreed Adam, Jennifer Bryce, and David B. Evans

16

Improving the Quality of Care in Developing Countries .................................................................................................

265

Disease Control Priorities in Developing Countries John W. Peabody, Mario M. Taguiwalo, David A. Robalino, and others

17

Demographic and Epidemiological Characteristics of Major Regions, 19902001 .......................................................... Global Burden of Disease and Risk Factors

281

Alan D. Lopez, Stephen Begg, and Ed Bos

Chapter 8

Improving the Health of Populations: Lessons of Experience Carol Ann Medlin, Mushtaque Chowdhury, Dean T. Jamison, and Anthony R. Measham

In the past 50 years, the world has experienced enormous and unprecedented gains in the health of human populations. Progress has been especially apparent in developing countries. Average life expectancy has risen by more than 60 percent, from 40 years in 1950 to 65 years today. In 1950, roughly 28 percent of children died before their fifth birthday, but by 1990, this number had fallen to 10 percent. Furthermore, many of the world’s most deadly and debilitating diseases, including leprosy, measles, poliomyelitis (polio), and many childhood illnesses, have been effectively contained in most areas and virtually eliminated in others. Smallpox, a highly contagious and deadly disease that affected more than 50 million people a year prior to 1950, has been completely eradicated. Researchers have identified economic growth, rising incomes, and better living conditions brought about by rapid social and political transformations in many societies as major contributors to these impressive health gains. However, in recent years, the role of scientific and technological progress has emerged as a crucial, but little understood, factor underlying these gains. As Davis (1956, 306–7) observes, “It seems clear that the great reduction of mortality in underdeveloped areas since 1940 has been brought about mainly by the discovery of new methods of disease treatment applicable at reasonable cost [and] by the diffusion of these new methods.” New research has sought to validate, and indeed quantify, this basic intuition. For example, Jamison, Lau, and Wang (2005) show that technological progress (which is broadly defined as the generation or adoption of new technologies), together with education, has been a far more important contributor to declining infant mortality rates in developing

countries than income growth. Furthermore, improvements in health brought about by investments in technological progress generate an important and positive feedback loop favoring economic growth and development in these countries. An important question that follows is what can be done to further consolidate these gains and ensure that the fruits of scientific and technology progress are placed in the hands of the people in developing countries who stand to benefit most? Because the work of the Disease Control Priorities Project (DCPP) focuses primarily on identifying the most costeffective interventions for diseases and conditions affecting the health of populations in developing countries, this work provides the starting point for analysis. The goal is to isolate the critical factors—in particular those “actionable” through specific public policies—that have contributed to the effective deployment and scaling up of proven cost-effective technologies and services in low-income settings. To address this question, the DCPP joined forces with the What Works Working Group of the Global Health Policy Research Network, an initiative led by the Center for Global Development in Washington, D.C., and funded by the Bill & Melinda Gates Foundation. DCPP authors were asked to identify outstanding examples of successful implementation of programs and projects geared toward the deployment of proven cost-effective interventions in their respective fields of international health and to speculate on what kinds of programmatic aspects and broader public policy decisions might have contributed to their success. From an initial set of nominations, the What Works Working Group selected a subset of cases that conformed to strict 165

©2006 The International Bank for Reconstruction and Development / The World Bank 1

selection criteria, researched them thoroughly, and produced a report to be widely disseminated to policy makers and leading health experts in both developed and developing countries. In parallel, the DCPP initiated a systematic review of the case materials to identify commonalities or factors that may have contributed to the deployment and scaling up of those interventions. The objective was to identify a set of specific policy levers and programmatic decisions that could facilitate the transplantation of those and other cost-effective interventions to new and different settings. This chapter presents the results of that study.

RESEARCH METHODS The study consisted of a qualitative analysis of a set of case studies selected to help illustrate how proven, cost-effective interventions have been successfully deployed and brought to scale with dramatic results in low- and middle-income countries in Africa, Asia, and Latin America and the Caribbean. We examined evidence culled from interviews, peer-reviewed articles published in journals, and official project evaluations and attempted to organize this information in a way that would allow us to reach tentative conclusions about the most significant elements associated with the interventions’ success. The study thus followed one of Mill’s (1843) five methods of experimental reasoning: the method of agreement. Such a method postulates that “if two or more instances of the phenomenon (A) . . . have only one circumstance (B) in common, the circumstance (B) in which alone all the instances agree is the cause (or effect) of the given phenomenon (A).” For this study, the phenomenon (A) is represented by success. Cases that qualified as successes had to conform to the following five criteria: • Scale. All cases selected for study involved a national, regional, or global scale. Pilot projects or interventions implemented on a subnational scale were not considered. • Importance. Selected cases addressed a problem of major public health significance that could be expressed, at the program’s inception, in terms of disability-adjusted life years, a composite measure of mortality and morbidity caused by the disease. • Health impact. Selected cases had documented evidence of a clear and measurable effect on the health of the population targeted by the intervention. Process indicators, including immunization coverage rates, were not considered an acceptable substitute for health impact data. • Duration. All cases selected for study had a life span of at least five consecutive years. • Cost-effectiveness. Selected cases relied on interventions that had been proven to be cost-effective at a threshold of approximately US$100 per disability-adjusted life year saved.

The unabashed focus on success meant that the study ignored potentially important information about factors that may be associated with programmatic failures or not-sosuccessful cases that did not meet the strict criteria described above. However, the inclusion of less-than-successful cases was not an option in light of time, resource constraints, and paucity of available documentation. Thus, a significant limitation of our study results from the lack of variance in the outcome observed. This type of selection bias is a common problem that may result from the nonrandom selection of cases in qualitative research. Although bias cannot be eliminated without expanding the study to include unsuccessful examples, working skillfully with the presumption of bias to increase the level of confidence in the findings is possible. First, counterfactual examples, even if purely speculative (what would have happened if . . . ?), can be used to further substantiate the hypothesis that circumstance (B) has directly contributed to the observed phenomenon (A). Second, theorizing in a constructive way about what the direction of the bias might be and, therefore, minimizing its impact on the results of the study are also possible. For example, any potential bias more than likely results from overdetermining causality rather than overlooking or ignoring key factors related to success. In a related point, the study design makes discerning the relative contributions of the various factors difficult, because weights cannot be assigned easily. Remarkably few rigorous studies of this sort attempt to track the implementation of proven, cost-effective interventions in the field. Although we have a good understanding of the efficacy of the available arsenal of interventions for treating and preventing diseases specific to low-income countries, we often know little about the range of programmatic and policy options that are needed to support these interventions in the real world. This study represents the first major contribution toward the development of a body of knowledge in that area, and the preliminary conclusions reached should be understood in that context (Collier and Brady 2004).

CASES From an initial set of nominations received from DCPP authors as well as from other international health researchers, we selected a subset of 17 cases for study. We could not consider many cases that were nominated because of the absence of reliable data. Thus, the 17 cases selected are merely a subset of the many successes in international health that have been achieved during the past 50 years, not the full universe. Nonetheless, the cases draw from all three continents of the developing world—Africa, Asia, and Latin America and the Caribbean—and involve both communicable and noncommunicable diseases as well as curative and preventive care. Most

166 | Disease Control Priorities in Developing Countries | Carol Ann Medlin, Mushtaque Chowdhury, Dean T. Jamison, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 2

cases are national-level programs, but a few involve regional initiatives, and one is global. Many near misses did not make the cut. The reasons for this exclusion varied. For example, a program in Costa Rica, El Salvador, and Guatemala to promote hand washing appears to have resulted in a dramatic decline in child morbidity and mortality but did not meet the duration criterion because it was fully operational for only three years (1996–99). In another example, the evidence of a health impact was mixed: a successful schistosomiasis control program in the Arab Republic of Egypt that included treatment of blood flukes in infected individuals was later linked to high prevalence rates of hepatitis C caused by the use of improperly sterilized syringes (Frank and others 2000). Nonetheless, the most common rationale for excluding a case from this study had to do with a lack of consistent documentation and of analysis of the health impact of the program in question. Thus, a reasonable conclusion is that the true universe of cases is much larger than the subset of cases we examined. Each case reviewed here illustrates how a discrete health intervention or combination of interventions was successfully brought to scale in a specific context. To gain insight into this process, we can distinguish between the intervention—for example, the tool or technology that has been proven to be costeffective for the treatment or prevention of a given disease— and the programmatic characteristics and policies that contributed to the successful delivery or deployment of the intervention through specially designed programs or projects. The following list of cases selected for review describes the programs or projects that were scaled up, identifies the specific intervention or interventions deployed, and summarizes the existing evidence about health outcomes and impact:1 • Chagas disease control. In 1991, seven countries— Argentina, Bolivia, Brazil, Chile, Paraguay, Uruguay, and later Peru—joined forces as part of an initiative for the Southern Cone countries led by the Pan American Health Organization to combat Chagas disease through a combination of surveillance activities, house-to-house spraying, and other vector control methods. Health impact—Disease incidence had fallen by 94 percent by 2000. By 2001, disease transmission had been halted in Chile, Uruguay, and large parts of Brazil and Paraguay. The project is ongoing. • Diarrheal treatment. In Egypt, the government launched a national program in the early 1980s to promote the use by mothers of locally manufactured oral rehydration salts in a four-part strategy that included tailoring product design and branding to accommodate local preferences and customs; strengthening production and distribution channels, both public and private; training health workers; and using social marketing and a mass media campaign. Health impact—Between 1982 and 1987, infant and child mortality

•

•

•

•

•

dropped by 36 and 43 percent, respectively. Mortality attributed to diarrhea fell 82 percent among infants and 62 percent among children. The project closed in 1991. Guinea worm eradication. Twenty countries in Asia and Sub-Saharan Africa began a global campaign to eradicate guinea worm in the mid 1980s. Led by the Carter Center, the United Nations Children’s Fund, the U.S. Centers for Disease Control and Prevention, and the World Health Organization, the campaign promoted improved water safety through deep-well digging, environmental control, and the use of cloth filters for drinking water; health education programs; and case management, containment, and surveillance. Health impact—By 1998, 9 million to 13 million cases of guinea worm had been prevented and global prevalence had dropped by 99 percent. The project is ongoing in three countries. Family planning. In Bangladesh, family planning has been promoted since the 1970s through a door-to-door outreach program conducted by young, married women who provide information about limiting family size or spacing pregnancies along with products. An extensive media campaign accompanied the outreach program. Health impact— Contraceptive use among married women in Bangladesh is approximately 50 percent today, compared with only 8 percent in the mid 1970s, and the average number of children per family is 3.3, down from 7 in the mid 1970s. The project is ongoing. Hib vaccination. Chile began to include the Hib vaccine as part of its national immunization program in 1996. In The Gambia, a similar initiative was introduced in 1997. Health impact—In Chile, the prevalence of Hib disease fell by 90 percent, and the incidence of pneumonia and other Hib-related illnesses fell by 80 percent. In The Gambia, the number of children developing Hib meningitis fell from 200 per 100,000 to 21 per 100,000 only 12 months following the introduction of the vaccine. The projects are ongoing in both countries. HIV/AIDS prevention. Thailand launched the 100 Percent Condom Program in 1991 to address the rising incidence of HIV/AIDS in the country. The program provided boxes of condoms to brothels free of charge, mandated the use of condoms by sex workers, and threatened brothels with penalties and closure for noncompliance. Health impact— By 1992, condom use in brothels had risen to more than 90 percent, up from 14 percent in 1989. The number of cases of new sexually transmitted infections fell from 200,000 in 1989 to 15,000 in 2001, and an estimated 200,000 new infections were averted between 1993 and 2000. The project is ongoing. Health improvement of the poor using financial incentives. In 1997, the Mexican government launched a new social welfare program designed to help lift rural families Improving the Health of Populations: Lessons of Experience | 167


•

•

•

•

•

out of poverty by providing cash payments in exchange for their participation in nutrition and supplementation programs, their use of prevention and basic health care services, and their children’s school attendance. Health impact— After five years, the children of participating families were 12 percent less likely to experience illness than those of nonparticipating families, and their nutritional status had improved. Adult health indicators also improved. The project is ongoing. Maternal health. The Sri Lankan government relied on professional midwives and sustained investments in the country’s health care system, including in rural areas, to improve maternal health. Health impact—The maternal mortality ratio fell from approximately 500 per 100,000 live births in 1950 to 60 per 100,000 in 2003. The project is ongoing. Measles elimination. In 1996, the seven southern African countries agreed to a coordinated immunization strategy, supported by improved surveillance and laboratory capacity, to eliminate measles by including the vaccine as part of routine immunization for all nine-month-old babies and organizing nationwide catch-up and follow-up campaigns for children age nine months to 14 years. Health impact— The number of measles cases reported annually in the region fell from 60,000 in 1996 to 117 in 2000. The number of deaths attributed to measles fell from 166 to 0 during the same period. The project is ongoing. Onchocerciasis control. The discovery of ivermectin (Mectizan) in 1978 and Merck’s decision to provide it free of charge to anyone who needed it allowed early successes based on weekly aerial spraying in 11 West African countries to be further consolidated and later expanded to the other 19 endemic countries in Central and East Africa. Health impact—In West Africa, disease transmission has been virtually halted, and 1.5 million previously infected people are now symptom free. In Central and East Africa, the program has helped prevent an estimated 40,000 cases of blindness each year. The Onchocerciasis Control Program (OCP) ended in 2002. The African Programme for Onchocerciasis Control is ongoing. Polio elimination. In 1985, the Pan American Health Organization launched a campaign to eradicate polio from the Americas. National vaccine days were held twice a year and were targeted at children under the age of five, regardless of their immunization status, to increase coverage in countries with weak routine immunization programs. An extensive surveillance system and mop-up campaigns to address outbreaks were crucial during the campaign’s final stages. Health impact—The last case of polio in the Americas was reported in 1991. Salt fluoridation. In Jamaica, a formal agreement between the Ministry of Health and the country’s only salt producer introduced fluoridation to salt in 1987 to prevent caries.

•

•

•

•

•

Health impact—By 1995, the severity of caries in children between the ages of 6 and 12 had fallen by more than 80 percent. The project is ongoing. Salt iodination. China launched the National Iodine Deficiency Disorders Elimination Program in 1993. The government requires producers to iodize salt and has stepped up its monitoring and enforcement capacity to ensure compliance. Health impact—Total goiter rates among children between the ages of 8 and 10 years fell from 20.4 percent in 1995 to 8.8 percent in 1999. The project is ongoing. Smallpox eradication. The campaign to eradicate smallpox, led by the World Health Organization and heavily financed by the United States, was launched in the mid 1960s. Strong leadership, dedication, and commitment on the part of the international community and the timely discovery of simple, new technologies—for example, the bifurcated needle and the “ring” strategy of surveillance and containment—characterized the effort. Health impact—The World Health Assembly declared smallpox eradicated in May 1980. Tobacco control. Poland passed groundbreaking legislation in 1995 imposing strong warning labels on cigarette packages, banning smoking from enclosed workplaces, and prohibiting tobacco sales to minors. South Africa passed similar legislation in 1999 to strengthen a previously imposed tax of 50 percent on the retail price of cigarettes. Health impact—Cigarette consumption dropped 10 percent between 1990 and 1998, resulting in a 30 percent decline in lung cancer among men age 20 to 44, a nearly 7 percent decline in cardiovascular disease, and a decline in the number of babies with low birthweight. South Africa witnessed a 30 percent decline in cigarette consumption in the 1990s, especially among youths and the poor. The projects are ongoing in both countries. Trachoma control. The Moroccan National Blindness Control Program, launched in 1991, promoted the use of “SAFE” interventions (surgery, antibiotics to control the infection, facial cleanliness, and environmental improvements), with the goal of eliminating trachoma by 2005. Health impact—Overall prevalence rates have fallen by 75 percent since 1999, and the prevalence of active disease in children under the age of 10 has seen a 90 percent reduction since 1997. The project is ongoing. Tuberculosis control. In 1991, China launched a 10-year program in 13 of its 31 mainland provinces to apply the directly observed therapy short course (DOTS) strategy to turberculosis (TB) control. Peru, previously one of 23 highburden countries that collectively account for 80 percent of the world’s new TB cases each year, launched a similar effort the same year. Health impact—Within two years, China had achieved a 95 percent cure rate for new cases and a cure rate of 90 percent for those patients who had previously completed treatment unsuccessfully. The number of people with


TB declined by more than 37 percent between 1999 and 2000. The project ended in 2001, but important elements have been incorporated in the 10-year National Plan for the Prevention and Control of TB (2001–10). In Peru, disease incidence declined each year by 6 percent. The program achieved a case detection rate of 70 percent and an 85 percent cure rate. The project is ongoing.

GENERAL FINDINGS Taken as a whole, the cases support four general findings. The first two have special relevance because they serve to disconfirm aspects of the prevailing wisdom about aid effectiveness— or at least present a serious challenge to such wisdom. First, these cases demonstrate that a wide range of proven, cost-effective interventions exists that can and have been brought to scale in developing countries, even in extremely low-income settings with limited health infrastructure and in challenging macropolicy environments. In West Africa, aerial spraying of the blackflies’ breeding sites, part of the strategy promoted by the OCP throughout the 1980s, “continued unabated through wars between member countries and coups that grounded all other aircraft” (Eckholm 1989, 20). In Sudan, despite the difficulties created by the more than 20-year civil war, and in other areas of Sub-Saharan Africa, the campaign to eradicate the guinea worm has made progress. The finding is significant in that it challenges a central tenet of the aideffectiveness literature: that only countries with a “good” policy environment can benefit from external financial assistance (Devarajan, Dollar, and Holmgren 2001). The aid-effectiveness literature has tended to focus on a different set of outcomes—for example, macroeconomic and structural reform—rather than on health outcomes, and this focus may partly explain the contradictory conclusions; however, an examination of whether such a conclusion is true goes well beyond the scope of this study. In any event, the cases reviewed for this study displayed a striking degree of variation in the political and economic contexts in which interventions were applied and brought to scale, and no clear pattern of association was apparent between this variation and successful outcomes in relation to health. Second, the cases provided new evidence of the importance of the public sector to achieving successful health outcomes. This finding was a surprise, especially considering the strength of recent evidence documenting “weak links in the chain between government spending for services to improve health and actual improvements in health status” (Filmer, Hammer, and Pritchett 2000, 199). The specific roles that the public sector played in achieving these outcomes varied tremendously. In some instances, such as promoting maternal health in Sri Lanka and controlling TB in China and Peru, governments were involved in direct service provision. In other instances, the

public sector’s regulatory or legislative authority was critical. Governments in Poland and South Africa passed strict laws, despite strong opposition from the tobacco industry, requiring explicit health warnings on cigarette packs, banning smoking in enclosed public places, and prohibiting tobacco media advertisements, among other things. Governments also used their authority creatively to encourage health-promoting behaviors and to discourage risky ones. In Mexico, the government provided direct cash payments to poor families in exchange for visits to health care clinics and school attendance. In Thailand, local police worked in collaboration with health officials to lend credibility to the government’s threat to shut down brothels that failed to comply with the no condom, no sex policy, giving teeth to the national campaign. Third, the cases reviewed for this study share a number of common features or attributes that appear to have contributed to the successful outcomes. Without exception, they enjoyed and managed to reap the benefits of strong leadership, effective management, realistic financing arrangements, country ownership, and openness and receptivity to learning by doing, constantly improving on strategies and processes by incorporating new research findings and technical innovation into program improvements. For example, successful projects appeared to benefit from a strong champion who could provide the necessary leadership to bring relevant stakeholders together, encourage them to focus and coordinate their activities, and instill in them a sense of purpose and enthusiasm for their work. However, we did find that leadership came packaged in many different shapes and sizes. In Jamaica, the curiosity and persistence of a Ministry of Health dentist led to the identification of the island’s only salt producer as the vehicle for fluoridation. In Mexico, President Ernesto Zedillo Ponce de León seized on the innovative proposal of a close adviser, Santiago Levy, then directorgeneral of social security, and launched a program linking education, health, and nutrition as part of an integrated strategy to lift rural families out of poverty, and the program was not abandoned when Zedillo left office. The new Vicente Fox administration, motivated by undeniable evidence of the program’s effectiveness, instead sought to expand the program into urban areas and added an educational component. In a less visible but nonetheless critical display of leadership and forward thinking, the sustained investments of the Sri Lankan government over a nearly 50-year period to build a rural health network emphasizing critical elements of maternal health have led to gains in the health of women unparalleled by countries at similar, and higher, income levels. Strong program management was needed to ensure that plans, once conceived, were implemented effectively. Successful cases had well-delineated goals that were clearly linked to inputs, activities, outputs, and outcomes. This factor was especially evident in the case of global or regional immunization Improving the Health of Populations: Lessons of Experience | 169


campaigns, given the many logistical challenges and the need for fluid and effective coordination of many countries and stakeholder groups, often within a highly constrained time frame. However, similar management skills are needed for health service delivery systems, especially when patient referral, tracking, and follow-up are essential components of the intervention. In China, incentive schemes to motivate physicians, extensive training and supervision of health care staff, and substantial investments in local TB dispensaries were all crucial elements in improving management capacity for large-scale rollout of the country’s DOTS program, which covered a population of 573 million in 1,208 counties in 13 provinces. A closely related requirement was having a realistic financing strategy that was compatible with a project’s goals. Even when large sums of money were involved, deployment of the intervention yielded tremendous returns at a relatively low cost per disability-adjusted life year. In the case of onchocerciasis control, for which donors have invested US$560 million over a period of 28 years, transmission has been virtually halted in 20 West African countries, and nearly 600,000 cases of blindness have been averted at an annual cost of only US$1 per person. In the case of guinea worm control, in which donors have invested approximately US$88 million over a 12-year period, disease prevalence has fallen by 99 percent, and only 35,000 people remain affected, down from 3.5 million, at a cost of US$5 to US$8 per person. Country ownership was another distinguishing feature of successful programs. A government’s willingness to commit scarce funding to scaling up an intervention can be an important indication of this ownership, although not the sole predictor. Despite the extremely constrained budgets of the seven participating countries, the campaign to eliminate measles in southern Africa was almost entirely funded by their ministries of health. The Thai government covered approximately 96 percent of the cost of the 100 Percent Condom Program. In Morocco, the government bore the bulk of the costs for implementing the SAFE strategy to address blindness caused by trachoma, with contributions from the United Nations Children’s Fund and the International Trachoma Initiative, an international public-private partnership. Most of the cases we reviewed benefited from new research findings and technical innovation. Successful cases appear to display the openness and receptivity needed to make good use of new knowledge and to support ongoing research when appropriate or when gaps in knowledge prove to be a hindrance to progress. In Bangladesh, a program to treat childhood diarrhea trained mothers to make their own salt solution when the authorities determined that mass production and distribution of prepackaged oral rehydration salts was unrealistic. Control of Chagas disease in the Southern Cone of Latin America required public health officials in each country to devise and deploy environmental control strategies appropri-

ate to local conditions and vector behavior. Finally, adoption of the ring vaccination strategy marked a crucial turning point in the global campaign to eradicate smallpox, enabling rapid containment of the disease in remote parts of the world without vaccination of every child. In sum, a small number of features appear to be common to all the successful cases. A reasonable hypothesis suggested by the evidence is that these five attributes represent the known set of necessary, but not sufficient, conditions for successfully implementing cost-effective health interventions in the developing world. Fourth, despite the obvious limitations of case study methods in hypothesis testing and confirmation, the evidence from the cases sheds important light on two important debates in international health policy. First, the cases suggest that much more is involved than what is currently understood about whether weak policy environments can make good use of carefully selected, strategic investments in health. As the next section indicates, different types of programmatic characteristics and policies are needed for the deployment of different types of interventions. How these characteristics interact with different policy environments—whether strong, weak, or in between—deserves further scrutiny and exploration. Second, evidence from the cases of successful government action should call into question any premature and overly general conclusions about public sector ineffectiveness in developing countries. Even though such a small sample of cases is surely insufficient to close the book on these important policy debates, it should at least encourage further study and refinement of the arguments.

INTERVENTION TYPE, PROGRAMMATIC CHARACTERISTICS, AND POLICIES Programmatic characteristics and policies associated with successful outcomes appear to vary by intervention type. The starting point for this discussion is the intervention, technology, or tool in question. What allows for the widespread deployment of a proven, cost-effective intervention? What are the steps for converting a proven, cost-effective intervention into a fully fledged health program that has been successfully brought to scale, preferably at the national level? Is it possible to distinguish between the specific health intervention and the programmatic characteristics and public policies associated with its successful deployment? The cases under review were grouped according to the primary type of intervention deployed by the program or project in question. The types of interventions varied in terms of their emphasis on the delivery of standardized products to a population (product-intensive interventions), the delivery of clinical services (service-intensive interventions), a personal


behavior change (behavioral change interventions), the control of environmental hazards (environmental control interventions), or some combination thereof. Further scrutiny of subgroupings of cases revealed that certain programmatic characteristics, delivery modalities, and public policy instruments also appeared to vary by intervention type. This finding appeared to substantiate the claim of the first edition of this volume (Jamison 1993, 11) that “commonalities of logistics, policy instruments, and approach” vary by intervention type and play a role in determining whether the intervention or interventions will be deployed successfully. The typology presented here differs from the one elaborated by World Development Report 2004: Making Services Work for Poor People (World Bank 2004), in that the classification depends on characteristics inherent to the intervention in question. By contrast, World Development Report 2004 identifies three classes of service delivery arrangements: individualoriented clinical services, population-oriented outreach services, and community- and family-oriented services that support self-care. The focus is on differences in the relationship between provider and client and how these differences interact with market and public sector dynamics.2 However, our focus was on how characteristics of the interventions themselves give rise to certain programmatic or policy imperatives that may contribute, ultimately, to successful health outcomes. This section presents the five intervention types and explores the clusters of programmatic characteristics and policies that appear to support the successful deployment of each intervention type, based on case study analysis. Product-Intensive Interventions These types of interventions (box 8.1) involve the simple transfer of a standardized technology to an individual or to an entire population. They can be targeted at either prevention or cure, but the distinguishing feature is standardization. Unlike service-intensive interventions, product-intensive interventions need not be tailored to the unique health care needs of the individual receiving treatment.

To the degree that product-intensive interventions place relatively low technical demands on health care staff at the point of delivery, they may be more easily deployed in low-resource settings than other types of interventions. Compared with service-intensive interventions, they are less transaction intensive, requiring fewer interactions between providers and clients. Also, compared with behavioral-change interventions, they are less dependent on individual compliance, requiring simply that individuals make themselves available for treatment. Productintensive interventions include mass drug administration (chemotherapy), childhood immunizations, mineral fortification, and nutritional supplementation. (These specific interventions are addressed in detail in chapters 20, 22, and 28.) Product-intensive interventions are often, though not necessarily, linked to vertical rather than horizontal delivery modalities. According to Gonzalez (cited in Mills 1983, 1972), the vertical approach “calls for the solution of a given health problem through the application of specific measures through single-purpose machinery.” By contrast, the horizontal approach “seeks to tackle . . . health problems on a wide front and on a long-term basis through the creation of a system of permanent institutions commonly known as ‘general health services.’” Where health systems are weak and poorly functioning, vertical programs—in particular, mass campaigns—can be an effective means of rapidly providing coverage to a large population. However, the same approach could result in an unfortunate duplication of effort in countries where the health care system is already strong and functioning properly. Mass Drug Administration. Of the product-intensive interventions, those that can be delivered in pill or capsule form in standardized doses, often through what is referred to as mass drug administration, are perhaps the least complex to deliver and, as a result, may be the least costly. Onchocerciasis, also known as river blindness, can be treated by a single dose of ivermectin administered annually to infected individuals. Lymphatic filariasis can be treated in much the same way using a two-drug combination therapy of albendazole plus either diethylcarbamazine or ivermectin administered annually in

Box 8.1

Product-Intensive Interventions: Illustrations from Cases Hib vaccine

Salt fluoridation

Ivermectin

Salt iodination

Measles vaccine

Smallpox vaccine

Oral polio vaccine Source: Authors.

Improving the Health of Populations: Lessons of Experience | 171 ©2006 The International Bank for Reconstruction and Development / The World Bank 7

single doses for four to six years (the estimated productive life span of the adult-stage parasite). The importance of product-intensive therapies can easily be illustrated by reference to the case of onchocerciasis control in most parts of Africa. Although aerial spraying, an environmental control intervention, had been used successfully to slow disease transmission in 11 West African countries, it was not a viable option for 19 countries of East and Central Africa because of geographical differences. However, Merck scientists’ discovery of ivermectin in 1978 and the company’s generous commitment to provide the drug free of charge to anyone who needed it changed the parameters of what was possible. Seizing the opportunity, the African Programme for Onchocerciasis Control, an international partnership led by the World Bank, the World Health Organization, the United Nations Development Programme, and the Food and Agriculture Organization of the United Nations, was created in 1995 with the goal of eliminating onchocerciasis as a disease of public health and socioeconomic importance in East and Central Africa. It quickly became apparent that the weak and sometimes nonfunctioning health systems of many African countries were not up to the task; thus, a new approach was tried that took advantage of the fact that the success of the intervention no longer depended on a clinic-based delivery system. Under the supervision of national public health ministries and nongovernmental organizations, community volunteers received training on organizing and managing the local ivermectin campaigns. The community-directed approach of treatment with ivermectin has been so successful that it has been considered as a possible model for delivering other types of treatments to remote areas. Immunizations. Product-intensive interventions may vary in complexity, which has implications for their delivery or deployment. For vaccines, the need to maintain an effective cold chain adds an additional layer of complexity to the delivery system. Other pertinent factors are whether the intervention can be delivered as a single shot or iteratively, whether it can be bundled together with other products or must be delivered separately, and whether the number of distribution points is few or many. In many cases, the characteristics of the disease or condition being addressed may affect the level of complexity. For example, the overwhelming success of the global effort to eradicate smallpox has been attributed, at least in part, to specific characteristics of the variola virus. Unlike other infectious diseases, such as malaria or yellow fever, smallpox depends solely on the human host and does not have an animal or insect carrier. Unlike polio, smallpox does not produce silent or asymptomatic infection, thereby facilitating diagnosis and surveillance of the disease (Tucker 2001). Other notable differences from other diseases have more to do with the vaccine than the virus. Tucker (2001, 64) explains that “a freeze-dried smallpox

vaccine was available that was easy to manufacture, cost only about a penny a dose, protected for several years with a single inoculation, and was relatively stable in warm climates, reducing the need for refrigeration. Whereas most vaccines took months to induce immunity, the smallpox vaccine acted with remarkable speed, providing nearly total protection within ten to twelve days.” This unique set of characteristics together meant that a “surveillance-containment” approach could replace mass vaccination entirely, in effect reducing the number of distribution points required by the intervention, thereby permitting major strides in the global eradication campaign. The more complex the intervention, the more challenging— and probably costly—it will likely be to implement. Interventions that can be delivered in a single shot or that can be easily incorporated into routine immunization (bundled) are clearly the easiest to implement. As the case of Hib vaccination in Chile illustrates, delivering the intervention was relatively straightforward after the government got past the hurdle of evaluating its cost-effectiveness relative to other interventions. The government determined that the creation of a combined diphtheria-tetanus-pertussis and Hib vaccine was worthwhile and that the vaccine could be administered as part of an already well-functioning system of routine immunization. Some of the common complexities associated specifically with immunizations range from the need for multiple inoculations administered at regular intervals, to the need to maintain a reliable cold chain, or to the need for the large population coverage required to achieve “herd immunity”—whereby the likelihood of person-to-person transmission is drastically reduced, even among the unimmunized population. In view of these potential complexities, polio elimination in the Americas represents a remarkable achievement. The oral polio vaccine must be administered in three properly spaced doses, and coverage must be high to prevent “silent” epidemics. In the 1970s, before the campaign was launched, polio caused an estimated 15,000 cases of paralysis and 1,750 deaths each year (Musgrove 1988). However, a carefully orchestrated campaign organized around achieving and maintaining high coverage through routine immunization and national vaccination days, the prompt identification of new cases, and the aggressive control of outbreaks led to the elimination of polio from the Americas in 1991. The creation of the Inter-Agency Coordinating Committee, made up of representatives from the Pan American Health Organization, the United Nations Children’s Fund, the U.S. Agency for International Development, the InterAmerican Development Bank, Rotary International, and the Canadian Public Health Association, played a key role not only in generating political and financial support, but also in helping address the logistical and managerial challenges inherent to the campaign. The Inter-Agency Coordinating Committee model was so effective that it was quickly duplicated at the country level.


The technical and logistical challenges associated with measles elimination in southern Africa were no less complex. Measles is one of the most contagious of all human diseases. The measles vaccine requires 90 percent coverage to achieve herd immunity and to stop the spread of the virus. Furthermore, it often requires two doses to be effective and must be administered to infants no earlier than nine months of age, or about six months later than other recommended vaccines. If given earlier, the vaccine will fail to trigger an active immune response, because infants are passively protected by their mothers’ antibodies until that age. Thus, the vaccination interval falls outside of what most routine immunizations require. To overcome this challenge, the southern African countries adopted a strategy known as catch up, keep up, and follow up. In each country, beginning with the program’s launch in 1996, the strategy involved organizing a national catch-up campaign in which mobile teams vaccinated all children, regardless of their vaccination status, between the approximate ages of 9 months and 14 years; sustained routine coverage; and ran at least one follow-up campaign several years later. The countries also strengthened their surveillance and laboratory capabilities to investigate all suspected measles cases. Mineral Fortification. A different type of product-intensive intervention, mineral fortification, requires fewer points of delivery and is far less labor intensive. However, potential challenges include the need for a different set of technical capacities than is typical for health sector solutions; the possibility of a need for significant initial investments to modify production processes or manufacturing capabilities; and the involvement of non–health sector entities, such as private industry. Jamaica’s salt fluoridation program beautifully illustrates the simplicity of a single delivery point for an intervention. With the agreement of the island’s only salt producer, Alkali Limited, in place, universal coverage was easy to achieve. All that was needed was a complementary legal and regulatory framework to oversee the process. In this case, the start-up costs were small: only US$3,000 worth or so of new equipment was needed, which the company was easily able to recoup with a slight increase in the price of salt. In China, salt fortification with iodine was more difficult, involving a larger investment in the production process and a

greater number of potential delivery points. Because salt production is licensed at the provincial level in China, implementing the change involved working with several layers of government bureaucracy; however, perhaps ironically, the system of central control eased the challenge. During a four-year period, 55 salt factories were upgraded and 112 iodination centers were established throughout the country to support the initiative. The government also introduced changes in bulk and retail packaging to help consumers more easily recognize iodized salt. The basic plan achieved nearly 90 percent coverage, but the remaining challenge is to address the numerous delivery points that function outside the national system, for instance, in areas where people live near the sea and produce their own salt. Summary. In sum, product-intensive interventions can be extraordinarily complex even though they involve fewer transactions between providers and clients and lower technical requirements at the point of delivery than other types of interventions, particularly service-intensive interventions. However, the relative simplicity of deployment when the scientific and technical issues of development and production have been addressed may help explain why product-intensive interventions are perceived to be easier to implement than other types of interventions and why countries experiencing political and economic instability might prefer them. Service-Intensive Interventions Service-intensive interventions (box 8.2) include the full range of diagnostic and therapeutic health services usually provided not only in the clinic setting, but also in the home or at school. Unlike product-intensive interventions, service-intensive interventions cannot easily be standardized and may require careful—and time-consuming—monitoring and reporting on patients’ progress. Thus service-intensive interventions are highly transaction intensive and typically place high technical demands on the health staff at the point of delivery. Examples range from primary care services, including essential obstetrical care, to surgical procedures, to treatment of communicable and noncommunicable diseases. The complexity of service-intensive interventions may vary, just as in the case of product-intensive interventions. The more

Box 8.2

Service-Intensive Interventions: Illustrations from Cases Bilamellar tarsal rotation procedure

Maternal health care using midwives

DOTS for TB

Primary and basic health care services

Source: Authors.


standardized the treatment protocol, the easier it will be to administer on a large scale. However, standardized or not, the transaction-intensive character of this type of intervention means that its successful deployment depends on the program’s or project’s ability to overcome potential (and likely) constraints on human resources. A related concern is the overall health system’s capacity to effectively manage competing demands on these resources. In contrast to product-intensive interventions, human capacity constraints for service-intensive interventions are harder, but not impossible, to address through community mobilization or the use of volunteers, because of the need for specialized training. Chapter 71 investigates developing countries’ experiences with new types of professionals in service delivery settings that have traditionally relied on physicians. Single-Shot Surgical Services. If the intervention is relatively standardized, it can sometimes be deployed using a vertical modality in a manner similar to the more standardized, singleshot, product-intensive interventions. This was the case of the surgical procedure used in Morocco as part of the broader SAFE strategy to address trachoma. A relatively simple surgical procedure, the bilamellar tarsal rotation procedure, can be used to halt corneal damage to prevent the onset of blindness caused by repeated trachoma infections. Morocco’s Ministry of Health organized mobile surgical teams of doctors and nurses to carry out the corrective surgery in small towns and communities throughout the country. In just eight years, the teams carried out more than 26,000 surgeries. The effort required the involvement of 43 physicians and 119 nurses working in 34 clinics. However, despite the relatively standardized nature of this kind of service-intensive intervention, human capacity constraints may slow progress. Compared with productintensive interventions for which community volunteers can be recruited to assist with distribution, service-intensive interventions require a more specialized workforce. Even when nurses and other health workers with lower-level skills can substitute for more highly trained physicians, constraints on human resource capacity may persist. Morocco faces a backlog of about 15,000 cases, many of which are urgent. Strengthened Outreach and Referral Systems. If the intervention is not easily standardized, or if it is highly transaction intensive, its successful deployment will also depend on welldeveloped outreach and referral systems. Outreach systems are needed to ensure that those requiring care will have access to care, and referral systems are needed to route patients requiring additional care toward specialized care and treatment facilities. However, ensuring that such systems are in place for specific programs and projects is a major challenge in countries where the health care system is already weak and under considerable strain.

The cases we reviewed relied on a variety of strategies to address this problem. Although the specific interventions varied, the strategies ranged from traditional investments in public sector provision to improve access, to supply-side incentives to address quality concerns, to demand-side incentives to strengthen the effective demand for health care services. For example, in an effort to improve maternal health even in remote areas, Sri Lanka adopted the traditional model of public sector provision, but with a twist. Instead of a physicianbased solution, which would have been extremely costly, Sri Lanka relied instead on professional midwives to provide widespread access to maternal health care, building on a strong health care system that provides free health care. Midwives serve a population of 3,000 to 5,000 each and live locally. They visit pregnant women in their homes, register them for care, and encourage them to attend prenatal clinics (run by doctors). Midwives receive 18 months of training and are backed up by supervision and a well-functioning referral network. Established procedures for service delivery and supervision, along with frequent in-service training, help keep midwives current and delivering high-quality services. Health clinics are supported by a network of cottage hospitals (clinics having doctors as well as nurses assigned to them), rural hospitals, and maternity homes at the secondary level; tertiary provincial hospitals with specialist services; teaching hospitals; and specialist maternity hospitals. China faced a similar dilemma with regard to establishing an effective system of outreach and referral to address a growing TB problem by scaling up DOTS. Although DOTS is relatively standardized as far as service interventions go (see chapter 16), the treatment protocol is highly transaction intensive, and complicated cases may require specialized treatment. DOTS is thus also highly dependent on well-developed systems of outreach and referral for its success. However, China faced a challenging situation because most village doctors who were needed to conduct patient diagnosis, treatment, and surveillance in rural areas were in private practice and had little incentive to treat patients for whom drugs were now provided free of charge. In response, the government created a financial scheme to provide incentives for these doctors to participate. For each patient enrolled in the treatment program, village doctors received US$1. They received an additional US$2 for each smear examination carried out in the county TB dispensary during a two-month period and another US$4 for each patient who completed treatment. Simultaneously, the government made significant administrative, managerial, and institutional investments. Tens of thousands of staff from TB dispensaries were trained, and supervisory systems were put into place. Furthermore, the government set up a national TB project office and a TB control center to oversee and coordinate the various levels of government involvement.


Demand-Side Incentives. Demand-side incentives can be designed to complement supply-side investments. Indeed, both skeptics and supporters of governments’ ability to translate public spending into effective service provision and positive health outcomes encourage the use of demand-side incentives as a means of quality control to improve routine care (Filmer, Hammer, and Pritchett 2000). Economists consider demandside incentives to be valuable tools for stimulating weak demand for services or for overcoming barriers to use that can artificially dampen demand. This was how at least two of the cases included in this study constructively used demand-side incentives. However, in neither case was this use an either-or proposition; that is, both demand-side and supply-side investments were relied on to generate the successful outcomes that qualified the cases for this study. In Peru, the newly revised National Tuberculosis Control Program offered food packages, employment training, and stipends to patients to improve compliance with the drug treatment regime. Simultaneously, the program was dramatically scaled up and the number of participating health centers rose from 977 to 6,539 over the next decade. In the clinics, nurses were the medical personnel responsible for administering DOTS. In isolated rural areas, the program recruited local leaders to serve under the direction of the nursing staff to administer the treatment and follow up with patients. Mexico’s Education, Health, and Nutrition Program (originally known as PROGRESA, but now called “Oportunidades”) also provides a compelling example of how a program can use demand-side incentives to stimulate demand for basic health care services. The program offers cash transfers to families in exchange for the attendance of mothers and children age five and under at nutrition monitoring clinics and to pregnant women if they agree to prenatal care visits and nutritional supplementation. The program also includes cash transfers to promote school attendance and performance. A rigorous evaluation provided evidence of the program’s effect on the use of health services: after just one year of implementation, attendance at health care clinics was significantly higher in participating localities. However, the increased demand for services was also met with significant improvements in the quality of services available through public providers. Health care providers in participating localities were paid more and

received more on-the-job training, and clinics benefited from a steadier flow of pharmaceutical and other supplies. Summary. In sum, service-intensive interventions are highly transaction intensive, especially compared with productintensive interventions. The more standardized the intervention, the more likely that it can be delivered by means of military-like campaigns in the same manner as productintensive interventions, although the skill level of the health workers involved will need to be higher. If complications of treatment are possible—or if the intervention cannot easily be standardized—its deployment will likely require fairly elaborate systems of outreach and referral. Although recent scholarship has strongly encouraged the use of demand-side mechanisms, particularly in an effort to address quality concerns in public sector service provision, evidence from the cases highlighted in this chapter suggests that a variety of modalities are possible and that a mix of supply- and demand-side incentives may even be desirable.

Behavioral Change Interventions Behavioral change interventions (box 8.3) are designed to induce or encourage an individual behavior change or habit modification to achieve specific health goals. The focus is usually on prevention, but need not be exclusively so—for example, the use of oral rehydration therapy to treat childhood diarrhea. Behavioral change interventions are often linked to the uptake of a specific product, as in the case of condoms and insecticide-treated bednets. However, unlike product-intensive interventions, behavioral change interventions require active participation by the individual and cannot be passively received in the form of an injection or supplement. Also, unlike service-intensive interventions, behavioral change interventions do not depend on the involvement of a health care professional on an ongoing basis. Illustrative examples include the uptake of oral rehydration therapy for use by mothers in the home, not the clinic; face washing to prevent trachoma; and condoms to prevent HIV infection or other sexually transmitted infections. As Jamison (2002) notes, some changes in behavioral practices associated with improved health, such as improved

Box 8.3

Behavioral Change Interventions: Illustrations from Cases Stopping smoking

Using nylon filters to purify water

Using condoms to prevent HIV/AIDS

Using oral rehydration salts

Source: Authors.


hygiene and better nutrition, are linked to rising incomes, but the pathway for this link is not entirely clear, especially at the individual level, which makes it difficult to predict which mix of programs and policies can be used to change behavior at the population level. Information plays an important role, but the evidence suggests that its effect may be limited if it is not combined with other mechanisms to induce behavioral change. The cases under review typically used a mix of strategies to induce behavioral change, including information, education, and communication (IEC) campaigns; regulatory policies; taxation or subsidies; and financial incentives or disincentives. The evidence is suggestive, but hardly conclusive, that a relative hierarchy exists among the available strategies and policy instruments and that some are more effective than others at altering how individuals perceive risk and weigh the costs and benefits of behavioral change. Chapter 11, for example, provides an in-depth discussion of how and when fiscal instruments may be used effectively to alter producers’ and consumers’ decisions in ways that encourage healthy behaviors. Information, Education, and Communication. Recent studies have challenged the effectiveness of mass IEC campaigns (Kremer and Miguel 2003), and evidence from the cases appears to support a degree of healthy skepticism. However, IEC campaigns did appear to have an effect in the cases under review when they were accompanied by the promotion of a new technology or a product. Also, acceptability appeared to increase if the product was adapted to fit the local circumstances or cultural context. In Sub-Saharan Africa, educational campaigns to stop transmission of the guinea worm to humans have encouraged the construction and maintenance of safe water sources (through deep-well digging and the application of larvicide to contaminated ponds) and the use of cloth or nylon filters to purify drinking water, in addition to case identification and containment. The primary IEC tool was so-called worm weeks—that is, weeks of intensive health education and community mobilization. In Egypt, in addition to nurses and physicians, mothers were a primary target of the campaign to promote the use of oral rehydration salts for the treatment of diarrhea in children, especially those under three years of age. Television was the primary educational medium and proved to be an effective strategy for reaching a broad population base, including rural, illiterate households. Appropriate product design and branding were essential. Oral rehydration salt packets were supplied in a 200-milliliter size, not the standard 1-liter packs, because mothers did not have appropriate containers at home and felt that a full liter was too much to give to a child to drink. By contrast, in Bangladesh, where few households had access to a radio, much less a television, health workers went door to door to teach mothers how to make the solution in their homes.

In these cases, the targeted population not only was aware of the health care problem, but also was eager to adopt solutions to address it. Clearly this situation does not always prevail, but a reasonable conclusion is that a relatively simple technology that addresses a recognizable, but as yet unmet, need will find a receptive audience. In Bangladesh, a mass media campaign to encourage families to have fewer children was backed up by a large cadre of female outreach workers, who went door to door in rural areas to provide information to young married women and to make family-planning commodities available to them. Market research indicates that almost all Bangladeshi women were in favor of family planning but were unable to go against their husbands’ objections if they were opposed to the use of contraceptives. The fact that the campaign and the provision of contraceptive commodities addressed an unmet need among Bangladeshi women may provide a partial explanation for the rapid acceptance of the program when it was launched on a large scale. Regulatory Policies. By contrast, other behavioral changes, such as using condoms to prevent HIV infection and other sexually transmitted infections and stopping smoking, have clearly been harder to induce, although the precise reasons for this difficulty remain elusive (see, in particular, chapters 18 and 46). Nevertheless, evidence from the cases suggests that governments can put the right mix of policies in place to either discourage high-risk behaviors or encourage health-promoting behaviors. For example, they may use regulatory policies to ensure compliance through nonfinancial means and may complement these by using fines and sanctions as an enforcement mechanism. The Thai government’s 100 Percent Condom Program is an excellent example of such a strategy. In 1991, the National AIDS Committee launched a national program to be implemented at the provincial level requiring all workers in brothels and other commercial sex establishments to refuse to have sex with any client not using a condom. The program had several components, including free distribution of condoms to health workers during regular health checks and a media campaign to raise awareness of the risks of HIV and the dangers associated with unprotected sex. What gave the program its unique character was its regulatory and enforcement component. Local governments, health authorities, and police officers were responsible for monitoring and enforcing condom use in the brothels. Those brothels that failed to comply with the strict policy would be fined or forced to shut down. The results were impressive. Condom use in brothels exceeded 90 percent in just the first year of the program, up from 14 percent in 1989. The number of new HIV infections fell by more than 80 percent, from 142,819 cases in 1991 to 25,790 cases in 2001. Furthermore, the program appears to have generated important spillover effects, or externalities, in unexpected places. For example, studies


indicate that indirect sex workers—a group that cannot be reached through similar enforcement strategies—have also begun to insist that their clients use condoms. Taxation and Subsidies. Another option for discouraging high-risk behaviors is the adoption of taxation policies. A 1997 study by the World Bank in partnership with the World Health Organization found that a price increase of 10 percent on cigarettes would lower smoking rates by about 4 percent in highincome countries and about 8 percent in low-income countries (Jha and Chaloupka 2000, 358). In South Africa, a 50 percent tax on the retail price of cigarettes contributed to a 30 percent decrease in consumption. In Poland, an increase in taxes on cigarettes from 30 to 47 percent of the retail price, in conjunction with other policies—including a ban on smoking in health care establishments, schools, enclosed spaces in the workplace, and elsewhere—contributed to a dramatic decline in smoking rates. Before the fall of communism, Poland had the highest cigarette consumption in the world, but by the end of the 1990s, there were 4 million fewer smokers compared with the previous decade, and cigarette consumption had fallen by 10 percent. These successes led to a 30 percent decrease in lung cancer among men age 20 to 44 and a 19 percent decrease among men age 45 to 64 over the same period. The section on service-intensive investments has already discussed the remarkable power of explicit subsidies to encourage health-promoting behaviors. The Mexican case of PROGRESA offers a by now familiar example of such a strategy. Although none of the cases included in this study dealt with subsidies explicitly directed at behavioral change interventions, evidence suggests that they have a significant effect. However, as Nugent and Knaul discuss in chapter 11, poorly targeted subsidies can be costly, particularly relative to the result achieved. Much more research is needed in this area to understand the specific contexts in which subsidies can achieve their desired effects and their cost-effectiveness relative to other types of interventions. Summary. In sum, behavioral change interventions differ from both product-intensive and environmental control interventions in that they require active participation by the individual for the intervention to be fully effective. In some cases, this requirement is also true for service-intensive interventions, but it is not as exclusively true as for behavioral change interventions. The degree to which incentives (or disincentives) are needed to induce (or discourage) behavior depends on the interaction between the usage characteristics of the intervention, the perceived risk of not using the intervention, and the perceived effectiveness of the intervention. To have an effect, policy incentives (and disincentives) must either succeed in changing the individual’s risk-benefit assessment or make ignoring the policy extremely costly.

Environmental Control Interventions As with behavioral change interventions, environmental control interventions are geared toward prevention and are used in conjunction with other treatments or alone when effective vaccines or other prophylaxes are unavailable. However, rather than focus on risk factors associated with individual behavior, environmental control interventions target risks associated with the physical environment that are largely beyond the individual’s control. The physical environment refers to media in the natural (water, air, or soil) or man-made (housing, roads) environment. Examples of environmental control interventions include many vector control strategies, such as aerial and household spraying, water and sanitation projects, and air quality control measures. (See, in particular, chapters 41 and 43.) Few of the cases reviewed for this study involved “pure” environmental control interventions; although in several cases environmental control measures were coupled with other types of interventions. Whenever activities involved in executing the intervention fall outside the realm of typical health care services, nonhealth government agencies will be involved, and strong political and technical leadership will be required of the ministry of health to ensure that proper attention is given to health care concerns during implementation. Successful interventions in this category also appeared to be associated with strong multicountry partnerships, particularly in relation to vector control activities. This factor raises an interesting question concerning governments’ capacity to engage in these types of partnerships. Technical capacity, although essential, is just the first hurdle, because what is ultimately required is a political and financial commitment at the highest levels in participating countries. In the case of Chagas disease control, the Southern Cone Initiative brought together the seven countries in the endemic region under a coordinated, comprehensive, Chagas disease control strategy. This multicountry approach was led by the Pan American Health Organization, following the recognition that disease transmission from neighboring countries was threatening the health gains achieved under Brazil’s national eradication plan. A central aim of the Southern Cone Initiative was to eliminate the protozoan parasite, Trypanosoma cruzi, in the region by coordinating technical efforts to detect and eliminate it. This coordination ensured consistent use of highly effective control measures across the region and limited any possibility of reinvasion. Infested homes throughout the region were treated with long-lasting pyrethroid insecticides and structurally improved to eliminate hiding places for the bloodsucking insects that spread the parasite. These coordinated environmental control efforts, combined with blood screening, proved to be highly successful at interrupting Chagas disease transmission in the region. Environmental control interventions also appear to be characterized by many consecutive years of sustained activity. In Improving the Health of Populations: Lessons of Experience | 177


some cases, this activity may take the form of ongoing maintenance of filters and distribution systems to prevent recontamination. In other cases, as in the case of vectorborne disease control in which elimination or eradication is within reach, the intervention must be sustained at least until transmission has been interrupted in humans. (The intervention may need to be sustained for much longer, or indefinitely, if the disease has an animal host.) In the case of onchocerciasis, the lifetime of the filarial load is 14 years, and vector spraying would need to be sustained for at least 14 years to cut transmission. If reinvasions or native vector population growth are allowed to take hold before the human loads die off, transmission will occur and the disease will not be effectively controlled. The OCP in West Africa has demonstrated the effectiveness of a long-term commitment to vector control in reducing the burden of onchocerciasis. Since its inception in 1974, the OCP has used aerial spraying of blackfly breeding sites to control vector populations and interrupt transmission. The original OCP area remains free of onchocerciasis transmission following the withdrawal of regular spraying after 14 years. This sustained attention proved to be highly successful in eliminating onchocerciasis transmission and infection. Even after the introduction of ivermectin drug therapy to the program, vector control has remained a key strategy for maintaining health benefits in the expansion area of the OCP. In sum, environmental control interventions are associated with intersectoral collaboration, multicountry partnerships, sustained activity, and attentiveness to context (for example, epidemiological conditions, patterns of disease transmission, and vector behavior). These factors place special capacity requirements on governments that may differ markedly from nonenvironmental interventions. Thus, to be effective, ministries of health must be capable of advocacy and influence within the broader structures of government.

Combination or Bundled Interventions A two-front battle involving both prevention and treatment must be waged against most diseases and conditions to achieve the desired effect on morbidity and mortality. Under such circumstances, a combination or bundling of interventions is needed, adding an additional layer of complexity to the deployment of any particular intervention. An effective malaria control strategy, for example, demands effective distribution and uptake of insecticide-treated bednets (a behavioral change intervention) and rapid treatment of malaria symptoms through strong outreach and referral systems (a serviceintensive intervention). Similarly, countries have adopted a dual approach to controlling the spread of HIV/AIDS: promoting safe sex practices (a behavioral control intervention) and supporting the scale-up of antiretroviral therapy (a serviceintensive intervention). In this context, global partnerships

have a critical role to play in providing technical assistance to countries in formulating policies and developing strategic plans that are tailored toward their specific needs and capabilities. Perhaps the most successful example of bundling interventions included in our study is the Moroccan National Blindness Control Program, launched in 1991. The program was based on the development in the mid 1980s of SAFE, a comprehensive strategy to treat and prevent trachoma. The philosophy of the new strategy, which was heavily researched and promoted under the support and guidance of the Edna McConnell Clark Foundation, was to augment the traditional medical approach to the treatment of trachoma with behavioral and environmental changes. The four main interventions the strategy recommended were surgery (service-intensive intervention); antibiotics (product-intensive intervention); face washing (behavioral change intervention); and environmental activities, including water and sanitation programs (environmental control intervention). The program consisted of a wide-ranging partnership that included five government divisions: the Ministry of Health, the Ministry of National Education, the Ministry of Employment, the Ministry of Equipment, and the National Office for Potable Water. Targets were set—Morocco’s political leaders were committed to eliminating trachoma by 2005—and the institutional and policy artillery to support the initiative was quickly put in place. Mobile surgical teams were deployed to small towns and villages to perform a simple, quick, and inexpensive procedure of the eyelid to halt corneal damage in infected patients; treatment campaigns were organized to distribute the newly discovered antibiotic, azithromycin, that could be administered in a single dose; IEC campaigns were launched at the community level with the participation of the Ministry of Education to educate the population about the causes of the disease and how to prevent it; and the National Office for Potable Water has expanded water and sanitation projects in many areas of the country. By 1999, prevalence levels had dropped 75 percent, from 28 to 6.5 percent, and acute infections in children had been reduced significantly.

CONCLUSION The accumulation of evidence presented in this study should help allay any remaining doubts about whether existing technologies and interventions, proven to be cost-effective in randomized controlled trials, can be successfully deployed to improve the lives and health of people throughout the developing world. The evidence suggests not only that it is possible, but also that it has been achieved in many parts of the world, in many different socioeconomic and political settings. The study also found important commonalities among programs and projects that appear to have contributed to the successful deployment and rapid scale-up of cost-effective


interventions. Strong leadership, effective management, realistic financing, country ownership, and application of new research findings and technical innovation all played a role in implementation and appeared to have made major contributions to the positive achievements of the cases under review. In some respects, the study also presents a sobering view of the difficulties inherent in moving from a cost-effective intervention to a successful program or project. No single formula is available, and identification of unique characteristics and attributes that will permit the large-scale, effective deployment of many known interventions is difficult. In addition, evidence from the case studies suggests that the programmatic characteristics and policies associated with successful outcomes vary depending on the type of intervention. Although no single formula exists, the implementation of the programs and projects structured around various types of interventions appears to depend on certain types of organizational, managerial, and financial capacities that can be anticipated and specifically targeted for strengthening before the full-scale launch of a program or project. Thus, the findings of this study may serve as pointers for future research seeking to understand the range of government capacities that are needed to support the successful deployment and scaling up of interventions in various contexts and in different parts of the world.

ACKNOWLEDGMENTS The authors gratefully acknowledge the helpful comments and feedback from Gerald T. Keusch, Phil Musgrove, John Peabody, and members of the What Works Working Group. Thanks also to Carol Kolb for providing excellent research assistance. The basic idea for the What Works Working Group, and for the material in this chapter, came principally from Richard Klausner, and we owe him special acknowledgment.

NOTES 1. Unless otherwise indicated, the background information and health impact data presented about the 17 cases reviewed for this study are drawn from Levine and What Works Working Group (2004). All materials are available at www.cgdev.org/publication/millionssaved. 2. According to World Development Report 2004 (World Bank 2004), because the relationship between provider and client differs, each of the three types of service arrangements will experience a different constellation of market, government, and accountability failures. The report proposes that if these failures are properly addressed and client power

increases, the quality of service delivery will improve, especially among poorer groups.

REFERENCES Collier, D., and H. E. Brady, eds. 2004. Rethinking Social Inquiry: Diverse Tools, Shared Standards. Lanham, MD: Rowman and Littlefield. Davis, K. 1956. “The Amazing Decline of Mortality in Underdeveloped Areas.” American Economic Review 46 (2): 305–18. Devarajan, S., D. Dollar, and T. Holmgren. 2001. Aid and Reform in Africa: Lessons from Ten Case Studies. Washington, DC: World Bank. Eckholm, E. 1989. “River Blindness: Conquering an Ancient Scourge.” New York Times Magazine, January 8. Filmer, D., J. S. Hammer, and L. H. Pritchett. 2000. “Weak Links in the Chain: A Diagnosis of Health Policy in Poor Countries.” World Bank Research Observer 15 (2): 199–224. Frank, C., M. K. Mohamed, G. T. Strickland, D. Lavanchy, R. R. Arthur, L. S. Magder, and others. 2000. “The Role of Parenteral Antischistosomal Therapy in the Spread of Hepatitis C Virus in Egypt.” Lancet 355 (9207): 887–91. Jamison, D. T. 1993. “Disease Control Priorities in Developing Countries: An Overview.” In Disease Control Priorities in Developing Countries, ed. D. T. Jamison, W. H. Mosley, A. R. Measham, and J. L. Bobadilla, 3–34. New York: Oxford University Press. ———. 2002. “Cost-Effectiveness Analysis: Concepts and Applications.” In Oxford Textbook of Public Health, 4th ed., ed. R. Detels, J. McEwen, R. Beaglehole, and H. Tanaka. Oxford, U.K.: Oxford University Press. Jamison, D. T., L. J. Lau, and J. Wang. 2005. “Health’s Contribution to Economic Growth in an Environment of Partially Endogenous Technical Progress.” In Health and Economic Growth: Findings and Policy Implications, ed. G. Lopez-Casasnovas, B. Rivera, and L. Currais, 67–91. Cambridge, MA: MIT Press. Jha, P., and F. Chaloupka. 2000. “The Economics of Global Tobacco Control.” British Medical Journal 321: 358–61. Kremer, M., and E. Miguel. 2003. “The Illusion of Sustainability.” http:// emlab.berkeley.edu/users/emiguel/miguel_illusion.pdf. Levine, R., and the What Works Working Group with Molly Kinder. 2004. Millions Saved: Proven Successes in Global Health. Washington, DC: Center for Global Development. Mill, J. S. 1843. “Of the Four Methods of Experimental Inquiry.” In A System of Logic, Raciocinative, and Inductive. Book 3. Reprint. Toronto: University of Toronto Press, 1974. Mills, A. 1983. “Vertical vs. Horizontal Health Programs in Africa: Idealism, Pragmatism, Resources, and Efficiency.” Social Science and Medicine 17 (24): 1971–81. Musgrove, P. 1988. “Is Polio Eradication in the Americas Economically Justified?”Bulletin of the Pan American Health Organization 22 (1): 1–16. Tucker, J. B. 2001. Scourge: The Once and Future Threat of Smallpox. New York: Grove Press. World Bank. 2004. World Development Report 2004: Making Services Work for Poor People. New York: Oxford University Press.



Chapter 9

Millennium Development Goals for Health: What Will It Take to Accelerate Progress? Adam Wagstaff, Mariam Claeson, Robert M. Hecht, Pablo Gottret, and Qiu Fang

The scale of the diseases and conditions that the Millennium Development Goals (MDGs) address is staggering: • Almost 11 million children died before their fifth birthday in 2000 (UNICEF 2001). Less than 1 percent of these 11 million deaths (79,000) occurred in high-income countries, compared with 42 percent in Sub-Saharan Africa, 35 percent in South Asia, and 13 percent in East Asia. • In 1998, an estimated 843 million people were considered undernourished on the basis of their food intake (FAO 2000). Of the estimated 140 million children under the age of five who were underweight, almost half (65 million) were in South Asia. • Of the 3.1 million people who died from HIV/AIDS in 2003, almost all (99 percent) were in the developing world—74 percent in Sub-Saharan Africa alone (UNAIDS 2004). Tuberculosis and malaria together killed an equal number; most of these deaths were among the poor. • In 1995, 515,000 women died during pregnancy or childbirth: 1,000 in the industrial world, contrasted with 252,000 in Sub-Saharan Africa (UNICEF 2001). This burden of death and suffering is heavily concentrated in the world’s poorest countries (Wagstaff and Claeson 2004). Death and disease matter in their own right, but they also act as a brake on poverty reduction. Nobel laureate Amartya Sen (2002) has described health as one of “the most important conditions of human life and a critically significant constituent of human capabilities which we have reason to value.” Health also matters because it influences the living standards of both households and countries. Health expenses can easily become burdensome

for households. In Vietnam, they are estimated to have pushed 3 million people into poverty in 1993 (Wagstaff and van Doorslaer 2003). Beyond the direct impact of ill health on households’ living standards through out-of-pocket expenditures, it indirectly affects labor income through productivity and the number of hours that people can work. The effects of illness on income, which may take time to appear, are often long lasting. Malnourished children are less likely to attend school and less likely to learn when they do attend, reducing their productivity in later life. The devastating economic consequences of illness and death are evident at the macroeconomic level as well. The AIDS epidemic alone has been estimated to reduce rates of economic growth by 0.3 to 1.5 percentage points annually (Bell, Devarajan, and Gersbach 2003). In the 1990s, the international community recognized the importance of health in development. In a period when overall official development assistance declined, development assistance to health rose in real terms. World Bank lending for health increased, with a doubling of the share of International Development Association disbursements going to health (OECD Development Assistance Committee 2000). The 1990s saw an increased global concern over the debt in the developing world, fueled in part by a perception that interest payments were constraining government health expenditures in developing countries. The enhanced Highly Indebted Poor Country Initiative, spearheaded by the International Monetary Fund and World Bank in response to the unsustainable debt burden of the poorest countries, was explicitly geared to channel freed resources into the health and other social sectors. The 181


Poverty Reduction Strategy Papers submitted by governments of developing countries seek debt relief or concessional (low-interest) International Development Association loans to set out their plans for fighting poverty on all fronts, including health. The 1990s also saw the development of major new global health initiatives and partnerships, including the Joint United Nations Programme on HIV/AIDS (UNAIDS); the Global Alliance for Vaccines and Immunization; the Stop TB Partnership; the Roll Back Malaria Partnership; the Global Fund to Fight AIDS, Tuberculosis, and Malaria; and the Global Alliance for Improved Nutrition. A range of new not-for-profit organizations were set up to spur the accelerated discovery and uptake in developing countries of low-cost health technologies to address the diseases of the poor; these organizations included the International AIDS Vaccine Initiative, the Medicines for Malaria Venture, the Global Alliance for Tuberculosis, and the International Trachoma Initiative. In addition, the scale of philanthropic involvement in international health increased, with the launch of the Bill & Melinda Gates Foundation and the Packard Foundation and the continued attention to global health issues by such established entities as the Rockefeller Foundation. These initiatives brought not only new resources—funds, ideas, energy, and mechanisms— but also new challenges to harmonization in the attempt to coordinate and link global goals with local actions in the fight against disease, death, and malnutrition in the developing world. As the 1990s closed, the international community decided that even more needed to be done. At the United Nations Millennium Summit in September 2001, heads of 147 states endorsed the MDGs, nearly half of which concern different aspects of health—directly or indirectly (box 9.1). Several other

goals are indirectly related to health—for example, the goals on education and gender. Gender equality is considered important to promoting good health among children. Other health outcomes than those included in the MDGs measure progress on health—for example, targets related to noncommunicable diseases. These targets are referred to as the MDG plus and are included in national priority setting, especially in many middle-income countries.

THE MILLENNIUM DEVELOPMENT GOALS FOR HEALTH: PROGRESS AND PROSPECTS Of the MDGs for which trend data are available or estimated, the fastest progress has been on malnutrition, whereas overall progress on under-five mortality and maternal mortality has been slower. A Mixed Score at Halftime In-depth analysis of the health-related MDGs shows a mixed score at halftime (Wagstaff and Claeson 2004): • The number of people living in on-track countries (countries that will reach the MDGs if they maintain the rate of progress they have already achieved during the period from 1990 to the present) matters. For the malnutrition target, 77 percent of the developing world’s people live in an ontrack country, but in Sub-Saharan Africa only 15 percent of the people live in an on-track country. • Different indicators show different levels of improvement. For under-five mortality, the developing world was reduced by an average of only a 2.5 percent in the 1990s, well short of the target of 4.3 percent.

Box 9.1

The Health-Related Millennium Development Goals Goal 1—eradicating extreme poverty and hunger. This goal includes as a target the halving between 1990 and 2015 of the proportion of people who suffer from hunger, with progress to be measured in terms of the prevalence of underweight children under five years of age. The target implies an average annual rate of reduction of 2.7 percent. Goal 4—reducing child mortality. The target is to reduce by two-thirds between 1990 and 2015 the under-five mortality rate, equivalent to an annual rate of reduction of 4.3 percent. Goal 5—improving maternal health. The target is to reduce by three-quarters between 1990 and 2015 the maternal

mortality ratio, equivalent to an annual rate of reduction of 5.4 percent. Goal 6—combating HIV/AIDS, malaria, and other diseases. The target is to halt and begin to reverse the spread of these diseases by 2015. Goal 7—ensuring environmental sustainability. This goal includes as a target the halving by 2015 of the proportion of people without sustainable access to safe drinking water. Goal 8—developing a global partnership for development. This goal includes as a target the provision of access to affordable essential drugs in developing countries.

Source: United Nations Millennium Declaration, the United Nations Millennium Summit 2000.

182 | Disease Control Priorities in Developing Countries | Adam Wagstaff, Mariam Claeson, Robert M. Hecht, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 18

• Regional differences are also pronounced, with Sub-Saharan Africa faring worse than other regions. In Africa, trends in reducing under-five mortality and underweight in children were barely above zero during the 1990s, and maternal mortality fell on average by just 1.6 percent a year compared with the annual target rate of 5.4 percent. • Evidence on how the poor are faring within countries is mixed. For malnutrition, the poorest 20 percent of the population within countries appears, on average, to have been experiencing broadly similar rates of reduction to the population as a whole. However, for under-five mortality, the rate has been falling more slowly among the poor, while better-off families are seeing faster rates of progress. Will the Second Half Go Better? As a comparison of the child mortality experiences in the 1980s and 1990s demonstrates, past performance is not necessarily a good predictor of future performance. The fact that a country is on track on the basis of its performance in the 1990s does not guarantee that it will maintain the required annual rate of reduction of malnutrition or mortality during the second half of the MDG “window” from 2000 to 2015. Countries currently off track may possibly get on track in the second half if they can combine good policies with expanded funding for programs that address both the direct and the underlying determinants of the health-related goals. Stimuli External to the Health Sector. The World Bank estimates that economic growth will fall somewhat in East Asia and the Pacific in 2000–15, turn from negative to positive in Europe and Central Asia as well as Sub-Saharan Africa, and increase somewhat in Latin America and the Caribbean, the Middle East and North Africa, and South Asia (Jones and others 2003). Primary education completion rates will probably grow faster in the new millennium as a result of the global education initiatives and partnerships on Education for All and the Fast-Track Initiative. However, higher rates of educational attainment among women of childbearing age will not be achieved until 2005 or so, and even then the first full round of effects on under-five mortality will not be felt until 2010. More relevant is the fact that gender gaps in secondary education may well narrow faster in the new millennium than in the 1990s as a result of the gender MDG (Goal 3: Eliminate gender disparity in primary and secondary education by 2005 and in all levels of education no later than 2015). To achieve parity with boys by 2015 in the proportion of the population who are age 15 and have completed secondary education, girls will have to achieve a faster growth in completion rates in the new millennium than in the 1990s in most regions, especially in South Asia and in East Asia and the Pacific. If the water MDG (ensuring that households have access to safe drinking water) is to be reached, access rates will need to grow much

faster in 2000–15, especially in Sub-Saharan Africa (Wagstaff and Claeson 2004). Gender equality in school and access to clean water will have a positive effect on progress toward the health MDGs. Even with economic growth and faster progress on these nonhealth goals, however, many regions will still miss many of the health targets. The picture is bleakest for underfive mortality—and for Sub-Saharan Africa. The Goals Matter for All Countries. These goals need to be taken seriously for three main reasons: • Faster progress is important even if targets are missed. A key message of this chapter is that progress can be accelerated in all countries through a judicious mix of spending and policy and institutional reform. • The goals facilitate benchmarking and monitoring of results. Because the goals focus on a limited set of outcomes, monitoring and evaluating progress toward the MDGs can show what is achievable and where faster progress can be made. • Focusing attention on national progress, as measured by distributional analysis of the MDGs, forces countries to consider how the benefits of progress are distributed among the rich and poor within each country—the poor risk being left behind even in countries making progress overall. One limitation of the MDGs and targets is that they are national averages. However, distributional analysis of MDG trends (Wagstaff and Claeson 2004) reminds us that progress needs to be for everyone, not just the better off. Progress has been uneven, with the poorer countries lagging behind the rest, and for under-five mortality, the poor within countries are lagging behind the rest of the population.

SCALING UP: DEFINING INTERVENTIONS AND REMOVING CONSTRAINTS A lack of interventions is not the primary obstacle to faster progress toward the goals, although new interventions that can be delivered by weak health systems could greatly improve progress—for example, malaria or HIV vaccines and effective vaginal microbicides to block the spread of HIV and other sexually transmitted infections. The main obstacle is the low levels of use—especially among the poor—of existing effective interventions. For example, if use of all the proven effective preventive and treatment interventions for childhood illness were to rise from current levels to reach all, the number of under-five deaths worldwide could fall by as much as 63 percent (World Bank 2003b). Array of Interventions, Programs, and Service Modalities The available interventions constitute a powerful arsenal for preventing and treating the main causes of malnutrition and death (table 9.1).1 The major diseases and conditions that the MDGs aim to prevent and control are discussed in several

Millennium Development Goals for Health: What Will It Take to Accelerate Progress? | 183 ©2006 The International Bank for Reconstruction and Development / The World Bank 19

Table 9.1 Effective Interventions to Reduce Illness, Deaths, and Malnutrition MDG

Preventive interventions

Treatment interventions

Child mortality

Breastfeeding; hand washing; safe disposal of stool; latrine use; safe preparation of weaning foods; use of insecticide-treated bednets; complementary feeding; immunization; micronutrient supplementation (zinc and vitamin A); prenatal care, including steroids and tetanus toxoid; antimalarial intermittent preventive treatment in pregnancy; newborn temperature management; nevirapine and replacement feeding; antibiotics for premature rupture of membranes; clean delivery

Case management with oral rehydration therapy for diarrhea; antibiotics for dysentery, pneumonia, and sepsis; antimalarials for malaria; newborn resuscitation; breastfeeding; complementary feeding during illness; micronutrient supplementation (zinc and vitamin A)

Maternal mortality

Family planning (lifetime risk); intermittent malaria prophylaxis; use of insecticide-treated bednets; micronutrient supplementation (iron, folic acid, calcium for those who are deficient)

Antibiotics for preterm rupture of membranes, skilled attendants (especially active management of third stage of labor), basic and emergency obstetric care

Nutrition

Exclusive breastfeeding for 6 months, appropriate complementary child feeding for next 6–24 months, iron and folic acid supplementation for children, improved hygiene and sanitation, improved dietary intake of pregnant and lactating women, micronutrient supplementation for prevention of anemia and vitamin A deficiency for mothers and children, anthelmintic treatment in school-age children

Appropriate feeding of sick child and oral rehydration therapy, control and timely treatment of infectious and parasitic diseases, treatment and monitoring of severely malnourished children, high-dose treatment of clinical signs of vitamin A deficiency

HIV/AIDS

Safe sex, including condom use; unused needles for drug users; treatment of sexually transmitted infections; safe, screened blood supplies; antiretrovirals in pregnancy to prevent maternal to child transmission and after occupational exposure

Treatment of opportunistic infections, co-trimoxazole prophylaxis, highly active antiretroviral therapy, palliative care

Tuberculosis

Directly observed treatment of infectious cases to prevent transmission and emergence of drug-resistant strains and treatment of contacts, Bacillus Calmette-Guérin immunization

Directly observed treatment to cure, including early identification of tuberculosis symptomatic cases

Malaria

Use of insecticide-treated bednets, indoor residual spraying (in epidemic-prone areas), intermittent presumptive treatment of pregnant women

Rapid detection and early treatment of uncomplicated cases, treatment of complicated cases (such as cerebral malaria and severe anemia)

Source: Authors.

chapters (for example, see chapters 15, 19, 21–24, 28–31, 44, and 45). The most cost-effective interventions and programs are also discussed in several chapters (see chapters 59–62 and 65). The chapters dealing with health systems and service delivery issues and other constraints related to the health MDGs are found in the latter part of the book (see chapters 66–68, and 73). In the case of child mortality, for example, diarrheal diseases, pneumonia, and malaria account for 52 percent of deaths worldwide (World Bank 2003b). For each of these major causes of childhood mortality, at least one proven effective preventive intervention and at least one proven effective treatment intervention exist, capable of being delivered in a low-income setting. In most cases, several proven effective interventions exist. For diarrhea—the second-leading cause of child deaths—no fewer than five proven preventive interventions and three proven treatment interventions are available. Effective Interventions Reaching Too Few People The high rates of malnutrition and death in the developing world have several causes. First, people do not receive the effec-

tive interventions that could save their lives or make them well nourished. In middle- and high-income countries, 90 percent of children are fully immunized, more than 90 percent of deliveries are assisted by a medically trained provider (that is, a doctor, nurse, or trained midwife, excluding traditional birth attendants), and more than 90 percent of pregnant women have at least one prenatal visit (UNICEF 2001). In South Asia, fewer than 50 percent of pregnant women receive a prenatal checkup, and only 20 percent of deliveries are assisted by a trained provider. The story is similar for other childhood interventions— and for interventions for other goals. Condom use to prevent transmission of HIV is low in much of Sub-Saharan Africa and South Asia, and inexpensive one-time treatment with antiretroviral medicine to prevent transmission from mother to child covers only a small fraction of at-risk pregnant women in most of the developing world. In Asia, where more than 7 million people are living with HIV/AIDS, no country has yet exceeded 5 percent antiretroviral therapy coverage among those who could benefit from it (World Bank 2003c).


Just as shortfalls in coverage vary across countries, so do they vary within countries, with the poor and other deprived groups consistently lagging. These groups are less likely to receive full basic immunization coverage, to have their deliveries attended by a trained provider, and to have at least one prenatal care visit to a medically trained provider. On the positive side, the poor are often making fastest progress in coverage, reflecting in part that the better off already have high coverage rates for many interventions.

Underuse of Effective Interventions Costs Lives The low use of effective interventions—in the developing world in general and among the poor in particular—translates into rates of mortality, morbidity, and malnutrition that are far higher than necessary. If use of all the proven effective childhood preventive and treatment interventions, for example, were to rise from their current levels to 99 percent—95 percent for breastfeeding—the number of under-five deaths worldwide could fall by as much as 63 percent (Jones and others 2003). Deaths from malaria and measles could be all but eliminated, and deaths from diarrhea, pneumonia, and HIV/AIDS could be reduced dramatically. If coverage rates of the key maternal mortality interventions were increased from current levels to 99 percent, an estimated 391,000 maternal deaths worldwide (74 percent of current maternal deaths) might be averted (Ramana 2003). One intervention stands out as especially important: access to essential obstetric care, which accounts for more than half the maternal deaths averted.

allocations. In practice, however, the amount of extra spending required would be difficult to attain on present trends and would even be prohibitively expensive. In the case of East Asia and the Pacific, for example, if economic growth proceeds as expected and the other relevant Millennium Development Targets are attained, the region would achieve the required rates of reduction of underweight and maternal mortality— assuming that economic growth is accompanied by the development of appropriate human resources for health—even if government health spending continues to grow at its current rate. However, the region would miss the under-five mortality target. To reach that target, a minimum of 5 percentage points would need to be added to the annual rate of growth of the government health share of gross domestic product (GDP). That would take the projected share of GDP spent on government health programs to 3.7 percent in 2015—more than twice what it would be if the 1990s pattern of growth continued (Wagstaff and Claeson 2004). In Sub-Saharan Africa, the situation is even starker. Even if faster economic growth materializes and the other targets are achieved, the share of government health spending in GDP would need to grow nearly sixfold over the coming decade, taking the share to 12.2 percent of GDP in 2015. This percentage compares with a 2000 figure of 1.8 percent and a 2015 forecast of 2.2 percent based on the 1990s annual growth in government spending for health. In conclusion, African countries will not be able to reach the MDGs simply by multiplying their health spending along the lines of historical expenditure patterns, because the multiples required are beyond any realistic expectation of what these governments will be able to do during the next 10 years.

WHAT DO COUNTRIES NEED TO DO? If the lack of interventions is not holding countries back from achieving the goals, what is? What do countries need to do to make progress toward the MDGs? In countries with good governance, additional government health spending does reduce child mortality (Rajkumar and Swaroop 2002). Development assistance has a stronger effect in countries with strong policies and institutions than in countries with only average-quality policies and institutions—and an insignificant effect in countries where policies and institutions are weak. This assertion is also consistent with the findings of a study undertaken by the World Bank for the MDG report, The Millennium Development Goals for Health: Rising to the Challenges (Wagstaff and Claeson 2004). The study includes other outcomes with child mortality and uses the World Bank’s Country Policy and Institutional Assessment index to measure the quality of policies and institutions. In principle, well-governed countries with good policies and institutions could achieve the goals simply by scaling up their expenditures on existing programs in proportion to current

What Are the Implications? Poorly governed countries cannot expect to make much progress toward the MDGs simply by scaling up their expenditures on existing programs in proportion to current allocations. Although well-governed countries could, in principle, simply scale up existing spending to reach the targets, this option is unlikely to be affordable for them or their donors. This situation has two implications: • First, targeting additional government spending to activities that will have the largest effect on the MDGs is important for both sets of countries. • Second, building good policies and institutions is important for all countries: doing so increases the productivity not just of additional spending but also of existing spending commitments. What do better policies and institutions entail in the health sector? Health systems are very broad, and weak policies and institutions can arise at several points along the pathway, from government health spending to health


outcomes (Claeson and others 2001). Countries can do a number of things, with help from donors, to build stronger policies and institutions.

Improving Expenditure Allocations and Targeting In most countries, government spending gets stuck in the cities and disproportionately accrues—in a financial sense—to people who are better off. Geographic Targeting. Resource allocation formulas can be used to reduce government spending gaps across regions and ideally to favor geographic zones that are furthest behind. These formulas have been used, for example, as part of Bolivia’s decentralization efforts since 1994 and have been associated with some large—and pro-poor—improvements in maternal and child health indicators. Targeting resources to poor regions and provinces may be most effectively implemented through nontraditional mechanisms for priority setting and implementation, such as social investment funds. In Bolivia, a recent impact evaluation concluded that such funds were responsible for a decline in under-five mortality from 88.5 to 65.6 per 1,000 live births over a five-year period (Newman and others 2002). Changing the Allocation of Spending across Care Levels. Spending on health in developing countries is characterized by a high concentration of spending on secondary and tertiary infrastructure and personnel. Some governments have tried to scale back the share of hospital spending. Tanzania, for example, reduced the share of hospital spending from 60 percent in 2000 to 43 percent in 2002. Chapter 3 deals with the issue of how to couple expenditure reallocations across levels of care with measures to improve performance at each level of the health care system. Targeting Specific Programs. Programs such as those delivering directly observed treatment short course (DOTS) for tuberculosis or integrated management of infant and childhood illness (IMCI) for child health are good examples of programs that may yield high returns to government spending at the margin. A recent World Bank study in India provides further support for the idea that the way government spending is allocated across programs makes a difference to its effect on the Millennium Development Indicators (World Bank 2003a). Successful public health programs—large-scale programs with a measurable health effect over at least a five-year period—are further discussed in chapter 8. All successful programs have several factors in common: technical innovation and stakeholder consensus, strong political leadership, coordination across agencies and management, effective use of information and financial resources, and participation of the beneficiary community.

Targeting Specific Population Groups. Many countries subsidize all government health services for everyone. These blanket subsidy schemes not only fail to target interventions that give rise to externalities but also fail to disproportionately benefit the poor—despite the stronger equity case for subsidizing their care and the fact that they tend to bear a disproportionate burden of malnutrition as well as child and maternal mortality. There are many proven ways to target the poor—for example, by delivering essential services in clinics or health posts that only poor families attend or by promoting and delivering services in a way that segments the market and appeals to those in low-income households. Targeting Spending to Remove Bottlenecks. A planning and budgeting approach is to assess—for a country—the health sector impediments to faster progress, to identify ways of removing them, and to estimate both the costs of removing them and the likely effects of their removal on MDG outcomes (Soucat and others 2002). MDG analysis along these lines— referred to sometimes as marginal budgeting for bottlenecks (MBB)—has begun in several African countries and in some states of India (UNICEF and World Bank 2003). In Mali, key bottlenecks were identified for supporting home-based practices and delivering periodic and continual professional care. They included low access to affordable commodities and the need for community-based support for home-based care; low geographical access to preventive professional care (immunization, vitamin A supplementation, and prenatal care); shortages of qualified nurses and midwives; and an absence of effective third-party payment mechanisms for the poor for professional continuous care. Important health systems bottlenecks, such as human resources, drug availability, and health care management, are discussed in chapters 71–73.

Improving Policies toward Households as Producers and Demanders of Care Households are at the center of any efforts to scale up; they not only demand and consume care, but they are also important producers of prevention and care. Policies to increase coverage of cost-effective interventions to reach the health MDGs, therefore, need to identify and influence the key constraints to both the production and the demand for those services at the household and community levels. Lowering Financial Barriers. Low income is a barrier to the use of most health interventions, and economic growth is an important weapon in the war against malnutrition and mortality. However, social protection programs are also important. Successful schemes aimed at households and communities are discussed in chapter 56.


One part of the affordability equation is price. User charges for MDG interventions are to be discouraged. Why? Many of those interventions involve benefits that spill over to people who do not receive the intervention; high coverage of immunization is a classic example. However, an equity case also can be made for reducing prices facing the poor and near poor, even where no spillovers occur. Subsidies should be targeted to services with spillovers and to the poor. In practice, subsidies are often badly targeted in at least one respect if not both. Exceptions exist. In Ifakara, Tanzania, a voucher program for mosquito nets was launched successfully for pregnant women and children under five (Schellenberg and others 2001). Some recent programs, especially in Latin America, have not only made health care affordable for the poor but have also made it profitable. Rather than simply reducing the cost of using specific interventions, these programs provide users with cash payments, which are linked to specific interventions and restricted to certain groups—often poor mothers and their children. The experience with these programs in targeting and achieving results is encouraging (Mesoamerica Nutrition Program Targeting Study Group 2002; Morris and others 2003; Palmer and others 2004). Risk aversion coupled with the unpredictability of illness provides a motivation for pooling risks through an insurance scheme. The Arab Republic of Egypt, for example, introduced a school health insurance program for all children attending school. The program resulted in larger increases in coverage among the poor and achieved considerable effect on use and out-of-pocket expenditures (Yip and Berman 2001). However, insurance in the developing world is very limited, and those who are least able to smooth consumption without insurance are the least likely to have insurance coverage (Musgrove, Zeramdini, and Carrin 2002). Another problem is that many of the schemes are small scale, and evaluations of these schemes do not generally measure health effect or effect on equity, thus resulting in limited evidence (Palmer and others 2004). Providing Information—Enhancing Knowledge. Lack of knowledge is a major factor behind poor health. It results in people not seeking care when needed, despite the absence of price barriers, and it also results in people—especially poor people—wasting limited resources on inappropriate care. Ignorance may also result in people not getting the maximum health gain out of inputs they have available to them and use. Many people do not know that hand washing confers much of the health benefit of piped water (see chapter 41). Not surprisingly, piped water has a much greater effect on the prevalence of diarrhea among the children of the better off and better educated. Better-educated women—especially those with a secondary education—achieve better health outcomes for themselves and their children not by using health-specific knowledge that they acquire at school, but by using general

numeracy and literacy skills learned at school to acquire healthspecific knowledge later in life. Although better-educated girls will mean healthier women and healthier children in years to come, a shorter and more direct route to increasing healthspecific knowledge and skills is through information dissemination, health promotion, and counseling in the health sector. Several success stories exist. In Brazil, after health workers trained by IMCI provided information and counseling at health facilities and in the community, health knowledge among mothers improved, as did feeding practices (Santos and others 2001). After only 18 months, the nutritional status of children in the area improved as well. Social marketing and media campaigns—for example, malaria and social marketing of insecticide-treated nets (see chapter 21)—have also proved effective in some circumstances. Reducing Time Costs Transportation systems, road infrastructure, and geography influence the demand for care delivered by formal providers through their effect on time costs, which can be substantial. In rural communities, where the roads are poor and the transportation unreliable, the time spent waiting for the transportation is also a major cost. Time costs tend to be a major issue for maternal mortality: health centers are unable to provide essential obstetric care for a complicated delivery, and women would have to travel to distant hospitals to get such services. Road rehabilitation and other transportation projects are important here, but so are subsidies linked to the use of health services. Malaysia and Sri Lanka provide free or subsidized transportation to hospitals in emergencies (Pathmanathan and others 2003). Other options for tackling inaccessibility include using outreach and establishing partnerships between government and nongovernmental organizations (NGOs), private providers, or community organizations. Providing Access to Water and Sanitation The availability of adequate supplies of water and improved sanitation is associated with better maternal and child health outcomes, at least among the better educated, even after controlling for other influences. This result is not altogether surprising. Hand washing is easier if the household has piped water that provides readily available quantities of safe water. The safe disposal of feces is easier if the household has an improved form of sanitation. The developing world lags well behind the industrial world in both; the poorer people fare especially badly. They are less likely to be connected to a network, and the sources they rely on tend to be more costly per liter than the networked services used by the better off. The challenge from a health perspective is to get maximum health benefits from investments in access to water and sanitation infrastructure. Efforts to work across sectors on water and health, in order to influence the health MDGs, are under way in Ethiopia, Peru, and Rwanda.


Improving Health Service Delivery Health providers—in the public and private sectors, as well as in both formal and informal sectors—should deliver interventions of relevance to the MDGs. Many are efficient, deliver high quality services, and are responsive to their patients. Many, however, are not; many are not even there to deliver any services at all. As a result, resources—public and private—are often nonexistent, underused, or wasted. Two things can make a difference. One is the quality of management. Better management means a clearer delineation of responsibilities and accountabilities inside organizations, a clearer link between performance and reward, and so on. Management means getting accountabilities right within an organization. The other thing that can make a difference is getting accountabilities right between the organization and the public (World Bank 2003d). Improving Management—Increasing Accountability within Provider Organizations. Management styles in governmentfunded and government-implemented health schemes have recently begun to change, focusing on performance—that is, on outputs and outcomes—rather than on inputs and processes. Good performance is rewarded, financially or in some other way. The focus is on clients and on the belief that an organization is ultimately accountable to its clients. A clientoriented strategy emphasizes customer choice and satisfaction. Business techniques enhance performance and are a standard part of strategic planning. This new approach is evident in several countries, and elements of the approach are visible in successful nutrition and child health programs (see chapter 56). For example, in Tamil Nadu’s Integrated Nutrition Program, community nutrition workers were given clearly defined duties. Information on outputs not only enabled the community to keep the workers accountable but also enabled the nutrition workers to see how their program was working. In Ceara’s Programa de Agentes de Saude, which is credited with a substantial reduction in child mortality (Victora and others 2000), health agents and nursesupervisors were assigned clear tasks and given clear responsibilities. The intended outcomes of the program were emphasized to health workers and members of the public, and the health agents were held accountable through communitybased monitoring and rewarded for good performance. Governance. The accountability of provider organizations to the public can be improved through enhanced governance or contracting. Having community representatives participate in the governance and oversight of providers can improve the productivity and quality of public sector providers. In Burkina Faso, participation of community representatives in public primary health care clinics increased immunization coverage, the availability of essential drugs, and the percentage of

women with two or more prenatal visits. In Peru, comparisons of primary health care clinics with and without community participation in governance suggested decreases in staff absenteeism and waiting times and suggested increases in perceived quality by patients (Cotlear 1999). The approach probably works best for primary care and in situations in which strong technical and advisory support is provided to community representatives who are close to the service being delivered. Contracting. Evidence on the effect of contracting within the public sector is mixed, and the experiences are mainly based on lessons learned from middle-income countries. In several countries in Europe and Central Asia, evidence shows a positive effect from performance-based payment, but that is not necessarily the same as contracting, which can occur without performance-related pay. The best evidence relates to the use of target payments for the attainment of a given level of coverage—for example, for immunization or cervical cytology at the primary care level (Langenbrunner 2003). In Argentina and Nicaragua, social security institutes have increased productivity by establishing capitation-based payments for an integrated package of inpatient and ambulatory services (Bitran 2001). Key influences on the success of contracts within the public sector include whether the provider has the ability to respond, whether service commitments are congruent with funding levels, whether output and key components of performance expectations are easily measurable, and how far capacity strengthening of the payer or funder is addressed. Contracting with nonprofit organizations is most common in low-income countries (see chapter 12, which contains a longer discussion of contracting with NGOs). Most cases have had positive effects on target outcome or output variables. In Bangladesh, contracts with nonprofit organizations for planning and implementing an expanded program on immunization project were credited with a dramatic increase in immunization. In Haiti, contracting for a primary health care package also significantly increased immunization coverage (Eichler, Auxilia, and Pollock 2001). In Bangladesh, Madagascar, and Senegal, significant reductions in nutrition rates were attributed to contracting initiatives (Marek and others 1999). Only a few cases assess efficiency. Contracting with nonprofits works best when the contractors have wellfunctioning accountability arrangements and strong intrinsic motivation and when the government makes timely payments to the NGOs. The government needs to be capable of assessing, selecting, and managing the ongoing relationship with contractors. The methodological quality of evaluating contracting is often poor and needs to be improved. An exception is the Cambodian contracting trial that used a rigorous cluster randomized design, but the intervention groups had greater input of resources than the control communities, which may have been partly responsible for the difference in performance.


Results on contracting with for-profit private service providers are also mixed. Experience from the hospital sector warns that weak government contracting capacity often allows the provider to capture efficiency gains or to expand volume— not necessarily of cost-effective services—to generate more income. In Zimbabwe, the cost per service decreased, but the lack of volume control led to an increase in total cost (McPake and Hongoro 1995). Other adverse outcomes are possible. In Brazil, contracting with for-profit hospitals led to increases in access, but also increases in fraud (false billing) and creamskimming to avoid costly patients (Slack and Savedoff 2001). These problems seem less pronounced in primary health care. In Peru and El Salvador, contracting with private primary health care providers increased access, choice, and consumer satisfaction (Fiedler 1996). Contracting with for-profit providers seems to work best when the government invests in the development of capacity to manage the contracting process (Mills, Bennett, and Russell 2001); when quality is at least as high in the private sector as in the public sector; and when the services involve primary care or other relatively observable services, such as diagnostic services.

Strengthening Core Public Health Functions Vulnerable populations need to be protected from risks and damages, informed, and educated. Public health regulations need to be established and enforced. Infrastructure needs to be in place to reduce the impact of emergencies and disasters on health. All this action needs to be implemented through a public health system that is transparent and accountable. Governments in developing countries generally recognize that these public health functions are important, but they often lack the capacity and financial resources to implement them. Indeed, few low-income countries invest in these public health functions. By employing public health professionals with core public health competencies, the government can develop and enforce standards; can monitor the health of communities and populations; and can emphasize health education, public information, health promotion, and disease prevention. Public action can help improve consumer knowledge and change attitudes so that private markets can operate effectively to meet the needs of the poor, for example, through social marketing of insecticidetreated bednets to reduce malaria transmission or of condoms for protection against HIV/AIDS. Government-Led Monitoring and Evaluation. Integrated disease surveillance, program assessment, and collection and analysis of demographic and vital registration data are essential if governments and donors are to ascertain whether policies and programs are positively affecting health goals. Governments can use a list of intermediate indicators and

proxies for the goals that can help monitor progress, test the impact of policies, and adjust programs going forward (World Bank 2001). Such indicators should be simple, easily measurable, representative, easy to understand, scientifically robust, and ethical. They need to be assessed regularly because the MDGs themselves are difficult to collect, thus entail delays, and are therefore not useful for regular monitoring of progress. Greater investments are needed in systems to monitor these intermediate indicators and to track expenditures on public health. Although some good practices in surveillance are being developed—for example, in Brazil, China, and India—few lowincome developing countries can afford to invest in the infrastructure required for strong surveillance systems. Most rely on alternative short- to medium-term solutions for data gathering, such as intermittent household surveys, health facility surveys, and simplified facility-based routine reporting. A few countries have made special efforts to improve the surveillance of a specific intervention, such as AIDS and tuberculosis treatment or childhood immunization, whereas others have attempted to monitor progress toward a specific MDG. INDEPTH (International Network of Field Sites with Continuous Demographic Evaluation of Populations and Their Health in Developing Countries), which is supported by the Rockefeller Foundation with help from other donors, coordinates a range of surveillance sites, many of them in Africa, and the Health Metrics network aims at improving the quality of surveillance data. Some governments are explicitly developing or modifying their monitoring and evaluation framework to focus on the MDGs. Intersectoral Actions—Going Beyond the Ministry of Health. A review of the evidence base for the key determinants of the health and nutrition MDGs identifies significant potential for intersectoral synergies (Wagstaff and Claeson 2004). Transportation Although roads and transport are vital for health services, especially for reducing maternal mortality, it is not just the physical infrastructure that matters. Also important are the availability of transportation and the affordability of its use, as shown in a study in Nigeria (Eissen, Efenne, and Sabitu 1997). Transportation and roads complement health services. A 10-year study in Rajasthan, India, found that better roads and transportation helped women reach referral facilities, but many women still died because no corresponding improvements took place at household and facility levels. Working with the transportation sector is also important for reducing HIV transmission in many settings and making progress on the HIV/AIDS-related MDG. Hygiene Improved hygiene (use of hand washing) and sanitation (use of latrines and safe disposal of children’s stools) are at least as important as drinking water quality in shaping health


outcomes, specifically in reducing diarrhea and associated child mortality (Esrey and others 1991). Constructing water supply and sanitation facilities is not enough to improve health outcomes; sustained human behavior change must accompany the infrastructure investment. By collaborating with other sectors, the health sector can develop public health promotion and education strategies and implement them in partnership with agencies that plan, develop, and manage water resources. The health sector can also work with the private sector to manufacture, distribute, and promote affordable in-home water purification solutions and safe storage vessels—and advocate for water, sanitation, and hygiene interventions in strategies to reduce poverty. Indoor Air Quality Indoor air pollution is caused by use of low-cost, traditional energy sources, such as coal and biomass for cooking and heating, the main source of energy for 3.5 billion people. Indoor air pollution is a major risk factor for pneumonia and associated deaths in children and for lung cancer in women who risk exposure during cooking (see chapter 42). Studies in China, Guatemala, and India are under way to improve access to efficient and affordable energy sources through local design, manufacturing, and dissemination of low-cost technologies, modern fuel alternatives, and renewable energy solutions. The community-based project in China was initiated by the Ministry of Health, which was troubled by the leveling off of child mortality reductions among the rural poor and was seeking ways to influence major environmental determinants of child mortality. The program combines appropriately improved stoves and ventilation with behavior-change modification; it is in an early stage of implementation, and results on outcomes are not yet available. Agricultural policies and practices influence food prices, farm incomes, diet diversity and quality, and household food security. Policies that focus on women’s access to land, training, and agricultural inputs; on their roles in production; and on their income from agriculture are more likely to have a positive effect on nutrition than interventions without a focus on women, particularly if combined with other strategies, such as women’s education and behavior change (Johnson-Welch 1999; Quisumbing 1995). The MDG agenda highlights the need not only to prioritize within health to achieve better health outcomes, but also to better inform priority setting in resource allocations between sectors, identifying intersectoral synergies and finding ways to maximize benefits for health.

COSTING AND FINANCING ADDITIONAL SPENDING FOR THE MDGS Additional health spending will be required in many countries to accelerate progress toward the health goals (see chapter 12). What will it cost, and how will extra spending be financed?

Cost of Achieving the MDGs Globally The global estimates of what it would cost to achieve the MDGs range from an additional US$20 billion to US$70 billion a year. A World Bank study (http://www.worldbank.org/html/extdr/ mdgassessment.pdf) estimates that the additional official development assistance required to meet the health goals is in the range of US$20 billion to US$25 billion per year, which is roughly four times the current amount of official development assistance spending for health in 2002 (US$6.5 billion) and three times all external financing, including that of foundations and loans from multilateral sources (see chapter 13). The dramatic shortfalls in resources required to achieve the MDGs were emphasized during the 2002 Monterrey Conference on Financing for Development, which brought significant attention to issues concerning the estimation of the cost of achieving the health MDGs. Another analysis conducted by the Commission on Macroeconomics and Health (2001) of the World Health Organization estimated that an additional US$40 billion to US$52 billion annually would be required until 2015 to scale up the coverage for malaria, tuberculosis, HIV/AIDS, childhood mortality, and maternal mortality (Kumaranayake, Kurowski, and Conteh 2001). A third study using the production frontiers approach estimated that between US$25 billion and US$70 billion of additional spending was needed to bring poorly performing countries up to the level of high performers (Preker and others 2003). A fourth study prepared by the World Bank for the Development Committee estimated at least US$30 billion annually in additional aid was needed to accelerate all the MDGs, including health (Development Committee 2003).Whatever the method of analysis, all global estimates show that reaching the MDGs will require significant additional resources compared with the current levels of funding for health. Cost of Achieving the MDGs in Countries Global estimates of what it costs to achieve the health MDGs are not very useful for countries wanting to plan and budget in order to reach the MDGs. The substantial range of estimates between US$20 billion and US$75 billion per year to achieve the MDGs at a global level has led to debates over the most appropriate costing method for country-specific analysis and to the development of new costing methodologies for obtaining consistent and reliable estimates to use for policy dialogue and decision making at the country levels. Some of the methods are summarized in box 9.2. Preliminary Country Cost Estimates. Table 9.2 provides a set of preliminary country-level estimates for the cost of removing bottlenecks and accelerating progress toward the health MDGs (MBB method) and for the cost of achieving the health MDGs (Millennium Project tools) in selected


countries. The estimates are presented for illustration of orders of magnitude and should not be used for intercountry comparison.

Encouraging Risk Pooling Rather Than Out-of-Pocket Spending. Health spending can be broken down into three categories:

Financing Extra Health Spending The additional resources needed to reach the MDGs are large at both country and global levels, as discussed in the previous section. The key question is how to finance the extra spending that is needed.

• private (out-of-pocket expenditures and private insurance) • public (financing from general revenues and social insurance contributions) • external sources (development assistance).

Box 9.2

Estimating the Cost of Scaling Up to Achieve the MDGs The following are the country-specific models for MDG cost analysis: • The MDG Needs Assessments Model developed by the United Nations Millennium Project, (Millennium Project 2004). The Millennium Project model yields total cost estimates for full coverage of the needs of a defined population with a comprehensive set of health interventions in a given year. It uses unit cost of covering one person multiplied by the total population in need in a given year to yield the direct health cost. Additional resource requirements are added (on the basis of assumptions rather than actual inputs) for, among other items, health system improvement, salary increases for human resources, administration and management, promotion of community demand, and research and development. • The Marginal Budgeting for Bottlenecks Model developed by the United Nations Children’s Fund, the World Bank, and the World Health Organization (Soucat and others 2002, 2004; UNICEF and World Bank 2003). The MBB model yields additional resources required for removing a set of health system bottlenecks that are considered to hinder the delivery of health services to the population through three delivery modes: familycommunity, outreach, and clinical levels. The MBB method also estimates the effect on outcomes (for instance, child and maternal mortality) of increased coverage and use of the health services provided. First, a set of high-impact services are selected on the basis of a country’s epidemiological needs. These services are the same as those cost-effective priority interventions identified in the relevant disease control priorities chapters. Second, health system bottlenecks hindering delivery of these services are identified. Then, strategies for

removal of bottlenecks are discussed, and the inputs are identified for improving coverage, for example, in a village. Cost estimates are based on these inputs by scaling up the cost to cover the district, province, or nation. • Elasticity estimates through econometric modeling developed by the World Bank staff (Wagstaff and Claeson 2004). A few studies have used econometric techniques to analyze the effect on MDG outcomes of certain crosssector determinants (such as economic growth, water and sanitation, education, and road infrastructure) as well as government expenditures on health. Econometric analysis has been used mostly to analyze the effect of changes in government health expenditures on outcomes using cross-sectional or panel data at a global scale. But in one particular study in India, the methodology was used to estimate the marginal costs of averting a child’s death at the state level. The estimates could vary from as low as US$2.40 per child death in a lowincome state to US$160 in a middle-income state in India. • The Maquette for Multisectoral Analysis of MDGs is under development by the World Bank (Bourguignon and others 2004). The thesis for this new approach is that development aid is a key ingredient of a country’s development process, but its effectiveness has to be assessed at the country level within each country’s local implementation and macroeconomic constraints. The objective of the model is to calculate the financial needs to attain a targeted path to 2015 and determine an optimal allocation of additional funding toward different social sectors for the MDGs. This modeling framework is still at an early stage of development and will be applied later to countries. This model is anticipated to draw extensively from results of other models, such as the elasticity analysis and MBB models.

Source: Millennium Project 2003, 2004; Soucat and others 2004; Bourguignon and others 2004.


Table 9.2 Alternative Cost Estimates Using Millennium Project and Marginal Budgeting for Bottlenecks Models Country

Model used

Cost estimate (US$ per capita per year)

Ethiopia

MBB

3.56

Madagascar (Toamasina)

MBB

2.38

Mali (one region)

MBB

3.97

Millennium Project

32.00

Bangladesh

Millennium Project

20.60

Cambodia

Millennium Project

22.50

Ghana

Millennium Project

24.70

Tanzania

Millennium Project

34.70

Uganda

Millennium Project

32.10

Source: Authors.

Private spending absorbs a larger share of income in poorer countries. In low-income countries, it absorbs a larger share of GDP, on average, than domestically financed public spending. In low-income and lower-middle-income countries, it invariably means out-of-pocket expenditures rather than private insurance (Musgrove, Zeramdini, and Carrin 2002). This situation leaves many near-poor households heavily exposed to the risk of impoverishing health expenses. The risk is clearly greater the poorer the country, because poorer countries tend, on average, to have larger shares of poor people (World Bank 2000). Governments thus have a major role to play in helping shape effective risk-pooling mechanisms, in addition to increasing their own spending and targeting it to services for the poor that will have a large positive effect on the MDGs.

Getting Governments to Spend What They Can Afford Government spending is an important part of the picture, and the issue is how much they can afford. Unlike private spending, government spending as a share of GDP is higher in richer countries. However, at any given per capita income, a surprising amount of variation occurs across countries in the share of GDP allocated to government health programs. Countries that appear able to spend similar shares of GDP on government health programs end up spending quite different amounts. How can extra domestic resources be mobilized if countries are spending less than they can afford? Domestically financed government health spending comes from general revenues, social insurance contributions, or both. The amount of general revenues flowing into the health sector is the product of the amount of general (tax and nontax) revenues collected by the government (the general revenue share) and the share of general revenues allocated to the health sector (the health share of government spending) (Hay 2003). Low government health spending could be attributable to either share or both shares being low. In poorer countries, both shares are typically lower

than they are in richer countries. However, differences exist across countries that cannot be explained by per capita income alone. Countries need to ascertain whether their low spending is caused by unduly low general revenues or by unduly low allocations to health and explore ways of making appropriate adjustments. Bolivia managed to raise its general revenue share consistently in the 1990s as the result of a sustained reform process begun in 1983. The health sector there has been one of the beneficiaries of this growth of tax revenues: government health spending as a share of GDP grew at an annual rate of nearly 10 percent in the 1990s. Although raising domestic resources takes time, countries that can apparently afford to spend more out of their own resources should be encouraged to start the process. Development agencies have a role here—in providing technical support of tax reform, in helping develop government commitment to health in public expenditure allocations, and in giving financial assistance, both to ease the adjustment costs and to provide support while the gap is being closed between current and affordable spending. Recognizing the Limits of Development Assistance. Official development assistance tends to account for a larger share of government health spending in poorer countries. Development assistance for health is especially important in Sub-Saharan Africa. Twelve countries in Sub-Saharan Africa had external funding exceeding 35 percent of total health expenditures in 2000 (World Bank 1998). Increased development assistance is needed to achieve the MDGs. Development assistance, however, is not without its drawbacks. Many donors require that assistance be kept in parallel budgets outside the ministry of finance, which risks undermining government efforts to appropriately plan and target expenditures. Such off-budget expenditures make it difficult in some countries to properly target resources to


particular interventions, geographic locations, or population groups, even though such targeting may be essential for improving the effect of expenditures on outcomes and the probability of reaching the health goals. Donors often require recipient governments to maintain separate accounts and to provide separate progress reports, thereby increasing the administrative burden on weak health ministries. Most important, donor commitments of expenditures in health are short term, whereas the needs are permanent. Thus, any external financing must at some point be substituted with additional domestic revenues or expenditure reallocations. This substitution or transition to domestic sources of funding has typically been difficult to achieve, leading to a dropoff in effort in important health programs, such as immunizations and reproductive health services. Consensus on how to improve aid effectiveness is growing among development partners, and partners at the High Level Forum on Health MDGs (http://www.hlfhealthmdgs. org). This agenda includes supporting countries in developing more MDG-responsive Poverty Reduction Strategy Papers, tracking resource flows, strengthening monitoring and evaluation, and more effectively dealing with the human resources crisis in health. Effective monitoring can help ensure that increased external funds do not simply lead to reduced domestic financing (the fungibility problem) but actually boost overall spending for health. In concert with moves affecting all development assistance, donors and governments are trying to see that in the health area external funds are pooled and that ministries can use a common management and reporting format. In addition, a research agenda to support acceleration toward the health MDGs is being proposed; it needs to focus on how to translate knowledge into action and on how to remove health systems constraints to scaling up coverage of costeffective interventions that are available but do not reach those who need them (Claeson and others 2004; Task Force on Health Systems Research 2004).

Bourguignon, F., M. Bussolo, H. Lofgren, H. Timmer, and D. van der Mensbrugghe. 2004. “Towards Achieving the Millennium Development Goals in Ethiopia: An Economywide Analysis of Alternative Scenarios.” World Bank, Washington, DC. Claeson, M., C. Griffin, T. Johnston, M. McLachan, A. Soucat, A. Wagstaff, and A. Yazbeck 2001. “Poverty-Reduction and the Health-Sector.” In Poverty Reduction Strategy Sourcebook. Washington, DC: World Bank. Claeson, M., A. Wagstaff, E. Bos, P. Hay, and J. Baudouy. 2004. “The Case for Mobilizing New Research behind the Health Millennium Development Goals.” In Global Forum Update on Research for Health 2005, 73–75. Geneva: Global Forum. Commission on Macroeconomics and Health. 2001. “Macroeconomics and Health: Investing in Health for Economic Development—Report of the Commission on Macroeconomics and Health.” December 20, World Health Organization, Geneva. Cotlear, D. 1999. “Peru: Improving Health Care for the Poor.” Human Development Department (Latin America and the Caribbean Human Development) Paper 57, World Bank, Washington, DC. Development Committee. 2003. “Supporting Sound Policies with Adequate and Appropriate Financing.” Discussion paper, World Bank, Washington DC. Eichler, R. 2001. “Improving Immunization Coverage in an Innovative Primary Health Care Delivery Model: Lessons from Burkina Faso’s Bottom up Planning, Oversight, and Resource Control Approach That Holds Providers Accountable for Results.” Discussion paper, World Bank, Washington, DC. Eissen, E., D. Efenne, and K. Sabitu. 1997. “Community Loan Funds and Transport Services for Obstetric Emergencies in Northern Nigeria.” International Journal of Gynecology and Obstetrics 59 (Suppl. 2): S237–44). Esrey, S. A., J. B. Potash, L. Roberts, and C. Shiff. 1991. “Effects of Improved Water Supply and Sanitation on Ascariasis, Diarrhea, Dracunculiasis, Hookworm Infection, Schistosomiasis, and Trachoma.” Bulletin of the World Health Organization 69 (5): 609–21. FAO (Food and Agriculture Organization of the United Nations). 2000. The State of Food Security in the World. Rome: FAO. Fiedler, J. L. 1996.“The Privatization of Health Care in Three Latin American Social Security Systems.” Health Policy and Planning 11 (4): 406–17. Filmer, D., and L. Pritchett. 1999.“The Impact of Public Spending on Health: Does Money Matter?” Social Science and Medicine 49, pp. 1309–23. Gwatkin, D., S. Rutstein, K. Johnson, and R. P. Pande. 2000. Socio-economic Differences in Health, Nutrition, and Population. Washington, DC: World Bank.

NOTE

Hay, R. 2003. “The ‘Fiscal Space’ for Publicly Financed Health Care.” Oxford Policy Institute Policy Brief, Washington, DC.

1. Intervention in this chapter refers to the direct action that leads to prevention or cure.

Johnson-Welch, C. 1999. “Focusing on Women Works: Research on Improving Micronutrient Status through Food-Based Interventions.” International Center for Research on Women, Washington, DC.

REFERENCES

Jones, G., R. W. Steketee, R. E. Black, Z. A. Bhutta, and S. S. Morris. 2003. “How Many Child Deaths Can We Prevent this Year?’ Lancet 362 (9377): 65–71.

Bell, C., S. Devarajan, and H. Gersbach. 2003. The Long-Run Economic Cost of AIDS: Theory and an Application to South Africa. Washington, DC: World Bank. Bitran, R. 2001. “Paying Health Providers through Capitation in Argentina, Nicaragua, and Thailand: Output, Spending, Organizational Impact, and Market Structure.” USAID Partners for Health Reform Project, Washington, DC. Bokhari, F., P. Gottret, and Y. Gai. Forthcoming. “Government Health Expenditures, Donor Funding and Health Outcomes.” World Bank, Washington, DC.

Kumaranayake, L., Christoph Kurowski, and Lesong Conteh. 2001. “Costs of Scaling Up Priority Health Interventions in Low-Income and Selected Middle-Income Countries: Methodology and Estimates.” Commission for Macroeconomics and Health Working Paper WG5:19, World Health Organization, Geneva. Langenbrunner, J. 2003. “Resource Allocation and Purchasing in ECA Region: A Review.” Discussion paper, World Bank, Washington, DC. Marek, T., I. Diallo, B. Ndiaye, and J. Rakotosalama. 1999. “Successful Contracting of Prevention Services: Fighting Malnutrition in Senegal and Madagascar.” Health Policy and Planning 14 (4): 382–89.


McPake, B, and C. Hongoro. 1995. “Contracting Out of Clinical Services in Zimbabwe.” Social Science and Medicine 41 (1): 13–24. Mesoamerica Nutrition Program Targeting Study Group. 2002. “Targeting Performance of Three Large-Scale, Nutrition-Oriented Programs in Central America and Mexico.” Food and Nutrition Bulletin 232 (2): 162–74. Millennium Project. 2003. “Millennium Development Goal Country Case Studies: Methodology and Preliminary Results.” October. United Nations, NY. ———. 2004. “Millennium Development Goals Needs Assessments: Country Case Studies of Bangladesh, Cambodia, Ghana, Tanzania, and Uganda.” Unpublished working paper for the Millennium Project. United Nations, NY. Mills, A., S. Bennett, and S. Russell. 2001. The Challenge of Health Sector Reform: What Must Governments Do? New York: St. Martin’s Press. Morris, S., E. Flores, P. Olinto, and J. Medina. 2003. “A Randomized Trial of Conditional Cash Transfers to Household and Peripheral Health Centres: Impact on Child Health and Demand for Health Services.” Presented at Fourth International Health Economics Association World Congress, San Francisco, CA, June. Musgrove, P., R. Zeramdini, and G. Carrin. 2002. “Basic Patterns in National Health Expenditure.” Bulletin of the World Health Organization 80 (2): 134–42. Newman, J., M. Pradhan, L. Rawlings, G. Ridder, R. Coa, and J. Evia. 2002. “An Impact Evaluation of Education, Health, and Water Supply Investments of the Bolivian Social Investment.” World Bank Economic Review 6 (2): 241–74. OECD (Organisation for Economic Co-operation and Development) Development Assistance Committee. 2000. Recent Trends in Official Development Assistance to Health. Paris: OECD. Palmer, N., D. Mueller, L. Gilson, A. Mills, and A. Haines. 2004. “Health Financing to Promote Access in Low Income Settings—How Much Do We Know?” Lancet 364: 1365–70. Pathmanathan, I., J. Liljestrand, J. M. Martins, L. C. Rajapaksa, C. Lissner, A. de Silva, and others. 2003. “Investing in Maternal Health: Learning from Malaysia and Sri Lanka.” Health, Nutrition, and Population Department, World Bank, Washington, DC. Preker, A. S., E. Suzuki, F. Bustero, A. Soucat, and J. Langenbrunner. 2003. “Costing the Millennium Development Goals.” Background paper to The Millennium Development Goals for Health: Rising to the Challenges, World Bank, Washington, DC. Quisumbing, A. R. 1995. “Gender Differences in Agricultural Productivity: A Survey of Empirical Evidence.” IFPRI Discussion Paper 5. International Food Policy Research Institute, Washington, DC. Rajkumar, A., and V. Swaroop. 2002. “Public Spending and Outcomes: Does Governance Matter?” Policy Research Working Paper 2840, World Bank, Washington, DC. Ramana, G. 2003. Background paper for The Millennium Development Goals for Health: Rising to the Challenges. World Bank, Washington, DC. Santos, I., C. G. Victora, J. Martines, H. Goncalves, D. P. Gigante, N. J. Valle, and G. Pelto. 2001. “Nutrition Counselling Increases Weight Gain among Brazilian Children.” Journal of Nutrition 131 (11): 2966–73. Schellenberg, J. R., S. Abdulla, R. Nathan, O. Mukasa, T. J. Marchant, N. Kikumbih, and others. 2001. “Effect of Large-Scale Social Marketing of

Insecticide-Treated Nets on Child Survival in Rural Tanzania.” Lancet 357 (9264): 1241–47. Sen, A. 2002. “Why Health Equity?” Health Economics 11 (8): 659–66. Slack, K., and W. D. Savedoff. 2001. “Public Purchaser–Private Provider Contracting for Health Services: Examples from Latin America and the Caribbean.” Sustainable Development Department Technical Paper 111, Inter-American Development Bank, Washington, DC. Soucat,A.,W.Van Lerberghe, F. Diop, S. Nguyen, and R. Knippenberg. 2002. “Marginal Budgeting for Bottlenecks: A New Costing and Reallocation Practice to Buy Health Results.” World Bank, Washington, DC. ———. 2004. “Marginal Budgeting for Bottlenecks: A New Costing and Resource Allocation Practice to Buy Health Results—Using Health Sector’s Budget Expansion to Progress toward the Millennium Development Goals in Sub-Saharan Africa.” Unpublished paper. World Bank, Washington, DC. Task Force on Health Systems Research. 2004. “Informed Choices for Attaining the Millennium Development Goals: Towards a Cooperative Agenda for Health Systems Research.” Lancet 364: 997–1003. UNAIDS (United Nations Joint Programme on HIV/AIDS). 2004. Report on the Global AIDS Epidemic. Geneva: UNAIDS. UNICEF (United Nations Children’s Fund). 2001. Progress since the World Summit for Children: A Statistical Review. New York: UNICEF. Victora, C., F. Barros, J. Vaughan, A. Silva, and E. Tomasi. 2000. “Explaining Trends in Inequities: Evidence from Brazilian Child Health Studies.” Lancet 356 (9235):1093–38. Wagstaff, A., and M. Claeson. 2004. The Millennium Development Goals for Health: Rising to the Challenges. Washington, DC: World Bank. ———. 2005. “The Millennium Development Goals for Health: Rising to the Challenges: Appendix A, pp. 169–174.” World Bank. Washington, DC. Wagstaff, A., and E. van Doorslaer. 2003. “Catastrophe and Impoverishment in Paying for Health Care: with Applications to Vietnam 1993–1998.” Health Economics 12 (11): 921–34. World Bank. 1998. Assessing Aid: What Works, What Doesn’t, and Why. Oxford, U.K.: Oxford University Press. ———. 2000. World Development Report 2000/2001: Attacking Poverty. New York: Oxford University Press. ———. 2001. “‘Health, Nutrition, and Population Development Goals: Measuring Progress Using the Poverty Reduction Strategy Framework.” Report of a World Bank Consultation, World Bank, Washington, DC. ———. 2003a. Attaining the Millennium Development Goals in India: How Likely and What Will It Take? Washington, DC: World Bank. ———. 2003b. Global Economic Prospects and the Developing Countries. Washington, DC: World Bank. ———. 2003c. World Development Indicators 2003. Washington, DC: World Bank. ———. 2003d. World Development Report 2004: Making Services Work for Poor People. Washington, DC: World Bank. Yip, W., and P. Berman. 2001. “Targeted Health Insurance in a Low Income Country and Its Impact on Access and Equity in Access: Egypt’s School Health Insurance.” Health Economics 10 (3): 207–20.


Chapter 19

Diarrheal Diseases Gerald T. Keusch, Olivier Fontaine, Alok Bhargava, Cynthia BoschiPinto, Zulfiqar A. Bhutta, Eduardo Gotuzzo, Juan Rivera, Jeffrey Chow, Sonbol A. Shahid-Salles, and Ramanan Laxminarayan

Diarrheal diseases remain a leading cause of preventable death, especially among children under five in developing countries. This chapter reviews and prioritizes a number of available interventions. The normal intestinal tract regulates the absorption and secretion of electrolytes and water to meet the body’s physiological needs. More than 98 percent of the 10 liters per day of fluid entering the adult intestines are reabsorbed (Keusch 2001). The remaining stool water, related primarily to the indigestible fiber content, determines the consistency of normal feces from dry, hard pellets to mushy, bulky stools, varying from person to person, day to day, and stool to stool. This variation complicates the definition of diarrhea, which by convention is present when three or more stools are passed in 24 hours that are sufficiently liquid to take the shape of the container in which they are placed. The frequent passage of formed stool is not diarrhea (Black and Lanata 2002). Although young nursing infants tend to have five or more motions per day, mothers know when the stooling pattern changes and their children have diarrhea (Ronsmans, Bennish, and Wierzba 1988). The interval between two episodes is also arbitrarily defined as at least 48 hours of normal stools. These definitions enable epidemiologists to count incidence, relapses, and new infections.

TRANSMISSION Diarrhea is caused by infectious organisms, including viruses, bacteria, protozoa, and helminths, that are transmitted from the stool of one individual to the mouth of another, termed

fecal-oral transmission. Some are well known, others are recently discovered or emerging new agents, and presumably many remain to be identified. They differ in the route from the stool to the mouth and in the number of organisms needed to cause infection and illness. Among bacteria, the ability to survive stomach acid is an important determinant of the inoculum size required to cause illness. For example, Shigella bacteria are resistant to low pH, and a few thousand organisms suffice, which are readily transferred by direct person-to-person contact or through contamination of inanimate objects, such as a cup. In contrast, bacteria readily killed by acid, such as Vibrio cholerae, require millions of organisms to cause illness, and therefore must first multiply in food or water to an infectious dose. Some pathogens, such as rotavirus, display a sharp host species preference, and others have a broad host range. Among Salmonella bacteria, certain bio-serotypes are adapted to infect animals and pose no threat to humans, and others are adapted to humans and do not infect animals. The majority, however, are not adapted to a specific host and can infect either humans or domestic animals, thus facilitating transmission of these organisms to humans. Less than a dozen of the more than 2,500 individual Salmonella cause the majority of human infections, reflecting the requirement for genes that encode essential virulence factors. The ability to identify virulence genes and their products has led to new molecular approaches to epidemiology and diagnosis, and undoubtedly will lead to new measures to prevent and treat diarrhea. Molecular methods also allow the separation of organisms that otherwise appear to be identical. Nonpathogenic Escherichia coli in normal stool cannot be 371


separated from diarrhea-causing E. coli by standard methods; however, identification of virulence genes or factors distinguishes five groups of E. coli that cause illnesses ranging from cholera-like watery diarrhea to neonatal diarrhea, persistent diarrhea, and bloody diarrhea (Nataro and Kaper 1998).

LABORATORY DIAGNOSIS Etiologic diagnosis of diarrhea is valuable for public health interventions and case management. Microbiological culture and microscopy remain the standard, despite their limited sensitivity. Their effectiveness is further reduced by antibiotic use, and patients with severe illness are more likely both to be cultured and to have taken antibiotics. Even when cultures are positive, the delay in laboratory identification limits their costeffectiveness for managing individual patients. The information is always epidemiologically and clinically important; however, during epidemics, culturing every patient is unnecessary when the causative organism is known. Antimicrobial resistance data are essential to guide initial antibiotic choices. New rapid tests to detect inflammatory mediators or white or red blood cells in stool offer the promise of distinguishing between secretory and inflammatory disease and optimizing case management (Huicho and others 1996). High background levels, probably from frequent infections, limits the use of such tests in developing countries, where they would be most useful (Gill and others 2003). Simple microscopy for protozoa or helminths can be quick and effective when the proper sample is obtained and a welltrained technician is available to examine a fresh specimen, but these prerequisites are often not available in developing countries. Newer immunological and nucleic acid–based tests to detect pathogen-specific factors hold great promise for all diarrhea agents, but they are too expensive or require specialized instrumentation and trained technicians. For the foreseeable future, then, syndromic diagnosis will be the norm.

SYNDROMIC DIAGNOSIS Three major diarrhea syndromes exist. They are acute watery diarrhea, which results in varying degrees of dehydration; persistent diarrhea, which lasts 14 days or longer, manifested by malabsorption, nutrient losses, and wasting; and bloody diarrhea, which is a sign of the intestinal damage caused by inflammation. The three are physiologically different and require specific management. Syndromic diagnosis provides important clues to optimal management and is both programmatically and epidemiologically relevant. Acute watery diarrhea can be rapidly dehydrating, with stool losses of 250 milliliters per kilogram per day or more, a

quantity that quickly exceeds total plasma and interstitial fluid volumes and is incompatible with life unless fluid therapy can keep up with losses. Such dramatic dehydration is usually due to rotavirus, enterotoxigenic E. coli, or V. cholerae (the cause of cholera), and it is most dangerous in the very young. Persistent diarrhea is typically associated with malnutrition, either preceding or resulting from the illness itself (Ochoa, Salazar-Lindo, and Cleary 2004). Even though persistent diarrhea accounts for a small percentage of the total number of diarrhea episodes, it is associated with a disproportionately increased risk of death. In India, persistent diarrhea accounted for 5 percent of episodes but 14 percent of deaths, and a mortality rate three times higher than briefer episodes (Bhan and others 1989). In Pakistan, persistent diarrhea accounted for 8 to 18 percent of episodes but 54 percent of deaths (Khan and others 1993). In Bangladesh, persistent diarrhea associated with malnutrition was responsible for nearly half of diarrhea deaths, and the relative risk for death among infants with persistent diarrhea and severe malnutrition was 17 times greater than for those with mild malnutrition (Fauveau and others 1992). Persistent diarrhea occurs more often during an episode of bloody diarrhea than an episode of watery diarrhea, and the mortality rate when bloody diarrhea progresses to persistent diarrhea is 10 times greater than for bloody diarrhea without persistent diarrhea. HIV infection is another risk factor for persistent diarrhea in both adults and children (Keusch and others 1992). Management focuses on overcoming the nutritional alterations initiated by persistent diarrhea. Bloody diarrhea, defined as diarrhea with visible or microscopic blood in the stool, is associated with intestinal damage and nutritional deterioration, often with secondary sepsis. Some dehydration—rarely severe—is common, as is fever. Clinicians often use the term bloody diarrhea interchangeably with dysentery; however, dysentery is a syndrome consisting of the frequent passage of characteristic, small-volume, bloody mucoid stools; abdominal cramps; and tenesmus, a severe pain that accompanies straining to pass stool. Those features show the severity of the inflammation. Agents that cause bloody diarrhea or dysentery can also provoke a form of diarrhea that clinically is not bloody diarrhea, although mucosal damage and inflammation are present, and fecal blood and white blood cells are usually detectable by microscopy. The release of host-derived cytokines causes fever, altering host metabolism and leading to the breakdown of body stores of protein, carbohydrate, and fat and the loss of nitrogen and other nutrients. Those losses must be replenished during convalescence, which takes much longer than the illness does to develop. For these reasons, bloody diarrhea calls for management strategies that are markedly different than those for watery or persistent diarrhea. New bouts of infection that occur before complete restoration of nutrient stores can initiate a downward spiral of nutritional status terminating in fatal protein-energy malnutrition (Keusch 2003).

372 | Disease Control Priorities in Developing Countries | Gerald T. Keusch, Olivier Fontaine, Alok Bhargava, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 32

DIARRHEA, ENVIRONMENT, AND POVERTY

Number of episodes per person per year

Diarrheal disease affects rich and poor, old and young, and those in developed and developing countries alike, yet a strong relationship exists between poverty, an unhygienic environment, and the number and severity of diarrheal episodes— especially for children under five. Poverty is associated with poor housing, crowding, dirt floors, lack of access to sufficient clean water or to sanitary disposal of fecal waste, cohabitation with domestic animals that may carry human pathogens, and a lack of refrigerated storage for food—all of which increase the frequency of diarrhea. Poverty also restricts the ability to provide age-appropriate, nutritionally balanced diets or to modify diets when diarrhea develops so as to mitigate and repair nutrient losses. The impact is exacerbated by the lack of adequate, available, and affordable medical care. Thus, the young suffer from an apparently never-ending sequence of infections, rarely receive appropriate preventive care, and too often encounter the health care system when they are already severely ill. Although the presence of blood in the stool is a recognized danger signal, prompting more urgent care seeking, even these patients either are not treated early or receive poor medical care. Ironically, the poor spend considerable amounts on inappropriate care and useless drugs purchased from local shops and untrained practitioners. If antibiotics are properly prescribed, poverty often limits the purchase of a full course of treatment or leads to cessation of treatment as soon as symptoms improve, even though the infection has not been cured.

6

PUBLIC HEALTH SIGNIFICANCE OF DIARRHEAL ILLNESSES Continuing surveillance and longitudinal studies allow tracking of current levels and trends in diarrhea incidence and mortality and provide the basis for future projections and for evaluations of different control strategies.

Morbidity Comparisons over time of the global burden of diarrheal diseases have revealed secular trends and demonstrated the impact of public health interventions (Bern and others 1992; Kosek, Bern, and Guerrant 2003; Snyder and Merson 1982). The long-term consequences of diarrhea are only now being systematically assessed and are not reflected in earlier studies. Reviews in 1992 (Bern and others) and 2003 (Kosek, Bern, and Guerrant) are similar in many ways—for example, assessing morbidity at least twice weekly—but differ significantly in the use of different sources for data on children under five and in the inclusion of studies differing in design and data

5 4 3 2 1 0 0–5 months

6–11 months

1 year

2 years

3 years

4 years

Age group 1955–79

1980–90

1990–2000

Source: Authors.

Figure 19.1 Median Age-Specific Incidences for Diarrheal Episodes per Child per Year from Three Reviews of Prospective Studies in Developing Areas, 1955–2000

collection protocols (and only the later study includes data from China). Remarkably, the estimated median incidence of diarrheal disease in children under five in developing countries has not changed much since the early 1990s (figure 19.1): 3.2 episodes per child per year in 2003 (Parashar and others 2003) compared with 3.5 episodes per child per year in 1993 (Jamison and others 1993). However, many fewer surveys were available for the most recent review (31 in 20 countries) compared with the 1993 consensus (276 in 60 countries), reflecting diminished support for the systematic collection of incidence data. Incidence rates in Sub-Saharan Africa and Latin America are clearly greater than in Asia or the Western Pacific, while subject to greater data limitations from individual countries. Incidence continues to show a peak in infants age 6 to 11 months, dropping steadily thereafter. The seemingly lower estimates of diarrheal incidence before 1980 (Snyder and Merson 1982) are likely due to methodological differences. These estimates are not precise or directly comparable; the trends are most relevant. The persistently high rates of diarrhea throughout the 1990s despite intensive efforts at control, particularly among children age 6 to 24 months, is of particular concern. Early childhood diarrhea during periods of critical postnatal development may have long-term effects on linear growth and on physical and cognitive functions. Data on the incidence of shigellosis, the principal cause of bloody diarrhea in developing countries, are even more limited. Kotloff and others’ (1999) review of studies on Shigella infection estimates that more than 113 million episodes occur every year in children under five in developing countries, or 0.2 episodes of bloody diarrhea per year caused by Shigella species. Diarrheal Diseases | 373


• advising mothers to increase fluids and continue feeding during future episodes.

Millions of deaths per year 5 4 3 2 1 0 1975

1980

1985

Snyder and Merson 1982 Bern and others 1992 Kosek, Bern, and Guerrant 2003

1990

1995

2000

2005

Trend estimate Parashar and others 2003 Boschi-Pinto and Tomaskovic forthcoming

Source: Authors.

Figure 19.2 Estimates of Diarrhea Mortality, 1975–2000

Mortality Bern and others (1992); Kosek, Bern, and Guerrant (2003); and Snyder and Merson (1982) also estimate diarrheal mortality using data from longitudinal studies with active surveillance in place (figure 19.2). The estimate before 1980 was 4.6 million deaths per year. This estimate dropped to 3.3 million per year between 1980 and 1990 and to 2.6 million per year between 1990 and 2000. Two other studies (Parashar and others 2003; Boschi-Pinto and Tomaskovic forthcoming) report even lower figures for 1990–2000: 2.1 million and 1.6 million deaths per year, respectively. Methodological variations (inclusion of studies with different designs and data collection methods and inclusion of data from China, different sources for estimating the number of children under five, and different strategies for calculating mortality for this age group) may account for some of the striking differences. However, the end of the 20th century witnessed significant reductions in diarrheal deaths in children under five. This steady decline in diarrheal mortality, despite the lack of significant changes in incidence, is most likely due to modern case management (introduced since the 1980s) and to the improved nutrition of infants and children. Major recommendations include the following: • counseling mothers to begin suitable home-prepared rehydration fluids immediately on the onset of diarrhea • treating mild to moderate dehydration early with oral rehydration solution (ORS), reserving intravenous electrolytes for severe dehydration • continuing breastfeeding and complementary foods during diarrhea and increasing intake afterward • limiting antibiotic use to cases of bloody diarrhea or dysentery and avoiding antidiarrheal and antimotility drugs

Victora and others’ (2000) review provides evidence that this strategy, and especially oral rehydration therapy (ORT), has influenced the outcome of dehydrating diarrhea. Data from 99 national surveys carried out in the mid 1990s and compiled by the United Nations Children’s Fund (UNICEF) increasingly show that diarrhea patients are appropriately managed in most parts of the world,with overall use rates of ORS or recommended home fluids reaching 49 percent. Country case studies in Brazil, the Arab Republic of Egypt, Mexico, and the Philippines showed a dramatic reduction of diarrhea mortality as ORT use rates increased from close to zero in the early 1980s to 35 percent in Brazil, 50 percent in Egypt, 81 percent in Mexico, and 33 percent in the Philippines in the early 1990s. Hospital admissions for diarrhea also plummeted (Victora and others 2000). As mortality attributable to acute dehydration decreased, the proportionate mortality associated with persistent diarrhea increased. Data from Brazil and Egypt suggest that even relatively low ORT use rates can positively affect mortality,because ORT use tends to be much higher for severe illness (Victora and others 2000). Worldwide mortality caused by Shigella infection is estimated to be 600,000 deaths per year among children under five, or a quarter to a third of all diarrhea-related mortality in this age group (Kotloff and others 1999). Because mortality caused by bloody diarrhea is not tracked separately, it is difficult to assess the impact of standard case management recommendations, and disease-specific trends cannot be tracked. In the past few years, however, data from the International Centre for Diarrheal Disease Research, in Bangladesh, have shown a marked decrease in the rate of hospitalization caused by Shigella, especially S. dysenteriae type 1, the most severe form of shigellosis. Some investigators have suggested that this decrease may be because Shigella infections are now in the low part of a 10-year cycle (Legros 2004). The observed change could also be explained by better case management with more efficacious antimicrobials. More comprehensive, syndrome-specific surveillance data will be required if rational control priorities are to be set, because the options for dehydrating and bloody diarrheal diseases differ substantially. Despite national data that indicate a significant decline in mortality (Baltazar, Nadera, and Victora 2002; Miller and Hirschhorn 1995), diarrheal diseases remain among the five top preventable killers of children under five in developing countries and among the top two in many.

Long-Term Consequences The long-term consequences of diarrheal diseases remain poorly studied, and analyses of global trends have not considered them. Niehaus and others (2002) recently evaluated the


long-term consequences of acute diarrheal disease on psychomotor and cognitive development in young children. Following a cohort of 47 children in a poor urban community in northeastern Brazil, they correlated the number of diarrheal episodes in the first two years of life with measures of cognitive function obtained four to seven years later. They found a significant inverse correlation (average decrease of 5.6 percent) between episodes of early diarrheal disease and overall intellectual capacity and concentration, even when controlling for maternal education or helminth infection, which are known to be independent predictors of malnutrition and cognitive defects. Test scores were also 25 to 65 percent lower in children with an earlier history of persistent diarrhea. Recent evidence suggests that genetic factors may also be involved in the developmental response to repeated diarrhea (Oria and others 2005). Better and more sensitive assessment tools are needed to define the relationships between diarrheal diseases and developmental disorders and to calculate individual and societal costs and the cost-effectiveness of interventions. In addition, early childhood malnutrition resulting from any cause reduces physical fitness and work productivity in adults (Dobbing 1990).

PREVENTIVE STRATEGIES Strategies for controlling diarrheal diseases have remained substantially unchanged since the 1993 edition of this volume (Martinez, Phillips, and Feachem 1993). The World Health Organization (WHO 2004) recently reevaluated these interventions to determine the extent to which they have been effectively implemented and their effect.

Promotion of Exclusive Breastfeeding Exclusive breastfeeding means no other food or drink, not even water, is permitted, except for supplements of vitamins and minerals or necessary medicines. The optimal duration of exclusive breastfeeding is six months (WHO 2001). A meta-analysis of three observational studies in developing countries shows that breastfed children under age 6 months are 6.1 times less likely to die of diarrhea than infants who are not breastfed (WHO Collaborative Study Team 2000). Exclusive breastfeeding protects very young infants from diarrheal disease in two ways: first, breast milk contains both immune (specific) and nonimmune (nonspecific) antimicrobial factors; second, exclusive breastfeeding eliminates the intake of potentially contaminated food and water. Breast milk also provides all the nutrients most infants need up to age 6 months. When exclusive breastfeeding is continued during diarrhea, it also diminishes the adverse impact on nutritional status.

Those data underpin the global campaign to promote exclusive breastfeeding for the first six months of life by increasing both the initiation and the duration of exclusive breastfeeding. The strategies include the following: • hospital policies and actions to encourage breastfeeding and discourage bottle feeding • counseling and education provided by peers or health workers • mass media and community education • mothers’ support groups. Interventions focused on hospital practices apply where most women deliver in such facilities. Such interventions have shown up to a 43 percent increase in exclusive breastfeeding with good institutional policies and retraining of health staff (Westphal and others 1995). Interventions focused on education and counseling increase exclusive breastfeeding by 4 to 64 percent (Sikorski and others 2002). Peer-counseled women are less likely to stop exclusive breastfeeding than are those who receive either professional support or no support, and their infants are 1.9 to 2.9 times less likely to have diarrhea (Barros and others 1995; Haider and others 1996). No large-scale peer counseling programs exist; therefore, feasibility is unknown. Community-based mother’s support groups are sustainable, but they have low coverage and are biased toward women who are already motivated to breastfeed (Bhandari and others 2003). Mass media can be effective where media coverage is high, where production skills are good, and where it addresses barriers to breastfeeding instead of just proclaiming its benefits. We found no studies that examined the relationship between breastfeeding promotion and diarrheal disease mortality; however, estimates suggest such promotion could decrease all-cause mortality in children under five by 13 percent (Jones and others 2003). Maternal HIV infection has put a new wrinkle in the “breast is best” dogma because of the risk of transmission of infection to the infant (De Cock and others 2000). There is a trade-off, however, between the risk of mortality associated with replacement feeding and the risk of HIV infection, especially where safe replacement feeding is difficult. For women who are HIVnegative or whose status is unknown, WHO currently recommends exclusive breastfeeding for at least six months (WHO 2000). The best option for HIV-positive women is acceptable, affordable, sustainable, and safe replacement feeding. If this option is not possible, there are four alternatives: (a) heattreated breast milk, (b) HIV-negative wet nurses, (c) uncontaminated donor milk, or (d) exclusive breastfeeding for six months and rapid discontinuation thereafter (WHO 2003). A danger of promoting replacement feeding is that uninfected women or women with unknown HIV status will adopt the practice. Even in high-prevalence communities, the best Diarrheal Diseases | 375


option for women with unknown status for the overall health of their children appears to be exclusive breastfeeding for six months. In Coutsoudis and others’ (1999) cohort study in South Africa, the risk of mother-to-infant transmission of HIV after three months of exclusive breastfeeding was similar to that with no breastfeeding and significantly lower than that with mixed feeding. Providing antiretroviral therapy to the mother should significantly extend the period of safe breastfeeding for the initially HIV-negative infants of HIV-positive mothers.

Improved Complementary Feeding Practices Ideally, complementary foods should be introduced at age 6 months, and breastfeeding should continue for up to two years or even longer to increase birth intervals (WHO 2003). There is a strong inverse association between appropriate, safe complementary feeding and mortality in children age 6 to 11 months. Malnutrition is an independent risk predictor for the frequency and severity of diarrheal illness. There is a vicious cycle in which sequential diarrheal disease leads to increasing nutritional deterioration, impaired immune function, and greater susceptibility to infection. The cycle may be broken by interventions to decrease infection incidence to reduce malnutrition (Keusch and Scrimshaw 1986) or improving nutritional status to reduce the burden of infection (Victora and others 1999). Improved feeding practices to prevent or treat malnutrition could save as many as 800,000 lives per year (Jones and others 2003). Pediatricians have long been aware of an increase in diarrhea incidence during weaning from exclusive breast milk feeding. Microbial contamination of complementary foods (Mondal and others 1996) and nutritionally inadequate diets during and after diarrhea episodes (Badruddin and others 1991) increase the risk. Contamination of complementary foods can potentially be reduced by educating caregivers on hygienic practices (Guptill and others 1993), improving home food storage (English and others 1997), fermenting foods to reduce pathogen multiplication (Kimmons and others 1999), or ingesting nonpathogenic probiotic microorganisms that colonize the gut and help resist pathogens (Allen and others 2004). These interventions have not been evaluated at scale in communities, and effectiveness trials are lacking. We could not find any reports on the effects of complementary feeding interventions on mortality. Five efficacy trials to improve the intake of complementary foods noted a net increase in energy intake of between 65 and 300 kilocalories a day and improvements of 0.25 to 0.46 standard deviations in weight-for-age and 0.04 to 0.35 standard deviations in heightfor-age (Caulfield, Huffman, and Piwoz 1999). By extrapolation, this increment in growth should translate into a 2 to 13 percent reduction in deaths associated with malnutrition (Black and others 1995).

Brown, Dewey, and Allen (1998) reviewed experiences with large-scale complementary feeding interventions in 14 countries. They demonstrate that it is possible to provide nutritionally improved complementary foods in diverse cultural settings and that poor mothers are willing to prepare new foods their children will eat. However, caregivers face considerable time and resource constraints in providing such foods, especially during episodes of illness. A pilot study in Brazil that implemented nutritional counseling through the Integrated Management of Childhood Illness Program reported significant weight gain in children age one year or more, but not in younger children (Santos and others 2001). Unfortified complementary foods do not meet all essential micronutrient requirements. Although improvements in vitamin A status do not significantly reduce the incidence of diarrhea and other common childhood illnesses, vitamin A supplementation can reduce the frequency of severe diarrhea (Barreto and others 1994) and mortality (Ross and others 1995). Chapter 28 describes interventions to promote vitamin A intake. Zinc supplementation also reduces the incidence of diarrhea.

Rotavirus Immunization Almost all infants acquire rotavirus diarrhea early in life, and rotavirus accounts for at least one-third of severe and potentially fatal watery diarrhea episodes—primarily in developing countries, where an estimated 440,000 vaccine-preventable rotavirus deaths per year occur (Parashar and others 2003), compared with about a dozen in a developed country such as France (Fourquet and others 2003). An effective rotavirus vaccine would have a major effect on diarrhea mortality in developing countries. In 1998, a quadrivalent Rhesus rotavirus–derived vaccine that reduced the frequency of severely dehydrating rotavirus— but not the overall incidence of rotavirus infections—was licensed in the United States (Glass and others 1999). It was cost-effective, even at US$100 for a full course of immunization, when direct economic losses resulting from health care expenses and indirect costs of lost productivity and wages for the caretakers were considered (Tucker and others 1998). The strategy was clear: use the high-priced vaccine routinely in industrial countries to subsidize its use in developing countries. However, postmarketing surveillance detected an apparent increase in a relatively rare event, intussusception, a condition in which the intestine telescopes on itself, causing a potentially serious obstruction (CDC 1999a). The relationship was strongest with the first dose of vaccine given with the first or second dose of diphtheria-pertussis-tetanus vaccine (Peter and others 2002), although this was counterbalanced by a decrease in the incidence of intussusception in older children (Murphy and others 2003).


The overall reduced incidence in immunized infants compared with nonimmunized infants in these studies suggested that the vaccine may actually protect against later adverse events. Nonetheless, the ensuing controversy led to a reversal of the recommendation for universal immunization in the United States and withdrawal of the vaccine from the market, precluding the possibility of its deployment in developing countries (CDC 1999b). Because very young infants are less prone to develop intussusception, initial immunization at birth might have been entirely safe. Despite this setback, efforts to produce an effective and safe rotavirus vaccine continue. The Rhesus vaccine has been relicensed to another manufacturer, and new vaccines derived from human or bovine rotavirus are undergoing field trials in developing countries (Dennehy 2005). A monovalent human rotavirus vaccine was introduced in Mexico in 2005. The entry of both China and India into rotavirus vaccine development and their potential for manufacturing quality vaccines at low cost will make it easier to deploy an effective vaccine where it is really needed.

Cholera Immunization Endemic cholera is primarily a pediatric disease, although adult morbidity and mortality are significant, especially during epidemics. The lethality of cholera is due to the physiological consequences of rapid and profound dehydration. Oral rehydration therapy has dramatically improved survival and reduced the cost of treatment. Wherever parenteral and oral rehydration is readily available, even in epidemic situations, a cholera mortality rate above 1 percent indicates failure of the public health system to provide appropriate case management. A vaccine would further reduce the morbidity and mortality associated with cholera in endemic areas; however, developing an effective, safe vaccine has proven difficult. The most immunogenic and protective vaccines tested thus far are administered orally. Two such vaccines have been licensed: an attenuated live vaccine and a heat-killed vaccine combined with recombinant cholera toxin B subunit, which functions as an immunoadjuvant (Graves and others 2000; Ryan and Calderwood 2000). Many developing countries can produce the killed vaccine, especially without cholera toxin B. Current oral cholera vaccines appear to be safe and offer reasonable protection for a limited period; however, the main users have been individual travelers from industrial countries who may be exposed to the risk of cholera while traveling in endemic areas. The use of oral cholera vaccine in mass vaccination campaigns as an adjunct to good case management, disposal of fecal waste, and access to safe water during humanitarian disasters has recently been reviewed (WHO 1999). Analysis of an

outbreak in Micronesia suggested that a single dose was useful in limiting the spread of cholera (Calain and others 2004). But because ORT is so inexpensive and useful in preventing death, immunization is not a high priority. Only Vietnam routinely deploys cholera vaccine. Operational information on the costs, logistics, and availability of vaccines for use by global programs and on the vulnerable populations in high-risk settings who would benefit from cholera vaccine remains limited. Although scientific interest in a cholera vaccine remains high, its public health priority is less than that of a vaccine for rotavirus or Shigella. Measles Immunization Measles is known to predispose to diarrheal disease secondary to measles-induced immunodeficiency. Feachem and Koblinsky (1983) estimate that measles vaccine given to 45 to 90 percent of infants would prevent 44 to 64 percent of measles cases, 0.6 to 3.8 percent of diarrheal episodes, and 6 to 26 percent of diarrheal deaths among children under five. Global measles immunization coverage is now approaching 80 percent, and the disease has been eliminated from the Americas, raising hopes for global elimination in the near future (GAVI 2005), with a predictable reduction in diarrhea as well. Improved Water and Sanitary Facilities and Promotion of Personal and Domestic Hygiene Human feces are the primary source of diarrheal pathogens. Poor sanitation, lack of access to clean water, and inadequate personal hygiene are responsible for an estimated 90 percent of childhood diarrhea (WHO 1997). Promotion of hand washing reduces diarrhea incidence by an average of 33 percent (Huttly, Morris, and Pisani 1997); it works best when it is part of a package of behavior change interventions. Effects on mortality have not been demonstrated. However, the required behavior change is complex, and significant resources are needed. Antiseptic soaps are more costly than plain hand soap and confer little advantage. Washing hands after defecating or handling children’s feces and before handling food is recommended, but it entails an average of 32 hand washes a day and consumes 20 liters of water (Graef, Elder, and Booth 1993). If soap is too costly, ash or mud can be used, but access to water remains essential (Esrey 1996). Six rigorous observational studies demonstrated a median reduction of 55 percent in all-cause child mortality associated with improved access to sanitation facilities (Esrey, Feachem, and Hughes 1985). The greatest effect of improving sanitation systems will be in areas of high population density and wherever the entire community, rather than single households, adopts the intervention. Current technology can be costly and difficult to maintain, and in some settings it is simply not feasible. Diarrheal Diseases | 377


CASE MANAGEMENT Two recent advances in managing diarrheal disease—(a) newly formulated ORS containing lower concentrations of glucose and salts and (b) zinc supplementation—used in combination with promotion of exclusive breastfeeding, general nutritional support, and selective and appropriate use of antibiotics, can further reduce the number of diarrheal deaths among children. Families and communities are key to achieving case management goals by making these recommendations routine practice in homes and health facilities.

New Oral Rehydration Solutions For more than 25 years, UNICEF and WHO have recommended a single formulation of glucose-based ORS considered optimal for cholera, irrespective of cause or age group affected. This formulation has proven effective and without significant adverse effects (Ruxin 1994), but because watery stools persist and duration of diarrhea is not reduced, mothers’ and health workers’ acceptance of current ORSs has been suboptimal. During the past 20 years, efforts to improve ORS to treat dehydration from all types of diarrhea and reduce stool output or duration have continued—for example, by reducing the sodium content in line with sodium losses for noncholera diarrhea. Compared with standard ORS, lower sodium and glucose ORS reduces stool output, vomiting, and the need for intravenous fluids (Hanh, Kim, and Garner 2001). If household use increases, new ORS can reduce childhood deaths from noncholera diarrhea (Duggan and others 2004), and it appears to be as effective as standard ORS for children or adults with cholera. A WHO expert group now recommends that ORS containing 75 milliequivalents of sodium and 75 millimoles of glucose per liter (total osmolarity, 245 milliosmoles per liter) be used everywhere (WHO and UNICEF 2004).

Zinc Supplementation A review of all relevant clinical trials indicates that zinc supplements given during an episode of acute diarrhea reduce both duration and severity and could prevent 300,000 deaths in children each year (Black 2003). WHO and UNICEF now recommend that all children with acute diarrhea be given zinc in some form for 10 to 14 days during and after diarrhea (10 milligrams per day for infants younger than 6 months and 20 milligrams per day for those older than 6 months) (WHO and UNICEF 2004). Pilot studies in Brazil, Egypt, Ethiopia, India, Mali, Pakistan, and the Philippines that include zinc routinely in the management of acute diarrhea not only show an improvement over ORS alone but also suggest two important new effects: (a) use rates of ORS increase, and (b) use rates of antidiarrheals and

antimicrobials decrease significantly (Baqui and others 2004). Large community-based studies are being implemented to corroborate these potentially important findings. Management of Bloody Diarrhea The primary treatment for shigellosis, the most common and severe cause of bloody diarrhea, is antimicrobials. The choice of effective, safe, and inexpensive oral drugs for use in developing countries has, however, become problematic because of the increasing prevalence of antimicrobial drug resistance (Salam 1998). Tetracycline, ampicillin, and the fixed-ratio combination of trimethoprim and sulfmethoxazole, once used as firstline treatment, are no longer reliably effective. When epidemic dysentery caused by multidrug-resistant S. dysenteriae type 1 appeared in Africa and Asia in the 1980s and 1990s, nalidixic acid was pressed into use (Salam and Bennish 1988). Nalidixic acid is a drug used primarily for urinary tract infections, but it is also effective against Shigella. Clinical responses were initially excellent, but with continued use, resistance to nalidixic acid has been increasing in many parts of the world (Dutta and others 2003). A number of other drugs have been tested and shown effective, including ceftriaxone, azithromycin, pivmecillinam, and some new generation 5-fluoroquinolones, such as ciprofloxacin (Salam 1998). Because of its effectiveness, safety, ease of administration by the oral route, short course, and low cost (US$0.10 for a three-day course for a 15-kilogram child), ciprofloxacin is the current drug of choice for shigellosis (Zimbasa Dysentery Study Group 2002). However, ciprofloxacin-resistant strains are already appearing (Pazhani and others 2004), and it is only a matter of time before resistance becomes widespread, especially if the drug is readily available and indiscriminately used. Because of these concerns, development of a vaccine for Shigella is critical. The Diseases of the Most Impoverished initiative, supported by the Bill & Melinda Gates Foundation (Nossal 2003), which promotes vaccine development for Shigella, cholera, and typhoid, is a significant advance since the previous edition of this volume.

COST-EFFECTIVENESS OF INTERVENTIONS Cost-effectiveness ratios of diarrheal disease interventions were calculated by World Bank region in terms of disability-adjusted life years (DALYs) averted for a model population of 1 million, following the standardized guidelines of the Disease Control Priorities Project for economic analyses (see chapter 15). Europe and Central Asia were excluded because data were lacking owing to the low prevalence of disease. Input variables included (a) region-specific diarrhea morbidity rates adapted from Kosek, Bern, and Guerrant (2003); (b) region-specific


underlying mortality rates and age structures provided by the Disease Control Priorities Project; (c) median intervention effectiveness rates (that is, percentage of diarrheal morbidity reduction and percentage of diarrheal mortality reduction); and (d) median per capita intervention costs gathered from the literature and from personal communications (table 19.1). Because approximately 90 percent of all cases in the developing world occur in children under five, the analysis focused on this age group alone. Uniform intervention effectiveness rates were assumed for all regions because region-specific information was not available. Regional variations in costeffectiveness were due to regional variations in the prevalence of diarrheal disease, in the diarrhea-attributable morbidity and mortality, and in the intervention cost, where region-specific information was available. Disability-adjusted life years are averted through the avoidance of cotemporaneous disability and mortality attributable to diarrhea. We did not consider long-term developmental and cognitive effects of childhood diarrhea or the external benefits of interventions unrelated to diarrhea (for instance, benefits of measles immunization unrelated to diarrhea or other health benefits of improved public water and sanitation). Therefore, our estimates err on the conservative side. We explored two general categories of interventions: early interventions that take place within the first year of life— breastfeeding promotion and immunizations for rotavirus (with the prototype Rhesus reassortant tetravalent vaccine), cholera (with live oral vaccine), and measles—and other interventions that treat an entire cohort of children under five simultaneously (improved water and sanitation). For early interventions, cost-effectiveness ratios were calculated by considering the cost of treating all newborns in a single year and the benefits (DALYs averted) from those treatments that occur over the first five years of life. These benefits include avoided mortality that allows individuals to live to the expected life expectancy for the region. Other interventions included ORT and improved water and sanitation infrastructure. Because a single year of these interventions yields only cotemporaneous benefits— because effectively treated individuals do not necessarily live to life expectancy given that they are likely to be reinfected the next year—we calculated cost-effectiveness of a five-year intervention. Analysis of a five-year intervention enabled us to consider the case in which an entire cohort of children age zero to four avoids early childhood diarrheal mortality because of the intervention and receives the benefit of living to life expectancy. Disability and deaths averted for those benefiting from improved water and sanitation were calculated from only the fraction of the model populations currently without access. For each region, the proportion of rural and urban children age zero to four currently without access to improved water and sanitation was calculated using region-specific information from World Bank Development Indicators (World Bank 2002)

for 2000. Infrastructure improvements for rural and urban populations were considered separately because of differences in infrastructure type and cost, although the same effectiveness rates were used for both. The per child treatment costs and effectiveness rates used are presented in table 19.1. Cost per treatment of ORT varied widely depending on the type and method of ORT implemented. Oral rehydration therapy can be as inexpensive as US$0.02 per child treated—the cost of a home remedy with sugar and salt. However, treatment can become substantially more expensive if commercially manufactured ORS is used or if there are substantial personnel or infrastructure costs (Martinez, Phillips, and Feachem 1993). Finally, our analysis considered only long-run marginal costs (which vary with the number of individuals treated) and did not include fixed costs of initiating a program where none currently exists. Figure 19.3 shows the cost-effectiveness of all interventions over the first five years of life. Two interventions administered during the first year of life—breastfeeding promotion (US$930 per DALY) and measles immunization (US$981 per DALY)— were the most cost-effective. ORT (US$1,062 per DALY) and water and sanitation in rural areas (US$1,974 per DALY) were the next most cost-effective, but only if they were implemented continuously for five years, thereby allowing an entire cohort of effectively treated children age zero to four to survive past the age at which they are most at risk for diarrheal infection, disability, and mortality. Rotavirus immunization (US$2,478 per DALY), cholera immunization (US$2,945 per DALY), and water and sanitation in urban areas (US$6,396 per DALY) were the least cost-effective. Among the early interventions, breastfeeding promotion was less effective than other interventions but also less expensive than rotavirus and measles vaccination (table 19.1). Cholera vaccination was less expensive than breastfeeding promotion, but it was also many times less effective because of the significantly higher prevalence of diarrhea that is not related to cholera—making cholera vaccination the least cost-effective of the early interventions considered. Oral rehydration therapy and water and sanitation interventions were more effective than breastfeeding and vaccination interventions in reducing morbidity and mortality caused by diarrhea, but they were also more expensive. However, our analysis for water and sanitation did not consider the benefits of this intervention other than those related to health, and the high cost-effectiveness ratio is more a limitation of our methodology than of the intervention itself. The high cost-effectiveness ratio for ORT is attributable to the high variation in reported treatment costs, which may inflate the median cost used in this analysis (table 19.2). Given the range of reported treatment costs (table 19.1), the costeffectiveness ratio of ORT could be as low as US$4 per DALY or as high as US$2,124 per DALY in low- and middle-income countries. High variation in reported treatment costs results in Diarrheal Diseases | 379


380 | Disease Control Priorities in Developing Countries | Gerald T. Keusch, Olivier Fontaine, Alok Bhargava, and others


Sources

Horton and others 1996

LAC

Feachem and Koblinsky 1984

Narula, Tiwari, and Puliyeh 2004

SA

Parashar and others 1998a

Cookson and others 1997

LAC

All

de Zoysa and Feachem 1985

Effectiveness (age 0 to 5)

Cookson and others 1997; Martinez, Phillips, and Feachem 1993

LMICs, EAP, MENA, SA, SSA

Costs

Cholera immunization with live oral vaccine

All


Martinez, Phillips, and Feachem 1993; Narula, Tiwari, and Puliyeh 2004

LMICs, EAP, LAC, MENA, SSA

Costs

Rotavirus immunization with RRV-TV

All


Horton and others 1996; Martinez, Phillips, and Feachem 1993

LMICs, EAP, MENA, SA, SSA

Costs

Breastfeeding promotion

Model regions

Bangladesh

Argentina

LMICs, Argentina

Brazil, Peru, R. B. de Venezuela

India

LMICs, India

LMICs

Brazil, Honduras, Mexico

LMICs, Brazil, Honduras, Mexico

Source regions or countries

1.70

3.65

104.30

53.80

1.86

8.98

Median cost/child (2001 US$)

—

1.70–5.60

—

3.33–104.30

0.46–3.26

0.46–17.50

Cost/child range (2001 US$)

0.095

8.54

4.5

Median diarrhea morbidity reduction (percent)

0.06–0.13

—

1–8

Morbidity reduction range (percent)

1.5

24.1

10.5

Median diarrhea mortality reduction (percent)

Table 19.1 Cost and Effectiveness Values Used to Calculate Cost-Effectiveness Ratios for Select Interventions for Diarrhea for Children under Age Five

1–2

—

4–17

Mortality reduction range (percent)

Diarrheal Diseases | 381


Duke 1999; Phillips, Feachem, and Mills 1987; Shann 2000

Feachem and Koblinsky 1983; Phillips, Feachem, and Mills 1987

EAP

SSA

Feachem and Koblinsky 1983

Esrey, Feachem, and Hughes 1985

Esrey, Feachem, and Hughes 1985

All

Esrey, Feachem, and Hughes 1985; Esrey and others 1991


All

Costs (urban)

All

Costs (rural)

Water supply and sanitation improvement

All


Duke 1999; Feachem and Koblinsky 1983; Phillips, Feachem, and Mills 1987; Martinez, Phillips, and Feachem 1993; Shann 2000

LMICs, LAC, MENA, SA

Costs

Measles immunization

LMICs

LMICs

LMICs

LMICs

Côte d’Ivoire, Ghana, Zambia

Indonesia, Papua New Guinea

LMICs, Côte d’Ivoire, Ghana, Indonesia, Papua New Guinea, Zambia

81.00

25.00

15.00

1.62

13.26

—

—

4.00–26.00

0.52–1.10

0.52–26.00

24

2.2

22–26

0.6–3.8

—

6.4–25.6

(Continues on the following page.)

65

16

382 | Disease Control Priorities in Developing Countries | Gerald T. Keusch, Olivier Fontaine, Alok Bhargava, and others


Shepard, Brenzel, and Nemeth 1986



Horton and Claquin 1983; Islam, Mahalanabis, and Majid 1994

Shepard, Brenzel, and Nemeth 1986; Qualls and Robertson 1989

EAP

LAC

MENA

SA

SSA

Boschi-Pinto and Tomaskovic forthcoming

LMICs

The Gambia, Malawi, Swaziland

Bangladesh

Arab Rep. of Egypt

Honduras

Indonesia

Bangladesh, Arab Rep. of Egypt, The Gambia, Honduras, Indonesia, Malawi, Swaziland, Turkey

Source regions or countries

5.51

2.91

4.89

2.59

0.71

5.50

Median cost/child (2001 US$)

0.02–11.00

0.02–5.80

0.02–9.75

0.02–5.16

0.02–1.40

0.02–11.00

Cost/child range (2001 US$)

0

Median diarrhea morbidity reduction (percent)

—

Morbidity reduction range (percent)

95

Median diarrhea mortality reduction (percent)

—

Mortality reduction range (percent)

Source: Authors. LMICs low- and middle-income countries; EAP East Asia and the Pacific; LAC Latin America and the Caribbean; MENA Middle East and North Africa; SA South Asia; SSA Sub-Saharan Africa; — not available. a. Effectiveness calculated based on vaccine efficacy reported in Parashar and others (1998) and under the assumption that rotavirus infection is responsible for 20 percent of all diarrheal morbidity and severe infection is responsible for 33.3 percent of all diarrheal mortality.

All


Horton and Claquin 1983; Islam, Mahalanabis, and Majid 1994; Qualls and Robertson 1989; Shepard, Brenzel, and Nemeth 1986; WHO and UNICEF 2001

Sources

LMICs

Costs

Oral rehydration therapy

Model regions

Table 19.1 Continued

Cost-effectiveness ratio (2001US$/DALY) 16,000 14,000 12,000 10,000 8,000 6,000 4,000 2,000 0 Low- and middleincome countries

East Asia and the Pacific

Breastfeeding promotion Water and sanitation (urban)

Latin America Middle East and and the Caribbean North Africa Rotavirus immunization Water and sanitation (rural)

South Asia

Cholera immunization ORT

Sub-Saharan Africa Measles immunization

Source: Authors.

Figure 19.3 Cost-Effectiveness: Intervention at Birth through Age 5 with Benefits that Occur over Five Years (age 0–4)

Table 19.2 Cost-Effectiveness Ratios of Oral Rehydration Therapy Interventions Based on Minimum, Median, and Maximum per Capita Costs (2001 US$/DALY) Region

Minimum cost Median cost Maximum cost

Low- and middle-income countries

4

1,062

2,124


4

132

260

Latin America and the Caribbean

20

2,570

5,120

Middle East and North Africa

10

2,564

5,113

South Asia

4

642

1,279

Sub-Saharan Africa

4

988

1,972

Source: Authors.

high variation in cost-effectiveness for the other regions as well. There remains little doubt, however, about the effect of widespread use of ORT on diarrhea morbidity and mortality and about the associated direct and indirect cost savings for treatment and hospitalization.

RESEARCH AGENDA Good evidence now supports the view that promoting ORT in conjunction with other key interventions, preventive as well as curative, has had a large role in the marked reduction in deaths of children caused by diarrhea (Victora and others 2000).

Preventive strategies—such as breastfeeding, improving complementary feeding and using micronutrient supplementation or fortification, and increasing coverage with the full set of Expanded Programme on Immunization vaccines (especially measles vaccine)—are all useful and effective (GAVI 2005). Failure to separately track the full impact of bloody diarrhea— especially Shigella infection—on morbidity and mortality or to effectively implement good clinical management (including guidelines for and control over the use of antibiotics) has contributed to the continuing burden of bloody diarrhea and dysentery worldwide and the alarming increase in antibiotic resistance. The challenges for the next decade will be to increase or ensure universal appropriate implementation of these interventions in developing countries and to avoid a situation in which they compete for funding and staff time. Delivery of good-quality services is essential, and much remains to be learned through research before this requirement can be met. Other interventions, such as vaccines against rotavirus, Shigella, or cholera, are either not yet available or not ready for universal administration. Progress toward the development of these vaccines, with the highest priority for the first two, is encouraging, but further investments in research and development will be required before large-scale implementation of these interventions can be considered. The cost of these vaccines will remain a major constraint for poor people, who cannot pay for the costs of development and ensure reasonable profits for industry. However, increased public investment in Diarrheal Diseases | 383


fundamental and applied research, vaccine purchase schemes, and development of low-cost, high-quality manufacturing capacity in developing countries may change the prevailing dynamics. By creating public-private partnerships for vaccine development, organized as targeted product development programs, the public sector, private foundations, and industry are taking steps toward these goals. Because of the fecal-oral transmission of enteric pathogens, improving the supply of safe water and the ability to safely dispose of fecal waste are the best ways to reduce the burden of morbidity and mortality. However, major investments and critical improvements in water and sanitary waste disposal on the necessary scale are unlikely to occur in the next decade or two. Local low-tech solutions can be useful, and enhanced efforts to find ways to improve water cleanliness at the point of use and to build simple latrines that will be used consistently are needed (chapter 41). However, in the face of HIV and the attention being given to tuberculosis and malaria, coordinated efforts to build safe water and sanitation capacity at the local level, one village at a time, that are sufficient to significantly influence the burden of illness are unlikely—even though many more infants and children die each year of preventable and treatable diarrhea than of HIV/AIDS. The cycle of research, followed by implementation, followed by research has enabled the development of improved tools to manage diarrheal diseases—tools that have the potential to further drive down diarrhea mortality. The challenge is to achieve high coverage and good practice with ORT and correct diarrhea case management, including antimicrobial and nutrition interventions. Interventions to integrate health care through programmatic initiatives such as the Integrated Management of Childhood Illness program, critically evaluated elsewhere in this book (chapter 63), could be essential to ensure this high coverage. Some concern remains that in low-resource settings such targeted vertical programs may be abandoned, to the detriment of the goals for disease burden reduction that they were established to achieve. The challenge posed by the case management of bloody diarrhea is a different matter. Until a vaccine is available, the keystone for managing bloody diarrhea will continue to be the early use of effective antimicrobial agents. That is made difficult by increasing drug resistance, aided by the widespread indiscriminate and inappropriate use of antimicrobials, and the increasingly difficult task of finding a safe, inexpensive, and effective oral agent and then ensuring that the drug is given in a clinically optimal manner. From a technical perspective, the development of a vaccine against Shigella infections is still in its infancy and in need of greater investment. For both watery and bloody diarrhea, the challenge of developing drugs to normalize the pathophysiology caused by the infection remains a scientific challenge and a distant hope.

CONCLUSIONS Existing interventions to prevent or treat diarrheal diseases have proven their efficacy in reducing mortality, but a major challenge for the next 10 years will be to scale up these interventions to achieve universal utilization coverage. The United Nations Millennium Development Goal to reduce the mortality rate among children under five by two-thirds by 2015 will be easier to attain if the scale-up goals are reached. New products and tools could significantly improve the efficacy of these interventions—for example, rapid specific diagnostics, new treatment strategies based on reversing the pathophysiology of the infection, simple and effective ways to produce clean water and control human waste, and vaccines to prevent illness. However, these products and tools will not become widely available in time to influence the achievement of the Millennium Development Goals. Continued investment in diarrheal disease research across the spectrum of basic, social and behavioral, and applied investigations is, therefore, essential, including expanded behavioral research to understand how parents assess risk and how actionable health messages can be presented in different cultures and settings.

REFERENCES Allen, S. J., B. Okoko, E. Martinez, G. Gregorio, and L. F. Dans. 2004. “Probiotics for Treating Infectious Diarrhea.” Cochrane Database Systematic Reviews (2): CD003048. Badruddin, S., A. Islam, K. H. Hendricks, Z. A. Bhutta, S. A. Shaikh, J. D. Snyder, and A. M. Molla. 1991. “Dietary Risk Factors Associated with Acute and Persistent Diarrhea in Karachi, Pakistan.” American Journal of Clinical Nutrition 51: 745–49. Baltazar, J. C., D. P. Nadera, and C. G. Victora. 2002. “Evaluation of the National Control of Diarrhoeal Diseases Programme in the Philippines, 1980–93.” Bulletin of the World Health Organization 80: 637–43. Baqui, A. H., R. E. Black, S. El Arifeen, M. Yunus, K. Zaman, N. Begum, and others. 2004. “Zinc Therapy for Diarrhoea Increased the Use of Oral Rehydration Therapy and Reduced the Use of Antibiotics in Bangladeshi Children.” Journal of Health, Population, and Nutrition 22 (4): 440–42. Barreto, M. L., L. M. P. Santos, A. M. O. Assis, M. P. N. Araujo, G. G. Farenzena, P. A. B. Santos, and R. L. Fiaccone. 1994. “Effect of Vitamin A Supplementation on Diarrhoea and Acute Lower Respiratory-Tract Infections in Young Children in Brazil.” Lancet 344: 228–31. Barros, F. C., T. C. Semer, S. Tonioli Filho, E. Tomasi, and C. G. Victora. 1995. “The Impact of Lactation Centers on Breastfeeding Patterns, Morbidity, and Growth: A Birth Cohort Study.” Acta Paediatrica 84: 1221–26. Bern, C., J. Martines, I. de Zoysa, and R. I. Glass. 1992. “The Magnitude of the Problem of Diarrhoeal Disease: A Ten-Year Update.” Bulletin of the World Health Organization 70: 705–14. Bhan, M. K., N. Bhandari, S. Sazawal, J. Clemens, and P. Raj. 1989. “Descriptive Epidemiology of Persistent Diarrhoea among Young Children in Rural North India.” Bulletin of the World Health Organization 67: 281–88.


Bhandari, N., R. Bahl, S. Mazumdar, J. Martines, R. E. Black, and M. K. Bhan. 2003. “Infant Feeding Study Group: Effect of Community-Based Promotion of Exclusive Breastfeeding on Diarrhoeal Illness and Growth: A Cluster Randomised Controlled Trial.” Lancet 361: 1418–23. Black, M. M., H. Dubowitz, J. Hutcheson, J. Berenson-Howard, and R. H. Starr, Jr. 1995. “A Randomized Clinical Trial of Home Intervention for Children with Failure to Thrive.” Pediatrics 95: 807–14. Black, R. E. 2003. “Zinc Deficiency, Infectious Disease, and Mortality in the Developing World.” Journal of Nutrition 133 (Suppl. 1): 1485S–89S. Black, R. E., and C. F. Lanata. 2002. “Epidemiology of Diarrheal Diseases in Developing Countries.” In Infections of the Gastrointestinal Tract, 2nd ed., ed. M. J. Blaser, P. D. Smith, J. I. Ravdin, H. B. Greenberg, and R. L. Guerrant, 11–29. Philadelphia: Lippincott, Williams, and Wilkins. Boschi-Pinto, C., and L. Tomaskovic. Forthcoming. “Deaths from Diarrhoeal Diseases among Children under Five Years of Age in the Developing World: A Review.” Bulletin of the World Health Organization. Brown, K., K. Dewey, and L. Allen. 1998. Complementary Feeding of Young Children in Developing Countries: A Review of Current Scientific Knowledge. WHO/NUT/98.1. Geneva: World Health Organization. Calain, P., J. P. Chaine, E. Johnson, M. L. Hawley, M. J. O’Leary, H. Oshitani, and C. L. Chaignat. 2004. “Can Oral Cholera Vaccination Play a Role in Controlling a Cholera Outbreak?” Vaccine 22: 2444–51. Caulfield, L. E., S. L. Huffman, and E. G. Piwoz. 1999. “Interventions to Improve Intake of Complementary Foods by Infants 6 to 12 Months of Age in Developing Countries: Impact on Growth and on the Prevalence of Malnutrition and Potential Contribution to Child Survival.” Food and Nutrition Bulletin 20:183–200. CDC (U.S. Centers for Disease Control and Prevention). 1999a. “Intussusception among Recipients of Rotavirus Vaccine: United States, 1998–1999.” Morbidity and Mortality Weekly Reports 48: 577–81. ———. 1999b. “Suspension of Rotavirus Vaccine after Reports of Intussusceptions: United States, 1999.” Morbidity and Mortality Weekly Reports 53 (34): 786–89. Cookson, S. T., D. Stamboulian, J. Demonte, L. Quero, C. M. De Arquiza, A. Aleman, and others. 1997. “A Cost-Benefit Analysis of Programmatic Use of CVD 103-Hgr Live Oral Cholera Vaccine in a High-Risk Population.” International Journal of Epidemiology 26: 212–19. Coutsoudis, A., K. Pillay, E. Spooner, L. Kuhn, and H. M. Coovadia. 1999. “Influence of Infant-Feeding Patterns on Early Mother-to-Child Transmission of HIV-1 in Durban, South Africa: A Prospective Cohort Study.” Lancet 354: 471–76. De Cock, K. M., M. G. Fowler, E. Mercier, I. de Vincenzi, J. Saba, E. Hoff, and others. 2000. “Prevention of Mother-to-Child HIV Transmission in Resource-Poor Countries: Translating Research into Policy and Practice.” Journal of the American Medical Association 283: 1175–82. Dennehy, P. H. 2005. “Rotavirus Vaccines: An Update.” Current Opinion in Pediatrics 17: 88–92. de Zoysa, I., and R. G. Feachem. 1985. “Interventions for the Control of Diarrhoeal Diseases among Young Children: Rotavirus and Cholera Immunization.” Bulletin of the World Health Organization 63: 569–83. Dobbing, J. 1990. “Early Nutrition and Later Achievement.” Proceedings of the Nutrition Society 49: 103–18. Duggan, C., O. Fontaine, N. F. Pierce, R. I. Glass, D. Mahalanabis, N. H. Alam, and others. 2004. “Scientific Rationale for a Change in the Composition of Oral Rehydration Solution.” Journal of the American Medical Association 291: 2628–31. Duke, T. 1999. “Haemophilus influenzae Type B Vaccine in Papua New Guinea: What Can We Expect, and How Should We Determine Priority

for Child Health Interventions?” Papua and New Guinea Medical Journal 42: 1–4. Dutta, S., D. Dutta, P. Dutta, S. Matsushita, S. K. Bhattacharya, and S. Yoshida. 2003. “Shigella dysenteriae Serotype 1, Kolkata, India.” Emerging Infectious Diseases 9: 1471–74. English, R. M., J. C. Badcock, T. Giay, T. Ngu, A. M. Waters, and S. A. Bennett. 1997. “Effect of Nutrition Improvement Project on Morbidity from Infectious Diseases in Preschool Children in Vietnam: Comparison with Control Commune.” British Medical Journal 315: 1122–25. Esrey, S. A. 1996. “Water, Waste, and Well-Being: A Multicountry Study.” American Journal of Epidemiology 143: 608–23. Esrey, S. A., R. Feachem, and J. M. Hughes. 1985. “Interventions for the Control of Diarrhoeal Diseases among Young Children: Improving Water Supplies and Excreta Disposal Facilities.” Bulletin of the World Health Organization 63: 757–72. Esrey, S. A., J. B. Potash, L. Roberts, and C. Shiff. 1991. “Effects of Improved Water Supply and Sanitation on Ascariasis, Diarrhoea, Dracunculiasis, Hookworm Infection, Schistosomiasis, and Trachoma.” Bulletin of the World Health Organization 69: 609–21. Fauveau, V., F. J. Henry, A. Briend, M. Yunus, and J. Chakraborty. 1992. “Persistent Diarrhea as a Cause of Childhood Mortality in Rural Bangladesh.” Acta Paediatrica Supplement 381: 12–14. Feachem, R. G. A., and M. A. Koblinsky. 1983. “Interventions for the Control of Diarrhoeal Diseases among Young Children: Measles Immunization.” Bulletin of the World Health Organization 61: 641–52. ———. 1984. “Interventions for the Control of Diarrhoeal Diseases among Young Children: Promotion of Breast-Feeding.” Bulletin of the World Health Organization 62: 271–91. Fourquet, F., J. C. Desenclos, C. Maurage, and S. Baron. 2003. “Acute Gastroenteritis in Children in France: Estimates of Disease Burden through National Hospital Discharge Data.” Archives of Pediatrics 10: 861–68. GAVI (Global Alliance for Vaccines and Immunization). 2005. “Outcomes: Most Recent Data on the Impact of Support from GAVI/The Vaccine Fund and the Work of GAVI Partners.” http://www.vaccinealliance. org/General_Information/About_alliance/progupdate.php. Gill, C., J. Lau, S. L. Gorbach, and D. H. Hamer. 2003.“Diagnostic Accuracy of Stool Assays for Inflammatory Bacterial Gastroenteritis in Developed and Resource-Poor Countries.” Clinical Infectious Diseases 37: 365–75. Glass, R. I., J. S. Bresee, U. D. Parashar, R. C. Holman, and J. R. Gentsch. 1999. “First Rotavirus Vaccine License: Is There Really a Need?” Acta Paediatrica Supplement 88: 2–8. Graeff, J. A., J. P. Elder, and E. M. Booth. 1993. Communication for Health and Behavior Change: A Developing Country Perspective. San Francisco, CA: Jossey Bass. Graves, P., J. Deeks, V. Demicheli, M. Pratt, and T. Jefferson. 2000.“Vaccines for Preventing Cholera.” Cochrane Database Systematic Reviews (4): CD000974. Guptill, K. S., S. A. Esrey, G. A. Oni, and K. H. Brown. 1993. “Evaluation of a Face-to-Face Weaning Food Intervention in Kwara State, Nigeria: Knowledge, Trial, and Adoption of a Home-Prepared Weaning Food.” Social Science and Medicine 36: 665–72. Haider, R., A. Islam, J. Hamadani, N. J. Amin, I. Kabir, M. A. Malek, and others. 1996. “Breastfeeding Counselling in a Diarrhoeal Hospital.” Bulletin of the World Health Organization 74: 173–79. Hanh, S. K., Y. J. Kim, and P. Garner. 2001. “Reduced Osmolarity Oral Rehydrations Solution for Treating Dehydration Due to Diarrhoea in Children: A Systematic Review.” British Medical Journal 323: 81–85.

Diarrheal Diseases | 385 ©2006 The International Bank for Reconstruction and Development / The World Bank 45

Horton, S., and P. Claquin. 1983. “Cost-Effectiveness and User Characteristics of Clinic-Based Services for the Treatment of Diarrhea: A Case Study in Bangladesh.” Social Science and Medicine 17: 721–29. Horton, S., T. Sanghvi, M. Phillips, J. Fielder, R. Perez-Escamilla, C. Lutter, and others. 1996. “Breastfeeding Promotion and Priority Setting in Health.” Health Policy and Planning 11: 156–68. Huicho, L., M. Campos, J. Rivera, and R. L. Guerrant. 1996. “Fecal Screening Tests in the Approach to Acute Infectious Diarrhea: A Scientific Overview.” Pediatric Infectious Disease 15: 486–94. Huttly, S. R., S. S. Morris, and V. Pisani. 1997. “Prevention of Diarrhoea in Young Children in Developing Countries.” Bulletin of the World Health Organization 75: 163–74. Islam, M. A., D. Mahalanabis, and N. Majid. 1994. “Use of Rice-Based Oral Rehydration Solution in a Large Diarrhea Treatment Centre in Bangladesh: In-House Production, Use, and Relative Cost.” Journal of Tropical Medicine and Hygiene 97: 341–46. Jamison, D. T., H. W. Mosley, A. R. Measham, and J. L. Bobadilla. 1993. Disease Control Priorities in Developing Countries. Oxford, U.K.: Oxford University Press. Jones, G., R. W. Steketee, R. E. Black, Z. A. Bhutta, S. S. Morris, and the Bellagio Child Survival Study Group. 2003. “How Many Child Deaths Can We Prevent This Year?” Lancet 362: 65–71. Keusch, G. T. 2001. “Toxin-Associated Gastrointestinal Disease: A Clinical Overview.” In Molecular Medical Microbiology, ed. M. Sussman, 1083–88. New York: Academic Press. ———. 2003. “The History of Nutrition: Malnutrition, Infection, and Immunity.” Journal of Nutrition 133: 336S–40S. Keusch, G. T., and N. S. Scrimshaw. 1986. “Selective Primary Health Care: Strategies for Control of Disease in the Developing World—XXIII. The Control of Infection to Reduce the Prevalence of Infantile and Childhood Malnutrition.” Reviews of Infectious Diseases 8: 273–87. Keusch, G. T., D. M. Thea, M. Kamenga, K. Kakanda, M. Mbala, and F. Davachi. 1992. “Persistent Diarrhea Associated with AIDS.” Acta Paediatrica Scandinavica 381 (Suppl.): 45–48. Khan, S. R., F. Jalil, S. Zaman, B. S. Lindblad, and J. Karlberg. 1993. “Early Child Health in Lahore, Pakistan: X—Mortality.” Acta Paediatrica Supplement 390: 109–17. Kimmons, J. E., K. H. Brown, A. Lartey, E. Collison, P. P. Mensah, and K. G. Dewey. 1999. “The Effects of Fermentation and/or Vacuum Flask Storage on the Presence of Coliforms in Complementary Foods Prepared for Ghanaian Children.” International Journal of Food Science and Nutrition 50: 195–201. Kosek, M., C. Bern, and R. L. Guerrant. 2003. “The Global Burden of Diarrhoeal Disease, as Estimated from Studies Published between 1992 and 2000.” Bulletin of the World Health Organization 81: 197–204. Kotloff, K. L., J. P. Winickoff, B. Ivanoff, J. D. Clemens, D. L. Swerdlow, P. J. Sansonetti, and others. 1999. “Global Burden of Shigella Infections: Implications for Vaccine Development and Implementation of Control Strategies.” Bulletin of the World Health Organizaton 77: 651–66. Legros, D. 2004. “Shigellosis: Report of a Workshop.” Journal of Health, Population and Nutrition 22: 445–49. Martinez, J., M. Phillips, and R. G. A. Feachem. 1993. “Diarrheal Diseases.” In Disease Control Priorities in Developing Countries, ed. D. Jamison, W. H. Moseley, A. R. Measham, and J. S. Bobadilla, 91–115. Oxford, U.K.: Oxford University Press. Miller, P., and N. Hirschhorn. 1995. “The Effect of a National Control of Diarrheal Diseases Program on Mortality: The Case of Egypt.” Social Science and Medicine 40: S1–30. Mondal, S. K., P. G. Gupta, D. N. Gupta, S. Ghosh, S. N. Sikder, K. Rajendran, and others. 1996. “Occurrence of Diarrheal Diseases in Relation to Infant Feeding Practices in a Rural Community in West Bengal, India.” Acta Paediatrica 85: 1159–62.

Murphy, B. R., D. M. Morens, L. Simonsen, R. M. Chanock, J. R. La Montagne, and A. Z. Kapikian. 2003. “Reappraisal of the Association of Intussusception with the Licensed Live Rotavirus Vaccine Challenges Initial Conclusions.” Journal of Infectious Diseases 187 (8): 1301–8. Narula, D., L. Tiwari, and J. M. Puliyeh. 2004. “Rotavirus Vaccines.” Lancet 364: 245–46. Nataro, J., and J. B. Kaper. 1998. “Diarrheagenic Escherichia coli.” Clinical Microbiological Reviews 11: 142–201. Niehaus, M. D., S. R. Moore, P. D. Patrick, L. L. Derr, B. Lorntz, A. A. Lima, and R. L. Guerrant. 2002. “Early Childhood Diarrhea Is Associated with Diminished Cognitive Function 4 to 7 Years Later in Children in a Northeast Brazilian Shantytown.” American Journal of Tropical Medicine and Hygiene 66: 590–93. Nossal, G. J. 2003. “Gates, GAVI, the Glorious Global Funds, and More: All You Ever Wanted to Know.” Immunology and Cell Biology 81: 20–22. Ochoa, T. J., E. Salazar-Lindo, and T. G. Cleary. 2004. “Management of Children with Infection-Associated Persistent Diarrhea.” Seminars in Pediatric Infectious Diseases 15: 229–36. Oria, R. B., P. D. Patrick, H. Zhang, B. Lorntz, C. M. de Castro Costa, G. A. Brito, and others. 2005. “APOE4 Protects Cognitive Development in Children with Heavy Diarrhea Burdens in Northeast Brazil.” Pediatric Research 57: 310–16. Parashar, U. D., J. S. Bresee, J. R. Gentsch, and R. I. Glass. 1998. “Rotavirus.” Emerging Infectious Diseases 4: 561–70. Parashar, U. D., E. G. Hummelman, J. S. Bresee, M. A. Miller, and R. I. Glass. 2003. “Global Illness and Deaths Caused by Rotavirus Disease in Children.” Emerging Infectious Diseases 9: 565–72. Pazhani, G. P., B. Sarkar, T. Ramamurthy, S. K. Bhattacharya, Y. Takeda, and S. K. Niyogi. 2004. “Clonal Multidrug-Resistant Shigella Dysenteriae Type 1 Strains Associated with Epidemic and Sporadic Dysenteries in Eastern India.” Antimicrobial Agents and Chemotherapy 48: 681–84. Peter, G., M. G. Myers, the National Vaccine Advisory Committee, and the National Vaccine Program Office. 2002. “Intussusception, Rotavirus, and Oral Vaccines: Summary of a Workshop.” Pediatrics 110: e67. Phillips, M. A., R. G. A. Feachem, and A. Mills. 1987. Options for Diarrhoeal Disease Control: The Cost and Cost-Effectiveness of Selected Interventions for the Prevention of Diarrhea. London: Evaluation and Planning Centre for Health Care. Qualls, N., and R. Robertson. 1989. “Potential Uses of Cost Analyses in Child Survival Programs: Evidence from Africa.” Health Policy and Planning 4: 50–61. Ronsmans, C., M. L. Bennish, and T. Wierzba. 1988. “Diagnosis and Management of Dysentery by Community Health Workers.” Lancet 8610: 552–55. Ross, D. A., B. R. Kirkwood, F. N. Binka, P. Arthur, N. Dollimore, S. S. Morris, and others. 1995. “Child Morbidity and Mortality Following Vitamin A Supplementation in Ghana: Time since Dosing, Number of Doses, and Time of Year.” American Journal of Public Health 85:1246–51. Ruxin, J. N. 1994. “Magic Bullet: The History of Oral Rehydration Therapy.” Medical History 38: 363–97. Ryan, E. T., and S. B. Calderwood. 2000. “Cholera Vaccines.” Clinical Infectious Diseases 31: 561–65. Salam, M. A. 1998. “Antimicrobial Therapy for Shigellosis: Issues on Antimicrobial Resistance.” Japanese Journal of Medical Science and Biology 51 (Suppl.): S43–62. Salam, M. A., and M. L. Bennish. 1988. “Therapy for Shigellosis: I. Randomized, Double-Blind Trial of Nalidixic Acid in Childhood Shigellosis.” Journal of Pediatrics 113: 901–7. Santos, I., C. G. Victora, J. Martines, H. Goncalves, D. P. Gigante, N. J. Valle, and G. Pelto. 2001. “Nutrition Counseling Increases Weight Gain among Brazilian Children.” Journal of Nutrition 131: 2866–73.


Shann, F. 2000. “Immunization: Dramatic New Evidence.” Papua and New Guinea Medical Journal 43: 24–29. Shepard, D. S., L. E. Brenzel, and K. T. Nemeth. 1986. “Cost-Effectiveness of Oral Rehydration Therapy for Diarrheal Diseases.” Technical Note 86–26, Population, Health and Nutrition Department, World Bank, Washington, DC.

———. 2000. “New Data on the Prevention of Mother-to-Child Transmission of HIV and Their Policy Implications.” Report of a WHO technical consultation on behalf of a United Nations Population Fund, United Nations Children’s Fund, and Joint United Nations Programme on HIV/AIDS interagency task team on mother-to-child transmission of HIV, Geneva, October 11–13.

Sikorski, J., M. J. Renfrew, S. Pindoria, and A. Wade. 2002. “Support for Breastfeeding Mothers.” Cochrane Database of Systematic Reviews (1): CD001141.

———. 2001. “The Optimal Duration of Exclusive Breastfeeding: Results of a WHO Systematic Review.” http://www.who.int/inf-pr-2001/ en/note2001-07.html.

Snyder, J. D., and M. H. Merson. 1982. “The Magnitude of the Global Problem of Acute Diarrhoeal Disease: A Review of Active Surveillance Data.” Bulletin of the World Health Organization 60: 604–13.

———. 2003. HIV and Infant Feeding—Framework for Priority Action. Geneva: WHO.

Tucker, A. W., A. C. Haddix, J. S. Bresee, R. C. Holman, U. D. Parashar, and R. I. Glass. 1998. “Cost-Effectiveness Analysis of a Rotavirus Immunization Program for the United States.” Journal of the American Medical Association 279: 1371–76. Victora, C. G., J. Bryce, O. Fontaine, and R. Monasch. 2000. “Reducing Deaths from Diarrhoea through Oral Rehydration Therapy.” Bulletin of the World Health Organization 78: 1246–55. Victora, C. G., B. R. Kirkwood, A. Ashworth, R. E. Black, S. Rogers, S. Sazawal, and H. Campbell. 1999. “Potential Interventions for the Prevention of Childhood Pneumonia in Developing Countries: Improving Nutrition.” American Journal of Clinical Nutrition 70: 309–20. Westphal, M. F., J. A. Taddei, S. I. Venancio, and C. M. Bogus. 1995. “Breastfeeding Training for Health Professionals and Resultant Institutional Changes.” Bulletin of the World Health Organization 73: 461–68. WHO (World Health Organization). 1997. Health and Environment in Sustainable Development Five Years after the Health Summit. WHO/ EHG/97.8. Geneva: WHO.

———. 2004. Family and Community Practices That Promote Child Survival, Growth, and Development—A Review of Evidence. Geneva: WHO. WHO Collaborative Study Team. 2000. “Effect of Breastfeeding on Infant and Child Mortality Due to Infectious Diseases in Less Developed Countries: A Pooled Analysis.” Lancet 355: 1104. WHO and UNICEF (United Nations Children’s Fund). 2001. “Reduced Osmolarity Oral Rehydration Salts (ORS) Formulation.” WHO/FCH/ CAH/01.22. Report from a meeting of experts jointly organized by the United Nations Children’s Fund and the World Health Organization, Geneva. ———. 2004. Joint Statement: Clinical Management of Acute Diarrhoea. WHO/FCH/CAH/04.7. Geneva: WHO; New York: UNICEF. World Bank. 2002. World Development Indicators. CD-ROM. Washington, DC: World Bank. Zimbasa (Zimbabwe, Bangladesh, South Africa) Dysentery Study Group. 2002. “Multicenter, Randomized, Double Blind Clinical Trial of Short Course versus Standard Course Oral Ciprofloxacin for Shigella Dysenteriae Type 1 Dysentery in Children.” Pediatric Infectious Disease Journal 21: 1136–41.

———. 1999. “Potential Use of Oral Cholera Vaccines in Emergency Situations.” WHO/CDS/CSR/EDC/99.4. Report of a WHO meeting, Geneva, May 12–13.

Diarrheal Diseases | 387 ©2006 The International Bank for Reconstruction and Development / The World Bank 47


Chapter 20

Vaccine-Preventable Diseases Logan Brenzel, Lara J. Wolfson, Julia Fox-Rushby, Mark Miller, and Neal A. Halsey

Vaccination against childhood communicable diseases through the Expanded Program on Immunization (EPI) is one of the most cost-effective public health interventions available (UNICEF 2002; World Bank 1993). By reducing mortality and morbidity, vaccination can contribute substantially to achieving the Millennium Development Goal of reducing the mortality rate among children under five by two-thirds between 1990 and 2015. Accelerated research into the development of new vaccines has been made possible in part by innovative publicprivate partnerships, such as the Global Alliance for Vaccines and Immunization (GAVI). GAVI focuses on expanding access by immunization programs in developing countries to new and underused vaccines, such as those for hepatitis B and Haemophilus influenzae type B (Hib). These newer, more expensive vaccines are challenging previous notions of the cost-effectiveness of immunization. Analyses of their costs and cost-effectiveness are particularly important because of the need to determine the level of resources required in the future to improve immunization programs, to cover the costs of new vaccines, and to allocate scarce public and external resources available for immunization in the most optimal manner. This chapter analyzes the costs and cost-effectiveness of scaling up the EPI and introducing selected new vaccines into the program. It also summarizes the epidemiology of diseases preventable through immunization and estimates the disease burden with and without immunization programs. In addition, the chapter discusses the organization, delivery, and financing of immunization programs and highlights future prospects and areas for further study. Several areas overlap with other chapters. For example, the vaccines that prevent measles, tuberculosis, diphtheria,

pertussis, Hib, and Neisseria meningitis prevent respiratory diseases. Some vaccines, such as those against measles and pertussis, prevent diseases that cause or contribute to malnutrition. Chapter 16 provides an in-depth review of tuberculosis and a discussion of the potential impact of bacillus Calmette-Guérin (BCG) vaccines. This chapter also does not discuss some new vaccines, including conjugate Streptococcus pneumoniae, influenza, typhoid fever, and rotavirus, because other chapters deal with those diseases and vaccines. Vaccines to prevent mumps and varicella that are routinely used in some developed countries are not included in most vaccination programs in developing countries. Other interventions that can reduce the burden of vaccine-preventable diseases and are not covered in this chapter include clean umbilical cord care to reduce the incidence of neonatal tetanus, vitamin A therapy to reduce the case-fatality rate (CFR) from measles, and intensive clinical care that can reduce the mortality associated with most of the vaccine-preventable diseases.

CAUSES AND EPIDEMIOLOGY OF DISEASES PREVENTED BY VACCINES USED IN NATIONAL IMMUNIZATION PROGRAMS The epidemiology and burden of vaccine-preventable diseases vary by country and region partly because of differences in vaccine uptake. Numerous other factors that contribute to the disease burden include geography, seasonal patterns, crowding, nutritional status, travel to and from other countries, and possibly genetic differences in populations that affect disease severity. Table 20.1 summarizes the features of selected vaccines 389


390 | Disease Control Priorities in Developing Countries | Logan Brenzel, Lara J. Wolfson, Julia Fox-Rushby, and others


Airborne droplet Close respiratory nuclei from or cutaneous sputum-positive contact persons

As long as spu- Usually under two No person-totum acid-fast weeks; some person transbacilli are chronic carriers mission positive

Common but Common not important in transmission

Not known; reactivation of old infection commonly causes disease

Spread

Transmission period

Subclinical infection

Duration of natural immunity

Lasting protective immunity not produced by infection; second attack possible

Humans

Humans (some bovine)

Reservoir

Pertussis

Humans

Lasting protective immunity not produced by infection; second attack possible

No

Incomplete and waning protection

Mild illness common: may not be diagnosed

Usually under three weeks (starts before cough is apparent)

Spores enter Close the body respiratory through wounds contact or the umbilical cord stump

Animal intestines; soil

Toxin-producing Bacterium bacterium (Bordetella (Clostridium pertussis) tetani)

Mycobacterium Toxin-producing tuberculosis bacterium (Corynebacterium diphtheriae)

Tetanus

Causative agent

Diphtheria

Tuberculosis

Category

Measlesa

Lifelong typespecific immunity

More than 100 subclinical infections for each paralytic case

A few days before and after acute symptoms

Fecal-oral; close respiratory contact

Humans

Humans

Bacterium (Haemophilus influenzae type B)

Hib

Close respiraClose respiratory contact and tory contact aerosolized droplets

Humans

Virus

Rubella

Lifelong

Lifelong

May occur in Common children under one, but relative importance is minimal

Close respiratory contact

Humans

Lifelong

Common

Uncertain; no pro- Lifelong tection against carriage

Common

Unknown, rare cases for several months

Bites by infected mosquitoes

Birds and mammals

Neisseria menin- Virus gitis groups A, B, C, Y, W135

Meningococcal Japanese disease encephalitis

Infected individ- Chronic carriage uals can trans- for months mit the disease when bitten by a mosquito vector during the viremic phase (the first three or four days of illness)

Bites by infected mosquitoes

Monkeys and humans

Virus

Yellow fever

Common, espe- Common cially in infants

Up to lifelong chronic carriage and transmission

Blood, perinatal, household, occupational, or sexual transmission

Humans

Virus

Hepatitis B

Uncertain; no If develops, protection lifelong against carriage and those previously infected may develop some disease (epiglottitis)

Common

Four days before A few days Chronic carriage rash until two before to seven for months days afterward days after rash; up to one year of age in congenitally infected

Close respiratory contact and aerosolized droplets

Humans

Virus (serotypes Virus 1, 2, and 3)

Poliomyelitis

Table 20.1 Selected Vaccine-Preventable Diseases and Vaccines

Vaccine-Preventable Diseases | 391


2 to 20 percent

Diphtheria toxoid (three to five primary including booster doses in most countries); intramuscular

BCG attenuated Mycobacterium bovis (1); intradermal

0 to 80 percent More than for pulmonary 87 percent tuberculosis; 75 to 86 percent for meningitis and miliary tuberculosis

Vaccine (number of doses); route

Vaccine efficacy

High population Crowding; low densities in socioeconomic regions with status historically poor control; low socioeconomic status; poor access to care; immunodeficiency; malnutrition; alcoholism; diabetes

CaseSee chapter 16 fatality rateb

Risk factors for infection (for unvaccinated individuals)

Killed wholecell or acellular pertussis (three to five, including booster doses in most countries); intramuscular

Up to 10 percent in infants and children

More than 70 to 90 per95 percent cent (more than 80 percent after two doses) in infants

Tetanus toxoid (three to five in children, including booster doses in many countries; five for women of childbearing age; adult boosters for injury prevention); intramuscular

25 to 90 percent

Wound contam- Young age; inated by soil; crowding umbilical cord; agricultural work

Highly transmissible; crowding; low socioeconomic status

OPV: more than 95 percent in industrial countries; 72 to 98 percent in developing countries; lower protection against type 3 than 1 and 2; IPV: more than 95 percent

Live (OPV) (three to four primary plus campaigns);c killed (IPV) (three to four)

Rubella (one or two); subcutaneous

95 percent at 12 95 percent (at months of age; 12 months 85 percent at and up) 9 months of age from one dose, more than 98 percent from two doses

Measles (two); subcutaneous

2 to 10 percent 0.05 to 10.0 per- Less than cent 0.1 percent

Poor environHighly transmismental hygiene sible agent with and sanitation nearly 100 percent infectivity except for isolated populations; crowding, low socioeconomic status

More than 95 percent for invasive disease

Capsular polysaccharide linked to protein Hib (three to five); intramuscular

Meningitis, 5 to 90 percent; pneumonia 5 to 25 percent

Failure to breastfeed; crowding; low socioeconomic status; immune deficiency, including HIV

Young age; forest workers; season (late rainy season, early dry season)

Yellow fever attenuated live virus (1 plus boosters); subcutaneous

75 to 95 per90 to 98 percent cent; efficacy against chronic infection in infants born to carrier mothers; more than 95 percent for exposure at older ages

Hepatitis B surface antigen (three to four); intramuscular

Acute, more 10 to 40 percent than 1 percent; chronic; 25 percent (delayed)

Carrier mother, sibling, or sex partner; multiple sex partners; intravenous drug use; unsafe injection practices

Live attenuated: 90 percent (after one dose at one year); 94 to 100 percent (after two doses one to two months apart); inactivated: 80 percent (declining to 55 percent after one year; no decrease in another study)

Live attenuated (two, China only); killed (two); booster commonly used but of uncertain value

5 to 30 percent


Unconjugated polysaccharides: poor efficacy under two years of age; conjugated polysaccharides: approximately 95 percent and up serogroup specific

Vaccines for A, C, Y, W135 only; unconjugated polysaccharides given subcutaneously or intramuscularly: one dose with repeat three to five years later for high-risk persons; conjugated: for C only or A, C, Y, + W135, one dose given intramuscularly

Untreated 90 to 100 percent; treated 5 to 20 percent

Crowding; respi- Young age; ratory viral infec- forest workers; tions, especially season influenza

392 | Disease Control Priorities in Developing Countries | Logan Brenzel, Lara J. Wolfson, Julia Fox-Rushby, and others


Tuberculosis

Unknown; some evidence that immunity wanes with time

Given at or near birth in populations at high risk

Category

Duration of immunity after primary series

Schedule


Usually given in childhood as combination vaccine (DTP)

Normally given as DTP vaccine to children; unimmunized pregnant women should be given two doses of tetanus toxoid or tetanusreduced diphtheria toxoid, and a total of five doses is required to provide protection through all childbearing years

Three-dose schedule recommended at 6, 10, and 14 weeks in developing countries for DTP vaccine; other schedules in common use; booster doses at 18 months and four to six years also suggested

Pertussis Unknown; wanes with time

Tetanus

Variable: probably 10 years or around five years; more longer in presence of natural boosting or booster doses

Diphtheria

OPV: four doses (birth, 6, 10, and 14 weeks) in polioendemic countries; birth dose may be omitted elsewhere with fourth dose given later; supplemental doses (up to 10) given in national campaigns for eradication; IPV: three to four doses: 2, 4, 6 to 18 months, and four to six years

Presumed lifelong for both OPV and IPV, but unknown

Poliomyelitis

First dose at 9 or 12 to 15 months); a second opportunity to receive a dose of measles vaccine (either through routine [18 months or four to six years] or supplemental immunization activities) should be provided for all children

Lifelong in most; rare cases of waning immunity after one dose, not two

Measlesa

First dose at 12 to 15 months; when given, a second dose with measles vaccine

Lifelong in most; presumed rare cases of waning immunity after one dose, not two

Rubella

Three or four doses; usually given during the same visit as for DTP

Unknown, but lasts for at least three years beyond period of greatest exposure

Hib

Several schedules: at birth, 6, and 14 weeks; with first three doses of DTP; birth dose needed if mother is a carrier and recommended if perinatal transmission of hepatitis B is frequent; four doses total can be given although only three are required

More than 15 years; further follow-up is continuing

Hepatitis B

Meningococcal Japanese disease encephalitis

One dose at 9 to 12 months with measles in countries where yellow fever poses a risk

Unconjugated: one dose at two years or older and second dose three to five years later for high risk; conjugate C: three doses at two, three, and four or two, four, and six months for infants; one dose for older children and adults; conjugate A, C, Y, W135 currently only approved for one dose at 11 years or older

Live: one year and two years; killed: days 0, 7, and 30 followed by booster two years later and then every three years

Unknown, may For at least 10 Unconjugated years and possi- wanes rapidly for be lifelong children under bly for life five, more than three to five years for older children; conjugated uncertain

Yellow fever

Vaccine-Preventable Diseases | 393


Recent trends to lower antibody levels in adults without booster doses because of waning immunity and less natural boosting

Comments

Five doses in adults provide protection for more than 20 years

Childhood: all countries; 78 percent coverage

Variability in whole cell vaccines; acellular vaccines used in some developed countries

All countries; 78 percent coverage

Lower efficacy when maternal antibody present

Routine first 110 countries in dose all coun2003 tries, 77 percent coverage; second opportunity, 164 out of 192 countries

Primary series Lower efficacy gives incomwhen maternal plete protection antibody present in developing countries

All countries; 79 percent routine, plus supplemental coverage

None

Efficacy lower if injected into fat

89 countries; 147 countries; global coverage global coverage less than 42 percent 18 percent

None

29 of 43 countries at risk using vaccine; 30 percent coverage in target population None

European countries, Canada (and United States in 2005)

None

Southeast Asia

Sources: WHO 2002, 2004. DTP diphtheria-tetanus-pertussis; IPV inactivated polio vaccine; OPV oral polio vaccine. a. Measles vaccine is given as measles, measles-rubella, or measles-mumps-rubella vaccine. The latter two vaccines are routinely used in industrial countries and are increasingly being adopted in other countries. The World Health Organization recommends that the combination measles-rubella or measles-mumps-rubella vaccines be introduced only after careful evaluation of public health priorities within each country and following the establishment of an adequate program for measles control as demonstrated by high coverage rates as part of a well-functioning childhood immunization program. b. Note that variations in case-fatality rates are related to access to care, type of care administered, setting, age at onset of disease, and other factors. The ranges presented in this table reflect both uncertainty as to actual case-fatality rates and the variability of populations. c. As of 2003, an injected IPV is given alone or in combination with OPV in 31 countries. IPV is currently not recommended for routine use in developing countries because of its relatively high cost and uncertain efficacy when given at 6, 10, and 14 weeks. The usual recommended IPV schedule is 2, 4, and 6 to 18 months. Routine use of OPV is expected to cease following polio eradication. Stockpiles of monovalent OPV for each of the three virus types are under development to protect against vaccine-associated paralytic poliomyelitis and outbreaks of circulating vaccine-derived polioviruses.

Reasons for varying efficacy are multifactorial, including differences in vaccines

All countries; 78 percent coverage

Status as of 158 countries the end of using BCG; 2001 85 percent coverage

in use in childhood immunization programs throughout the world.

Burden of Vaccine-Preventable Diseases A number of vaccine-preventable diseases are not reportable events in many countries. The estimates of the burden of disease by the World Health Organization (WHO) are based on a combination of often incomplete vital registration data, mortality survey data, and mathematical models using numerous assumptions. Most models of vaccine-preventable diseases are derived from the susceptible fraction of the population (calculated from natural immunity from presumed historical infections in regions without previous vaccination and historical immunization coverage rates), infectivity rates of disease, sequelae of diseases, and estimates of local CFRs. The degree of accuracy of these models is only as good as the data supporting the assumptions. The disease burden is most appropriately represented by a range of values reflecting uncertainty. In this chapter, we estimate the burden of disease as the number of deaths and DALYs per World Bank region in 2001. The following description draws in part on discussion of methods for burden of disease calculations reflected in the Global Immunization and Vision Strategy of WHO and the United Nations Children’s Fund (UNICEF) (Wolfson and Lydon 2005).

Diphtheria Diphtheria is caused by a toxin-producing strain of the bacterium Corynebacterium diphtheriae, which is transmitted by means of respiratory droplets. The 2001 WHO estimates of diphtheria mortality are extrapolations from reported deaths in countries with full or partial vital registration systems. Before the widespread use of immunization, more than 5 percent of people living in temperate climates suffered from clinical diphtheria at some point during their lifetimes (Griffith 1979). Rates exceeding 100 cases per 100,000 population were seen in Europe during World War II (Galazka, Robertson, and Oblapenko 1995). The CFRs from respiratory tract diphtheria have been 2 to 20 percent, with an average of 10 percent for patients receiving good medical care (Feigin, Stechenberg, and Hertel 2004).To estimate diphtheria deaths in the absence of vaccination and to project future deaths with and without vaccination, we assumed an average incidence rate of 15 per 100,000 and CFRs of 2.5 percent in developed countries,5.0 percent in Europe and Central Asia, and 10.0 percent elsewhere (Birmingham and Stein 2003; Galazka and Robertson forthcoming).

Tetanus Clostridium tetani is maintained in nature and is found in all countries. Spores remain viable for many years in soil and dust,

especially in areas contaminated by animal feces (Cherry and Harrison 2004). The organism is usually transmitted through burns, cuts, and other penetrating injuries. Neonatal tetanus is the most common presentation in developing countries. The portal of entry is usually the umbilical stump but has been associated with circumcision and other surgical procedures (Birmingham and others 2004; Stanfield and Galazka 1984). Children born to women who do not have protective levels of tetanus antibody are susceptible to neonatal tetanus. The estimated burden of neonatal tetanus assumes that in areas with low rates of skilled delivery, all births not protected by the immunization of pregnant women are subject to a preimmunization era neonatal tetanus mortality rate expressed as deaths per 1,000 live births (Birmingham and others 2004; Griffiths and others 2004). In other areas, we assume that births not protected through immunization or skilled delivery are subject to an incidence and CFR equal to 25 percent of the preimmunization era neonatal tetanus mortality rate.1 CFRs are directly associated with the quality of medical care available. With the availability of secondary and tertiary care, CFRs have declined to 25 percent or less (Cherry and Harrison 2004; Wassilak and others 2004). The CFRs used to derive cases from estimated deaths range from 40 percent in developed countries to 80 percent in the poorest developing countries. We estimate the tetanus burden other than for neonates by applying an estimated age distribution of total tetanus to the estimated neonatal tetanus deaths (Galazka and others forthcoming) and region-specific CFRs, which indicate a range of from 27 percent among children age one to four in developed countries to 65 percent among those age 80 or older in developing countries.

Pertussis Bordetella pertussis is transmitted through respiratory excretions and occurs throughout the world. Most pertussis in developing countries occurs in school-age children. In developed countries, mild or asymptomatic infections in adults are believed to be common sources of transmission to very young infants (Edwards and Decker 2004). Clinical manifestations include an initial 7 to 10 days of rhinorrhea progressing to a cough that becomes paroxysmal or spasmodic, usually associated with profuse rhinorrhea (Cherry and Heininger 2004). Clinical pneumonia is seen in approximately 10 percent of infants. Our estimates for the burden of pertussis followed the model described in Crowcroft and others (2003). We estimated that the proportion of susceptible children becoming infected in countries with vaccination coverage of less than 70 percent over the previous five years was 30 percent by age 1, 80 percent by age 5, and 100 percent by age 15. For countries with coverage of more than 70 percent in the past five years, we assumed

394 | Disease Control Priorities in Developing Countries | Logan Brenzel, Lara J. Wolfson, Julia Fox-Rushby, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 54

that 10 percent of susceptible children were infected by age 1, 60 percent by age 5, and 100 percent by age 15. A vaccine efficacy of 80 percent was assumed for preventing infection and 95 percent for preventing deaths. The CFR was 0.20 percent in infants, 0.04 percent in children age one to four, and 0 percent in those older than five in low-mortality countries; and 3.7 percent among infants, 1 percent among children age one to four, and 0 percent in those older than five in high-mortality countries. Poliomyelitis Before the availability of polio vaccines, as many as 90 percent of children in the developing world were infected with all three types of the polio virus in the first two or three years of life (Sutter and Kew 2004). In developed countries, transmission occurred primarily in school-age children and more than 90 percent of infections were asymptomatic; 4 to 8 percent of children had nonspecific febrile illness and less than 1 percent developed acute flaccid paralysis (Sutter and Kew 2004). Children with residual paralysis require rehabilitation. Surgical intervention is necessary if contractures develop because of the lack of rehabilitative services following the acute illness. These children are at increased risk of premature death because of late onset postpolio muscle atrophy (postpolio syndrome), which occurs 20 to 40 or more years after acute illness. Disease burden estimates are based on actual active surveillance. The estimated 1,000 deaths a year caused by polio reflect past infections and current deaths. Following Robertson (1993), we obtained the number of cases and deaths in the absence of immunization by applying an incidence rate of 1 per 1,000 population under age five and CFRs of from 2.5 percent in developed countries to 10.0 percent in Sub-Saharan Africa. To determine current cases, we applied an estimate of notification efficiency to reported cases. Measles Measles is an acute respiratory viral infection. Children born to immune mothers are protected against clinical measles from passively acquired maternal antibodies until they are five to nine months of age. More than 90 percent of infections are associated with clinical disease (Krugman 1963). Complications include pneumonia, diarrhea, encephalitis, and blindness, especially in children with vitamin A deficiency. In recent years, CFRs have been estimated at 3 percent in many developing countries, but historically they have been as high as 30 percent in some community-based studies (Aaby 1988; Aaby and Clements 1989; Moss, Clements, and Halsey 2003; Perry and Halsey 2004). For a disease such as measles in which infection is almost universal in the absence of immunity, small changes in the CFR result in large changes in estimates of total mortality. Increased complication and mortality rates occur in children who are

younger than five, vitamin A deficient, or infected with HIV or who have acquired measles from a household contact (Perry and Halsey 2004). Declines in CFRs in the past two decades are associated with the tendency of the disease to infect older children, decreased crowding, and improved nutritional status in many developing countries (Perry and Halsey 2004). At the same time, recent studies indicate CFRs of 0.4 to 9.7 percent in Sub-Saharan African countries with low immunization coverage (Perry forthcoming). Considerable controversy is associated with the number of deaths resulting from measles, because of difficulty in accurately specifying the cause of death in children afflicted with measles and in separating complications of measles from those of other conditions. In addition, CFRs, which have decreased rapidly in many countries, vary significantly. The natural history model used in this chapter is based on Stein and others (2003), modified to account for the effect of supplementary immunization activities. We derived estimates of the burden of disease in countries with high-quality surveillance data and high sustained coverage of measles vaccine by adjusting the number of reported cases by a reporting efficiency factor ranging from 5 to 40 percent. In estimating the future burden of disease, the averted burden of disease, and the burden in countries without both adequate surveillance and sustained high coverage, we assumed that the average number of cases per year is equal to the number of children in the current birth cohort who are not protected by either routine or supplemental vaccination. WHO (2005a) estimates that in 2001, 611,000 deaths (approximately 5 percent of all childhood mortality) were attributable to measles. An alternative proportional mortality approach, which is based on retrospective verbal autopsy studies in 18 countries to derive the proportional causes of child deaths in 42 highmortality countries, also has appeared in the literature (Morris, Black, and Tomaskovic 2003). This model suggests that measles may have accounted for approximately 3 percent of all childhood deaths in 2000. In countries with a high disease burden, the true number of measles deaths may be somewhere between the proportional mortality and natural history estimates. WHO (2005b) uses a hybrid method that estimates that measles was responsible for an average of 4 percent of mortality among children under five between 2000 and 2003, or approximately 400,000 deaths per year. If the actual number of deaths in 2001 was 400,000, then the cost per death averted will be lower than what has been estimated for this chapter, and the effect of increasing coverage will be overestimated because fewer deaths could be prevented. Both of the approaches described have strengths and limitations. We adopt the natural history approach for this analysis because the chapter includes deaths at all ages and the model can adapt to recent changes in CFRs and coverage rates. Vaccine-Preventable Diseases | 395


However, the natural history method is sensitive to the accuracy of parameter inputs such as CFRs and may underestimate the effect of herd immunity. Further modeling efforts would need to incorporate sensitivity testing around a range of parameter estimates. In the absence of vaccination, the measles virus would infect almost 100 percent of the population, including most of the 688 million children under five in the developing world. Using the methods described here, approximately 125 million cases and 1.8 million to 2.0 million deaths per year would be expected in the absence of vaccination. Haemophilus influenzae Type b (Hib) Hib is transmitted through the respiratory tract and causes meningitis, pneumonia, septic arthritis, skin infections, epiglottitis, osteomyelitis, and sepsis. Deaths caused by Hib occur primarily from meningitis and pneumonia. In developed countries, approximately half of diagnosed invasive infections are meningitis (Wenger and Ward 2004). In developing countries, a larger proportion of identified cases is meningitis resulting from underdiagnosis of other clinical syndromes (Martin and others 2004; Peltola 2000). Intervention studies have demonstrated significant reductions in pneumonia in vaccinated compared with unvaccinated children (Levine and others 1998; Mulholland and others 1997). Although infections occur throughout the world, the incidence of Hib disease may be lower in some Asian countries than in Africa and the Americas (Gessner and others 2005). We derived estimates of Hib disease burden from incidence rates and CFRs for meningitis and pneumonia. We derived country-specific estimates of the incidence of Hib meningitis from the literature on incidence in the prevaccine era (Bennett and others 2002). For countries without meningitis incidence data, we used the average incidence in countries with similar epidemiological profiles. Regional averages ranged from 219 cases per 100,000 to 3 per 100,000 population in children under one, and 1 to 15 per 100,000 population in children age one to four. The CFR for meningitis is nearly 100 percent in the absence of intensive antibiotic therapy, but it can be reduced to 5 to 8 percent when appropriate therapy is available (Swartz 2004). We derived CFRs in a manner similar to that used for incidence rates and adjusted them on the basis of countryspecific data on access to care. Regional means ranged from 3 to 32 percent. Estimating the burden of Hib pneumonia is much more complex. A rapid assessment method assumes five pneumonia cases for every meningitis case (WHO 2001). An alternative approach assumes that Hib is responsible for a fixed proportion (about 20 percent) of acute lower respiratory infection deaths in the absence of immunization (Peltola 2000). We derived pneumonia CFRs from a literature review of lower respiratory infections in children (Bennett and others 2002), with

average CFRs ranging from 1 percent among infants in developed countries to 12 percent in Sub-Saharan Africa. Hepatitis B In many developed countries, most transmission of hepatitis B occurs during or after adolescence, coinciding with the onset of sexual activity and of drug abuse involving unsafe reuse of needles and syringes (McQuillan and others 1999). In many African countries, transmission occurs primarily in early childhood through mucosal contact with infectious body fluids and unsafe injection practices (Margolis, Alter, and Hadler 1997). Some Asian countries have a high rate of chronic carrier states, and the primary mode of transmission is mothers to infants (Beasley 1988; Mast and others 2004). The rate of symptomatic disease is only about 1 percent in infancy and 10 percent in early childhood, but it increases to 30 to 40 percent in adults. Serosurveys for carrier states of hepatitis B are available for almost all nations (WHO 1996). Models of hepatitis B disease burden are based on estimated ratios between infected and carriage states at various ages or estimates of the percentage of carriers that progress to hepatoma, fulminant hepatitis, or cirrhosis at later stages of life (Miller and McCann 2000). The model we used for estimating hepatitis B mortality estimates the age- and sex-specific progression of hepatitis B surface antigen infection to disease incorporating competing mortality, particularly because individuals infected with HIV are more likely to perish from HIV before the full mortality impact from hepatitis B infection (Gay and others 2001; Griffiths, Hutton, and Pascoal 2005). Whereas most vaccine-preventable diseases that result in death occur at an early age shortly after the age of vaccination, deaths from hepatitis B occur many years into the future. Countries that introduce hepatitis B vaccines today will not reap most of the benefits for many years. In the absence of vaccination, we estimated approximately 1.4 million future deaths attributable to hepatitis B for the 2001 birth cohort after accounting for competing mortality. Global vaccination of 35 percent would prevent more than 500,000 of those future deaths. Discounting the value of future hepatitis B deaths to their equivalent value in the present to make the burden of disease prevented equivalent to that of other vaccine-preventable diseases results in approximately 87,000 deaths averted.

Yellow Fever Yellow fever virus is transmitted by mosquitoes, primarily Aedes eqypti, with a three- to six-day incubation period. Patients present with intense headache, fever, chills, and myalgia, among other symptoms. Although once much more widespread, yellow fever is now limited to West and Central Africa, the northern half of South America, and Panama. In approximately


15 to 20 percent of yellow fever patients, severe disease occurs, with liver and kidney failure and cardiovascular collapse. The CFR varies, with increased severity in older adults (Monath 2004). The average CFR in patients in Africa with jaundice is 20 percent (Monath and others 1980; Nasidi and others 1989). On the basis of surveillance data adjusted for underreporting, WHO (1992) estimates the global burden of yellow fever at 200,000 cases and 30,000 deaths in 1990. Most cases and deaths occur in 33 African countries, where 1 in 80 cases is assumed to be reported. In South American countries, 1 in 10 cases is assumed to be reported. We use the implied incidence rate and a CFR of 15 percent to project future mortality. Between 1990 and 2001, some improvement in routine coverage of yellow fever vaccine occurred, but the overall burden of yellow fever is unlikely to have declined.

ESTIMATES OF THE CURRENT BURDEN OF VACCINE-PREVENTABLE DISEASES AND OF THE BURDEN AVERTED BY VACCINATION Table 20.2 provides WHO estimates of deaths from selected vaccine-preventable diseases for 2001, taking immunization coverage rates into account. The greatest burden of disease is in Sub-Saharan Africa, which accounts for 58 percent of pertussis deaths, 41 percent of tetanus deaths, 59 percent of measles deaths, and 80 percent of yellow fever deaths. East Asia and the Pacific has the greatest burden from hepatitis B, with 62 percent of deaths worldwide. South Asia also experienced a high disease burden, particularly for tetanus and measles. Table 20.2 also shows the extent of mortality in the absence of immunization and the estimated number of deaths averted by vaccination. In 2001, vaccination averted up to 52 percent of yellow fever deaths, 61 percent of measles deaths, 69 percent of tetanus deaths, 78 percent of pertussis deaths, 94 percent of diphtheria deaths, and 98 percent of polio deaths that would have occurred in the absence of vaccination. These results demonstrate the significant effect that vaccination programs have had on worldwide disease burden. The figures also show that vaccination programs have been less successful in reducing the disease burden in Sub-Saharan Africa, where coverage rates are lower. Table 20.3 reports WHO estimates of disability-adjusted life years (DALYs) lost from vaccine-preventable diseases by region for 2001, demonstrating the high burden of disease worldwide from disability associated with sequelae of hepatitis B (liver cancer and cirrhosis), pertussis, and tetanus.2

Turk 1982; WHO 1974). A standard immunization schedule was established in 1984 on the basis of a review of immunological data for the original EPI vaccines: BCG, diphtheriatetanus-pertussis (DTP), oral polio, and measles vaccines (Halsey and Galazka 1985). Today, national immunization programs in developing countries are responsible for improving access to the traditional EPI antigens and introducing new vaccines. In 2002, the EPI introduced the Reaching Every District strategy, which focused on achieving an 80 percent coverage rate of DTP3 in 80 percent of districts and using immunization contacts to deliver other high-priority child health interventions. In addition to delivering vaccinations, national immunization programs are concerned with the quality and safety of immunization through the adoption of safe injection technologies (autodisabled syringes, storage boxes, and incinerators) and proper cold chain and vaccine stock maintenance. In most developing countries, immunizations are provided through a system of fixed facilities at different levels of the health system. Immunization campaigns are discrete, timelimited efforts at national or subnational levels that usually focus on specific antigens (for example, polio). Mobile strategies rely on the use of specialized vehicles to transport health professionals and vaccines to deliver services to remote or migrating populations. Outreach is a strategy by which staff members from a health facility travel to villages and surrounding areas to administer vaccines. Extended outreach refers to more targeted and intensive efforts. In 1999, the major international development partners involved in immunization (for example, WHO, UNICEF, the World Bank, and bilateral donors) joined the Bill & Melinda Gates and Rockefeller Foundations, the vaccine industry, and nongovernmental organizations to create GAVI (http://www. vaccinealliance.org) to increase access to new and underused vaccines in the world’s poorest countries, improve access to basic immunization services, and accelerate research and development pertaining to new vaccines and delivery technology. Through the Vaccine Fund, GAVI raised more than US$1.3 billion to strengthen immunization systems, introduce new vaccines, and support safe injection practices. More than US$3 billion has been pledged for the next 10 years. Between 2000 and 2003, an additional 4 million children were vaccinated with DTP3, 42 million with hepatitis B, nearly 5 million with Hib, and more than 3 million with yellow fever vaccine.

EXPANDED PROGRAM ON IMMUNIZATION

COSTS AND COST-EFFECTIVENESS OF EXISTING VACCINATION PROGRAMS

WHO initiated the EPI in 1974 to provide countries with guidance and support to improve vaccine delivery and to help make vaccines available for all children (Hadler and others 2004;

Brenzel and Claquin (1994) and GAVI (2004) estimate the cost per fully immunized child (FIC) for the traditional six EPI antigens as approximately US$20.3 We evaluated the cost per Vaccine-Preventable Diseases | 397


Table 20.2 Estimated Number of Deaths in the Absence of Vaccination, Deaths from Vaccine-Preventable Diseases, and Deaths Averted by Vaccination, All Ages, by Region and Vaccine, 2001 (thousands)

Disease

Total

High income


Europe and Central Asia



South Asia

SubSaharan Africa

Diphtheria If no vaccination

78

3

28

4

8

5

21

10

Estimated deaths

5

1

1

1

1

1

3

1

73

3

27

4

8

5

18

9

1,343

7

377

4

138

93

428

296

Deaths averted Pertussis If no vaccination

301

1

3

1

6

8

108

176

1,042

7

374

4

132

85

320

120

If no vaccination

936

1

110

1

20

23

543

239

Estimated deaths

293

1

27

1

1

4

140

121

Deaths averted

643

1

83

1

19

19

403

118

Estimated deaths Deaths averted Tetanus

Poliomyelitis If no vaccination

52

1

15

1

3

4

17

11

1

1

1

0

0

0

0

0

51

n.a.

15

1

3

4

17

11

2,000

6

301

36

6

55

567

1,025

676

1

77

4

1

7

239

348

1,237

5

229

28

6

40

351

578

If no vaccination

468

1

28

2

9

14

199

216

Estimated deaths

463

1

28

2

5

14

199

215

5

1

1

1

4

1

1

1

If no vaccination

600

34

370

36

11

17

75

58

Estimated deaths

600

34

370

36

11

17

75

58

Deaths avertedc

1

1

1

1

1

1

1

1

If no vaccination

63

n.a.

n.a.

n.a.

8

n.a.

n.a.

54

Estimated deaths

30

n.a.

n.a.

n.a.

6

n.a.

n.a.

24

Deaths averted

33

n.a.

n.a.

n.a.

2

n.a.

n.a.

30

Estimated deathsa Deaths averted Measles If no vaccination Estimated deathsb Deaths averted Hib

Deaths averted Hepatitis B

Yellow fever

Source: Mathers and others 2006 and authors’ calculations. n.a. not available. Note: Totals may not add due to rounding. a. Primarily deaths at older ages caused by delayed effect of poliomyelitis in childhood. b. See text for discussion of uncertainty regarding measles estimates. The values shown here are an updated version of the 2001 estimates. c. Deaths averted to date from the use of the hepatitis B vaccine in infant immunization programs are minimal, largely because of the long time period (20 to 40 years) to see mortality effects.


Table 20.3 DALYs Lost from Vaccine-Preventable Diseases, All Ages By Region, 2001 (thousands)

Disease Diphtheria

Total 164

High income 1

East Asia and the Pacific 18

Europe and Central Asia 2

Latin America and the Caribbean 8

Middle East and North Africa 1

South Asia 90

SubSaharan Africa 45

Tetanus

8,342

5

762

2

17

110

3,965

3,481

Pertussis

11,542

139

584

81

366

326

3,930

6,116

Poliomyelitis Measles

145

8

49

2

6

8

55

17

23,129

23

2,318

236

13

470

6,527

13,539

2,169

86

675

79

95

111

585

536

Hepatitis Ba Acute hepatitis B Liver cancer Cirrhosis of the liver Meningitisb Lower respiratory infectionsc

9,168

1,223

5,925

379

277

138

464

762

15,780

2,146

3,890

2,084

1,513

686

4,249

1,212

5,607

131

1,071

403

591

328

2,142

941

85,920

2,314

10,827

2,111

3,043

2,974

34,196

30,455

Source: Mathers and others 2006 and Authors’ calculations. Note: Totals may not add due to rounding. a. Includes all DALYs attributable to the three conditions. Hepatitis B is the underlying cause of only a portion of the liver cancer and cirrhosis of the liver DALYs. b. Includes all DALYs attributable to meningitis, including Hib, S. pneumococcus, and N. meningitides. c. Includes all DALYs attributable to lower respiratory infections, including Hib and S. pneumococcus.

FIC for the childhood EPI cluster antigens by World Bank region on the basis of published and unpublished data. These studies used a standard costing approach that estimated the costs of labor, vaccines, supplies, transportation, communication, training, maintenance, and overhead and included the annualized value of equipment, vehicles, and building space (Khaleghian 2001; USAID, Asia–Near East Region 1988; WHO 1988). The number of FICs in these studies was measured using community-based sample surveys (Henderson and Sundaresen 1982). Our literature review found 102 estimates of total and unit immunization program costs from 27 countries between 1979 and 2003 for different immunization delivery strategies (Berman and others 1991;1 Beutels 1998, 2001; Brenzel 2005; Brenzel and Claquin 1994; Brinsmead, Hill, and Walker 2004; Creese 1986; Creese and Domínguez-Ugá 1987; DomínguezUgá 1988; Edmunds and others 2000; Griffiths and others 2004; Levin and others 2001; Pegurri, Fox-Rushby, and Walker 2005; Robertson and others 1992; Soucat and others 1997; Steinglass, Brenzel, and Percy 1993). All costs were converted to 2001 U.S. dollar equivalents. Because total and unit costs are related to population size, table 20.4 reports populationweighted results only. National immunization program refers to total national costs for all strategies. The population-weighted mean cost per FIC for all regions and all strategies is approximately US$17, with a range of US$3 to US$31. The lowest mean population-weighted cost per FIC

was for extended outreach services (US$5.81), perhaps because the strategy is a more targeted approach. Routine facility-based strategies had lower average costs (US$13.65 per FIC) than campaigns (US$26.82 per FIC) or mobile strategies (US$25.84 per FIC). Higher unit costs associated with these strategies are possibly attributable to a different mix of inputs as well as greater expenses for per diems, fuel, and social mobilization. The results also vary by World Bank region, with East Asia and the Pacific (US$13.25) and Sub-Saharan Africa (US$14.21) having lower estimates of cost per FIC than Europe and Central Asia (US$24.12) and the Middle East and North Africa (US$22.15). The findings of our analysis are generally supported by the literature (Creese 1986; Brenzel and Claquin 1994; Khaleghian 2001), which has shown that variation in the cost per FIC is related to the mix of delivery strategies, the prices of key inputs such as vaccines, and the overall scale of programs. In addition, an analysis of 13 national financial sustainability plans for immunization reveals a wide range in the cost per FIC by region and strategy.4 Recurrent costs are the lion’s share of total immunization costs (80 percent for fixed facility strategy and 92 percent for campaigns), which has implications for the need for continuous and predictable program financing. Labor costs account for the largest share (roughly 30 to 46 percent of total cost) for all strategies except extended outreach. Vaccine costs range from 8 percent for mobile strategies to 29 percent for extended Vaccine-Preventable Diseases | 399


Table 20.4 Estimates of the Population-Weighted Annual Cost for the Traditional Vaccines per FIC, by Immunization Strategy and Region, 2001 (2001 US$) East Asia and the Pacific (n 4)

Europe and Central Asia (n 1)

Latin America and the Caribbean (n 1)

Middle East and North Africa (n 1)

—

—

18.10

20.00 (18–22) n2

24.12

Campaign

—

Mobile

Strategy National immunization program Fixed facility

Outreach

Extended outreach

Mean for all strategies

South Asia (n 10)

SubSaharan Africa (n 15)

All regions (n 32)

22.15

24.82 (23–27) n2

21.05 (17–26) n2

23.52 (17–27) n6

—

—

13.79 (6–24) n7

6.31 (3–31) n6

13.65 (3–31) n 16

—

—

—

—

26.82 (13–28) n3

26.82 (13–28) n3

—

—

—

—

—

25.84 n1

25.84 n1

6.50 (4–9) n2

—

—

—

7.11 n1

—

7.10 (4–9) n3

—

—

—

—

—

5.81 (5.8–13) n3

5.81 (5.8–13) n3

13.25 (4–22)

24.12

18.10

22.15

17.11 (6–27)

14.21 (3–31)

16.91 (3–31)

Source: Authors’ calculations for the traditional vaccines based on the literature. — not available. Note: Mean values are used in the analysis. Ranges for estimates are reported in parentheses. Europe and Central Asia, Latin America and the Caribbean, and the Middle East and North Africa are limited to one observation for each region, which may not be indicative of the cost per FIC in each region. However, in lieu of using region-specific estimates, the overall average (US$13.65) would be applied, which may underestimate the cost per FIC in these more developed regions, where higher unit costs for delivery of health services would be expected.

outreach strategies. Transportation costs account for the second-largest share of EPI costs for mobile strategies, while building costs account for a greater share of fixed facility strategies. Using data from table 20.4 on costs per FIC and multiplying by the size of the population covered, we estimate US$1.17 billion for the total cost of immunization programs in developing countries in 2001, with a range of US$717 million to US$1.48 billion. At US$20 per FIC, the cost of the six traditional vaccines in developing countries would have amounted to US$1.57 billion in 2001. Table 20.5 shows that the estimated cost per death averted ranges from US$205 in South Asia and Sub-Saharan Africa to US$3,540 in Europe and Central Asia. These results suggest that the cost per death averted rises with coverage rates. Europe and Central Asia, Latin America and the Caribbean, and the Middle East and North Africa had higher coverage rates in 2001, resulting in fewer deaths that could be averted. The table also shows that the cost per DALY from the traditional EPI vaccines ranges from US$7 to US$438, depending on region, mix of strategy, and levels of scale.

Our analysis highlights the variation in cost per FIC by region and strategy and demonstrates the value of more disaggregated results for making policy decisions. However, given the limited sample of estimates available for the regions and strategies, the results should be used as an indicative guide for policy making and not as a substitute for country-specific costeffectiveness evaluations of strategies. In addition, our estimates do not take into account household costs, such as time spent seeking services, and other social costs. Our estimates also do not consider the direct and indirect costs of acute illnesses prevented by vaccination or the costs of long-term complications from disease and of adverse events associated with vaccination (though the latter are unlikely to have a significant impact on costs because rates of serious complications are extremely low). Furthermore, the analysis focuses on FICs and underemphasizes the benefits of partial immunization. Future economic evaluations of immunization program alternatives could consider these factors as a critical step in determining the allocation of scarce resources among high-priority health interventions.


Table 20.5 Average Cost per FIC, Total Immunization Cost, Cost per Death Averted and Cost per DALY for the Traditional Immunization Program by Region East Asia and the Pacific

Strategy Cost/FIC (2001 US$) (from table 20.4)

13.25

Percentage of FIC

78.22

24.12

316

Estimated deaths averted (thousands, from table 20.2)

728

Estimated cost/death averted (2001 US$)

434 85

395


18.10

93.72

Estimated total immunization cost (2001 US$ millions)

Estimated cost/DALY (2001 US$)



22.15

86.36

131

SubSaharan Africa

South Asia 17.11

90.90

14.21

58.86

50.20

174

152

227

172

37

174

153

1,109

867

3,540

1,030

993

205

205

438

166

16

7

Source: Authors’ calculations. Note: DALY estimates are the sum total for diphtheria, pertussis, tetanus, polio, and measles from table 20.3.

• First, the largest projected coverage increase of 9 percentage points (figure 20.1) may not require additional infrastructure investments. • Second, how and to what extent fixed costs would change by region is uncertain, and a conservative approach would be to exclude them. • Third, because most immunization costs are recurrent costs, the analysis focuses on these.

90 80 70 60 50 40 30 20 10 10

08

20

06

20

04

20

02

20

00

20

98

20

96

19

94

19

92

19

90

19

88

19

86

19

84

19

82

19

80

0 19

WHO (2004) estimates that in 2001, 30 million children were inadequately immunized with DTP. Achieving higher coverage rates by improving access for remote populations, accelerating immunization delivery strategies, and introducing new vaccines will mean increasing the level of investment (Batt, FoxRushby, and Castillo-Riquelme 2004). We estimated the costs of scaling up EPI coverage for a hypothetical population of 1 million in each region between 2002 and 2011. Costs were reported in 2001 dollars, and a 3 percent discount rate was applied. Brenzel (2005) provides details on the methods. The costs of scaling up coverage are based on vaccine and delivery costs per dose. We derived vaccine costs from the unit price of each vaccine (provided by WHO, UNICEF, and the Vaccine Fund); wastage rates for vaccines and injection supplies by strategy; the required injection supplies; and the number of doses per FIC. A 2 percent adjustment was made for inflation. We used data on the cost per FIC generated earlier to derive delivery costs per dose by strategy and region by subtracting the costs of vaccines, injection supplies, and fixed costs. Fixed costs were excluded from the scaling-up exercise because they were assumed to remain constant during the projection period.

Percentage of FICs 100

19

COST-EFFECTIVENESS OF INCREASING IMMUNIZATION COVERAGE FOR THE TRADITIONAL EPI

Europe and Central Asia East Asia and the Pacific Latin America and the Caribbean Middle East and North Africa South Asia Sub-Saharan Africa Developed countries

Source: Authors’ estimation.

Figure 20.1 Coverage of FICs Projected to 2011

• Finally, because the scale factor is derived from the unit costs of a health center visit, the assumption of constant fixed costs in the short run appears reasonable. Previous studies have found that the main cost drivers of immunization costs are the mix of strategies and the scale of immunization programs (Brenzel and Claquin 1994; Domínguez-Ugá 1988; Robertson and others 1992; Soucat and others 1997). Countries are unlikely to achieve 90 percent or more coverage relying on fixed facilities alone because of limited population access. We estimate the proportion of FICs obtained for each strategy by region.5 The best mix of strategies for increasing coverage will vary by country depending on the Vaccine-Preventable Diseases | 401


dispersion of the population, the access to health facilities, the vaccines being delivered, and the effectiveness of various strategies in reaching target populations. Estimates are also adjusted for the level of scale by a factor derived from the unit cost per health center contact by coverage level (Mulligan and others 2003), and details are provided in Brenzel (2005). The total additional cost of reaching higher coverage levels was divided by the number of deaths averted. Coverage projections for 2002–11 were based on statistical modeling of official WHO and UNICEF estimates for the period between 1995 and 2002 for all developing countries. The model relates coverage in future years to that in the previous year, with the relationship between past and future coverage differing for each region and economic status combination. Figure 20.1 shows historical and projected coverage rates by region. The figure shows that coverage increased in all the regions during the late 1980s under universal childhood immunization. After 1990, when funding for universal childhood immunization waned, the figure indicates the subsequent stagnation and, in some cases, the declines in coverage rates. For the scaling-up period, we project that the coverage of FICs will increase from 78 to 79 percent in East Asia and the Pacific, from 92 to 95 percent in Europe and Central Asia, from 88 to 90 percent in Latin America and the Caribbean, from 91 to 95 percent in the Middle East and North Africa, from 70 to 79 percent in South Asia, and from 52 to 61 percent in Sub-Saharan Africa. The projections show that three of the six regions are expected to achieve 90 percent FIC by 2011. East Asia and the Pacific, South Asia, and Sub-Saharan Africa will require additional intensive efforts to achieve higher coverage rates. Table 20.6 reports the results of the scaling-up analysis for the traditional EPI vaccines, for tetanus toxoid vaccination for women of reproductive age, and for selected new vaccines. The discounted incremental cost per child vaccinated with the traditional EPI vaccines ranges from US$10.89 in Latin America and the Caribbean to US$12.84 in the Middle East and North Africa. The number of discounted deaths averted because of full immunization depends on incremental coverage rates and varies from 747 in Europe and Central Asia to 14,584 in SubSaharan Africa, resulting in regional variations in the discounted incremental cost per death averted from US$169 in Sub-Saharan Africa to US$1,754 in Europe and Central Asia.6 DALYs were estimated indirectly based on the ratio of deaths to DALYs for each disease in 2001. This ratio is applied to the hypothetical population in each World Bank region over the projection period. Calculated this way, the number of DALYs averted will not account for changes in the average age of infection that ordinarily results from expanding immunization coverage. This method over-estimates the number of DALYs and thus under-estimates the cost/DALY. Cost-effectiveness ratios should be treated as indicative only. The cost/DALY ranges from $2 to $20 for scaling up traditional immunizations.

For tetanus toxoid immunization, the additional discounted cost per person vaccinated ranges from US$3.28 to US$4.06. The cost per death averted varies from US$271 to more than US$190,000. The results of this analysis fall within the range of estimates reported in the literature (Berman and others 1991; Steinglass, Brenzel, and Percy 1993). Differences in coverage levels and in protection against neonatal tetanus through skilled delivery contribute to the variation in results across regions. The analysis shows both an increase in costs and potential benefits from scaling up immunization programs. In practice, the costs and benefits related to scaling up in any one region will be highly dependent on a few countries or subnational areas within countries. Aggregate country- or region-level data do not reveal the efficiency that could best be obtained by targeting immunization efforts on specific countries or geographic areas rather than making diffuse investments across regions. For instance, Miller and others (1998) show that India and Nigeria contribute the most to estimates of global measles deaths; therefore, reducing transmission in those countries would contribute the most to reducing the global disease burden caused by measles. Despite its importance for policy, empirical and countryspecific evidence on how immunization program costs change as coverage increases is lacking. Because scaling up immunization coverage will require more intensive efforts to find unvaccinated children, an extra cost for vaccinating each additional child is generally expected. Nevertheless, most costeffectiveness studies assume constant returns to scale (Elbasha and Messonnier 2004; Karlsson and Johannesson 1998) even when emerging evidence suggests that the cost of vaccinating each additional child may rise with the size of delivery unit (Valdmanis, Walker, and Fox-Rushby 2003). Box 20.1, which focuses on scaling up traditional immunization coverage, and box 20.2, which focuses on new antigens, summarize the results of two studies that shed more light on this subject.

COSTS AND COST-EFFECTIVENESS OF ADDING NEW ANTIGENS TO THE CURRENT IMMUNIZATION SCHEDULE We also estimated the additional costs per person vaccinated and cost per death averted of introducing new and underused vaccines into the traditional EPI in a hypothetical population of 1 million in each region between 2002 and 2011. The new vaccines considered protect against hepatitis B, yellow fever, Hib, measles, rubella, Japanese encephalitis, and meningococcal A, as well as inactivated polio vaccine (IPV). For comparison purposes, we assumed that new vaccines were introduced in 2002. The additional cost of combination vaccines is net of the original cost of DTP vaccination to avoid duplication. The


Table 20.6 Average Cost per Person Vaccinated and per Death Averted for Scaling Up Immunization Coverage and Adding in Selected New Vaccines in a Hypothetical Population of 1 million for 2002–11 (2001 US$, current vaccine prices) Europe and Central Asia




South Asia

SubSaharan Africa

Traditional EPI (mix of strategies) Incremental discounted cost/person vaccinated Incremental discounted deaths averted Incremental discounted cost/death averted

12.03

11.54

10.89

12.84

11.58

11.16

3,165

747

2,552

4,576

7,584

14,584

478

1,754

791

698

274

169

Tetanus toxoid (mix of strategies) Incremental discounted cost/person vaccinated Incremental discounted deaths averted Incremental discounted cost/death averted

4.06

3.34

343

2 190,000

1,541

3.28

3.34

3.98

3.88

200

465

2,815

2,412

3,117

1,880

271

394

Second opportunity for measles (fixed facility) Incremental discounted cost/person vaccinated Incremental discounted deaths averted Incremental discounted cost/death averted

1.08

1.05

0.98

1.19

1.04

1.00

1,138

599

95

1,304

2,509

9,646

119

199

1,906

228

74

23

DTP-hepatitis B and Hib (pentavalent) vaccine (mix of strategies) Incremental discounted cost/person vaccinated

15.14

14.61

Incremental discounted deaths averted

47

19

Incremental discounted cost/death averted

40,000

15.69 116

85,000

16.23 274

25,000

14,000

15.24 192

11.68 1,796

14,000

1,433

Yellow fever (campaigns) Incremental discounted cost/person vaccinated

n.a.

n.a.

1.43

n.a.

n.a.

1.42

Incremental discounted deaths averted

n.a.

n.a.

94

n.a.

n.a.

376

Incremental discounted cost/death averted

n.a.

n.a.

2,810

n.a.

n.a.

834

Incremental discounted cost/person vaccinated (mix of strategies) Hepatitis B monovalent (birth dose)

2.26

2.15

2.36

2.37

2.24

2.02

DTP-hepatitis B (tetravalent)

7.85

7.57

7.34

8.03

7.55

7.26

Rubella (campaigns)

1.20

1.19

1.20

1.07

1.19

1.19

Meningococcal A (fixed facilities)

n.a.

n.a.

n.a.

2.73

n.a.

2.33

Japanese encephalitis (fixed facilities)

4.56

n.a.

n.a.

n.a.

4.37

n.a.

Injectable polio vaccine (monovalent) Injectable polio vaccine (combination with DTP)

7.12

6.72

6.42

7.32

6.85

6.60

13.88

14.84

14.62

15.28

14.77

14.19

Source: Authors’ calculations. Note: n.a. refers to not applicable when a specific disease is not prevalent in a specific region.

delivery cost per FIC was apportioned to individual antigens on the basis of the share of number of doses per FIC for that antigen (Brenzel 2005). Cost estimates are based on the number of doses required for full immunity (that is, hepatitis B, Hib, and IPV vaccines require three doses for full immunity, and meningococcal A requires two doses for full immunity). Results are reported in table 20.6. The analysis also assumes that an additional visit to a health facility is required for new doses (depending on timing in the

EPI schedule).Combination vaccines may be more cost-efficient because of potential savings in supplies, syringes, and health workers’ time, in addition to the overall health benefits of reducing the number of required injections. However, if the combination vaccine does not reduce the number of visits a child would ordinarily need to make to a health facility, any cost savings may be subsumed by the higher costs of increasing coverage. The discounted incremental cost per person ranges from less than US$1 to US$16.23, depending on the unit price of Vaccine-Preventable Diseases | 403


Box 20.1

Marginal Costs of Immunization Services in India A study in Tamil Nadu evaluated immunization costs and coverage using a longitudinal panel dataset of immunization program costs (Brenzel 1995). Data were collected from a stratified, random sample of facilities between 1989 and 1991 for the North Arcot District Polio Control Program.a The sample included 120 observations of 59 different health centers: 17 followed for three years (29 percent), 27 followed for two years (46 percent), and 15 with a single observation (25 percent). Total immunization costs included the cost of labor, vaccines, injection supplies, transportation, and overhead and the value of equipment, vehicles, and buildings. During this period, coverage rates for FICs increased from 5 to 77 percent. The table shows that the cost per dose and the cost per FIC increased during this period.b Changes in the cost per dose were highly statistically significant, whereas no statistical differences were apparent in the cost per FIC during the study period. Comparison of Total Facility Immunization Costs, Immunization Activity, and Unit Costs by Year, North Arcot District Polio Control Program, 1989–91 (2001 US$) Indicator

Year 1

Year 2

Year 3

Overall

Total costs

996

1,337

980

1,104

Variable costs

697

1,260

917

958

Cost/dose Cost/FIC

1.09

1.98

1.33

1.47

13.11

27.92

17.07

19.37

The study used data from the health facility sample to explain the determinants of immunization costs, which were modeled as a function of outputs, input prices, and other production-related variables that influence the cost function with respect to outputs. A random effects estimation was performed on the analysis sample relating the natural logarithm of health facility costs to the type of polio vaccine in use, estimated target population, and size of geographical area serviced by the health facility and natural logarithms of the number of FICs per facility, the number of hours spent by a village health nurse on immunization services per facility, and the number of small pieces of equipment used for immunization service delivery. The analysis revealed a significant association between facility cost and the number of FICs, the hours worked by village health nurses, the area served, and the type of polio vaccine. When calculated using mean values, the marginal cost per FIC was Rs 24.43 (US$1.30) lower than the associated average cost per FIC of Rs 183 (US$9.80), implying that the average cost curve lies above the marginal cost curve for the sample of health facilities in India. A declining relationship is apparent between costs and coverage for this sample of facilities, calling into question assumptions of constant returns to scale. The results suggest that, in India, average cost-effectiveness ratios would overestimate total resource needs. Using a single-point estimate of average unit costs to determine the use of scarce public health resources will result in suboptimal resource allocations.

Source: Brenzel (1995). a. The program was a joint effort by the Indian Council for Medical Research, the Centre for Advanced Research in Virology at the Christian Medical Centre and Hospital in Vellore, and the governments of Tamil Nadu and India. b. Higher costs in the second year reflect a change in the organization of the primary health care system in 1990 to improve access to basic services.

vaccine, the type of vaccine, the delivery strategy, and the coverage levels. The results lead to several conclusions: • First, the additional incremental cost per person vaccinated is relatively small for some new vaccines. • Second, because fixed costs are excluded, the results represent conservative estimates of additional costs. • Third, because of price uncertainty, cost variations are greatest for newer vaccines, such as the DTP-IPV combination. The second opportunity for measles has the lowest cost per death averted, ranging from US$23 to US$1,906 for fixed

facility strategies, and from US$65 to US$1,363 for campaigns These results are consistent with the literature. Foster, McFarland, and John (1993) find an incremental cost per death averted ranging from US$335 to US$552 in urban areas and from US$327 to US$706 in rural areas. The Africa Measles Partnership (2004) estimates a cost per death averted of US$131 to US$393 in the African context, but these figures include the costs of infrastructure. In the hypothetical populations, the incremental cost per death averted for the pentavalent vaccine ranged from US$1,433 to more than US$85,000, depending mostly on the number of potential deaths that could be averted. Although a


Box 20.2

An Immunization Costing Study of Adding New Vaccines to the EPI in Peru Data were collected from 19 government health facilities in US$ per year three districts in Peru, including five hospitals and 14 health 10 centers (Walker and others 2004). Total annual costs per 9 center included vaccines, supplies, personnel, cold chain, 8 overhead, and shared inputs. The average cost per dose for 7 Marginal cost traditional EPI antigens plus yellow fever varied from 6 US$1.50 to US$3.20 per dose as shown in the table, with 5 4 vaccines and personnel accounting for the bulk of costs. At 2,000 doses, the marginal cost of delivering one 3 more dose is US$1.08, increasing to US$5.33 for 12,000 2 Average cost doses. Average and marginal costs are equal (US$1.18) 1 when 5,000 doses are provided per site. When an outlier 0 20,000 5,000 10,000 15,000 0 delivering many vaccines at a high cost was removed, costNumber of doses delivered minimizing output rose to 6,000 doses at US$1.11. Although each vaccination facility is likely to be associa- Source: Authors‘ calculations. ted with different average and marginal costs, considering Marginal and Average Vaccination in Sample Facilities in Peru vaccine provision across a range of providers is relevant, (2001 US$) because targets for vaccination can be set by site. Information about marginal costs can help determine incremental cost per dose of vaccine of US$0.20, US$4.14, what the most efficient size for vaccination facilities is in and US$4.24, respectively. Adding these new vaccines the long run and how to minimize costs across different increased the total cost of providing 5,100 doses from size units in the short run, given targets (see figure). US$5,840 to US$9,415 and changed the minimum average When hepatitis B, Hib, and the pentavalent vaccine (DTP-hepatitis B-Hib) are added to the delivery schedule, cost from US$1.18 per dose to US$1.68. Therefore, the addition of new vaccines shifts both average and marginal the total annual additional cost increases to US$4,121, costs upward. US$11,886, and US$25,261, respectively, with an average Mean Cost per Dose by Type of Facility, Selected Districts in Peru (2001 US$)

Health post

Health center

Rural hospital

Provincial hospital

Department hospital (Ayacucho)

National hospital

Vaccines

0.59

0.87

1.39

1.03

0.60

0.31

Syringes

0.04

0.05

0.07

0.04

0.05

0.03

Personnel

0.46

0.28

1.17

0.33

0.76

0.29

Cost items Recurrent items

Other

0.05

0.03

0.03

0.04

0.03

0.13

Capital items

0.01

0.02

0.09

0.01

0.03

0.02

Direct costs

1.15

1.25

2.75

1.45

1.47

0.78

Indirect costs

0.33

0.26

0.41

0.30

0.45

1.19

Average cost

1.48

1.51

3.17

1.79

1.92

1.98

Source: Walker and others (2004). Note: Totals may not sum exactly because of rounding.

Vaccine-Preventable Diseases | 405 ©2006 The International Bank for Reconstruction and Development / The World Bank 65

wide range of results was found, these estimates are supported by the literature. Miller (1998) estimated between US$3,127 and US$3.2 million per life saved for Hib vaccine. Brinsmead, Hill, and Walker’s (2004) systematic review of the literature on the cost-effectiveness of Hib vaccine finds wide variations in results because of methodological differences and epidemiological and health system characteristics. The discounted incremental cost of introducing the pentavalent (DTP– hepatitis B–Hib) vaccine is roughly equal to the total mean cost of the traditional vaccine package estimated earlier. This finding implies that introducing this combination vaccine may double the financial requirements, an implication that is supported by data from national financial sustainability plans for immunization (Lydon 2004). The incremental discounted cost per person vaccinated with a birth dose of hepatitis B is approximately US$2, and that for the tetravalent vaccine was between US$7 and US$8. The 10year time period for our analysis is too short to accumulate deaths averted resulting from hepatitis B vaccination because deaths from liver cancer occur at older ages. Beutels’s (1998, 2001) reviews of studies of the cost-effectiveness of introducing hepatitis B vaccine indicate that results vary depending on assumptions of endemicity and the methodology used, with a cost per death averted ranging from US$3,500 to US$271,800. Rubella vaccination had a low additional cost per person vaccinated, at slightly more than US$1. Golden and Shapiro (1984) found that vaccinating all prepubertal children with rubella vaccine had the highest benefit-cost ratio (ranging from US$1.70 to US$1.96). Most benefits were future cost savings from longterm institutional care. When rubella was delivered in combination with measles and mumps, the benefit-cost ratios varied from US$4.70 to US$38.80 (Hinman and others 2002). The additional cost per person vaccinated with one dose of Japanese encephalitis vaccine was between US$4.37 and US$4.56. A study in Thailand using two doses showed a cost per child ranging from US$2.31 to US$4.20, depending on the mode of delivery (Siraprapasiri, Sawaddiwudhipong, and Rojanasuphot 1997). Ding and others (2003) estimate a cost per case averted of US$258 and a cost per DALY averted of US$16.80 for a five-dose inactivated Japanese encephalitis vaccine. Our analysis suggests an additional discounted cost per person vaccinated for injectable polio vaccine of between US$6.60 and US$7.32, depending on coverage levels and mix of delivery strategy. The additional discounted unit cost of the combination DTP-IPV vaccine was higher, ranging from US$13.88 to US$15.28. These results are also sensitive to the current prices of the vaccine, which will probably decline in coming years. Brenzel (1995) finds that in India the cost per case prevented for the combination DTP-polio vaccine was much lower than for oral polio vaccine (OPV), primarily because the combination vaccine was associated with a greater reduction in the number of polio cases. Miller and others (1996) suggest that

introducing IPV into routine vaccination in the United States would cost an additional US$15 million to US$28 million depending on the type of schedule adopted, resulting in a cost per vaccine-associated paralytic poliomyelitis case prevented of approximately US$3 million. Sangrugee, Caceres, and Cochi (2004) found that the least costly option would be for programs to stop providing OPV after postpolio eradication and certification and that optionally introducing IPV with universal IPV had the highest costs and the lowest expected number of vaccine-associated paralytic poliomyelitis cases. If the unit price of IPV fell to US$0.47, switching to IPV from OPV would be economically worthwhile.

FINANCIAL SUSTAINABILITY OF IMMUNIZATION PROGRAMS Even though research has demonstrated that vaccination against childhood diseases is one of the most cost-effective health interventions, governments in many developing countries are considering how to meet the financing requirements of immunization programs, particularly as new vaccines are introduced and programs are scaled up. GAVI is working with countries to prepare for the transition from grant funding and to secure the overall financial sustainability of national programs. Approximately 55 countries have prepared national financial sustainability plans for immunization. These plans help countries evaluate the current and future costs and financing of national immunization programs and identify strategies to address future funding gaps (GAVI 2004; http://www.who. int/immunization_financing/en). According to a recent analysis of financial sustainability plans, specific costs for immunization programs represent an average of 2 percent of total health spending and 6 percent of government health spending and are equivalent to less than 0.2 percent of gross domestic product on average. However, this profile changes after new and more expensive vaccines are introduced. In some countries, program-specific costs for immunization can reach as high as 20 percent of government health spending with introduction of combination vaccines (Lydon 2004). This share is related to the current unit price of the vaccine, which is expected to decline. Governments and their development partners are challenged to find ways to finance and sustain immunization programs. In countries that are implementing reforms to achieve greater transparency and fiscal discipline through sectorwide approaches and medium-term expenditure frameworks, the additional financing requirements are compounded by the need to operate within a fixed budget for the health sector, so that increased funding needs for one program may necessitate budget cuts for others. This example illustrates the potential tradeoffs that exist at the country level, which create both opportunities for more open policy dialogue in relation to


priority setting for the use of scarce public funds and risks that the cost of new vaccines may not be readily integrated into national plans and budgets. Because of the financial implications of reaching higher coverage levels and simultaneously introducing new vaccines, policy makers will not only have to weigh the cost-worthiness of alternative investments but also have to understand their long-term budgetary implications.

tion of routine BCG vaccination, given the low risk of acquiring tuberculosis in early childhood. If the BCG were not administered during the first month of life, program costs would be reduced by the value of one visit and by the costs associated with vaccine purchase, shipping, storage, and administration.

RESEARCH AGENDA IMPROVING THE COSTS AND COSTEFFECTIVENESS OF IMMUNIZATION PROGRAMS The cost-effectiveness of immunization programs could be improved by either reducing costs or improving programs’ health benefits. Programs could reduce costs by using a more efficient mix of delivery strategies, reducing vaccine wastage, and using lower-cost inputs while maintaining the same quality of service. Reductions in the price of vaccines in the near future will also reduce costs. Innovations in vaccine technology may result in more widespread use of vaccine vial monitors, and increased use of heat-stable vaccines could potentially reduce the cost of the cold chain, although these innovations may themselves add to costs. The number of children and adults immunized can be increased by creating additional demand for vaccination; reducing missed opportunities; and reducing the dropout rate between the first and third doses of DTP, hepatitis B, and other vaccines. Finally, changes in the EPI schedule could affect total costs by reducing the number of doses required to achieve immunity and thereby reducing the number of visits, resulting in savings in the costs of labor, supplies, transport, and perhaps overhead. The EPI schedule was established in 1984 based on a review of immune responses to diphtheria, tetanus, pertussis, polio, and measles vaccines starting at different ages and with varying intervals between doses (Halsey and Galazka 1985). The EPI schedule administers three doses of DTP at the shortest possible intervals to complete the immunization series as early in life as possible. However, if the primary series could be reduced to two doses with a booster dose at 12 to 15 months of age, the cost savings from reduced visits and one fewer dose of DTP in countries that administer a fourth dose of DTP would be considerable. Additional serological studies would be needed to compare the existing EPI schedule with the theoretical schedule before a new schedule could be adopted. Also, other vaccines to be introduced into immunization programs would need to be revaluated in this schedule. Two doses of IPV administered beginning at two months of age induce protective levels of antibodies between 95 and 100 percent for each of the three polio types (Halsey and others 1997; Plotkin and Vidor 2004). Some countries with a low incidence of tuberculosis (such as those of Eastern Europe) are considering the discontinua-

Private and public sector investment in research and development pertaining to new vaccines and improved use of existing vaccines is considerable. Most research and development is focusing on vaccines likely to have the greatest effect in the developed world and the best financial return; however, by means of public-private partnerships for product development, foundations have stepped in to support vaccine research and development for diseases for which the greatest burden occurs in developing countries. New vaccines are being developed that could be incorporated into EPI schedules, including vaccines that protect against rotavirus, S. pneumoniae, malaria, cervical cancer associated with human papilloma virus, HIV/AIDS, and dengue. New and improved vaccines are also being developed to protect against meningococcal infections in infancy and Japanese encephalitis (NIH 2000). WHO recently created the Initiative for Vaccine Research Department to facilitate global coordination of research and development efforts for these and other vaccines. In compiling data for this chapter, we noted a number of key gaps in knowledge that could usefully drive a research agenda and contribute to more evidence-based policy making in the future (Fox-Rushby and others 2004). First, little is currently known about how and why delivery costs change with increasing numbers of vaccinations and at higher coverage rates and whether economies of scale can be achieved. Little is known about the relative cost-effectiveness of different strategies to increase coverage given different baseline coverage rates. This issue relates to other questions of the optimal timing for introducing new vaccines and of how decisions should vary given different epidemiological and economic settings. Future research should therefore consider the extent to which costeffectiveness analyses need to be repeated for every country or context or whether (and how) estimating and validating relationships across countries and accounting for uncertainty in estimates of costs and effects are possible. Second, more attention needs to be given to measuring effect. For example, even though the coverage of single antigens required to reach particular levels of FICs should be accounted for, economic evaluations need to move beyond such indicators of output to measuring effect on the quantity and quality of life. In evaluating different schedules, methodological research needs to focus on how to incorporate the combined Vaccine-Preventable Diseases | 407


effects of multiple vaccinations in this respect. Remarkably few studies have considered the effect on nonhealth benefits, such as economic growth and welfare. The larger the package of vaccinations considered, the more important this question becomes.

CONCLUSIONS This chapter confirms that vaccination of children and women with the traditional EPI vaccines is a highly cost-effective public health intervention, although cost-effectiveness ratios vary by region, delivery strategy, and level of scale. Overall, vaccination has had a significant effect on reducing mortality and morbidity from childhood diseases and will be a priority intervention for achieving the child health Millennium Development Goals. Improving and sustaining measles control are among the most cost-effective interventions in highmortality regions. Establishing and maintaining high immunization coverage rates in many of the poorest developing countries have proven challenging for those with high population growth rates, limited infrastructure and resources, and fluctuating demand for services. According to historical coverage rate trends, Europe and Central Asia, Latin America and the Caribbean, and the Middle East and North Africa are expected to achieve 90 percent coverage of FIC by 2011, with East Asia and the Pacific, South Asia, and Sub-Saharan Africa lagging behind. Increasing and sustaining higher immunization coverage rates will require further efforts so that disease control can be maintained, particularly when a perception exists at the community level that vaccine-preventable diseases are no longer a major public health issue. At higher coverage rates, further disease burden reductions will be smaller, which will affect relative cost-effectiveness. Targeted approaches in countries or at subnational levels could potentially yield high returns, especially in those areas with poor control of vaccine-preventable diseases. Our analysis shows that the cost per FIC will increase as countries scale up immunization coverage and introduce new vaccines. Adding more antigens to traditional EPIs has been successfully accomplished in many countries, especially for Hib and hepatitis B vaccines. Although many of the new vaccines under consideration are more expensive than those for the original six targeted EPI diseases, they may still be relatively cost-effective compared with other interventions and with treatment costs. Our analysis shows a wide range of costeffectiveness estimates depending on the type of vaccine, vaccine prices, coverage levels, and delivery strategy, with the additional incremental cost per person being relatively small for some new vaccines. Declines in unit prices of new vaccines also will affect cost-effectiveness results.

Financing and sustaining immunization programs are challenges that governments in developing countries and their development partners will face. The financial implications of reaching higher coverage levels and the simultaneous desire to introduce new vaccines will require policy makers to consider both the relative cost-effectiveness of interventions and the long-term budgetary implications. Although global and regional estimates of cost-effectiveness of interventions are useful guides, further analytical work will be needed to evaluate the relative benefits (deaths and cases averted and DALYs) and costs (delivery and treatment) of vaccines for different delivery strategies and higher coverage rates, particularly at the country level.

ACKNOWLEDGMENTS The authors thank Tina Proveaux for editorial and technical assistance and Howard Barnum, Mariam Claeson, Felicity Cutts, Tony Measham, and Philip Musgrove for reviewing drafts of the manuscript. Santiago Cornejo and Ravi Cheerukupalli provided valuable inputs.

NOTES 1. For our analysis, the preimmunization era neonatal tetanus mortality rate per 1,000 live births is used: developed countries, 0.1; East Asia and the Pacific, 4.7; Europe and Central Asia, 0.4; Latin America and the Caribbean, 4.4; Middle East and North Africa, 4.7; South Asia, 15.3; and Sub-Saharan Africa, 10.2. 2. Because disease classification does not have a one-to-one correspondence with those prevented by vaccine, according to table 20.3 is based on estimates of the proportion of these illnesses that may be preventable by specific vaccines. For example, some meningitis and acute lower respiratory infections are caused by Hib or S. pneumoniae, and some cirrhosis is caused by hepatitis B. 3. A fully immunized child is a standard term that refers to a child who has received one dose of BCG vaccine, three doses each of oral polio vaccine and DTP vaccines, and one dose of measles vaccine. The number of FICs does not include children who have been partially immunized, so this measure underestimates the total effect on the disease burden. However, the number of FICs is representative of the effectiveness of the delivery system in providing access to immunization services to children. The authors are aware that fully vaccinating a child does not correspond to full immunity. 4. The mean population-weighted cost per FIC for the financial sustainability plans for immunization was US$21.06. The plans use DTP3 coverage as a proxy for FICs rather than coverage measured through populationbased surveys (http://www.who.int/immunization_financing/en). 5. Assumptions about the relative distribution of FICs by strategy and region were based loosely on such factors as the proportion of the population with access to health services for fixed facilities and the likelihood of active mobile strategies. 6. A proxy for the total number of deaths averted is the sum of the individual deaths averted for each antigen in the traditional EPI. This figure may overestimate the actual number of deaths averted by fully immunizing children and therefore underestimate the cost per death averted. However, the values estimated by region appear to support previously reported estimates, and direct estimation of deaths averted was impossible given data and model limitations.


REFERENCES Aaby, P. 1988. “Malnutrition and Overcrowding/Intensive Exposure in Severe Measles Infection: Review of Community Studies.” Reviews of Infectious Diseases 10: 478–91. Aaby, P., and C. J. Clements. 1989. “Measles Immunization Research: A Review.” Bulletin of the World Health Organization 67: 443–48. Africa Measles Partnership. 2004. “Measles Investment Case.” Board of the Global Alliance for Vaccines and Immunization. http://www. vaccinealliance.org/resources/Measles_Investment_Case_FINAL_w_ addendum.pdf. Batt, K., J. Fox-Rushby, and M. Castillo-Riquelme. 2004.“The Costs, Effect, and Cost-Effectiveness of Strategies to Increase Coverage of Routine Immunizations in Low- and Middle-Income Countries: Systematic Review of the Grey Literature.” Bulletin of the World Health Organization 82: 689–96. Beasley, R. P. 1988. “Hepatitis B Virus: The Major Etiology of Hepatocellular Carcinoma.” Cancer 61: 1942–56. Bennett, J. V., A. E. Platonov, M. P. E. Slack, P. Mala, A. H. Burton, and S. E. Robertson. 2002. Haemophilus influenzae Type B (Hib) Meningitis in the Pre-vaccine Era: A Global Review of Incidence, Age Distributions, and Case-Fatality Rates. WHO/V&B/02.18. Geneva: World Health Organization. http://www.who.int/vaccines-documents/DocsPDF02/ www696.pdf. Berman, P., J. Quinley, B. Yusuf, S. Anwar, U. Mustaini, A. Azof, and B. Iskandar. 1991. “Maternal Tetanus Immunization in Aceh Province, Sumatra: The Cost-Effectiveness of Alternative Strategies.” Social Science and Medicine 33: 185–92.

Creese, A. L., and M. A. Domínguez-Ugá. 1987. “Cost-Effectiveness of Immunization Programs in Colombia.”Pan American Health Organization Bulletin 21: 377–94. Crowcroft, N. S., C. Stein, P. Duclos, and M. Birmingham. 2003. “How Best to Estimate the Global Burden of Pertussis?” Lancet Infectious Diseases 3: 413–18. Ding, D., P. E. Kilgore, J. D. Clemens, L. Wei, and X. Zhi-Yi. 2003. “CostEffectiveness of Routine Immunization to Control Japanese Encephalitis in Shanghai, China.” Bulletin of the World Health Organization 81: 334–42. Domínguez-Ugá, M. A. 1988. “Economic Analysis of the Vaccination Strategies Adopted in Brazil in 1982.” Bulletin of the World Health Organization 22: 250–68. Edmunds, D. J., A. Dejene, Y. Mekkonen, M. Haile, W. Alemnu, and D. J. Nokes. 2000. “The Cost of Integrating Hepatitis B Virus Vaccine into National Immunization Programs: A Case Study from Addis Ababa.” Health Policy and Planning 15: 408–16. Edwards, K. M., and M. D. Decker. 2004. “Pertussis Vaccine.” In Vaccines, ed. S. A. Plotkin and W. A. Orenstein, 471–528. Philadelphia: Saunders. Elbasha, E. H., and M. L. Messonnier. 2004. “Cost-Effectiveness Analysis and Health Care Resource Allocation: Decision Rules under Variable Returns to Scale.” Health Economics 13: 21–35. Feigin, R. D., B. W. Stechenberg, and P. Hertel. 2004. “Diphtheria.” In Textbook of Pediatric Infectious Diseases, ed. R. D. Feigin, J. D. Cherry, G. J. Demmler, and S. L. Kaplan, 1305–13. Philadelphia: Elsevier.

Beutels, P. 1998. “Economic Evaluations Applied to HB Vaccination: General Observations.” Vaccine 16: S84–92.

Foster, S. O., D. A. McFarland, and A. M. John. 1993. “Measles.” In Disease Control Priorities in Developing Countries, ed. D. T. Jamison, W. H. Mosley, A. R. Measham, and J. L. Bobadilla, 161–87. New York: Oxford University Press and World Bank. http://www.fic.nih.gov/dcpp/ dcp1/dcp1-ch8.pdf.

. 2001. “Economic Evaluations of Hepatitis B Immunization: A Global Review of Recent Studies (1994–2000).” Health Economics 10: 751–74.

Fox-Rushby, J. A., M. Kaddar, R. Levine, and L. Brenzel. 2004. “The Economics of Vaccination in Low- and Middle-Income Countries.” Bulletin of the World Health Organization 82: 640.

Birmingham, M., and C. Stein. 2003. “The Burden of Vaccine-Preventable Diseases.” In The Vaccine Book, ed. B. R. Bloom and P.-H. Lambert, 1–21. San Diego, CA: Elsevier.

Galazka, A., M. Birmingham, M. Kurian, and F. Gasse. Forthcoming. “Tetanus.” In The Global Epidemiology of Infectious Disease, ed. C. J. L. Murray and A. D. Lopez. Cambridge, MA: Harvard University Press.

Birmingham, M., L. Wolfson, M. Kurian, U. Griffiths, F. Gasse, and J. Vandelaer. 2004. “Estimating the Burden of Neonatal Tetanus.” Unpublished manuscript.

Galazka, A. M., and S. E. Robertson. Forthcoming. “Diphtheria.” In The Global Epidemiology of Infectious Diseases, ed. C. J. L. Murray and A. D. Lopez, Cambridge, MA: Harvard University Press.

Brenzel, L. 1995. “Final Report on the Longitudinal Cost-Effectiveness Study of the North Arcot District Polio Control Program (NADPCP).” Resources for Child Health Project, U.S. Agency for International Development, Arlington, VA.

Galazka, A. M., S. E. Robertson, and G. P. Oblapenko. 1995. “Resurgence of Diphtheria.” European Journal of Epidemiology 11: 95–105.

. 2005. “Methods Used to Estimate the Costs of Scaling Up Immunization Services for the Vaccine Preventable Disease Chapter, Disease Control Priorities Project.” World Bank, Washington, DC. Brenzel, L., and P. Claquin. 1994. “Immunization Programs and Their Costs.” Social Science and Medicine 39: 527–36.

GAVI (Global Alliance for Vaccines and Immunization). 2004. “Guidelines for Preparing a National Immunization Financial Sustainability Plan.” Geneva, GAVI. http://www.who.int/immunization_financing/tools/ en/FSP_Guidelines_April%202004_En.pdf. Gay, N. J., W. J. Edmunds, E. Bah, and C. B. Nelson. 2001. Estimating the Global Burden of Hepatitis B. Geneva: World Health Organization.

Brinsmead, R., S. Hill, and D. Walker. 2004. “Are Economic Evaluations of Vaccines Useful to Decision Makers? Case Study of Haemophilus Influenzae Type B Vaccines.” Pediatric Infectious Disease Journal 23: 32–37.

Gessner, B. D., A. Sutanto, M. Linehan, I. G. G. Djelantik, T. Fletcher, K. Ingerani, and others. 2005. “The Incidence of Vaccine-Preventable Haemophilus influenzae Type B Pneumonia and Meningitis in Indonesian Children Using a Hamlet-Randomized Vaccine Probe Design.” Lancet 365 (9453): 43–52.

Cherry, J. D., and R. E. Harrison. 2004. “Tetanus.” In Textbook of Pediatric Infectious Diseases, ed. R. D. Feigin, J. D. Cherry, G. J. Demmler, and S. L. Kaplan, 1766–76. Philadelphia: Elsevier.

Golden, M., and G. L. Shapiro. 1984. “Cost-Benefit Analysis of Alternative Programs of Vaccination against Rubella in Israel.” Public Health 98: 179–90.

Cherry, J. D., and U. Heininger. 2004. “Pertussis and Other Bordetella Infections.” In Textbook of Pediatric Infectious Diseases, ed. R. D. Feigin, J. D. Cherry, G. J. Demmler, and S. L. Kaplan, 1588–1608. Philadelphia: Elsevier.

Griffith, A. H. 1979. “The Role of Immunization in the Control of Diphtheria.” Developments in Biological Standards 43: 3–13.

Creese, A. L. 1986. “Cost-Effectiveness of Potential Immunization Interventions against Diarrheal Disease.” Social Science and Medicine 23: 231–40.

Griffiths, U. K., G. Hutton, and E. D. Pascoal. 2005.“The Cost-Effectiveness of Introducing Hepatitis B Vaccine into Infant Immunization Services in Mozambique.” Health Policy Plan 20 (1): 50–59. Griffiths, U. K., L. J. Wolfson, A. Quddus, M. Younus, and R. A. Hafiz. 2004. “Incremental Cost-Effectiveness of Supplementary Immunization


Activities to Prevent Neo-natal Tetanus in Pakistan.” Bulletin of the World Health Organization 82: 643–51. Hadler, S. C., S. L. Cochi, J. Bilous, and F. T. Cutts. 2004. “Vaccination Programs in Developing Countries.” In Vaccines, ed. S. A. Plotkin and W. A. Orenstein, 1407–42. Philadelphia: Saunders. Halsey, N. A., M. Blatter, G. Bader, M. L. Thoms, F. F. Willingham, J. C. O’Donovan, and others. 1997. “Inactivated Poliovirus Vaccine Alone or Sequential Inactivated and Oral Poliovirus Vaccine in Two-, Four-, and Six-Month-Old Infants with Combination Haemophilus influenzae Type B/Hepatitis B Vaccine.” Pediatric Infectious Disease Journal 16: 675–79. Halsey, N., and A. Galazka. 1985. “The Efficacy of DPT and Oral Poliomyelitis Immunization Schedules Initiated from Birth to 12 Weeks of Age.” Bulletin of the World Health Organization 63 (6): 1151–69. Henderson, R. H., and T. Sundaresan. 1982. “Cluster Sampling to Assess Immunization Coverage: A Review of Experience with a Simplified Sampling Method.” Bulletin of the World Health Organization 60: 253–60. Hinman, A. R., B. Irons, M. Lewis, and K. Kandola. 2002. “Economic Analyses of Rubella and Rubella Vaccines: A Global Review.” Bulletin of the World Health Organization 80: 264–70. Karlsson, G., and M. Johannesson. 1998. “Cost-Effectiveness Analysis and Capital Costs.” Social Science and Medicine 46: 1183–91. Khaleghian, P. 2001. “Immunization Financing and Sustainability: A Review of the Literature.” Special Initiatives Report 40. Bethesda, MD: Partnerships for Health Reform Project, Abt Associates. Krugman, S. 1963. “Measles and Poliomyelitis Vaccines.” New York State Journal of Medicine 63: 2973–77. Levin, A., S. England, J. Jorissen, B. Garshong, and J. Teprey. 2001. Case Study on the Costs and Financing of Immunization Services in Ghana. Report by PHR plus. Bethesda, MD: Abt Associates. Levine, M. M., R. Lagos, O. S. Levine, I. Heitmann, N. Enriquez, M. E. Pinto, and others. 1998. “Epidemiology of Invasive Pneumococcal Infections in Infants and Young Children in Metropolitan Santiago, Chile, a Newly Industrializing Country.” Pediatric Infectious Disease Journal 17: 287–93. Lydon, P. 2004. “Financial Sustainability Plan Analysis: A Look across 22 GAVI Countries.” World Health Organization, Geneva. Margolis, H. S., M. J. Alter, and S. C. Hadler. 1997. “Viral Hepatitis.” In Viral Infections of Humans: Epidemiology and Control, ed. A. S. Evans and R. A. Kaslow, 363–418. New York: Plenum. Martin, M., J. M. Casellas, S. A. Madhi, T. J. Urquhart, S. D. Delport, F. Ferrero, and others. 2004. “Impact of Haemophilus influenzae Type B Conjugate Vaccine in South Africa and Argentina.” Pediatric Infectious Disease Journal 23: 842–47. Mast, E., F. Mahoney, M. A. Kane, and H. S. Margolis. 2004. “Hepatitis B Vaccine.” In Vaccines, ed. S. A. Plotkin and W. A. Orenstein, 299–338. Philadelphia: Saunders. Mathers, C. D., A. D. Lopez, and C. J. L. Murray. 2006. “The Burden of Disease and Mortality by Condition: Data, Methods, and Results for the Year 2001.” In Global Burden of Disease and Risk Factors. ed. Alan D. Lopez, Colin D. Mathers, Majid Ezzati, Dean T. Jamison, and Christopher J. L. Murray. New York: Oxford University Press. McQuillan, G. M., P. J. Coleman, D. Kruszon-Moran, L. A. Moyer, S. B. Lambert, and H. S. Margolis. 1999. “Prevalence of Hepatitis B Virus Infection in the United States: The National Health and Nutrition Examination Surveys, 1976 through 1994.” American Journal of Public Health 89: 14–18. Miller, M. A. 1998. “An Assessment of the Value of Haemophilus influenzae Type B Conjugate Vaccine in Asia.” Pediatric Infectious Disease Journal 17: S152–59. Miller, M. A., and L. McCann. 2000. “Policy Analysis of the Use of Hepatitis B, Haemophilus influenzae Type B-, Streptococcus pneumoniae-

Conjugate, and Rotavirus Vaccines in National Immunization Schedules.” Health Economics 9: 19–35. Miller, M. A., S. C. Redd, S. Hadler, and A. Hinman. 1998. “A Model to Estimate the Potential Economic Benefits of Measles Eradication for the United States.” Vaccine 20: 1917–22. Miller, M. A., R. W. Sutter, P. M. Strebel, and S. C. Hadler. 1996. “CostEffectiveness of Incorporating Inactivated Poliovirus Vaccine into the Routine Childhood Immunization Schedule.” Journal of the American Medical Association 276: 967–71. Monath, T. P. 2004. “Yellow Fever Vaccine.” In Vaccines, ed. S. A. Plotkin and W. A. Orenstein, 1095–176. Philadelphia: Saunders. Monath T. P., R. B. Craven, A. Adjukiewicz, M. Germain, D. B. Francy, L. Ferrara, and others. 1980. “Yellow Fever in The Gambia, 1978–79: Epidemiologic Aspects with Observations on the Occurrence of Orungo Virus Infections.” American Journal of Tropical Medicine and Hygiene 29: 912–28. Morris, S. S., R. E. Black, and L. Tomaskovic. 2003. “Predicting the Distribution of Under-Five Deaths by Cause in Countries without Adequate Vital Registration Systems.” International Journal of Epidemiology 32: 1041–51. Moss, W. J., C. J. Clements, and N. A. Halsey. 2003. “Immunization of Children at Risk of Infection with Human Immunodeficiency Virus.” Bulletin of the World Health Organization 81: 61–70. Mulholland, K., S. Hilton, R. Adegbola, S. Usen, A. Oparaugo, C. Omosigho, and others. 1997. “Randomised Trial of Haemophilus influenzae Type B Tetanus Protein Conjugate Vaccine [Corrected] for Prevention of Pneumonia and Meningitis in Gambian Infants.” Lancet 349: 1191–97. Mulligan, J.-A., J. A. Fox-Rushby, T. Adam, B. Johns, and A. Mills. 2003. “Unit Costs of Health Care Inputs in Low- and Middle-Income Regions.” Disease Control Priorities Project Working Paper 9. DCPP, National Institutes of Health, Bethesda, MD. http://www.fic.nih.gov/ dcpp/wpb9.pdf. Nasidi, A., T. P. Monath, K. DeCock, O. Tomori, R. Cordellier, O. D. Olaleye, and others. 1989. “Urban Yellow Fever Epidemic in Western Nigeria, 1987.” Transactions of the Royal Society of Tropical Medicine and Hygiene 83: 401–6. NIH (National Institutes of Health). 2000. “Jordan Report 20th Anniversary: Accelerated Development of Vaccines.” http://www. niaid.nih.gov/dmid/vaccines/jordan20/. NIH, Bethesda. Pegurri, E., Fox-Rushby, J., and Walker, D. 2005. “The Effects and Costs of Expanding Coverage of Immunization Services in Developing Countries: A Systematic Literature Review.” Vaccine 23: 1624–35. Peltola, H. 2000. “Worldwide Haemophilus influenzae Type B Disease at the Beginning of the 21st Century: Global Analysis of the Disease Burden 25 Years after the Use of the Polysaccharide Vaccine and a Decade after the Advent of Conjugates.” Clinical Microbiology Reviews 13: 302–17. Perry, R. T. Forthcoming. Perry, R. T., and N. A. Halsey. 2004. “The Clinical Significance of Measles: A Review.” Journal of Infectious Diseases 189 (Suppl. 1): S4–16. Plotkin, S. A., and E. Vidor. 2004. “Poliovirus Vaccine: Inactivated.” In Vaccines, ed. S. A. Plotkin and W. A. Orenstein, 625–50. Philadelphia: Saunders. Robertson, R. L., A. J. Hall, P. E. Crivelli, Y. Lowe, H. M. Inskip, and S. K. Snow. 1992. “Cost-Effectiveness of Immunizations: The Gambia Revisited.” Health Policy and Planning 7: 111–22. Robertson, S. E. 1993. The Immunological Basis for Immunization Series Module 6: Poliomyelitis. WHO/EPI/GEN/93.16. Geneva: World Health Organization. Sangrugee N, V. Caceres, and S. Cochi. 2004. “Cost Analysis of Post-polio Certification Immunization Policies.” Bulletin of the World Health Organization 82: 9–15.


Siraprapasiri T., W. Sawaddiwudhipong, and S. Rojanasuphot. 1997. “Cost-Benefit Analysis of Japanese Encephalitis Vaccination Program in Thailand.” Southeast Asian Journal of Tropical Medicine and Public Health 28: 143–48. Soucat, A., D. Levy-Bruhl, X. De Bethune, P. Gbedonou, J.-P. Lamarque, O. Bangoura, and others. 1997. “Affordability, Cost-Effectiveness, and Efficiency of Primary Health Care: The Bamako Initiative Experience in Benin and Guinea.” International Journal of Health Planning and Management 12: S81–108. Stanfield, J. P., and A. Galazka. 1984. “Neonatal Tetanus in the World Today.” Bulletin of the World Health Organization 62: 647–69. Stein, C. E., M. Birmingham, M. Kurian, P. Duclos, and P. Strebel. 2003. “The Global Burden of Measles in the Year 2000: A Model That Uses Country-Specific Indicators.” Journal of Infectious Diseases 187 (Suppl. 1): S8–15. Steinglass, R., L. Brenzel, and A. Percy. 1993. “Tetanus.” In Disease Control Priorities in Developing Countries, ed. D. T. Jamison, W. H. Mosley, A. R. Measham, and J. L. Bobadilla, 189–220. New York: Oxford University Press and World Bank. Sutter, R. W., and O. M. Kew. 2004. “Poliovirus Vaccine: Live.” In Vaccines, ed. S. A. Plotkin and W. A. Orenstein, 651–706. Philadelphia: Saunders. Swartz, M. N. 2004. “Bacterial Meningitis: A View of the Past 90 Years.” New England Journal of Medicine 351: 1826–28. Turk, D. C. 1982. “Clinical Importance of Haemophilus influenzae: 1981.” In Haemophilus influenzae, ed. S. H. Sell and P. G. Wright, 3–9. New York: Elsevier.

Delivering Routine Immunization Services in Peru.” Bulletin of the World Health Organization 82: 676–82. Wassilak, S, G. F. Trudy, V. Murphy, M. H. Roper, and W. A. Orenstein. 2004.“Tetanus Toxoid.”In Vaccines, ed. S.A. Plotkin and W.A. Orenstein, 745–82. Philadelphia: Saunders. Wenger, J. D., and J. Ward. 2004. “Haemophilus influenzae Vaccine.” In Vaccines, ed. S. A. Plotkin and W. A. Orenstein, 229–68. Philadelphia: Saunders. WHO (World Health Organization). 1974. Handbook of Resolutions. Vol. 1, 1.8. World Health Assembly, Fourteenth plenary meeting, 23 May 1974. Geneva: WHO. . 1988. EPICost. Geneva: WHO. . 1992. Global Health Situation and Projections: Estimates. WHO/HST/92.1. Geneva: WHO. whqlibdoc.who.int/hq/1992/ WHO_HST_92.1.pdf. . 1996. “HBsAG Endemicity.” http://wwwstage/vaccinessurveillance/graphics/htmls/hepbprev.htm. WHO, Geneva. . 2001. Estimating the Local Burden of Haemophilus influenzae Type b (Hib) Disease Preventable by Vaccination: A Rapid Assessment Tool. WHO/V&B/01.27. Geneva: WHO. . 2002. Core Information for the Development of Immunization Policy, 2002 Update. WHO/V&B/02.28. Geneva: WHO. http://www. who.int/vaccines-documents/DocsPDF02/www557.pdf. . 2004. “Progress toward Global Immunization Goals, 2001.” http://www.who.int/vaccines/. WHO, Geneva.

UNICEF (United Nations Children’s Fund). 2002. State of the World’s Vaccines and Immunization. New York: United Nations.

. 2005a. “Progress in Reducing Global Measles Deaths: 1999–2003.” Weekly Epidemiological Record 80 (9): 78–81.

USAID (U.S. Agency for International Development), Asia–Near East Region. 1988. “Resources for Child Health Project.” Asia-Near East Bureau Guidance for Costing of Health Services Delivery Projects, Arlington, VA.

. 2005b. World Health Report 2005: Make Every Mother and Child Count. Geneva: WHO.

Valdmanis, V., D. Walker, and J. Fox-Rushby. 2003. “Are Vaccination Sites in Bangladesh Scale Efficient?” International Journal of Technology Assessment in Health Care 19: 692–97. Walker, D., N. R. Mosqueira, M. E. Penny, C. F. Lanata, A. D. Clark, C. F. B. Sanderson, and J. Fox-Rushby. 2004. “Variation in the Costs of

Wolfson, L., and P. Lydon. 2005. “Methodology for Estimating Baseline and Future Levels of Costing (and Impact) for the Global Immunization Vision and Strategy 2005–2015, Draft 1.1.” World Health Organization, Geneva. World Bank. 1993. Investing in Health: World Development Report, 1993. New York: Oxford University Press.



Chapter 24

Helminth Infections: Soil-Transmitted Helminth Infections and Schistosomiasis Peter J. Hotez, Donald A. P. Bundy, Kathleen Beegle, Simon Brooker, Lesley Drake, Nilanthi de Silva, Antonio Montresor, Dirk Engels, Matthew Jukes, Lester Chitsulo, Jeffrey Chow, Ramanan Laxminarayan, Catherine M. Michaud, Jeff Bethony, Rodrigo Correa-Oliveira, Xiao Shu-Hua, Alan Fenwick, and Lorenzo Savioli

Helminth infections caused by soil-transmitted helminths (STHs) and schistosomes are among the most prevalent afflictions of humans who live in areas of poverty in the developing world. The morbidity caused by STHs and schistosomes is most commonly associated with infections of heavy intensity. Approximately 300 million people with heavy helminth infections suffer from severe morbidity that results in more than 150,000 deaths annually (Crompton 1999; Montresor and others 2002). In addition to their health effects, helminth infections also impair physical and mental growth in childhood, thwart educational advancement, and hinder economic development. Because of the geographic overlap of these afflictions and their impact on children and adolescents, the World Health Organization (WHO); the World Bank; and other United Nations agencies and bilaterals; and civil society are working to integrate STH and schistosome control through a program of periodic school-based, targeted anthelmintic drug treatments.

CAUSES AND CHARACTERISTICS OF HELMINTH INFECTIONS Emphasis is placed on the four most common STH infections and the three most common schistosome infections. Together, these infections account for most of the global helminth disease burden.

Soil-Transmitted Helminths The four most common STHs are roundworm (Ascaris lumbricoides), whipworm (Trichuris trichiura), and the anthropophilic hookworms (Necator americanus and Ancylostoma duodenale). Recent estimates suggest that A. lumbricoides infects 1.221 billion people, T. trichiura 795 million, and hookworms 740 million (de Silva and others 2003) (table 24.1). The greatest numbers of STH infections occur in the Americas, China and East Asia, and Sub-Saharan Africa. Strongyloides stercoralis is also a common STH in some of these regions, although detailed information on the prevalence of strongyloidiasis is lacking because of the difficulties in diagnosing human infection. The life cycles of Ascaris, Trichuris, and hookworm follow a general pattern. The adult parasite stages inhabit the gastrointestinal tract (Ascaris and hookworm in the small intestine; Trichuris in the colon), reproduce sexually, and produce eggs, which are passed in human feces and deposited in the external environment. STH infections rarely cause death. Instead, the burden of disease is related less to mortality than to the chronic and insidious effects on the hosts’ health and nutritional status (Stephenson, Latham, and Ottesen 2000; Stoltzfus and others 1997). Hookworms have long been recognized as an important cause of intestinal blood loss leading to iron deficiency and protein malnutrition. The iron deficiency anemia that accompanies moderate and heavy hookworm burdens is sometimes referred to as hookworm disease (Hotez and others 2004). When host

467 ©2006 The International Bank for Reconstruction and Development / The World Bank 73

Table 24.1 Global Prevalence and Distribution of Helminth Infections Helminth infections STH infections

Total cases

Major geographic areas

2 billion

Ascariasis

1.221 billion

Sub-Saharan Africa, India, China and East Asia

Trichuriasis

795 million

Sub-Saharan Africa, India, China and East Asia

Hookworm

740 million

Sub-Saharan Africa, Americas, China and East Asia

Schistosomiasis

187 million

S. haematobium

119 million

S. mansoni S. japonicum

67 million 1 million

Sub-Saharan Africa Sub-Saharan Africa, Americas China and East Asia

Source: de Silva and others 2003.

iron stores are depleted, the extent of iron deficiency anemia is linearly related to the intensity of hookworm infection (Stoltzfus and others 1997). Because of their underlying poor iron status, children, women of reproductive age, and pregnant women are frequently the ones most susceptible to developing hookworm anemia (Brooker, Bethony, and Hotez 2004). Iron deficiency anemia during pregnancy has been linked to adverse maternal-fetal consequences, including prematurity, low birthweight, and impaired lactation (WHO 2002). Chronic STH infections resulting from Ascaris, Trichuris, and hookworm can dramatically affect physical and mental development in children (WHO 2002). Studies have also shown that the growth and physical fitness deficits caused by chronic STH infections are sometimes reversible following treatment with anthelmintic drugs (Stephenson, Latham, and Ottesen 2000). The effects on growth are most pronounced in children with the heaviest infections, but light infections may also contribute to growth deficits if the nutritional status of the community is poor (Stephenson, Latham, and Ottesen 2000). Schistosomiasis Five major species of parasitic trematodes of the family Schistosomatidae—Schistosoma haematobium, S. intercalatum, S. japonicum, S. mansoni, and S. mekongi—infect humans. These parasites have a complex, indirect life cycle involving an intermediate snail host. Disease is caused primarily by schistosome eggs, which are deposited by adult worms in the blood vessels surrounding the bladder or intestines. Urinary schistosomiasis, in which the bladder is affected, is caused by infection with S. haematobium, which occurs mainly in Africa. Intestinal schistosomiasis results from infection with S. mansoni, which occurs in the Middle East, South America, and Africa, and from

infection with S. japonicum, which occurs in parts of China and the Philippines (Ross and others 2002). Two other schistosome species are known to cause intestinal schistosomiasis in restricted geographical areas: S. intercalatum, found in Central Africa, and S. mekongi, found in Cambodia and the Lao People’s Democratic Republic. Schistosomiasis is estimated to affect 187 million people worldwide (table 24.1). A serious acute illness accompanied by fever and lymphadenopathy, known as Katayama Syndrome, can result from heavy schistosome infections. Chronic disease is mostly due to perforation of blood vessels and entrapment of eggs by host tissues. The host’s reaction to entrapped eggs results in granuloma formation. S. haematobium causes bladder wall pathology, leading to ulcer formation, hematuria, and dysuria. Granulomatous changes and ulcers of the bladder wall and ureter can lead to bladder obstruction, dilatation, secondary urinary tract infections and subsequent bladder calcification, renal failure, lesions of the female and male genital tracts, and hydronephrosis. S. haematobium is also associated with increased risk of bladder cancer. The morbidity commonly associated with S. mansoni infection includes lesions of the liver, portal vein, and spleen, leading to periportal fibrosis, portal hypertension, hepatosplenomegaly, splenomegaly, and ascites. Schistosomiasis also causes chronic growth faltering and can contribute to anemia (Ross and others 2002).

EPIDEMIOLOGY OF STH INFECTIONS AND SCHISTOSOMIASIS The most striking epidemiological features of human helminth infections are aggregated distributions in human communities, predisposition of individuals to heavy (or light) infection, rapid reinfection following chemotherapy, and age-intensity profiles that are typically convex (with the exception of hookworm). For all the major human STH and schistosome infections studied to date, worm burdens exhibit a highly aggregated (overdispersed) distribution so that most individuals harbor just a few worms in their intestines, although a few hosts harbor disproportionately large worm burdens (Anderson and May 1991). As a rule, 20 percent of the host population harbors approximately 80 percent of the worm population. This overdispersion has many consequences, both with regard to the population biology of the helminths and the public health consequence for the host, because heavily infected individuals are simultaneously at highest risk of disease and the major source of environmental contamination. One feature that may help explain overdispersion is that individuals tend to be predisposed to heavy (or light) infections. Predisposition has been demonstrated for all four major STHs and the schistosomes. The underlying cause of such predisposition remains poorly understood. However, a combination of heterogeneity in

468 | Disease Control Priorities in Developing Countries | Peter J. Hotez, Donald A. P. Bundy, Kathleen Beegle, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 74

exposure to infection or differences in susceptibility to infection and the ability to mount effective immunity (genetic and nutritional factors) is likely to be important. People of all ages rapidly reacquire infection following treatment, but in schistosomiasis, older people reacquire infection at slower rates than younger ones (Kabatereine and others 1999). The rate of reinfection is specific to certain species of helminths and depends on the life expectancy of that species (short-lived helminths reinfect more rapidly), on the intensity of transmission within a given community, and on the treatment efficacy and coverage. The basic reproductive rate (Ro) describes the transmission potential of a parasite (and thus its ability to reinfect the host). It defines the average number of female offspring produced during the life span of the parasite that survive to reproductive maturity in the absence of density dependence. Ro is determined by parasite immigration and death rates as well as by host density (and, in schistosomiasis, also snail density). A parasite will fail to become established unless Ro is greater than unity (Anderson and May 1991). Adult worms usually survive between one and four years, whereas eggs can sometimes remain viable for several more years in the environment. Therefore, reinfection rates will remain high until adults are removed with chemotherapy and until infective stages, through time, become uninfective. In reality, densitydependent processes regulate parasite populations; at endemic equilibrium, the effective reproductive ratio equals unity (that is, each female replaces herself). Control programs rely on reducing the effective reproductive ratio long enough for the parasite population to be driven to local elimination. Theoretically, Ro provides useful insights, and it is helpful to think of control programs attempting to break the transmission cycle by reducing Ro to less than unity. Therefore, estimates can be made about how long and how many rounds of chemotherapy are required to treat intestinal helminths. For example, A. lumbricoides with an Ro of three and a life expectancy of one year will need to be treated annually with a drug that is 95 percent efficacious and with coverage of more than 91 percent of the population. Where Ro is five—that is, in areas where transmission is higher—treatment must be given more frequently than once a year (Anderson and May 1991). The age-dependent patterns of infection prevalence are generally similar among the major helminth species, exhibiting a rise in childhood to a relatively stable asymptote in adulthood (figure 24.1). Maximum prevalence of A. lumbricoides and T. trichiura is usually attained before five years of age, and the maximum prevalence of hookworm and schistosome infections is usually attained in adolescence or in early adulthood. The nonlinear relationship between prevalence and intensity has the consequence that the observed age-prevalence profiles provide little indication of the underlying profiles of age intensity (age in relation to worm burden). Because intensity is

a. Prevalence

Percentage infected 100 90 80 70 60 50 40 30 20 10 0 0

10

20

30

40

50

Age (years)

A. lumbricoides T. trichiura

Hookworm S. haematobium

b. Intensity

Mean number of worms 110 100 90 80 70 60 50 40 30 20 10 0 0

5

10

15

20

25 30 Age (years)

35

40

A. lumbricoides (worms 2)

Hookworm (worms 7)

T. trichiura (actual numbers)

S. haematobium

45

50

Source: Bundy 1995; reproduced and modified from Hotez, Ardra, and others 2005.

Figure 24.1 Age-Associated Prevalence and Intensity Profiles of STH and Schistosome Infections: Typical Age Profiles of Prevalence and Intensity of STH Infections and Schistosomiasis

linked to morbidity, the age-intensity profiles provide a clearer understanding of which populations are vulnerable to the different helminths (figure 24.1). For A. lumbricoides and T. trichiura infections, the age-intensity profiles are typically convex in form, with the highest intensities in children 5 to Helminth Infections: Soil-Transmitted Helminth Infections and Schistosomiasis | 469


15 years of age (Bundy 1995). For schistosomiasis, a convex pattern is also observed, with a similar peak but with a plateau in adolescents and young adults 15 to 29 years of age (Kabatereine and others 1999). In contrast, the age-intensity profile for hookworm exhibits considerable variation, although intensity typically increases with age until adulthood and then plateaus (Brooker, Bethony, and Hotez 2004). In East Asia it is also common to find the highest intensities among the elderly. However, more generally, children and young adults are at higher risk of both harboring higher levels of infection (thus greater levels of morbidity) and becoming reinfected more quickly. Both may occur at vital stages in a child’s intellectual and physical development. Risk Factors

Climate, Water, and Season. Adequate warmth and moisture are key features for each of the STHs. Wetter areas exhibit increased transmission, and in some endemic areas, both STH and schistosome infections exhibit marked seasonality (Brooker and Michael 2000). Recent use of geographical information systems and remote sensing has identified the distributional limits of STH and schistosomes on the basis of temperature and rainfall patterns (Brooker and Michael 2000). For schistosomiasis, specific snail intermediate hosts prefer certain types of aquatic environments. Construction of dams is known to extend the range of snail habitats, thereby promoting the reemergence of schistosomiasis.

BURDEN OF THE DISEASE

Both host-specific and environmental factors have been identified that may affect the risk of acquiring or harboring heavyintensity helminth infections. Genetics. No genes that control for human helminth infection have yet been identified. However, recent genome scans have identified a locus possibly responsible for controlling S. mansoni infection intensity on chromosome 5q31-33 and loci controlling A. lumbricoides intensity on chromosomes 1 and 13. There is also evidence for genetic control of pathology attributable to S. mansoni, with linkage reported to a region containing the gene for the interferon gamma receptor 1 subunit (Quinnell 2003). Behavior, Household Clustering, and Occupation. Specific occupations, household clustering, and behaviors influence the prevalence and intensity of helminth infections (Bethony and others 2001), particularly for hookworm, in which the highest intensities occur among adults (Brooker, Bethony, and Hotez 2004). Engagement in agricultural pursuits, for example, remains a common denominator for hookworm infection. Behavioral and occupational factors, through their effect on water contact, interact with environmental factors to produce variation in the epidemiology of schistosomiasis. Poverty, Sanitation, and Urbanization. STH and schistosomiasis depend for transmission on environments contaminated with egg-carrying feces. Consequently, helminths are intimately associated with poverty, poor sanitation, and lack of clean water. The provision of safe water and improved sanitation are essential for the control of helminth infection. Although the STH and schistosome infections are neglected diseases that occur predominantly in rural areas, the social and environmental conditions in many unplanned slums and squatter settlements of developing countries are ideal for the persistence of A. lumbricoides (Crompton and Savioli 1993). Schistosomiasis transmission can also occur in urban areas.

The revised estimates in 2003 (de Silva and others 2003) use the methodology developed by Chan and others (1994) and build on recent applications of geographical information systems to derive updated atlases of helminth infections. To reflect recent changes in the epidemiology of infection, de Silva and others used data from only 1990 onward. These data confirm that STH infections are the most prevalent infections of humans and that a large proportion of the population in developing countries is at risk. Of the 187 million cases of schistosomiasis estimated to occur worldwide, most are caused by S. haematobium in Sub-Saharan Africa (table 24.1). WHO (2002) estimates that 27,000 people die annually from STH infections and schistosomiasis (case fatality rate of 0.0014 percent). Many investigators, however, believe that this figure is an underestimate. Crompton (1999) estimated that 155,000 deaths annually occur from these infections (case fatality rate of 0.08 percent), whereas Van der Werf and others (2003), using the limited data available from Africa, estimated the schistosomiasis mortality alone at 280,000 per year (case fatality rate of 0.014 percent) because of nonfunctioning kidneys (from S. haematobium) and hematemesis (from S. mansoni). Therefore, the difference between estimates for helminth-associated mortality is more than 10-fold. Because it is uncommon for STHs and schistosomes to kill their human host, citing mortality figures provides only a small window on their health impact. Instead, measurements of disease burden using disability-adjusted life years (DALYs) and similar tools portray a more accurate picture for helminthic disease burden. WHO estimates the global burden of disease from STH infections and schistosomiasis on the basis of the enormous number of infected individuals, together with an associated low disability weight (Van der Werf and others 2003). However, because an estimated 2 billion people are infected with STHs and schistosomes, even minor adjustments to the disability weights produce enormous variations in DALYs or other measurements of disease burden. This helps to


explain why, for instance, in 1990 the disease burden for the STH infections and schistosomiasis was almost 18 million DALYs, whereas the 2001 estimate was only 4.7 million DALYs. In the intervening 11 years, the DALYs were as low as 2.6 million. Such disparities are substantial when one considers that the 1990 estimate ranks helminths close to major disease entities such as tuberculosis, measles, and malaria, whereas the lowest estimate during the 1990s ranks helminth infections on a par with gonorrhea, otitis media, and iodine deficiency. The Disease Control Priorities Project helminth working group has determined that the WHO global burden of disease estimates are low because they do not incorporate the full clinical spectrum of helminth-associated morbidity and chronic disability, including anemia, chronic pain, diarrhea, exercise intolerance, and undernutrition (King, Dickman, and Tisch 2005). However, for this chapter, the average disability weights estimated by WHO are used throughout. Some of the specific controversies are described below. A. Lumbricoides and T. Trichiura infections Because the most significant physical and intellectual growth disturbances occur as a consequence of moderate and heavy worm burdens, the age-associated epidemiology of A. lumbricoides and T. trichiura infections has focused attention on infected school-age children in developing countries (Bundy 1995). In a revised estimate of the probable number of ascariasis infections worldwide and a better categorization of the morbidity, de Silva, Chan, and Bundy (1997) indicated that 59 million of the 1.2 billion people infected (including 51 million children less than 15 years of age) were at risk of faltering growth, decreased physical fitness, or both as a result of infection. They estimated that about 1.5 million children would never make up the deficit in growth, even if treated. In addition to these chronic, insidious effects, they estimated that about 11.5 million individuals (almost all of them children) were at risk of more acute clinical illness. Their figures also indicated that at least 10,500 deaths annually were directly attributable to one of the serious complications of ascariasis; children account for more than 90 percent of those deaths. The actual threshold at which A. lumbricoides and T. trichiura worm burdens result in childhood morbidity is controversial because of the nonlinear relationship between intensity and pathogenesis and the difficulties of measuring and attributing morbidity in underserved populations suffering from other underlying conditions (Bundy 1995). Hookworm Infection Hookworm infection causes more DALYs lost than any other helminthiasis with the exception of lymphatic filariasis. Even these DALY measurements may still underestimate the true disease burden of iron deficiency anemia and protein

malnutrition resulting from hookworm disease. Iron deficiency anemia alone results in approximately 12 million DALYs lost annually, making it the world’s most important nutrition problem. Data on the epidemiology of iron deficiency anemia in East Africa and elsewhere point to the important contribution of hookworms to this condition (Stoltzfus and others 1997). In Tanzania, where hosts’ iron stores are often depleted, there is a correlation between the number of adult hookworms in the intestine and the amount of host blood loss (Stoltzfus and others 1997). However, it is unclear whether current disability weights effectively incorporate the full contribution of hookworm to severe iron deficiency anemia among iron-depleted populations or whether they take host protein losses and malnutrition into account. There is increasing interest in the importance of hookworm anemia in preschool children, especially in Africa (Brooker, Bethony, and Hotez 2004), where infants and preschool children are particularly vulnerable to the developmental and behavioral deficits caused by iron deficiency anemia (Stephenson, Latham, and Ottesen 2000). Closer assessment of the impact of hookworm on another important iron-deficient population—namely, women of reproductive age—could also significantly increase current DALY estimates. Approximately 44 million of these women harbor hookworms (Bundy, Chan, and Savioli 1995). In addition, severe anemia in pregnancy is associated with neonatal prematurity, reduced birthweight, and impaired lactation (Christian, Khatry, and West 2004).

Schistosomes Scientists and public health workers disagree on the current assessments of both morbidity and mortality attributable to schistosomiasis. Several investigators have now initiated a process to recalculate the burden of disease attributable to schistosomiasis, focusing much more on the clinical course of the different types of schistosomiasis and chronic sequelae (King, Dickman, and Tisch 2005; Michaud, Gordon, and Reich 2003). Through a comprehensive literature review combined with mathematical modeling, Van der Werf and others (2003) estimate that urinary schistosomiasis in Africa results in approximately18 million cases of bladder wall pathology and 20 million cases of hydronephrosis, and African intestinal schistosomiasis results in approximately 8.5 million cases of hepatomegaly. Mortality in Africa attributable to urinary and intestinal schistosomiasis was extrapolated from these figures using a limited number of studies reporting case fatality rates for nonfunctioning kidney and hematemesis. From these extrapolations, Fenwick and others (2003) conclude that in Africa the mortality attributable to urinary schistosomiasis could be as high as 150,000 per year, and the number dying as a result of intestinal schistosomiasis could be as high as 130,000 per year. Helminth Infections: Soil-Transmitted Helminth Infections and Schistosomiasis | 471


COST-EFFECTIVENESS ANALYSIS OF INTERVENTIONS Classifying Interventions The three major interventions are anthelmintic drug treatment, sanitation, and health education. Anthelmintic Drug Treatment. Anthelmintic drug treatment (“deworming”) is aimed at reducing morbidity by decreasing the worm burden. Repeated chemotherapy at regular intervals (periodic deworming) in high-risk groups can ensure that the levels of infection are kept below those associated with morbidity (figure 24.2) and will frequently result in immediate improvement in child health and development. Anthelmintic drug treatment can prevent the development of irreversible consequences of schistosomiasis in adulthood. For ascariasis and trichuriasis, for which intensity peaks among school-age children, frequent and periodic deworming may reduce transmission over time. Obstacles that diminish the effectiveness of periodic deworming are the low efficacy of single-dose mebendazole and albendazole for the treatment of hookworm and trichuriasis, respectively (Adams and others 2004; Albonico and others 1994); high rates of posttreatment reinfection for STHs in areas of high endemicity (Albonico and others 1995); and diminished efficacy with frequent and repeated use (Albonico and others 2003), possibly because of anthelmintic resistance (see the section “Research and Development”). Improved Sanitation. Improved sanitation is aimed at controlling transmission by reducing soil and water contaminaAlbendazole administration

80 High to moderate intensity 60 40 Total prevalence 20 0 1

2

3

4

Health Education. Health education is aimed at reducing transmission and reinfection by encouraging healthy behaviors. For STH infections and schistosomiasis, the aim is to reduce contamination of soil and water by promoting the use of latrines and hygienic behavior. Without a change in defecation habits, periodic deworming cannot attain a stable reduction in transmission. Health education can be provided simply and economically and presents no contraindications or risks. Furthermore, its benefits go beyond the control of helminth infections. In this perspective, it is reasonable to include this component in all helminth control programs. Other Control Measures. In specific epidemiological conditions, environmental or chemical control of snails can be useful tools for reducing the transmission of schistosomiasis. Research to develop new tools for control is in progress, including vaccine development programs for hookworm infection and schistosomiasis (see “Research and Development”). Choosing Interventions Periodic deworming stands out as the most cost-effective means to reduce the morbidity of STH and schistosome infections. Periodic Anthelmintic Therapy. Periodic anthelmintic therapy, or periodic deworming, represents the main measure in areas where infections are intensely transmitted, resources for disease control are limited, and funding for sanitation is lacking. Drug treatment can be administered in the community using different strategies:

Prevalence (percent)

0

tion. Sanitation is the only definitive intervention to eliminate STH infections, but to be effective it should cover a high percentage of the population. Therefore, because of the high costs involved, implementing this strategy is difficult where resources are limited (Asaolu and Ofoezie 2003). Moreover, when used as the primary means of control, it can take years or even decades for sanitation to be effective (Brooker, Bethony, and Hotez 2004).

5 6 7 8 Time (months)

9

10

11

12

13

Source: Albonico and others, forthcoming.

Figure 24.2 Predicted Effect on Ascaris and Trichuris Prevalence Following Frequent and Periodic Dewormings with Benzimidazole Anthelmintics

• Universal treatment. The entire community is treated, irrespective of age, sex, infection status, and other characteristics. • Targeted treatment. Treatment targets population groups, which may be defined by age, sex, or other social characteristics, irrespective of the infectious status. • Selective treatment. Treatment targets individual-level application of anthelmintic drugs, which is selected on the basis of either diagnosis or a suspicion of current infection. Recommended drugs for use in public health interventions to control STH infection are the benzimidazole anthelmintics


(BZAs), albendazole (single dose: 400 mg, reduced to 200 mg for children between 12 and 24 months), or mebendazole (single dose: 500 mg), as well as levamisole or pyrantel pamoate (WHO 2002). Praziquantel (PZQ) (single dose: 40–60 mg/kg) is the major drug used for the treatment of schistosomiasis. However, therapy with oxamniquine has been the cornerstone for treatment of S. mansoni infection in South American national control programs over the past 20 years. The efficacy of oxamniquine and PZQ is comparable, although that of PZQ is slightly better. The BZAs and PZQ are inexpensive; they have undergone extensive safety testing and have been used by millions of individuals with only a few minor side effects. Drugs that do not need dosage according to weight, such as BZAs (in school-age children), are considered easier to use for population-based interventions; however, the use of proxy indicators—for example, substituting height for weight—has proved a successful implementation strategy for PZQ (Hall and others 1999). Distribution Strategy and Frequency of Treatment. The selection of the distribution strategy and the frequency of treatment is based on epidemiological data. The recommended strategy for helminth control is a population-based approach, in which individuals in targeted communities are treated irrespective of their infection status (WHO 2002). This strategy is justified for several reasons, including the simplicity and safety of delivering treatment. Individual diagnosis is difficult and expensive and offers no safety benefit. The intrinsic transmission potential of the parasite species determines the frequency of treatment (see “Epidemiology of STH Infections and Schistosomiasis,” earlier in this chapter). To control morbidity in areas of intense transmission (prevalence greater than 70 percent and more than 10 percent of moderateand heavy-intensity infection), WHO (2002) recommends treatment two or three times a year for STH infections. In areas with a lower intensity of transmission (prevalence between 40 and 60 percent and less than 10 percent of moderate- and heavy-intensity infection), intervention once a year is recommended (WHO 2002). School-Age Children as a High-Risk Population. School-age children typically have the highest intensity of worm infection of any age group, and chronic infection negatively affects all aspects of children’s health, nutrition, cognitive development, learning, and educational access and achievement (World Bank 2003). Regular deworming can cost-effectively reverse and prevent much of this morbidity. Furthermore, schools offer a readily available, extensive, and sustained infrastructure with a skilled workforce that is in close contact with the community. With support from the local health system, teachers can deliver the drugs safely. Teachers need only a few hours of training to understand the rationale for deworming and to learn how to give out the pills and keep a record of their distribution. School-

based deworming also has major externalities for untreated children and the whole community. By reducing transmission in the community of Ascaris and Trichuris infections, deworming substantially improves the health and school participation of both treated and untreated children, both in treatment schools and in neighboring schools (Bundy and others 1990; Miguel and Kremer 2003). These observations provided a basis for the adoption of resolution 54.19 at the 2001 World Health Assembly, which urged member states to ensure access to essential drugs for STH and schistosome infections in endemic areas for the treatment of clinical cases and groups at high risk for morbidity (box 24.1). To achieve this goal, WHO has developed a broad partnership that promotes the incorporation of deworming into existing institutions and programs, for both the education sectors and the health sectors. The Partnership for Parasite Control was launched in 2001 with the aim of mobilizing resources and promoting synergy among public and private efforts for the control of soil-transmitted helminths and schistosomiasis at global and national levels. School-based deworming has its full effect when delivered within an integrated school health program that includes elements of the Focusing Resources on Effective School Health (FRESH) framework. Other At-Risk Populations. Not only school-age children can benefit from treatment. Preschool children (one to five years of age) are vulnerable to the developmental and behavioral deficits caused by iron deficiency anemia, and recent analyses by Brooker, Bethony, and Hotez (2004) indicate that hookworm is an important contributor to anemia in that age group (see “Estimating Intervention Effectiveness”). Women of reproductive age (15 to 49 years of age) are particularly susceptible to iron deficiency anemia because of iron loss during menstruation and because of increased needs during pregnancy (Bundy, Chan, and Savioli 1995). In certain circumstances, male worker populations can also be at increased risk (Guyatt 2000).

Estimating Intervention Effectiveness The evidence base for the health and educational effect of periodic deworming has accumulated significantly over the past decade. STH Infections. All the anthelmintic drugs mentioned above substantially reduce the number of adult worms in the gastrointestinal tract. This effect is also reflected in reduced fecal egg counts. In some cases, however, the efficacy of single-dose mebendazole or albendazole on hookworm and Trichuris infections is low (Adams and others 2004; Albonico and others 1994). Moreover, pyrantel pamoate has little effect on T. trichiura.

Helminth Infections: Soil-Transmitted Helminth Infections and Schistosomiasis | 473 ©2006 The International Bank for Reconstruction and Development / The World Bank 79

Box 24.1

The 54th World Health Assembly The 54th World Health Assembly, which met in May 2001, urged member states to ensure access to essential drugs for schistosomiasis and STH infections in endemic areas for the treatment of clinical cases and groups at high risk for morbidity. The helminth infections of concern are the major schistosomes and STHs outlined in the text. The World Health Assembly determined that simple and sustainable control measures can relieve a generally underestimated and unnecessary disease burden in hightransmission areas. The following minimal targets, aimed at reducing morbidity by 80 percent, can be achieved by all

countries in which such disease is endemic as an integral part of the primary health care system: (a) access to adequate diagnosis and essential anthelmintic drugs in all health services in all endemic areas, even at peripheral levels, for the treatment of symptomatic cases and of children, women, and other groups at high risk of morbidity; (b) regular administration of chemotherapy to at least 75 percent of all school-age children at risk for morbidity by 2010; and (c) sustained, community-based efforts to improve sanitation, clean water supplies, and health education.

Source: WHO 2002.

Overall, however, anthelmintic treatment significantly improves physical and cognitive outcomes in the following ways: • Preschool children. Periodic distribution of anthelmintics has a positive effect on motor and language development and reduces malnutrition in very young children (Stoltzfus and others 2004). • School-age children. Treating school-age children has a considerable effect on their nutritional status (Stoltzfus and others 2004), anemia, physical fitness, appetite, growth (Stephenson, Latham, and Ottesen 2000), and intellectual development (Drake and others 2000). • Women of reproductive age. Studies of pregnant women conducted by Christian, Khatry, and West (2004) in Nepal indicate that albendazole treatment improves maternal hemoglobin as well as birth-weight and child survival. Schistosomiasis. As with STH infections, anthelmintic chemotherapy for schistosomiasis has an important effect on child development, growth, and physical fitness (WHO 2002). Richter (2003) recently summarized details of the effect of PZQ on organ pathology. In S. haematobium infections, reversal of urinary tract pathology can be seen six months after a cure. In S. mansoni and S. japonicum infections, much of the intestinal pathology regresses after chemotherapy. However, more than one PZQ treatment is usually necessary to reverse hepatic pathology, especially in areas of intense transmission. Early intervention with PZQ is preferable to reverse organ pathology. Intervention Costs Several studies have evaluated the costs of school-based periodic deworming in several different settings, whereas comparable studies on other interventions are still lacking.

Periodic Deworming. The advantage of periodic deworming lies in its simplicity (one tablet per child) and safety. Teachers and other personnel without medical training can easily apply the simple measures, which can be incorporated without difficulty in existing health and nonhealth activities that reach the high-risk group. Several organizations, including nongovernmental organizations, include an STH and schistosome infection-control package within their routine activities and, with very limited budgets, relieve the burden of helminth infections in the population covered. The costs of albendazole and PZQ are available through the International Drug Price Indicator Guide (http://www.msh.org). Delivery systems for deworming have often depended on vertical programs, in which mobile teams visit schools or communities to carry out treatment (WHO 2002). Estimated costs for this approach are outlined in table 24.2. For STH infections in Tanzania, Nigeria, and Montserrat, the costs range from US$0.21 to US$0.51 per treatment. However, by training teachers and other school officials to administer anthelmintic drugs, the system could achieve low-cost delivery by “piggy-backing” on existing programs in the educational sector (WHO 2002). Specific examples of such programs conducted in Ghana and Tanzania are summarized in the section “Implementation of Control Strategies: Lessons of Experience,” later in this chapter. It was found that delivery of school-based targeted anthelmintic treatment could cost as little as US$0.03 per child, which may be as low as one-tenth of the estimated costs for vertical delivery (WHO 2002). Thus, at current drug prices, the total cost (drug plus delivery) of a single treatment with albendazole or mebendazole may be as low as US$0.05, and that of a combined treatment with PZQ may be as low as US$0.25 per child (WHO 2002).


Table 24.2 Recent Examples of Delivery Costs for a Single Mass Treatment Delivery cost per treatment Strategy

Drug

Country

US$

Percentage of total cost

Mobile team

Albendazole

Montserrat

0.51

67

Albendazole

Bangladesh

—

42

Levamisole

Nigeria

0.32

81

PZQ

Tanzania

0.21

24

Albendazole

Ghana

0.04

17

Albendazole

Tanzania

0.03

13

0.16–0.21

40–47

School-based Out-of-school children

Arab Rep. of Egypt

Source: Guyatt 2003. — not available.

Integrating drug distribution through the school system rather than using mobile teams, along with a marked decline in the price of BZAs and PZQ, has resulted in a 10-fold reduction in delivery costs. However, those costs are artificially low because they do not include the external costs for the coordinating center responsible for supporting those approaches (Guyatt 2003). It has been estimated, for instance, that mass albendazole treatment of school-age children in Kenya could cost more than US$3 million each year, equivalent to some 4 percent of current national public expenditure on health care (Guyatt 2003). This analysis has not been evaluated against actual operations, however, and current estimates from the parasite control authorities in Kenya suggest that the actual cost is likely to be far less. Large-scale chemotherapy programs for helminth control continue to rely heavily on donor support, suggesting that some affected countries may be unable to support the costs of deworming. Monitoring of control programs is an important part of the managerial process, and it should be carried out at minimum cost so as not to divert resources from the intervention (Brooker and others 2004). It is recommended that, at the planning stage, approximately 5 to 10 percent of the program budget be reserved for monitoring activities (Montresor and others 2002). Improved Sanitation. When sanitation improvements are made alongside deworming, the results obtained last longer. However, the investment needed to reach the level required to interfere with STH transmission could be high. To correctly evaluate the advantage of such investments, one must take into account the consequences for other health indicators and for economic development. An efficient sanitation infrastructure removes the underlying cause of most poverty-related communicable diseases and can boost the economic development of a country. The resources needed to improve hygienic standards can be huge and require the cooperation of several sectors of society (Asaolu and Ofoezie 2003). Currently, these are

qualitative judgments, and no cost-effectiveness analysis (CEA) estimates exist for sanitation in this context. Health Education and Communication. Measures to increase the health awareness of the population are included as an essential component of any population-based activity aimed at controlling morbidity attributable to helminth infections. However, the effectiveness of those activities in reducing transmission of infection varies according to different reports. In some cases, health education can decrease costs, increase levels of knowledge, and decrease reinfection rates (Lansdown and others 2002). Health education efforts can build trust and engage communities, aspects that are crucial to the success of public health initiatives. No CEA estimates exist for health education in this context.

Linking Costs and Effects of Interventions Interventions to reduce morbidity from helminth infections fall into two categories: targeting the transmission mechanisms and treating individuals directly. The former encompasses improvements in infrastructure, including water supply and sanitation, and health education. The latter entails the periodic drug treatment of the population. Substantial improvements through prevention may be a long-term outcome of economic growth in general, because wealthier households have improved sanitation facilities and practices, but those improvements are not an option in the short term without large investments in infrastructure. As shown in the previous section, deworming options dominate on both effectiveness and cost-effectiveness criteria. Costs continue to fall as drug costs decrease. With better data and detailed mapping of disease distribution within communities, targeting individuals at high risk becomes more feasible, thus improving the costeffectiveness of control programs (Michaud, Gordon, and Reich 2003). Helminth Infections: Soil-Transmitted Helminth Infections and Schistosomiasis | 475


Box 24.2

The High Cost-Effectiveness of Mass Treatment for Helminth Infection The combination of low-cost treatment and high prevalence rates suggests that the cost per DALY averted from treating helminth infections will be quite low. Following the consistent framework described in mass treatment of school-age children for both STH infections and schistosomiasis proves to be extremely cost-effective. In fact, benefitcost ratios would be even higher if the analyses incorporated the additional benefits associated with externalities for the untreated. For a population of 1 million people in low- and middle-income countries, if treatment is limited to school-age children treated 1.1 times per year with

albendazole and then reinfected, the cost per DALY averted is estimated at US$3.41 for STH infections. That is, if spending were capped at US$1 million, total DALYs would be reduced by nearly 300,000. The estimate of cost per DALY is higher for schistosomiasis relative to STH infections because of higher drug costs and lower disability weights. Depending on whether generics or original formulations are used, the cost per DALY averted ranges from US$3.36 to US$6.92. However, in combination, treatment with both albendazole and PZQ proves to be extremely cost effective, in the range of US$8 to US$19 per DALY averted.

Source: Authors.

Evidence from existing programs that narrow the intervention to school-age children (a high-risk group) shows that the treatment costs of chemotherapy for helminth infections are quite low—well below US$1 per school-age child. This finding is in part due to the accessibility of the target group and the cost savings of incorporating delivery into existing school and health programs. Moreover, as discussed in the following sections, the economic benefits of targeting this group may be substantial. Still other targeted groups may also have low cost per treatment when treatment is merged into existing programs. For example, interventions through prenatal care programs for pregnant women may be cost-effective. Likewise, evidence on costs of treatment through existing integrated management of infant and childhood illness (IMCI) programs for small children and health campaigns (such as vaccination and micronutrient programs) find low cost per case treated (Montresor and others 2002). Several factors can potentially alter the ranking of interventions in regard to cost-effectiveness, although there are no existing studies to evaluate this. Previous analysis may underestimate the effectiveness and overestimate the cost-benefit ratios of mass treatment of school-age children if the externalities of treatment are not considered (Miguel and Kremer 2003). The cost-effectiveness of school-based deworming programs will change as the programs are extended to cover children who are not enrolled in school. Such program extensions are likely to have greater costs because they entail additional staff and outreach efforts per case treated. However, the effectiveness of mass treatment of school-age children (both enrolled and not enrolled) may be greater. Children who are not enrolled in school come from households with lower income levels. Lower income, which leads to poorer sanitation conditions, is associated with greater incidence and intensity of

infections. Expanding mass treatment to children not enrolled in school will result in treating populations that have higher incidence and intensity, thus raising effectiveness (box 24.2). Distributional and Equity Consequences Interventions to control helminth infections can have equity implications in several dimensions. Programs designed to target communities with high prevalence or high intensity of helminth infection focus on areas with lower income, as described in the sections on the causes, characteristics, and epidemiology of such infections. Although no studies undertake benefit-incidence analysis of public spending on such health services, this targeting implies that state subsidies on deworming services will be of most benefit to lower-income groups. With the increasing availability of poverty maps, empirical evaluation of the equity implications of deworming will be feasible.

AVERTED, AVERTABLE, AND NONAVERTABLE BURDEN In the short run, deworming can avert helminth infections. In the long run, it is assumed that as income levels grow and infrastructure improves, the number of infections averted by reducing transmission will increase. However, given the slow rate of poverty reduction in the 1990s for the poorest regions, such as Sub-Saharan Africa, waiting for economic development to lead to a reduction in infections is only, at best, a slow-paced solution for the majority of the infected population. It is more likely that most averted infections will depend on periodic deworming. Thus, the question remains as to what portion of


existing infections is potentially avertable through recommended interventions and what portion is currently averted with existing programs. For schistosomiasis, successful programs in several countries, including Brazil, China, and the Arab Republic of Egypt, and the issues related to the sustainability of these successes have been described (see “Implementation of Control Strategies: Lessons of Experience” later in this chapter). However, the number of averted schistosomiasis infections in Sub-Saharan Africa is likely to be small, because few serious attempts at widespread control have been made in recent years, and not much of the burden of STH and schistosome infections is currently averted through private treatment. In part, the low number of averted infections may be due to the lack of information on the part of infected individuals, the insidious nature of the condition, and the lack of drugs in the public or private health delivery system.

ECONOMIC BENEFITS OF INTERVENTION The characteristics of helminth infections make a compelling case for public sector intervention if based only on the evidence related to the intervention’s effect on health. From an economic perspective, the public sector has several reasons to become involved in improving health outcomes. First, other benefits may be gained, in addition to the benefit for the treated individual. Second, some forms of intervention are almost pure public goods; that is, no one can be excluded from using the goods or services the interventions deliver, and the private sector is thus unlikely to deliver them. Finally, preventive measures, such as information on the value of washing hands, may not be delivered through the private sector. The lack of knowledge about infections and subclinical symptoms may make individuals less likely to seek treatment. In analyzing the gains of interventions for worm control, one should account for the burden of helminth infections, which extends well beyond the health impacts and DALYs. The economic implications may be quite large. The negative correlation between helminth infections and income level is clearly demonstrated both within and between countries (de Silva and others 2003). However, causality cannot be inferred from this established relationship; poverty promotes higher worm burdens, yet poor health induced by helminths can lead to lower income. There may also be opportunity costs to uninfected household members residing with infected persons. Few studies have been designed to evaluate, either directly or indirectly, the magnitude of the effect of deworming on economic productivity. The indirect evidence at the micro level suggests that helminth infection has a significant impact on adult productivity and, subsequently, on earnings. More direct evidence for children shows that helminth infection has long-term implications for educational attainment and economic status.

Studies are increasingly documenting a causal impact of adult health (broadly defined) on labor force participation, wages, and productivity in developing countries (Thomas and Strauss 1997). Moreover, helminth infection is known to affect some of the health conditions related to productivity—namely, iron deficiency anemia and wasting. Guyatt (2000) reviews numerous studies relating these conditions to physical fitness and productivity; Haas and Brownlie (2001) review studies on the effect of iron supplementation on work. The studies generally show productivity gains linked to better health along the various health dimensions studied. However, although some evidence points to the indirect impact of STHs on income earnings, these relationships have not been adequately studied, either directly or indirectly. More compelling links between helminth infection and economic well-being may exist for children. The strong association between worm burden and poor health outcomes for children suggests that infections may affect school enrollment, attendance, grade repetition, and grade attainment. In turn, the potential impact on educational outcomes has implications for the assessment of the economic benefits of intervention. Numerous studies have demonstrated the benefits of schooling, showing that the return on education is quite high. Increased education is associated with, among other things, higher worker productivity and generally higher productivity in nonmarket production activities, including greater farmer efficiency and productivity (Psacharopoulos and Patrinos 2002). Although observational studies show that lower levels of learning and schooling are linked to helminth infection (World Bank 2003), establishing a causal relationship requires adequately controlling for all unobserved or confounding factors. Miguel and Kremer (2003) note that several methodological issues hamper many existing randomized treatment-control evaluations. First, externalities associated with interventions can lead to underestimating impacts among the untreated population. Second, sample selection and attrition issues can affect the validity of findings, although the direction of this effect is ambiguous. Third, existing studies typically evaluate the impact of deworming on cognitive skills, likely the culmination of several years of health and education investments, as assessed by tests administered to treated and untreated children. Although studies find an effect on cognitive skills for those with the heaviest worm burden, they do not focus on other important education outcomes, which are likely to be more affected in the short run by health improvements, such as school enrollment and school attendance. The study by Miguel and Kremer (2003) in Kenya attempts to address those shortcomings through improved study design and analytical methods. In addition to providing health gains, deworming reduced total primary school absenteeism by at least one-quarter in the first two years of the project. The gains were largest for the youngest children, who suffered from more Helminth Infections: Soil-Transmitted Helminth Infections and Schistosomiasis | 477


Beyond the current impacts on schooling and implications for cognition, helminth infection in children can have longterm implications for economic outcomes in adulthood through its effect on physical growth. Height has been shown to affect wage-earning capacity as well as participation in the labor force for men and women (Thomas and Strauss 1997). This relationship may be strongest in settings where infection rates are highest—that is, low-income areas, where physical endurance yields high returns in the labor market.

Net presented value of discounted wages (US$) 125 100 75 50 25 0 0.0

2.5 5.0 7.5 10.0 12.5 15.0 17.5 20.0 22.5 Increase in school participation per year per pupil (percent)

25.0

Note: Assumptions are as follows: a 7 percent return to an additional year of school; wage gains earned over 40 years in the workforce, discounted at 5 percent per year with no wage growth; and annual wage earnings of US$400 per year, which is below the estimated agricultural and nonagricultural annual wages for low-income countries in the World Bank (2003).

IMPLEMENTATION OF CONTROL STRATEGIES: LESSONS OF EXPERIENCE Two case studies illustrate the profound health effects of periodic deworming.

Figure 24.3 Returns to School Participation

Case Study Number 1: Periodic Deworming in Ghana and Tanzania intense worm infections. Externalities would cause a substantial underestimation of this effect. In terms of cost-effectiveness as an educational intervention, deworming proved to be far more effective at improving school attendance than other educational interventions implemented in a study in Kenya. Deworming offers a high rate of return, increasing the net present value of discounted wages by more than US$30 per treated child compared with per treatment costs of under US$1. For realistic estimates of returns to schooling, these results show in general that the net present discounted value of lifetime earnings is high compared with the costs of treatment even for small gains in school participation (figure 24.3). Bleakley (2003) examined the effect of a hookworm control program undertaken about 1910 in the southern part of the United States. Hookworm infection was estimated to cause a 23 percent drop in the probability of school attendance, and children with greater exposure to the hookworm eradication campaign were more likely to be literate. Moreover, the longterm follow-up of affected cohorts showed that hookworm infection in childhood led to significantly lower wages in adulthood. Helminth infections in preschool-age children can have consequences for subsequent schooling, such as delaying primary school enrollment and school attainment, thereby affecting future labor market outcomes. Bobonis, Miguel, and Sharma (2003) conducted a study of preschool-age children, using iron supplementation and deworming drugs administered to children two to six years of age. Preliminary results indicate that, in addition to the weight gain associated with treatment, average preschool participation rates increased sharply by 6.3 percentage points among assisted children older than two, reducing preschool absenteeism by roughly one-fifth.

The Partnership for Child Development (PCD) undertook an evaluation of the use of schools in Ghana and Tanzania for the delivery of health interventions, including research into the processes, costs, and benefits (PCD 1999). The effort also involved operations research and evaluation of programs with regard to health and education outcomes and people’s perceptions of the programs (Hall and others 1999). The results demonstrated the following: • Simple interventions, such as deworming, have the potential to improve children’s health and educational achievement, especially for those worst affected and most disadvantaged. • The delivery of school-based health services is efficient and cost-effective and is supported by the key stakeholders involved. Implementers of the school health programs in the education and health sectors and the community are positive regarding the teacher’s role in health provision, as long as the health interventions are simple, safe, familiar, and effective and are seen as responding to local needs. • The provision of health services through schools need not require long and complex training, nor significantly add to the workload of teachers or administrators. • Delivery through the existing education sector could occur effectively without any additional infrastructure, as long as the existing educational system is adequately functional. The results of the evaluation of these programs also highlighted the need for deworming to be carried out in the context of a wider framework of school health, which includes core activities such as effective and nondiscriminatory school health policies, provision of safe water and sanitation, and effective


health education (http://www.freshschools.org and http://www. schoolsandhealth.org).

Case Study Number 2: Schistosomiasis Control in Egypt In 1937, the prevalence of schistosomiasis in rural areas was about 50 percent, almost every boy had blood in his urine by the age of 12, and bladder cancer was the commonest cancer in Egypt. Molluscicides, from copper sulfate to niclosamide, have been used to try to kill the host snails, and drugs from antimonybased compounds, through niridazole, metrifonate, and PZQ, have been used to treat the millions of infected Egyptians. Finally, after a 14-year control campaign using PZQ, the prevalence of schistosomiasis has been reduced to below 10 percent. With infection intensities now low, the serious health consequences of schistosomiasis have disappeared. The program was started in 1988, when using loans from the African Development Bank and the World Bank, Egypt invested heavily in the purchase of PZQ, encouraging local production, to control morbidity caused by schistosomiasis. Since the drug was first made available in 1988, some 45 million doses have been dispensed. A television campaign has encouraged people to submit samples for diagnosis and to receive free treatment if their diagnoses are positive. Since 1997, a mass chemotherapy campaign was used to target populations in high-prevalence villages and children in selected governorates where prevalence was greater than 20 percent. In addition, molluscicides have been applied in canals around high-prevalence villages. The widespread use of PZQ has given dramatic results. Morbidity, including hematuria, has almost disappeared, and bladder cancer is on the decline.

RESEARCH AND DEVELOPMENT Among the important tasks to be done to control helminth infections are collection of better data on helminth disease burden, research on the health and economic effects (and safety) of periodic deworming, monitoring of the emergence of anthelmintic drug resistance, and development of new tools to supplement or complement existing control strategies. Health and Economic Impact Overall, better estimates of disease burden are needed (Michaud, Gordon, and Reich 2003), especially with respect to obtaining a consistent and agreed-on estimate for the DALYs attributed to helminth infections. In a systematic review of randomized deworming trials, Dickson and others (2000) conclude that, although data support the effects of deworming on weight gain, there are inconsistencies among trials and insufficient evidence as to whether such interventions improve cogni-

tive performance. Plausible mechanisms by which helminths suppress growth in childhood and exert negative impacts on intelligence, cognition, and school performance are largely unstudied and unknown. In addition, some reports have questioned whether albendazole itself could adversely affect growth (Forrester and others 1998). Those issues require clarification as widespread deworming programs become more common. The impact of helminths on populations other than schoolchildren, including preschool-age children, women of childbearing age, and adult workers, appears to be substantial. However, those populations are understudied. Also unclear is the impact of childhood STH and schistosome infections on productivity in adulthood. The effect of chemotherapy on many of the manifestations of schistosomiasis has not been assessed systematically. It has been postulated that PZQ treatment of schistosomiasis promotes partial immunity by destroying worms in the vasculature and releasing parasite antigens (Colley and Secor 2004). In contrast, the frequent and periodic treatment of STH infections (Albonico and others 1995) do not appear to promote natural protective immunity. The role of helminths and coinfections also warrants further exploration. Some studies suggest that HIV-1 infection may promote susceptibility to schistosomiasis (Secor, Karanja, and Colley 2004), and human T-cell lymphotropic virus-1 (HTLV-1) infection may promote susceptibility to strongyloidiasis. In addition, emerging evidence indicates that STH and schistosome infections may promote susceptibility to other infectious agents, possibly including HIV/AIDS and malaria (Fincham, Markus, and Adams 2003). This phenomenon, if verified in an epidemiologic study, would further increase helminth-associated DALY estimates.

Anthelmintic Drug Resistance and New Drug Development A concern about the feasibility of sustainable control with BZAs is the possible emergence of drug resistance among human STHs. BZA resistance occurs because of the spread of point mutations in nematode-tubulin alleles. This phenomenon has already resulted in widespread BZA drug resistance among STHs of ruminant livestock. There is still no direct evidence for BZA resistance among human STHs, although such resistance could account for an observed failure of mebendazole for human hookworm in southern Mali, as well as a diminished efficacy against hookworm in Zanzibar following frequent and periodic use of mebendazole (Albonico and others 2003). PZQ resistance must also be considered, especially as it begins to be widely used in Sub-Saharan Africa (Hagan and others 2004). Should PZQ resistance develop, there will be new demands for antischistosomal drugs. Recently, the artemisins have shown activity against schistosomulae and were successful in protecting against S. japonicum in China (Hagan and others 2004). Helminth Infections: Soil-Transmitted Helminth Infections and Schistosomiasis | 479


Anthelmintic Vaccines The high rates of reinfection that can occur following treatment with anthelmintic drugs and concern about emerging drug resistance have prompted the search for alternative control tools. For most helminth infections, reduction in adult worm burden has been considered the “gold standard” for vaccine development. For schistosomiasis, however, a vaccine that targets parasite fecundity and egg viability, thereby reducing pathology and transmission, would also represent an important breakthrough. A 28-kDa glutathione S-transferase (GST) has shown promise as a protective antigen for S. haematobium infection (Capron and others 2005). The S. haematobium vaccine project based on GST has successfully passed phase 1 testing; the research group, which is based at the Pasteur Institute, is embarking on phase 2 clinical trials in Senegal and Niger. Additional schistosomiasis vaccines are also undergoing early-stage development. Efforts are also under way by the Human Hookworm Vaccine Initiative to develop and test a first-generation recombinant hookworm vaccine (Brooker and others 2005; Hotez, Bethony, and others 2005). The first vaccine manufactured under current good manufacturing practices and tested for quality control and toxicity is the Na-ASP-2 hookworm vaccine, which was developed from research demonstrating human correlates of immunity and partial protection data in vaccinated laboratory animals. Phase 1 human trials for evaluating the safety and immunogenicity of the Na-ASP-2 hookworm vaccine are in progress. Additional research is needed to determine how an anthelmintic vaccine can be incorporated into existing control programs, as well how it would be used for at-risk populations not currently targeted for periodic deworming in schools.

CONCLUSIONS: PROMISES AND PITFALLS Fulfilling the mandate of World Health Assembly resolution 54.19 will require the regular treatment of hundreds of millions of children over decades. The obstacles in this undertaking are formidable, and success will depend on the ability of countries to identify or create reliable and sustained infrastructures for this purpose. A focus on using preexisting school systems may be key to achieving this goal. The treatment of schoolchildren for A. lumbricoides, T. trichiura, and schistosome infections achieves large externalities that reduce infection in other vulnerable age groups. However, the different epidemiology of hookworm raises concerns about the risks to preschool children and women of reproductive age who remain untreated. Providing regular treatment to these populations appears to be a less cost-effective option, largely because of the absence of a preexisting infrastructure. This situation presents a strong argument for developing a hookworm vaccine that could be used to protect these vulnerable groups. It has yet to be seen whether the emergence of BZA drug resistance is a genuine

concern that could derail global deworming efforts in much the same way that resistance to DDT and chloroquine has affected the ambitions for global malaria control. It is possible that the specific dynamics of helminth populations will provide sufficient genetic flow to maintain susceptibility in much the same way that insecticides remain the effective staple of global agribusiness. Until new technologies become available, anthelmintic chemotherapy for school-age children remains the most practical and substantive means to control STH and schistosome infections in the developing world.

REFERENCES Adams, V. J., C. J. Lombard, M. A. Dhansay, M. B. Markus, and J. E. Fincham. 2004. “Efficacy of Albendazole against the Whipworm Trichuris Trichiura—A Randomized, Controlled Trial.” South African Medical Journal 94: 972–76. Albonico, M., Q. Bickle, M. Ramsan, A. Montresor, L. Savioli, and M. Taylor. 2003. “Efficacy of Mebendazole and Levamisole Alone or in Combination against Intestinal Nematode Infections after Repeated Targeted Mebendazole Treatment in Zanzibar.” Bulletin of the World Health Organization 81: 343–52. Albonico, M., A. Montresor, D. W. Crompton, and L. Savioli. Forthcoming. “Intervention for the Control of Soil-Transmitted Helminthiasis.” Advances in Parasitology. Albonico, M., E. Renganathan, A. Bosman, U. M. Kisumku, K. S. Alawi, and L. Savioli. 1994. “Efficacy of a Single Dose of Mebendazole on Prevalence and Intensity of Soil-Transmitted Nematodes in Zanzibar.” Tropical and Geographic Medicine 46: 142–46. Albonico, M., P. G. Smith, E. Ercole, A. Hall, H. M. Chwaya, K. S. Alawi, and L. Savioli. 1995. “Rate of Reinfection with Intestinal Nematodes after Treatment of Children with Mebendazole or Albendazole in a Highly Endemic Area.” Transactions of the Royal Society of Tropical Medicine and Hygiene 89: 538–41. Anderson, R. M., and R. M. May. 1991. Infectious Diseases of Humans. Oxford, U.K.: Oxford University Press. Asaolu, S. O., and I. E. Ofoezie. 2003. “The Role of Health Education and Sanitation in the Control of Helminth Infections.” Acta Tropica 86: 283–94. Bethony, J., J. T. Williams, H. Kloos, J. Blangero, L. Alves-Fraga, G. Buck, and others. 2001. “Exposure to Schistosoma mansoni Infection in a Rural Area in Brazil: II. Household Risk Factors.” Tropical Medicine and International Health 6: 136–45. Bleakley, H. 2003. “Disease and Development: Evidence from Hookworm Eradication in the American South.” Journal of the European Economic Association 1: 376–86. Bobonis, G., E. Miguel, C. Sharma. 2003. “Iron Deficiency Anemia and School Participation.” University of California–Berkeley. http://emlab. berkeley.edu/users/emiguel/miguel_anemia.pdf. Brooker, S., J. Bethony, and P. J. Hotez. 2004. “Human Hookworm Infection in the 21st Century.” Advances in Parasitology 58: 197–288. Brooker, S., J. M. Bethony, L. Rodrigues, N. Alexander, S. Geiger, and P. J. Hotez. 2005. “Epidemiological, Immunological and Practical Considerations in Developing and Evaluating a Human Hookworm Vaccine.” Expert Review of Vaccines 4: 35–50. Brooker, S., and E. Michael. 2000. “The Potential of Geographical Information Systems and Remote Sensing in the Epidemiology and Control of Human Helminth Infections.” Advances in Parasitology 47: 245–87.


Brooker, S., S. Whawell, N. B. Kabatereine, A. Fenwick, and R. M. Anderson. 2004. “Evaluating the Epidemiological Impact of National Control Programmes for Helminths.” Trends in Parasitology 11: 537–45. Bundy, D. A. 1995. “Epidemiology and Transmission of Intestinal Helminths.” In Enteric Infection 2, Intestinal Helminths, ed. M. J. G. Farthing, G. T. Keusch, and D. Wakelin, 5–24. London: Chapman & Hall Medical. Bundy, D. A., M. S. Chan, and L. Savioli. 1995. “Hookworm Infection in Pregnancy.” Transactions of the Royal Society of Tropical Medicine and Hygiene 89: 521–22. Bundy, D. A., M. S. Wong, L. L. Lewis, and J. Horton. 1990. “Control of Geohelminths by Delivery of Targeted Chemotherapy through Schools.” Transactions of the Royal Society of Tropical Medicine and Hygiene 84: 115–20. Capron, A., G. Riveau, M. Capron, and F. Trottein. 2005. “Schistosomes: The Road from Host-Parasite Interactions to Vaccines in Clinical Trials.” Trends in Parasitology 21: 143–49. Chan, M. S., G. F. Medley, D. Jamison, and D. A. Bundy. 1994. “The Evaluation of Potential Global Morbidity Attributable to Intestinal Nematode Infections.” Parasitology 109: 373–87. Christian, P., S. K. Khatry, and K. P. West. 2004. “Antenatal Anthelmintic Treatment, Birthweight, and Infant Survival in Rural Nepal.” Lancet 364: 981–83. Colley, D. G., and E. W. Secor. 2004. “Immunoregulation and World Health Assembly Resolution 54.19: Why Does Treatment Control Morbidity?” Parasitology International 53: 143–50. Crompton, D. W. 1999. “How Much Helminthiasis Is There in the World?” Journal of Parasitology 85: 397–403. ———. 2001. “Ascaris and Ascariasis.” Advances in Parasitology 48: 285–375. Crompton, D. W., and L. Savioli. 1993. “Intestinal Parasitic Infections and Urbanization.” Bulletin of the World Health Organization 71: 1–7.

Haas, J. D., and T. Brownlie. 2001. “Iron Deficiency and Reduced Work Capacity: A Critical Review of the Research to Determine a Causal Relationship.” Journal of Nutrition 131 (Suppl.): 676S–88S. Hagan, P., C. C. Appleton, G. C. Coles, J. R. Kusel, and L. A. TchuemTchuente. 2004. “Schistosomiasis Control: Keep Taking the Tablets.” Trends in Parasitology 20: 92–97. Hall, A., C. Nokes, S. T. Wen, S. Adjei, C. Kihamia, L. Mwanri, and others. 1999. “Alternatives to Bodyweight for Estimating the Dose of Praziquantel Needed to Treat Schistosomiasis.” Transactions of the Royal Society of Tropical Medicine and Hygiene 93: 652–58. Hotez, P. J., S. Ardra, J. Bethony, M. E. Bottazzi, A. Loukas, R. CorreaOliveira, and S. Brooker. 2005. “Helminth Infections of Children: Prospects for Control.” In Hot Topics in Infection and Immunity in Children, ed. A. J. Pollard and A. Finn. New York: Springer. Hotez, P. J., J. Bethony, M. E. Bottazzi, S. Brooker, and P. Buss. 2005. “Hookworm—‘The Great Infection of Mankind.’” Public Library of Science Medicine 2: e67. Hotez, P. J., S. Brooker, J. M. Bethony, M. E. Bottazzi, A. Loukas, and S. H. Xiao. 2004. “Current Concepts: Hookworm Infection.” New England Journal of Medicine 351: 799–807. Kabatereine, N. B., B. J. Vennervald, J. H. Ouma, J. Kemijumbi, A. E. Butterworth, D. W. Dunne, and A. J. Fulford. 1999. “Adult Resistance to Schistosomiasis Mansoni: Age-Dependence to Reinfection Remains Constant in Communities with Diverse Exposure Patterns.” Parasitology 118: 101–5. King, C. H., K. Dickman, and D. J. Tisch. 2005. “Reassessment of the Cost of Chronic Helmintic Infection: A Meta-analysis of DisabilityRelated Outcomes in Endemic Schistosomiasis.” Lancet 365: 1561–69. Lansdown, R., A. Ledward, A. Hall, W. Issac, E. Yona, J. Matulu, and others. 2002. “Schistosomiasis, Helminth Infection, and Health Education in Tanzania: Achieving Behaviour Change in Primary Schools.” Health Education Research 17: 425–33.

de Silva, N. R., S. Brooker, P. J. Hotez, A. Montresor, D. Engles, and L. Savioli. 2003. “Soil-Transmitted Helminth Infections: Updating the Global Picture.” Trends in Parasitology 19: 547–51.

Michaud, C. M., W. S. Gordon, and M. R. Reich. 2003. “The Global Burden of Disease Due to Schistosomiasis.” Disease Control Priorities Project Working Paper 19. http://www.fic.nih.gov/dcpp/ wps/wp19.pdf.

de Silva, N. R., M. S. Chan, and D. A. P. Bundy. 1997. “Morbidity and Mortality Due to Ascariasis: Re-estimation and Sensitivity Analysis of Global Numbers at Risk.” Tropical Medicine and International Health 2: 519–28.

Miguel, E. A., and M. Kremer. 2003. “Worms: Identifying Impacts on Education and Health in the Presence of Treatment Externalities.” Econometrica 72 (1): 159–217.

Dickson, R., S. Awasthi, P. Williamson, C. Demellweek, and P. Garner. 2000. “Effects of Treatment for Intestinal Helminth Infection on Growth and Cognitive Performance in Children: Systematic Review of Randomised Trials.” British Medical Journal 320: 1697–701. Drake, L. J., M. C. H. Jukes, R. J. Sternberg, and D. A. P. Bundy. 2000. “Geohelminth Infections (Ascariasis, Trichuriasis, and Hookworm): Cognitive and Developmental Impacts.” Seminars in Pediatric Infectious Diseases 11: 245–51. Fenwick, A., L. Savioli, D. Engels, N. R. Bergquist, and M. H. Todd. 2003. “Drugs for the Control of Parasitic Diseases: Current Status and Development in Schistosomiasis.” Trends in Parasitology 19: 509–15. Fincham, J. E., M. B. Markus, and V. J. Adams. 2003. “Could Control of Soil-Transmitted Helminthic Infection Influence the HIV/AIDS Pandemic?” Acta Tropica 86: 315–33. Forrester, J. E., J. C. Bailar III, S. A. Esrey, M. V. Jose, B. T. Castillejos, and G. Ocamp. 1998. “Randomised Trial of Albendazole and Pyrantel in Symptomless Trichuriasis in Children.” Lancet 353: 1103–8. Guyatt, H. L. 2000. “Do Intestinal Nematodes Affect Productivity in Adulthood?” Parasitology Today 16: 153–58. ———. 2003. “The Cost of Delivering and Sustaining a Control Programme for Schistosomiasis and Soil-Transmitted Helminthiasis.” Acta Tropica 86: 267–74.

Montresor, A., D. W. T. Crompton, T. W. Gyorkos, and L. Savioli. 2002. Helminth Control in School-Age Children: A Guide for Managers of Control Programmes. Geneva: World Health Organization. PCD (Partnership for Child Development). 1999. “The Cost of LargeScale School Health Programmes Which Deliver Anthelmintics to Children in Ghana and Tanzania.” Acta Tropica 73 (2): 183–204. Psacharopoulos, G., and H. Patrinos. 2002. “Returns to Investment in Education: A Further Update.” Working Paper 2881, World Bank, Washington, DC. Quinnell, R. J. 2003. “Genetics of Susceptibility to Human Helminth Infection.” International Journal of Parasitology 33: 1219–31. Richter, J. 2003. “The Impact of Chemotherapy on Morbidity Due to Schistosomiasis.” Acta Tropica 86: 161–83. Ross, A. G., P. B. Bartley, A. C. Sleigh, G. R. Olds, Y. Li, G. M. Williams, and D. P. McManus. 2002. “Schistosomiasis.” New England Journal of Medicine 346: 1212–20. Secor, W. E., D. M. Karanja, and D. G. Colley. 2004. “Interactions between Schistosomiasis and Human Immunodeficiency Virus in Western Kenya.” Memorias do Instituto Oswaldo Cruz 99 (5 Suppl. 1): 93–95. Stephenson, L. S., M. C. Latham, and E. A. Ottesen. 2000. “Malnutrition and Parasitic Helminth Infections.” Parasitology 121 (Suppl.): S23–28. Helminth Infections: Soil-Transmitted Helminth Infections and Schistosomiasis | 481


Stoltzfus, R. J., H. M. Chwaya, A. Montresor, J. M. Tielsch, J. K. Jape, M. Albonico, and L. Savioli. 2004. “Low Dose Daily Iron Supplementation Improves Iron Status and Appetite but Not Anemia, Whereas Quarterly Anthelmintic Treatment Improves Growth, Appetite, and Anemia in Zanzibari Preschool Children.” Journal of Nutrition 134: 348–56. Stoltzfus, R. J., M. L. Dreyfuss, H. M. Chwaya, and M. Albonico. 1997. “Hookworm Control as a Strategy to Prevent Iron Deficiency Anemia.” Nutrition Reviews 55: 223–32. Thomas, D., and J. Strauss. 1997. “Health and Wages: Evidence on Men and Women in Urban Brazil.” Journal of Econometrics 77: 159–85.

Van der Werf, M. J., S. J. de Vlas, S. Brooker, C. W. Looman, N. J. Nagelkerke, J. D. Habbema, and D. Engels. 2003. “Quantification of Clinical Morbidity Associated with Schistosome Infection in SubSaharan Africa.” Acta Tropica 86: 125–39. WHO (World Health Organization). 2002. Prevention and Control of Schistosomiasis and Soil-Transmitted Helminthiasis. WHO Technical Series Report 912. Geneva: WHO. World Bank. 2003. School Deworming at a Glance. Public Health at a Glance Series. http://www.worldbank.org/hnp.


Chapter 25

Acute Respiratory Infections in Children Eric A. F. Simoes, Thomas Cherian, Jeffrey Chow, Sonbol ShahidSalles, Ramanan Laxminarayan, and T. Jacob John

Acute respiratory infections (ARIs) are classified as upper respiratory tract infections (URIs) or lower respiratory tract infections (LRIs). The upper respiratory tract consists of the airways from the nostrils to the vocal cords in the larynx, including the paranasal sinuses and the middle ear. The lower respiratory tract covers the continuation of the airways from the trachea and bronchi to the bronchioles and the alveoli. ARIs are not confined to the respiratory tract and have systemic effects because of possible extension of infection or microbial toxins, inflammation, and reduced lung function. Diphtheria, pertussis (whooping cough), and measles are vaccine-preventable diseases that may have a respiratory tract component but also affect other systems; they are discussed in chapter 20. Except during the neonatal period, ARIs are the most common causes of both illness and mortality in children under five, who average three to six episodes of ARIs annually regardless of where they live or what their economic situation is (Kamath and others 1969; Monto and Ullman 1974). However, the proportion of mild to severe disease varies between high- and lowincome countries, and because of differences in specific etiologies and risk factors, the severity of LRIs in children under five is worse in developing countries, resulting in a higher casefatality rate. Although medical care can to some extent mitigate both severity and fatality, many severe LRIs do not respond to therapy, largely because of the lack of highly effective antiviral drugs. Some 10.8 million children die each year (Black, Morris, and Bryce 2003). Estimates indicate that in 2000, 1.9 million of them died because of ARIs, 70 percent of them in Africa and Southeast Asia (Williams and others 2002). The World Health Organization (WHO) estimates that 2 million children under five die of pneumonia each year (Bryce and others 2005).

CAUSES OF ARIS AND THE BURDEN OF DISEASE ARIs in children take a heavy toll on life, especially where medical care is not available or is not sought.

Upper Respiratory Tract Infections URIs are the most common infectious diseases. They include rhinitis (common cold), sinusitis, ear infections, acute pharyngitis or tonsillopharyngitis, epiglottitis, and laryngitis—of which ear infections and pharyngitis cause the more severe complications (deafness and acute rheumatic fever, respectively). The vast majority of URIs have a viral etiology. Rhinoviruses account for 25 to 30 percent of URIs; respiratory syncytial viruses (RSVs), parainfluenza and influenza viruses, human metapneumovirus, and adenoviruses for 25 to 35 percent; corona viruses for 10 percent; and unidentified viruses for the remainder (Denny 1995). Because most URIs are self-limiting, their complications are more important than the infections. Acute viral infections predispose children to bacterial infections of the sinuses and middle ear (Berman 1995a), and aspiration of infected secretions and cells can result in LRIs. Acute Pharyngitis. Acute pharyngitis is caused by viruses in more than 70 percent of cases in young children. Mild pharyngeal redness and swelling and tonsil enlargement are typical. Streptococcal infection is rare in children under five and more common in older children. In countries with crowded living conditions and populations that may have a genetic predisposition, poststreptococcal sequelae such as acute rheumatic fever and carditis are common in school-age children but may also 483


occur in those under five. Acute pharyngitis in conjunction with the development of a membrane on the throat is nearly always caused by Corynebacterium diphtheriae in developing countries. However, with the almost universal vaccination of infants with the DTP (diphtheria-tetanus-pertussis) vaccine, diphtheria is rare. Acute Ear Infection. Acute ear infection occurs with up to 30 percent of URIs. In developing countries with inadequate medical care, it may lead to perforated eardrums and chronic ear discharge in later childhood and ultimately to hearing impairment or deafness (Berman 1995b). Chronic ear infection following repeated episodes of acute ear infection is common in developing countries, affecting 2 to 6 percent of school-age children.The associated hearing loss may be disabling and may affect learning. Repeated ear infections may lead to mastoiditis, which in turn may spread infection to the meninges. Mastoiditis and other complications of URIs account for nearly 5 percent of all ARI deaths worldwide (Williams and others 2002).

Lower Respiratory Tract Infections The common LRIs in children are pneumonia and bronchiolitis. The respiratory rate is a valuable clinical sign for diagnosing acute LRI in children who are coughing and breathing rapidly. The presence of lower chest wall indrawing identifies more severe disease (E. Mulholland and others 1992; Shann, Hart, and Thomas 1984). Currently, the most common causes of viral LRIs are RSVs. They tend to be highly seasonal, unlike parainfluenza viruses, the next most common cause of viral LRIs. The epidemiology of influenza viruses in children in developing countries deserves urgent investigation because safe and effective vaccines are available. Before the effective use of measles vaccine, the measles virus was the most important viral cause of respiratory tract–related morbidity and mortality in children in developing countries. Pneumonia. Both bacteria and viruses can cause pneumonia. Bacterial pneumonia is often caused by Streptococcus pneumoniae (pneumococcus) or Haemophilus influenzae, mostly type b (Hib), and occasionally by Staphylococcus aureus or other streptococci. Just 8 to 12 of the many types of pneumococcus cause most cases of bacterial pneumonia, although the specific types may vary between adults and children and between geographic locations. Other pathogens, such as Mycoplasma pneumoniae and Chlamydia pneumoniae, cause atypical pneumonias. Their role as a cause of severe disease in children under five in developing countries is unclear. The burden of LRIs caused by Hib or S. pneumoniae is difficult to determine because current techniques to establish bacterial etiology lack sensitivity and specificity. The results of

pharyngeal cultures do not always reveal the pathogen that is the cause of the LRI. Bacterial cultures of lung aspirate specimens are often considered the gold standard, but they are not practical for field application. Vuori-Holopainen and Peltola’s (2001) review of several studies indicates that S. pneumoniae and Hib account for 13 to 34 percent and 1.4 to 42.0 percent of bacterial pneumonia, respectively, whereas studies by Adegbola and others (1994), Shann, Gratten, and others (1984), and Wall and others (1986) suggest that Hib accounts for 5 to 11 percent of pneumonia cases. Reduced levels of clinical or radiological pneumonia in clinical trials of a nine-valent pneumococcal conjugate vaccine provide an estimate of the vaccine-preventable disease burden (valency indicates the number of serotypes against which the vaccine provides protection; conjugate refers to conjugation of polysaccharides to a protein backbone). In a study in The Gambia, 37 percent of radiological pneumonia was prevented, reflecting the amount of disease caused by S. pneumoniae, and mortality was reduced by 16 percent (Cutts and others 2005). Upper respiratory tract colonization with potentially pathogenic organisms and aspiration of the contaminated secretions have been implicated in the pathogenesis of bacterial pneumonia in young children. Infection of the upper respiratory tract with influenza virus or RSVs has been shown to increase the binding of both H. influenzae (Jiang and others 1999) and S. pneumoniae (Hament and others 2004; McCullers and Bartmess 2003) to lining cells in the nasopharynx. This finding may explain why increased rates of pneumococcal pneumonia parallel influenza and RSV epidemics. A study in South Africa showed that vaccination with a nine-valent pneumococcal conjugate vaccine reduced the incidence of virus-associated pneumonia causing hospitalization by 31 percent, suggesting that pneumococcus plays an important role in the pathogenesis of virus-associated pneumonia (Madhi, Petersen, Madhi, Wasas, and others 2000). Entry of bacteria from the gut with spread through the bloodstream to the lungs has also been proposed for the pathogenesis of Gram-negative organisms (Fiddian-Green and Baker 1991), but such bacteria are uncommon etiological agents of pneumonia in immune-competent children. However, in neonates and young infants, Gram-negative pneumonia is not uncommon (Quiambao forthcoming). Viruses are responsible for 40 to 50 percent of infection in infants and children hospitalized for pneumonia in developing countries (Hortal and others 1990; John and others 1991; Tupasi and others 1990). Measles virus, RSVs, parainfluenza viruses, influenza type A virus, and adenoviruses are the most important causes of viral pneumonia. Differentiating between viral and bacterial pneumonias radiographically is difficult, partly because the lesions look similar and partly because bacterial superinfection occurs with influenza, measles, and RSV infections (Ghafoor and others 1990).

484 | Disease Control Priorities in Developing Countries | Eric A. F. Simoes, Thomas Cherian, Jeffrey Chow, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 90

In developing countries, the case-fatality rate in children with viral pneumonia ranges from 1.0 to 7.3 percent (John and others 1991; Stensballe, Devasundaram, and Simoes 2003), with bacterial pneumonia from 10 to 14 percent and with mixed viral and bacterial infections from 16 to 18 percent (Ghafoor and others 1990; Shann 1986). Bronchiolitis. Bronchiolitis occurs predominantly in the first year of life and with decreasing frequency in the second and third years. The clinical features are rapid breathing and lower chest wall indrawing, fever in one-third of cases, and wheezing (Cherian and others 1990). Inflammatory obstruction of the small airways, which leads to hyperinflation of the lungs, and collapse of segments of the lung occur. Because the signs and symptoms are also characteristic of pneumonia, health workers may find differentiating between bronchiolitis and pneumonia difficult. Two features that may help are a definition of the seasonality of RSVs in the locality and the skill to detect wheezing. RSVs are the main cause of bronchiolitis worldwide and can cause up to 70 or 80 percent of LRIs during high season (Simoes 1999; Stensballe, Devasundaram, and Simoes 2003). The recently discovered human metapneumovirus also causes bronchiolitis (Van den Hoogen and others 2001) that is indistinguishable from RSV disease. Other viruses that cause bronchiolitis include parainfluenza virus type 3 and influenza viruses. Influenza. Even though influenza viruses usually cause URIs in adults, they are increasingly being recognized as an important cause of LRIs in children and perhaps the second most important cause after RSVs of hospitalization of children with an ARI (Neuzil and others 2002). Although influenza is considered infrequent in developing countries, its epidemiology remains to be investigated thoroughly. The potential burden of influenza as a cause of death in children is unknown. Influenza virus type A may cause seasonal outbreaks, and type B may cause sporadic infection. Recently, avian influenza virus has caused infection, disease, and death in small numbers of individuals, including children, in a few Asian countries. Its potential for emergence in human outbreaks or a pandemic is unknown, but it could have devastating consequences in developing countries (Peiris and others 2004) and could pose a threat to health worldwide. New strains of type A viruses will almost certainly arise through mutation, as occurred in the case of the Asian and Hong Kong pandemics in the 1950s and 1960s.

HIV Infection and Pediatric LRIs Worldwide, 3.2 million children are living with HIV/AIDS, 85 percent of them in Sub-Saharan Africa (UNAIDS 2002). In southern Africa, HIV-related LRIs account for 30 to 40 percent of pediatric admissions and have a case-fatality rate of 15 to

34 percent, much higher than the 5 to 10 percent for children not infected with HIV (Bobat and others 1999; Madhi, Petersen, Madhi, Khoosal, and others 2000; Nathoo and others 1993; Zwi, Pettifior, and Soderlund 1999). Pneumocystis jiroveci and cytomegalovirus are important opportunistic infections in more than 50 percent of HIV-infected infants (Jeena, Coovadia, and Chrystal 1996; Lucas and others 1996). Gramnegative bacteria are also important in more than 70 percent of HIV-infected malnourished children (Ikeogu, Wolf, and Mathe 1997). Patient studies have confirmed the frequent association of these bacteria but added S. pneumoniae and S. aureus as important pathogens (Gilks 1993; Goel and others 1999). The first South African report on the overall burden of invasive pneumococcal disease reported a 41.7-fold increase in HIVinfected children compared with uninfected children (Farley and others 1994).

INTERVENTIONS Interventions to control ARIs can be divided into four basic categories: immunization against specific pathogens, early diagnosis and treatment of disease, improvements in nutrition, and safer environments (John 1994). The first two fall within the purview of the health system, whereas the last two fall under public health and require multisectoral involvement.

Vaccinations Widespread use of vaccines against measles, diphtheria, pertussis, Hib, pneumococcus, and influenza has the potential to substantially reduce the incidence of ARIs in children in developing countries. The effects of measles, diphtheria, and pertussis vaccines are discussed in chapter 20. The limited data on influenza in developing countries do not permit detailed analysis of the potential benefits of that vaccine. This chapter, therefore, focuses on the potential effects of Hib and pneumococcal vaccines on LRIs. Hib Vaccine. Currently three Hib conjugate vaccines are available for use in infants and young children. The efficacy of Hib vaccine in preventing invasive disease (mainly meningitis, but also pneumonia), has been well documented in several studies in industrialized countries (Black and others 1992; Booy and others 1994; Eskola and others 1990; Fritzell and Plotkin 1992; Heath 1998; Lagos and others 1996; Santosham and others 1991) and in one study in The Gambia (K. Mulholland and others 1997). All studies showed protective efficacy greater than 90 percent against laboratory-confirmed invasive disease, irrespective of the choice of vaccine. Consequently, all industrialized countries include Hib vaccine in their national immunization programs, resulting in the virtual elimination of Acute Respiratory Infections in Children | 485


invasive Hib disease because of immunity in those vaccinated and a herd effect in those not vaccinated. Available data from a few developing countries show a similar herd effect (Adegbola and others 1999; Wenger and others 1999). The initial promise and consequent general perception was that Hib vaccine was to protect against meningitis, but in developing countries the vaccine is likely to have a greater effect on preventing LRIs. The easily measured effect is on invasive disease, including bacteraemic pneumonia. The vaccine probably has an effect on nonbacteremic pneumonia, but this effect is difficult to quantify because of the lack of an adequate method for establishing bacterial etiology. In Bangladesh, Brazil, Chile, and The Gambia, Hib vaccine has been associated with a reduction of 20 to 30 percent in those hospitalized with radiographically confirmed pneumonia (de Andrade and others 2004; Levine and others 1999; K. Mulholland and others 1997; WHO 2004a). However, results of a large study in Lombok, Indonesia, were inconclusive with regard to the effect of Hib vaccine on pneumonia (Gessner and others 2005). Pneumococcal Vaccines. Two kinds of vaccines are currently available against pneumococci: a 23-valent polysaccharide vaccine (23-PSV), which is more appropriate for adults than children, and a 7-valent protein-conjugated polysaccharide vaccine (7-PCV). A 9-valent vaccine (9-PCV) has undergone clinical trials in The Gambia and South Africa, and an 11-valent vaccine (11-PCV) is being tried in the Philippines. Studies of the efficacy of the polysaccharide vaccine in preventing ARIs or ear infection in children in industrialized countries have shown conflicting results. Whereas some studies of this vaccine show no significant efficacy (Douglas and Miles 1984; Sloyer, Ploussard, and Howie 1981), studies from Finland show a generally protective effect against the serotypes contained in a 14-PSV (Douglas and Miles 1984; Karma and others 1980; Makela and others 1980). The efficacy was more marked in children over two years of age than in younger children. The only studies evaluating the effect of the polysaccharide vaccine in children in developing countries are a series of three trials conducted in Papua New Guinea (Douglas and Miles 1984; Lehmann and others 1991; Riley and others 1981; Riley, Lehmann, and Alpers 1991). The analysis of the pooled data from these trials showed a 59 percent reduction in LRI mortality in children under five at the time of the vaccination and a 50 percent reduction in children under two. On the basis of these and other studies, the investigators concluded that the vaccine had an effect on severe pneumonia. The greater-thanexpected efficacy in these trials was attributed to the greater contribution of the more immunogenic adult serotypes in pneumonia in Papua New Guinea (Douglas and Miles 1984; Riley, Lehmann, and Alpers 1991). On account of the poor immunogenicity of the antigens in the 23-PSV against prevalent pediatric serotypes, attention is now directed at more

immunogenic conjugate vaccines (Mulholland 1998; Obaro 1998; Temple 1991). The 7-PCV and 9-PCV have been evaluated for efficacy against invasive pneumococcal disease in four trials, which demonstrated a vaccine efficiency ranging from 71.0 to 97.4 percent (58 to 65 percent for HIV-positive children, among whom rates of pneumococcal disease are 40 times higher than in HIVnegative children) (Black and others 2000; Cutts and others 2005; Klugman and others 2003; O’Brien and others 2003). In the United States, the 7-PCV was included in routine vaccinations of infants and children under two in 2000. By 2001 the incidence of all invasive pneumococcal disease in this age group had declined by 69 percent and disease caused by the serotypes included in the vaccine and related serotypes had declined by 78 percent (Whitney and others 2003). Similar reductions were confirmed in a study in northern California (Black and others 2001). A slight increase in rates of invasive disease caused by serotypes of pneumococcus not included in the vaccine was observed, but it was not large enough to offset the substantial reduction in disease brought about by the vaccine. The studies also found a significant reduction in invasive pneumococcal disease in unvaccinated older age groups, especially adults age 20 to 39 and age 65 and older, suggesting that giving the vaccine to young children exerted a considerable herd effect in the community. Such an advantage is likely to occur even where the prevalence of adult HIV disease is high and pneumococcal disease may be recurrent and life threatening. The effect of the vaccine on pneumococcal pneumonia as such is difficult to define given the problems of establishing the bacterial etiology of pneumonia. Three studies have evaluated the effect of the vaccine on radiographic pneumonia (irrespective of the etiological agent) and have shown a 20.5 to 37.0 percent reduction in radiographically confirmed pneumonia (9.0 percent for HIV-positive individuals) (Black and others 2000; Cutts and others 2005; Klugman and others 2003). Several field trials have evaluated the efficacy of PCV against ear infection. Even though the vaccine resulted in a significant reduction in culture-confirmed pneumococcal otitis, no net reduction of ear infection was apparent among vaccinated children, probably because of an increase in the rates of otitis caused by types of pneumococci not covered by the vaccine, H. influenzae and Moraxella catarrhalis (Eskola and others 2001; Kilpi and others 2003). However, a trial in northern California showed that the vaccine had a protective effect against frequent ear infection and reduced the need for tympanostomy tube placement (Fireman and others 2003). Thus, a vaccine for ear infection may be beneficial in developing countries with high rates of chronic otitis and conductive hearing loss and should be evaluated by means of clinical trials. The most striking public health benefit of a vaccine in developing countries would be a demonstrable reduction in mortality. Although the primary outcome in The Gambia trial


was initially child mortality, it was changed to radiological pneumonia. Nevertheless, the trial showed a 16 percent (95 percent confidence level, 3 to 38) reduction in mortality. This trial was conducted in a rural area in eastern Gambia where access to round-the-clock curative care, including case management, is difficult to provide. This trial demonstrates that immunization delivered through outreach programs will have substantial health and economic benefits in such populations. One additional study evaluating the effect of an 11-PCV on radiological pneumonia is ongoing in the Philippines; results are expected in the second half of 2005.

Case Management The simplification and systematization of case management for early diagnosis and treatment of ARIs have enabled significant reductions in mortality in developing countries, where access to pediatricians is limited. WHO clinical guidelines for ARI case management (WHO 1991) use two key clinical signs: respiratory rate, to distinguish children with pneumonia from those without, and lower chest wall indrawing, to identify severe pneumonia requiring referral and hospital admission. Children with audible stridor when calm and at rest or such danger signs of severe disease as inability to feed also require referral. Children without these signs are classified as having an ARI but not pneumonia. Children showing only rapid breathing are treated for pneumonia with outpatient antibiotic therapy. Children who have a cough for more than 30 days are referred for further assessment of tuberculosis and other chronic infections. Pneumonia Diagnosis Based on Rapid Breathing. The initial guidelines for detecting pneumonia based on rapid breathing were developed in Papua New Guinea during the 1970s. In a study of 200 consecutive pediatric outpatients and 50 consecutive admissions (Shann, Hart, and Thomas 1984), 72 percent of children with audible crackles in the lungs had a respiratory rate of 50 or more breaths per minute, whereas only 19 percent of children without crackles breathed at such a rapid rate. Therefore, the initial WHO guidelines used a threshold of 50 breaths per minute, at or above which a child with a cough was regarded as having pneumonia. The major concern was the relatively low sensitivity of this approach, which could miss 25 to 40 percent of cases of pneumonia. A study in Vellore, India, found that sensitivity could be improved by lowering the threshold to 40 for children age 1 to 4, while keeping the 50 breaths per minute cutoff for infants age 2 months through 11 months (Cherian and others 1988). Subsequent studies showed that when these thresholds were used, sensitivity improved from 62 to 79 percent in the Philippines and from 65 to 77 percent in Swaziland, but at the same time, the specificity fell from 92 to 77 percent in the Philippines and 92 to 80 percent in Swaziland (Mulholland and

others 1992). On the basis of these and other data (Campbell, Byass, and others 1989; Kolstad and others 1997; Perkins and others 1997; Redd 1994; Simoes and others 1997; Weber and others 1997), WHO recommends a respiratory rate cutoff of 50 breaths per minute for infants age 2 through 11 months and 40 breaths per minute for children age 12 months to 5 years. Rapid breathing, as defined by WHO, detects about 85 percent of children with pneumonia, and more than 80 percent of children with potentially fatal pneumonia are probably successfully identified and treated using the WHO diagnostic criteria. Antibiotic treatment of children with rapid breathing has been shown to reduce mortality (Sazawal and Black 2003). The problem of the low specificity of the rapid breathing criterion is that some 70 to 80 percent of children who may not need antibiotics will receive them. Nevertheless, for primary care workers for whom diagnostic simplicity is essential, rapid breathing is clearly the most useful clinical sign. Pneumonia Diagnosis Based on Chest Wall Indrawing. Children are admitted to hospital with severe pneumonia when health workers believe that oxygen or parenteral antibiotics (antibiotics administered by other than oral means) are needed or when they lack confidence in mothers’ ability to cope. The rationale of parenteral antibiotics is to achieve higher levels of antibiotics and to overcome concerns about the absorption of oral drugs in ill children. The Papua New Guinea study (Shann, Hart, and Thomas 1984) used chest wall indrawing as the main indicator of severity, but studies from different parts of the world show large differences in the rates of indrawing because of variable definitions. Restriction of the term to lower chest wall indrawing, defined as inward movement of the bony structures of the chest wall with inspiration, has provided a better indicator of the severity of pneumonia and one that can be taught to health workers. It is more specific than intercostal indrawing, which frequently occurs in bronchiolitis. In a study in The Gambia (Campbell, Byass, and others 1989), a cohort of 500 children from birth to four years old was visited at home weekly for one year. During this time, 222 episodes of LRI (rapid breathing, any chest wall indrawing, nasal flaring, wheezing, stridor, or danger signs) were referred to the clinic. Chest indrawing was present in 62 percent of these cases, many with intercostal indrawing. If all children with any chest indrawing were hospitalized, the numbers would overwhelm pediatric inpatient facilities. Studies in the Philippines and Swaziland (E. Mulholland and others 1992) found that lower chest wall indrawing was more specific than intercostal indrawing for a diagnosis of severe pneumonia requiring hospital admission. In the Vellore study (Cherian and others 1988), lower chest wall indrawing correctly predicted 79 percent of children with an LRI who were hospitalized by a pediatrician. Acute Respiratory Infections in Children | 487


Antimicrobial Options for Oral Treatment of Pneumonia. The choice of an antimicrobial drug for treatment is based on the well-established finding that most childhood bacterial pneumonias are caused by S. pneumoniae or H. influenzae. A single injection of benzathine penicillin, although long lasting, does not provide adequate penicillin levels to eliminate H. influenzae. WHO has technical documents to help assess the relevant factors in selecting first- and second-line antimicrobials and comparisons of different antimicrobials in relation to their antibacterial activity, treatment efficacy, and toxicity (WHO 1990). The emergence of antimicrobial resistance in S. pneumoniae and H. influenzae is a serious concern. In some settings, in vitro tests show that more than 50 percent of respiratory isolates of both bacteria are resistant to co-trimoxazole, and penicillin resistance to S. pneumoniae is gradually becoming a problem worldwide. In pneumonia, unlike in meningitis, in vitro resistance of the pathogen does not always translate into treatment failure. Reports from Spain and South Africa suggest that pneumonia caused by penicillin-resistant S. pneumoniae can be successfully treated with sufficiently high doses of penicillin. Amoxicillin is concentrated in tissues and in macrophages, and drug levels are directly correlated with oral dosages. Therefore, higher doses than in the past—given twice a day—are now being used to successfully treat ear infections caused by penicillin-resistant S. pneumoniae. Amoxicillin is clearly better than penicillin for such infections. The situation with co-trimoxazole is less clear (Strauss and others 1998), and in the face of high rates of cotrimoxazole resistance, amoxicillin may be superior for children with severe pneumonia. Intramuscular Antibiotics for Treatment of Severe Pneumonia. Even though chloramphenicol is active against both S. pneumoniae and H. influenzae, its oral absorption is erratic in extremely sick children. Thus, the WHO guidelines recommend giving intramuscular chloramphenicol at half the daily dose before urgent referral of severe pneumonia cases. An additional rationale is that extremely sick children may have sepsis or meningitis that are difficult to rule out and must be treated immediately. Although intravenous chloramphenicol is superior to intramuscular chloramphenicol, the procedure can delay urgently needed treatment and adds to its cost. Investigators have questioned the adequacy and safety of intramuscular chloramphenicol. Although early studies suggested that adult blood levels after intramuscular administration were significantly less than those achieved after intravenous administration, the intramuscular route gained wide acceptance following clinical reports that confirmed its efficacy. Local complications of intramuscular chloramphenicol succinate are rare, unlike the earlier intramuscular preparations. Although concerns about aplastic anemia following

chloramphenicol are common, this complication is extremely rare in young children. There is no evidence that intramuscular chloramphenicol succinate is more likely to produce side effects than other forms and routes of chloramphenicol. Hypoxemia Diagnosis Based on WHO Criteria. The ARI case-management and integrated management of infant and childhood illness (IMCI) strategies depend on accurate referral of sick children to a hospital and correct inpatient management of LRI with oxygen or antibiotics. Hypoxemia (deficiency of oxygen in the blood) in children with LRI is a good predictor of mortality, the case-fatality rate being 1.2 to 4.6 times higher in hypoxemic LRI than nonhypoxemic LRI (Duke, Mgone, and Frank 2001; Onyango and others 1993), and oxygen reduces mortality. Thus, it is important to detect hypoxemia as early as possible in children with LRI to avert death. Although diagnoses of acute LRIs are achieved very easily by recognizing tachypnoea, and although severe LRI is associated with chest wall indrawing, the clinical recognition of hypoxemia is more problematic. Different sets of clinical rules have been studied to predict the presence of hypoxemia in children with LRI (Cherian and others 1988; Onyango and others 1993; Usen and others 1999). Although some clinical tools have a high sensitivity for detecting hypoxemia, a good number of hypoxemic children would still be missed using these criteria. Pulse oximetry is the best tool to quickly detect hypoxemia in sick children. However, pulse oximeters are expensive and have recurring costs for replacing probes, for which reasons they are not available in most district or even referral hospitals in developing countries. Treatment Guidelines. Current recommendations are for cotrimoxazole twice a day for five days for pneumonia and intramuscular penicillin or chloramphenicol for children with severe pneumonia. The problems of increasing resistance to cotrimoxazole and unnecessary referrals of children with any chest wall indrawing have led to studies exploring alternatives to the antibiotics currently used in ARI case management. One study indicated that amoxicillin and co-trimoxazole are equally effective for nonsevere pneumonia (Catchup Study Group 2002), though amoxicillin costs twice as much as co-trimoxazole. With respect to the duration of antibiotic treatment, studies in Bangladesh, India, and Indonesia indicate that three days of oral co-trimoxazole or amoxicillin are as effective as five days of either drug in children with nonsevere pneumonia (Agarwal and others 2004; Kartasasmita 2003). In a multicenter study of intramuscular penicillin versus oral amoxicillin in children with severe pneumonia, Addo-Yobo and others (2004) find similar cure rates. Because patients were treated with oxygen when needed for hypoxemia and were switched to other antibiotics if the treatment failed, this regimen is not appropriate for treating severe pneumonia in an outpatient setting.


WHO recommends administering oxygen, if there is ample supply, to children with signs and symptoms of severe pneumonia and, where supply is limited, to children with any of the following signs: inability to feed and drink, cyanosis, respiratory rate greater than or equal to 70 breaths per minute, or severe chest wall retractions (WHO 1993). Oxygen should be administered at a rate of 0.5 liter per minute for children younger than 2 months and 1 liter per minute for older children. Because oxygen is expensive and supply is scarce, especially in remote rural areas in developing countries, WHO recommends simple clinical signs to detect and treat hypoxemia. Despite those recommendations, a study of 21 first-level facilities and district hospitals in seven developing countries found that more than 50 percent of hospitalized children with LRI were inappropriately treated with antibiotics or oxygen (Nolan and others 2001)—and in several, oxygen was in short supply. Clearly, providing oxygen to hypoxemic babies is lifesaving, though no randomized trials have been done to prove it. Prevention and Treatment of Pneumonia in HIV-Positive Children. Current recommendations of a WHO panel for managing pneumonia in HIV-positive children and for prophylaxis of Pneumocystis jiroveci are as follows (WHO 2003): • Nonsevere pneumonia up to age 5 years. Oral co-trimoxazole should remain the first-line antibiotic, but oral amoxicillin should be used if it is affordable or if the child has been on co-trimoxazole prophylaxis. • Severe or very severe pneumonia. Normal WHO casemanagement guidelines should be used for children up to 2 months old. For children from 2 to 11 months, injectable antibiotics and therapy for Pneumocystis jiroveci pneumonia are recommended, as is starting Pneumocystis jiroveci pneumonia prophylaxis on recovery. For children age 12 to 59 months, the treatment consists of injectable antibiotics and therapy for Pneumocystis jiroveci pneumonia. Pneumocystis jiroveci pneumonia prophylaxis should be given for 15 months to children born to HIV-infected mothers; however, this recommendation has seldom been implemented.

COST-EFFECTIVENESS OF INTERVENTIONS Pneumonia is responsible for about a fifth of the estimated 10.6 million deaths per year of children under five. Where primary health care is weak, reducing mortality through public health measures is a high priority. As noted earlier, the available interventions are primary prevention by vaccination and secondary prevention by early case detection and management. The cost-effectiveness of Hib vaccines is discussed in chapter 20. We did not attempt an analysis of the cost-effectiveness

of pneumococcal vaccines, because global and regional estimates of the pneumococcal pneumonia burden are currently being developed and will not be available until later in 2005. In addition, current vaccine prices are relatively stable in developed countries, but the prices for low- and middle-income countries are expected to be substantially lower when vaccines are purchased through a global tender. We evaluate case-management intervention strategies for LRIs in children under five. Health workers who implement case management diagnose LRIs on the basis of fast breathing, lower chest wall indrawing, or selected danger signs in children with respiratory symptoms. Because this method does not distinguish between pneumonia and bronchiolitis, nor between bacterial and viral pneumonia, we group these conditions into the general category of “clinical pneumonia” (Rudan and others 2004). This approach assumes that a high proportion of clinical pneumonia is of bacterial origin and that health workers can considerably reduce case fatality through breathing rate diagnosis and timely administration of antibiotics (Sazawal and Black 2003). We calculated treatment costs by World Bank region using standardized input costs provided by the volume editors and costs published in the International Drug Price Indicator Guide (Management Sciences for Health 2005) and other literature (table 25.1). The analysis addresses four categories of case management, which are distinguished by the severity of the infection and the point of treatment: • nonsevere pneumonia treated by a community health worker • nonsevere pneumonia treated at a health facility • severe pneumonia treated at a hospital • very severe pneumonia treated at a hospital. Information about these categories of case management and their outcomes is drawn from a report on the methodology and assumptions used to estimate the costs of scaling up selected health interventions aimed at children (WHO and Child Adolescent Health forthcoming). We assumed a total of three follow-up visits for each patient treated by a community health worker rather than the twice-daily follow-ups for 10 days recommended by the report. We also assumed that all severe pneumonia patients receive an x-ray examination, rather than just 20 percent as suggested by the report. Moreover, we assumed a five-hour workday for a community health worker, the minimum workday required for community health workers under the Child Health and Survival initiative of the U.S. Agency for International Development (Bhattacharyya and others 2001). Table 25.2 presents region-specific estimates of average treatment costs per episode for the four case-management strategies. Because we considered the prices of tradable commodities such as drugs and oxygen to be constant across Acute Respiratory Infections in Children | 489


Table 25.1 Inputs for Case Management of Pneumonia in Low- and Middle-Income Countries Condition and intervention

Cost per unit (2001 US$)

Quantity

Percentage of patients

Nonsevere pneumonia at the community level Oral amoxicillin (15 mg/kg)

0.03/dose

3 doses/day for 3 days

100

6 doses

100

1.83/hour

1 initial 1-hour visit and 3 follow-up visits

100

0.03/dose

Acetaminophen (100-mg tablet)

0.001/dose

a

Community health worker hour

Nonsevere pneumonia at the facility level Oral amoxicillin (15 mg/kg)


100

Acetaminophen (100-mg tablet)

0.001/dose

6 doses

100

Oral salbutamol (2-mg tablet)

0.003/dose


Outpatient health facility visita

10

1.72/visit

1 visit

100

Oral amoxicillin (15 mg/kg)

0.03/dose


100

Nebulized salbutamol (2.5 mg)

0.13/dose


50

Injectable ampicillin (50 mg/kg)

0.21/dose


100

1 test

100

Severe pneumonia at the hospital level

X-raya

9.21/test b

Oxygen (1 liter/minute)

20/day

Inpatient hospital carea

10.8/day

3.5 days

50

3 days

100


100

Very severe pneumonia at the hospital level Oral amoxicillin (15 mg/kg)

0.03/dose

Nebulized salbutamol (2.5 mg)

0.13/dose


50

Injectable ampicillin (50 mg/kg)

0.21/dose


100

Injectable gentamicin (2.5 mg/kg)

0.14/dose

1 dose/day for 10 days

100

Oral prednisolone (1 mg/kg)

0.02/dose

1 dose/day for 3 days

a

5

9.21/test

1 test

100

Oxygen (1 liter/minute)b

20/day

5 days

100

Inpatient hospital carea

10.8/day

5 days

100

X-ray

Source: Management Sciences for Health 2005. Note: We assumed that the average patient weighs 12.5 kilograms. a. Provided by the volume editors. Input costs vary by region. b. Median costs obtained from Dobson 1991; Pederson and Nyrop 1991; Schneider 2001; WHO 1993.

Table 25.2 Average per Episode Treatment Costs of Case-Management Interventions for Acute Lower Respiratory Infection (2001 US$) Region Low- and middle-income countries East Asia and the Pacific

Nonsevere, community level

Nonsevere, facility level

Severe, hospital level

Very severe, hospital level

8

2

82

172

6

2

75

160


13

4

134

256


22

3

113

223

South Asia

5

2

66

148

Sub-Saharan Africa

7

2

64

145

Source: Authors’ calculations.

regions, regional variations were due to differences in hospital and health worker costs. Latin America and the Caribbean and the Middle East and North Africa had the highest treatment costs.

We calculated region-specific cost-effectiveness ratios (CERs) for a model population of 1 million in each region, following the standardized guidelines for economic analyses (see chapter 15 for details). Input variables included the treatment


costs detailed in tables 25.1 and 25.2, region-specific LRI morbidity rates, adapted from Rudan and others (2004), region-specific mortality rates and age structures provided by the volume editors, and region-specific urban to rural population ratios (World Bank 2002). The Europe and Central Asia region was excluded from this analysis because of a lack of incidence information. In the absence of region-specific information, we assumed uniform intervention effectiveness rates. Disability-adjusted life years are averted through reduced duration of illness and decreased mortality with treatment. We assumed an average illness duration of 8.5 days for those not treated and of 6.0 days for those treated. We used a case-fatality reduction of 36.0 percent on account of treatment (Sazawal and Black 2003) and a diagnosis specificity of 78.5 percent for patients diagnosed based on breath rate alone. The disability weight cotemporaneous with infection was 0.28. We did not consider disabilities caused by chronic sequelae of LRIs because it is unclear whether childhood LRI causes long-term impaired lung function or whether children who develop impaired lung function are more prone to infection (von Mutius 2001). Because a single year of these interventions yields only cotemporaneous benefits—because effectively treated individuals do not necessarily live to life expectancy given that they are likely to be infected again the following year—we calculated the cost-effectiveness of a five-year intervention. This time period enabled us to consider the case in which an entire cohort of newborns to four-year-olds avoids early childhood clinical pneumonia mortality because of the intervention and receives the benefit of living to life expectancy. Finally, this analysis considered only long-run marginal costs, which vary with the number of individuals treated, and did not include the fixed costs of initiating a program where none currently exists. Table 25.3 presents the region-specific CERs of the four case-management categories as well as the CER for providing all four categories to a population of 1 million people. Among all low- and middle-income countries, treatment of nonsevere clinical pneumonia was more cost-effective at the facility level

than at the community level, and of all four case-management categories, treatment of very severe clinical pneumonia at the hospital level was the least cost-effective. Treatment of nonsevere clinical pneumonia at the facility level was more costeffective than treatment by a community health worker because of the lower cost of a single visit to a health facility than of multiple visits by a health worker. The CER of providing all levels of treatment to all low- and middle-income countries was estimated at US$398 per disability-adjusted life year. Because we assumed that effectiveness rates were constant, regional variations in the CER for each case-management category were due only to variations in the intervention costs, and the relative cost-effectiveness rankings for the strategies was the same for all the regions. Variation in the CERs for providing all categories of care was also due to region-specific urban to rural population ratios. We assumed that all patients in urban areas seek treatment at the facility level or higher, whereas 80 percent of nonseverely ill patients in rural areas receive treatment at the community level and the remainder seek treatment at the facility level.

IMPLEMENTATION OF ARI CONTROL STRATEGIES: LESSONS OF EXPERIENCE The lessons of ARI prevention and control strategies that have been implemented by national programs include the vaccination and case-management strategies discussed below. Vaccine Strategies Hib vaccine was introduced into the routine infant immunization schedule in North America and Western Europe in the early 1990s. With the establishment of the Global Alliance for Vaccines and Immunization (GAVI) and the Vaccine Fund, progress is being made in introducing it in developing countries, although major hurdles remain. By 2002, only 84 of the 193 WHO member nations had introduced Hib vaccine. Five

Table 25.3 CERs of Case-Management Interventions for Pneumonia (2001US$/disability-adjusted life year) Region Low- and middle-income countries

Nonsevere, community level

Nonsevere, facility level

208

50

Severe, hospital level 2,916

Very severe, hospital level 6,144

Provision of all four interventions 398


439

91

6,511

13,945

900


547

424

14,719

28,106

1,941


733

180

6,810

13,438

1,060

South Asia

140

28

1,931

4,318

264

Sub-Saharan Africa

139

24

1,486

3,376

218

Source: Authors’ calculations.

Acute Respiratory Infections in Children | 491 ©2006 The International Bank for Reconstruction and Development / The World Bank 97

countries have since been approved for support from GAVI for Hib vaccine introduction in 2004–5. The United States added 7-PCV to the infant immunization program in 2000. Several other industrialized countries have plans to introduce the vaccine into their national immunization programs in 2005, whereas others recommend the use of the vaccine only in selected high-risk groups. In some of these last countries, the definition of high risk is quite broad and includes a sizable proportion of all infants. The currently licensed 7-PCV lacks certain serotypes important in developing countries,but the 9-PCV and 11-PCV would cover almost 80 percent of serotypes that cause serious disease worldwide. Despite the success of Hib vaccine in industrial countries and the generally appreciated importance of LRIs as a cause of childhood mortality, as a result of a number of interlinked factors, uptake in developing countries has been slow. Sustained use of the vaccine is threatened in a few of the countries that have introduced the vaccine. First, the magnitude of disease and death caused by Hib is not recognized in these countries, partly because of their underuse of bacteriological diagnosis (a result of the lack of facilities and resources). Second, because the coverage achieved with traditional Expanded Program on Immunization vaccines remains low in many countries, adding more vaccines has not been identified as a priority. Third, developing countries did not initiate efforts to establish the utility of the vaccine until after the vaccine had been licensed and used routinely for several years in industrialized countries. Consequently, Hib vaccination has been perceived as an intervention for rich countries. As a result of all these factors, actual demand for the vaccine has remained low, even when support has been available through GAVI and the Vaccine Fund. In 2004, the GAVI board commissioned a Hib task force to explore how best to support national efforts to make evidencebased decisions about introducing the Hib vaccine. On the basis of the task force’s recommendations, the GAVI board approved establishment of the Hib Initiative to support those countries wishing either to sustain established Hib vaccination or to explore whether introducing Hib vaccine should be a priority for their health systems. A consortium consisting of the Johns Hopkins Bloomberg School of Public Health, the London School of Hygiene and Tropical Medicine, the Centers for Disease Control and Prevention, and the WHO has been selected to lead this effort.

Case-Management Strategies Sazawal and Black’s (2003) meta-analysis of community-based trials of the ARI case-management strategy includes 10 studies that assessed its effects on mortality, 7 with a concurrent control group. The meta-analysis found an all-cause mortality reduction of 27 percent among neonates, 20 percent among infants, and 24 percent among children age one to four. LRI-

specific mortality was reduced by 42, 36, and 36 percent, respectively. These data clearly show that relatively simplified, but standardized, ARI case management can have a significant effect on mortality, not only from pneumonia, but also from other causes in children from birth to age four. Currently, the ARI case-management strategy has been incorporated into the IMCI strategy, which is now implemented in more than 80 countries (see chapter 63). Despite the huge loss of life to pneumonia each year, the promise inherent in simplified case management has not been successfully realized globally.One main reason is the underuse of health facilities in countries or communities in which many children die from ARIs. In Bangladesh, for example, 92 percent of sick children are not taken to appropriate health facilities (WHO 2002). In Bolivia, 62 percent of children who died had not been taken to a health care provider when ill (Aguilar and others 1998). In Guinea, 61 percent of sick children who died had not been taken to a health care provider (Schumacher and others 2002). Schellenberg and others’ (2003) study in Tanzania shows that children of poorer families are less likely to receive antibiotics for pneumonia than children of better-off families and that only 41 percent of sick children are taken to a health facility. Thus, studies consistently confirm that sick children, especially from poor families, do not attend health facilities. A number of countries have established large-scale, sustainable programs for treatment at the community level: • The Gambia has a national program for community-level management of pneumonia (WHO 2004b). • In the Siaya district of Kenya, a nongovernmental organization efficiently provides treatment by community health workers for pneumonia and other childhood diseases (WHO 2004b). • In Honduras, ARI management has been incorporated in the National Integrated Community Child Care Program, whereby community volunteers conduct growth monitoring, provide health education, and treat pneumonia and diarrhea in more than 1,800 communities (WHO 2004b). • In Bangladesh, the Bangladesh Rural Advancement Committee and the government introduced an ARI control program covering 10 subdistricts, using volunteer community health workers. Each worker is responsible for treating childhood pneumonia in some 100 to 120 households after a three-day training program. • In Nepal during 1986–89, a community-based program for management of ARIs and diarrheal disease was tested in two districts and showed substantial reductions in LRI mortality (Pandey and others 1989, 1991). As a result, the program was integrated into Nepal’s health services and is being implemented in 17 of the country’s 75 districts by female community health volunteers trained to detect and treat pneumonia.


• In Pakistan, the Lady Health Worker Program employs approximately 70,000 women, who work in communities providing education and management of childhood pneumonia to more than 30 million people (WHO 2004b).

RESEARCH AND DEVELOPMENT AGENDA The research and development agenda outlined below summarizes the priorities that have been established by advisory groups to the Initiative for Vaccine Research (vaccine intervention strategies) and the WHO Division of the Child and Adolescent Health (case-management strategies). Vaccine Intervention Strategies The GAVI task force on Hib immunization made a number of recommendations that vary depending on the country. Countries that have introduced Hib vaccine should focus on documenting its effect and should use the data to inform national authorities, development partners, and other agencies involved in public health to ensure sustained support to such vaccination programs. Countries eligible for GAVI support that have not yet introduced Hib vaccines are often hindered by a lack of local data and a lack of awareness of regional data. They can address these issues through subregional meetings at which country experts can pool data and review information from other countries. In addition, most of the countries need to carry out economic analyses that are based on a standardized instrument. Finally, all countries that face a high Hib disease burden need to develop laboratory facilities so that they can establish the incidence of Hib meningitis at selected sites. Countries in which the disease burden remains unclear may have limited capacity to document the occurrence of Hib disease using protocols that are based on surveillance for meningitis invasive disease. They will need to explore the possibilities of using alternative methods for measuring disease burden, including the use of vaccine-probe studies. On the basis of experience with introducing Hib and hepatitis B vaccines, GAVI took a proactive approach and in 2003 established an initiative based at the Johns Hopkins School of Public Health in Baltimore to implement an accelerated development and introduction program for pneumococcal vaccines (the PneumoADIP; see http://www.preventpneumonia.org). The program’s intent is to establish and communicate the value of pneumococcal vaccines and to support their delivery. Establishing the value of the vaccine involves developing local evidence about the burden of disease and the vaccines’ potential effect on public health. This effort can be accomplished through enhanced disease surveillance and relevant clinical trials in a selected number of lead countries. Once established, the evidence base will be communicated to decision makers and key opinion leaders to ensure that data-driven decisions are made. Once the cost-effectiveness of routine vaccination is

established, delivery systems will have to be established, and countries will need financial support so that the vaccines can be introduced into their immunization programs. These activities are being initiated before the launch of vaccine formulations designed for use in developing countries, so as to inform capacity planning, product availability, and pricing.

Case-Management Strategies In 2003, WHO’s Division of Child and Adolescent Health convened a meeting to review data and evidence from recent ARI case-management studies and to suggest the following revisions to case-management guidelines and future research priorities: • Nonsevere pneumonia: — Improve the specificity of clinical diagnostic criteria. — Reassess WHO’s current recommended criteria for detecting and managing treatment failure, given the high rates of therapy failure. — Reanalyze data from short-course therapy studies to better identify determinants of treatment failure. — Carry out placebo-controlled trials among children presenting with wheezing and pneumonia in selected settings that have a high prevalence of wheezing to determine whether such children need antibiotics. • Severe pneumonia: In a randomized clinical trial in a controlled environment, Addo-Yobo and others (2004) showed that oral amoxicillin is as effective as parenteral penicillin or ampicillin; however, the following actions need to be undertaken before it can be recommended on a general basis: — Analyze data on exclusions from the trial. — Identify predictors that may help distinguish children who require hospitalization and who subsequently deteriorate. — Reassess WHO’s current recommended treatment failure criteria for severe pneumonia, given the overall high rates of therapy failure. — Conduct descriptive studies in a public health setting in several centers worldwide, to evaluate the clinical outcomes of oral amoxicillin in children age 2 to 59 months who present with lower chest wall indrawing. — Document the effectiveness of WHO’s treatment guidelines for managing children with pneumonia and HIV infection. • LRI deaths: — To help develop more effective interventions to reduce LRI mortality, study the epidemiology of LRI deaths in various regions in detail, using routine and advanced laboratory techniques. • Oxygen therapy: — Carry out studies to show the effectiveness of oxygen for managing severe respiratory infections. Acute Respiratory Infections in Children | 493


— Collect baseline information about the availability and delivery of oxygen and its use in hospital settings in lowincome countries. — Explore the utility of pulse oximetry for optimizing oxygen therapy in various clinical settings. — Undertake studies to improve the specificity of clinical signs in the overlapping signs and symptoms of malaria and pneumonia. — Study rapid diagnostic tests for malaria to assess their effectiveness in differentiating between malaria and pneumonia. — Examine the effect of widespread use of cotrimoxazole on sulfadoxine-pyrimethamine resistance to Plasmodium falciparum. • Etiology: Data on the etiology of pneumonia in children are somewhat out of date, and new etiological studies are needed that use modern technology to identify pathogens.

CONCLUSIONS: PROMISES AND PITFALLS The evidence clearly shows that the WHO case-management approach and the wider use of available vaccines will reduce ARI mortality among young children by half to two-thirds. The systematic application of simplified case management alone, the cost of which is low enough to be affordable by almost any developing country, will reduce ARI mortality by at least onethird. The urgent need is to translate this information into actual implementation. The case-management strategy has to be applied and prospectively evaluated so that emerging problems of antimicrobial resistance, reduced efficacy of current treatment with the recommended antimicrobials, or emergence of unexpected pathogens can be detected early and remedial steps can be taken rapidly. If community-level action by health workers is supplemented by the introduction of the IMCI strategy at all levels of primary care, then both applying and evaluating this strategy will be easier. Such synergy may also help in gathering information that will help further fine-tune clinical signs, so that even village health workers can better distinguish bronchiolitis and wheezing from bacterial pneumonia. The criticism that the case-management steps may result in overuse of antimicrobials should be countered by documenting their current overuse and incorrect use by doctors and other health workers. Although there is a resurgent interest in basing interventions at the community level, our analysis suggests that doing so may not be cost-effective. Indeed, ARI case management at the first-level facility may still be the most cost-effective when coupled with better care-seeking behavior interventions. The international medical community is only beginning to appreciate the potential benefits of Hib and pneumococcal vaccines. They are currently expensive compared with Expanded Program on Immunization vaccines, but the price of Hib

vaccine may fall with the entry of more manufacturers into the market in the next few years. Nevertheless, convincing evidence of the vaccines’ cost-effectiveness is required to facilitate national decisions on introducing the vaccine and using it sustainedly. In low-income countries, positive cost-benefit and cost-effectiveness ratios alone appear to be insufficient to enable the introduction of these vaccines into national immunization programs.

REFERENCES Addo-Yobo, E., N. Chisaka, M. Hassan, P. Hibberd, J. M. Lozano, P. Jeena, and others. 2004. “Oral Amoxicillin versus Injectable Penicillin for Severe Pneumonia in Children Aged 3 to 59 Months: A Randomised Multicentre Equivalency Study.” Lancet 364 (9440): 1141–48. Adegbola, R. A., A. G. Falade, B. E. Sam, M. Aidoo, I. Baldeh, D. Hazlett, and others. 1994. “The Etiology of Pneumonia in Malnourished and Well-Nourished Gambian Children.” Pediatric Infectious Disease Journal 13 (11): 975–82. Adegbola, R. A., S. O. Usen, M. Weber, N. Lloyd-Evans, K. Jobe, K. Mulholland, and others. 1999. “Haemophilus influenzae Type B Meningitis in The Gambia after Introduction of a Conjugate Vaccine.” Lancet 354 (9184): 1091–92. Agarwal, G., S. Awasthi, S. K. Kabra, A. Kaul, S. Singhi, and S. D. Walter (ISCAP Study Group). 2004. “Three-Day versus Five-Day Treatment with Amoxicillin for Non-Severe Pneumonia in Young Children: A Multicentre Randomised Controlled Trial.” British Medical Journal 328: 791. http://bmj.bmjjournals.com/cgi/content/full/328/7443/791. Aguilar, A. M., R. Alvarado, D. Cordero, P. Kelly, A. Zamora, and R. Salgado. 1998. Mortality Survey in Bolivia: The Final Report—Investigating and Identifying the Causes of Death for Children under Five.Vienna,VA: Basic Support for Institutionalizing Child Survival Project. Berman, S. 1995a. “Otitis Media in Children” New England Journal of Medicine 332 (23): 1560–65. . 1995b. “Otitis Media in Developing Countries.” Pediatrics 96 (1, part 1): 126–31. Bhattacharyya, K., P. Winch, K. LeBan, and M. Tien. 2001. “Community Health Worker Incentives and Disincentives: How They Affect Motivation, Retention, and Sustainability.” Basic Support for Institutionalizing Child Survival Project for the U.S. Agency for International Development, Arlington, VA. Black, R. E., S. S. Morris, and J. Bryce. 2003. “Where and Why Are 10 Million Children Dying Every Year?” Lancet 361 (9376): 2226–34. Black, S. B., H. R. Shinefield, B. Fireman, E. Lewis, P. Ray, J. R. Hansen, and others (Northern California Kaiser Permanente Vaccine Study Center Group). 2000. “Efficacy, Safety, and Immunogenicity of Heptavalent Pneumococcal Conjugate Vaccine in Children.” Pediatric Infectious Disease Journal 19 (3): 187–95. Black, S. B., H. R. Shinefield, B. Fireman, and R. Hiatt. 1992. “Safety, Immunogenicity, and Efficacy in Infancy of Oligosaccharide Conjugate Haemophilus influenzae Type B Vaccine in a United States Population: Possible Implications for Optimal Use.” Journal of Infectious Diseases 165 (Suppl. 43): S139–43. Black, S. B., H. R. Shinefield, J. Hansen, L. Elvin, D. Laufer, and F. Malinoski. 2001. “Postlicensure Evaluation of the Effectiveness of Seven-Valent Pneumococcal Conjugate Vaccine.” Pediatric Infectious Disease Journal 20 (12): 1105–7. Bobat, R., H. M. Coovadia, D. Moodley, and A. Coutsoudis. 1999. “Mortality in a Cohort of Children Born to HIV–1 Infected Women from Durban, South Africa.” South African Medical Journal 89 (6): 646–48.


Booy, R., S. Hodgson, L. Carpenter, R. T. Mayon-White, M. P. Slack, J. A. Macfarlane, and others. 1994. “Efficacy of Haemophilus influenzae Type B Conjugate Vaccine PRP-T.” Lancet 344 (8919): 362–66. Bryce, J., C. Boschi-Pinto, K. Shibuya, R. E. Black, and the WHO Child Health Epidemiology Reference Group. 2005. “WHO Estimates of the Causes of Death in Children.” Lancet 365: 1147–52. Campbell, H., J. R. M. Armstrong, and P. Byass. 1989.“Indoor Air Pollution in Developing Countries and Acute Respiratory Infection in Children.” Lancet 1 (8645): 1012. Campbell, H., P. Byass, A. C. Lamont, I. M. Forgie, K. P. O’Neill, N. LloydEans, and B. M. Greenwood. 1989. “Assessment of Clinical Criteria for Identification of Severe Acute Lower Respiratory Tract Infections in Children.” Lancet 1 (8633): 297–99. Catchup Study Group. 2002. “Clinical Efficacy of Co-Trimoxazole versus Amoxicillin Twice Daily for Treatment of Pneumonia: A Randomized Controlled Clinical Trial in Pakistan.” Archives of Disease in Childhood 86: 113–18. Cherian, T., T. J. John, E. A. Simoes, M. C. Steinhoff, and M. John. 1988. “Evaluation of Simple Clinical Signs for the Diagnosis of Acute Lower Respiratory Tract Infection.” Lancet 2: 125–28. Cherian, T., E. A. Simoes, M. C. Steinhoff, K. Chitra, M. John, P. Raghupathy, and others. 1990. “Bronchiolitis in Tropical South India.” American Journal of Diseases of Children 144 (9): 1026–30. Cutts, F. T., S. M. A. Zaman, G. Enwere, S. Jaffar, O. S. Levine, J. B. Okoko, and others. 2005. “Efficacy of Nine-Valent Pneumococcal Conjugate Vaccine against Pneumonia and Invasive Pneumococcal Disease in The Gambia: Randomised, Double-Blind, Placebo-Controlled Trial.” Lancet 365 (9465): 1139–46. de Andrade, A. L., J. G. de Andrade, C. M. Martelli, S. A. Silva, R. M. de Oliveira, M. S. Costa, and others. 2004. “Effectiveness of Haemophilus influenzae B Conjugate Vaccine on Childhood Pneumonia: A CaseControl Study in Brazil.” International Journal of Epidemiology 33 (1): 173–81. Denny, F. W. Jr. 1995. “The Clinical Impact of Human Respiratory Virus Infections.” American Journal of Respiratory and Critical Care Medicine 152 (4, part 2): S4–12. Dobson,M.1991.“Oxygen Concentrators Offer Cost Savings for Developing Countries: A Study Based on New Guinea.” Anaesthesia 146: 217–19. Douglas, R. M., and H. B. Miles. 1984. “Vaccination against Streptococcus pneumoniae in Childhood: Lack of Demonstrable Benefit in Young Australian Children.” Journal of Infectious Diseases 149 (6): 861–69. Duke T, J. Mgone, and D. Frank. 2001. “Hypoxaemia in children with severe pneumonia in Papua New Guinea.” International Journal of Tuberculosis and Lung Disease 5: 511–19. Eskola, J., H. Kayhty, A. K. Takala, H. Peltola, P. R. Ronnberg, E. Kela, and others. 1990. “A Randomized, Prospective Field Trial of a Conjugate Vaccine in the Protection of Infants and Young Children against Invasive Haemophilus influenzae Type B Disease.” New England Journal of Medicine 323 (20): 1381–87. Eskola, J., T. Kilpi, A. Palmu, J. Jokinen, J. Haapakoski, E. Herva, and others. 2001. “Efficacy of a Pneumococcal Conjugate Vaccine against Acute Otitis Media.” New England Journal of Medicine 344 (6): 403–9. Farley, J. J., J. C. King, P. Nair, S. E. Hines, R. L. Tressier, and P. E. Vink. 1994. “Invasive Pneumococcal Disease among Infected and Uninfected Children of Mothers with Human Immunodeficiency Virus Infection.” Journal of Pediatrics 124: 853–58. Fiddian-Green, R. G., and S. Baker. 1991. “Nosocomial Pneumonia in the Critically Ill: Product of Aspiration or Translocation?” Critical Care Medicine 19: 763–69. Fireman, B., S. B. Black, H. R. Shinefield, J. Lee, E. Lewis, and P. Ray. 2003. “Impact of the Pneumococcal Conjugate Vaccine on Otitis Media.” Pediatric Infectious Disease Journal 22 (1): 10–16.

Fritzell, B., and S. Plotkin. 1992. “Efficacy and Safety of a Haemophilus influenzae Type B Capsular Polysaccharide-Tetanus Protein Conjugate Vaccine.” Journal of Pediatrics 121 (3): 355–62. Gessner B. D., A. Sutanto, M. Linehan, I. G. Djelantik, T. Fletcher, I. K. Gerudug, and others. 2005. “Incidences of Vaccine-Preventable Haemophilus Influenzae Type B Pneumonia and Meningitis in Indonesian Children: Hamlet-Randomised Vaccine-Probe Trial.” Lancet 365 (9453): 43–52. Ghafoor, A., N. K. Nomani, Z. Ishaq, S. Z. Zaidi, F. Anwar, M. I. Burney, and others. 1990. “Diagnoses of Acute Lower Respiratory Tract Infections in Children in Rawalpindi and Islamabad, Pakistan.” Reviews of Infectious Diseases 12 (Suppl. 8): S907–14. Gilks, C. F. 1993. “Pneumococcal Disease and HIV Infection.” Annals of Internal Medicine 118: 393–94. Goel, A., L. Bamford, D. Hanslo, and G. Hussey. 1999. “Primary Staphylococcal Pneumonia in Young Children: A Review of 100 Cases.” Journal of Tropical Pediatrics 45 (4): 233–36. Hament, J. M., P. C. Aerts, A. Fleer, H. Van Dijk, T. Harmsen, J. L. Kimpen, and T. F. Wolfs. 2004. “Enhanced Adherence of Streptococcus pneumoniae to Human Epithelial Cells Infected with Respiratory Syncytial Virus.” Pediatric Research 55 (6): 972–78. Heath, P. T. 1998. “Haemophilus influenzae Type B Conjugate Vaccines: A Review of Efficacy Data.” Pediatric Infectious Disease Journal 17 (9 Suppl.): S117–22. Hortal, M., C. Mogdasy, J. C. Russi, C. Deleon, and A. Suarez. 1990. “Microbial Agents Associated with Pneumonia in Children from Uruguay.” Reviews of Infectious Diseases 12 (Suppl. 8): S915–22. Ikeogu, M. O., B. Wolf, and S. Mathe. 1997. “Pulmonary Manifestations in HIV Seropositive and Malnourished Children in Zimbabwe.” Archives of Disease in Childhood 76: 124–28. Jeena, P. M., H. M. Coovadia, and V. Chrystal. 1996. “Pneumocystis carinii and cytomegalo Virus Infections in Severely Ill HIV-Infected African Infants.” Annals of Tropical Paediatrics 16: 361–68. Jiang, Z., N. Nagata, E. Molina, L. O. Bakaletz, H. Hawkins, and J. A. Patel. 1999. “Fimbria-Mediated Enhanced Attachment of Nontypeable Haemophilus influenzae to Respiratory Syncytial Virus-Infected Respiratory Epithelial Cells.” Infection and Immunity 67: 187–92. John, T. J. 1994. “Who Determines National Health Policies?” In Vaccination and World Health: Fourth Annual Public Health Forum of the London School of Hygiene and Tropical Medicine, ed. F. T. Cutts and P. G. Smith, 205–11. Chichester, U.K.: John Wiley. John, T. J., T. Cherian, M. C. Steinhoff, E. A. Simoes, and M. John. 1991. “Etiology of Acute Respiratory Infections in Children in Tropical Southern India.” Reviews of Infectious Diseases 13 (Suppl. 6): S463–69. Kamath, K. R., R. A. Feldman, P. S. S. Rao, and J. K. Webb. 1969. “Infection and Disease in a Group of South Indian Families.” American Journal of Epidemiology 89: 375–83. Karma, P., J. Luotonen, M. Timonen, S. Pontynen, J. Pukander, E. Herva, and others. 1980. “Efficacy of Pneumococcal Vaccination against Recurrent Otitis Media: Preliminary Results of a Field Trial in Finland.” Annals of Otology, Rhinology, and Laryngology Suppl. 89 (3, part 2): 357–62. Kartasasmita, C. 2003. “Three versus Five Days Oral Cotrimoxazole for Nonsevere Pneumonia.” Paper presented at the World Health Organization Consultative Meeting on Reviewing Current Research and Management of Acute Respiratory Infections, Geneva, September 29– October 1. Kilpi, T., H. Ahman, J. Jokinen, K. S. Lankinen, A. Palmu, H. Savolainen, and others. 2003. “Protective Efficacy of a Second Pneumococcal Conjugate Vaccine against Pneumococcal Acute Otitis Media in Infants and Children: Randomized, Controlled Trial of a Seven-Valent Pneumococcal Polysaccharide-Meningococcal Outer Membrane Protein Complex Conjugate Vaccine in 1,666 Children.” Clinical Infectious Diseases 37 (9): 1155–64. Acute Respiratory Infections in Children | 495


Klugman, K. P., S. A. Madhi, R. E. Huebner, R. Kohberger, N. Mbelle, N. Pierce, and others. 2003. “A Trial of a 9-Valent Pneumococcal Conjugate Vaccine in Children with and Those without HIV Infection.” New England Journal of Medicine 349 (14): 1341–48.

Neuzil, K. M., Y. Zhu, M. R. Griffin, K. M. Edwards, J. M. Thompson, S. J. Tollefson, and P. F. Wright. 2002. “Burden of Interpandemic Influenza in Children Younger Than 5 Years: A 25-Year Prospective Study.” Journal of Infectious Diseases 185: 147–52.

Kolstad, P. R., G. Burnham, H. D. Kalter, N. Kenya-Mugisha, and R. E. Black. 1997. “The Integrated Management of Childhood Illness in Western Uganda.” Bulletin of the World Health Organization 75 (Suppl. 1): 77–85.

Nolan T., P. Angos, A. J. Cunha, L. Muhe, S. Qazi, E. A. Simoes, and others. 2001. “Quality of Hospital Care for Seriously Ill Children in LessDeveloped Countries.” Lancet 357 (9250): 106–10.

Lagos, R., I. Horwitz, J. Toro, O. San Martin, P. Abrego, C. Bustamante, and others. 1996. “Large Scale, Postlicensure, Selective Vaccination of Chilean Infants with PRP-T Conjugate Vaccine: Practicality and Effectiveness in Preventing Invasive Haemophilus influenzae Type B Infections.” Pediatric Infectious Disease Journal 15: 216–22. Lehmann, D., T. F. Marshall, I. D. Riley, and M. P. Alpers. 1991. “Effect of Pneumococcal Vaccine on Morbidity from Acute Lower Respiratory Tract Infections in Papua New Guinean Children.” Annals of Tropical Paediatrics 11 (3): 247–57. Levine, O. S., R. Lagos, A. Munoz, J. Villaroel, A. M. Alvarez, P. Abrego, and others. 1999. “Defining the Burden of Pneumonia in Children Preventable by Vaccination against Haemophilus influenzae Type B.” Pediatric Infectious Disease Journal 18 (12): 1060–64.

Obaro, S., A. Leach, and K. W. McAdam. 1998. “Use of Pneumococcal Polysaccharide Vaccine in Children,” Lancet 352 (9127): 575. O’Brien, K. L., L. H. Moulton, R. Reid, R. Weatherholtz, J. Oski, L. Brown, and others. 2003. “Efficacy and Safety of Seven-Valent Conjugate Pneumococcal Vaccine in American Indian Children: Group Randomised Trial.” Lancet 362 (9381): 355–61. Onyango F. E., M. C. Steinhoff, E. M. Wafula, S. Wariua, J. Musia, and J. Kitonyi. 1993. “Hypoxaemia in Young Kenyan Children with Acute Lower Respiratory Infection.”British Medical Journal 306 (6878): 612–15. Pandey, M. R., N. M. Daulaire, E. S. Starbuck, R. M. Houston, and K. McPherson. 1991. “Reduction in Total Under-Five Mortality in Western Nepal through Community-Based Antimicrobial Treatment of Pneumonia.” Lancet 338 (8773): 993–97.

Lucas, S. B., C. S. Peacock, A. Hounnou, K. Brattegaard, K. Koffi, M. Honde, and others. 1996. “Disease in Children Infected with HIV in Abidjan, Côte d’Ivoire.” British Medical Journal 312: 335–38.

Pandey, M. R., P. R. Sharma, B. B. Gubhaju, G. M. Shakya, R. P. Neupane, A. Gautam, and others. 1989. “Impact of a Pilot Acute Respiratory Infection (ARI) Control Programme in a Rural Community of the Hill Region of Nepal.” Annals of Tropical Paediatrics 9 (4): 212–20.

Madhi, S. A., K. P. Klugman, and the Vaccine Trialist Group. 2004. “A Role for Streptococcus pneumoniae in Virus-Associated Pneumonia.” Nature Medicine 10 (8): 811–13.

Pederson, J., and M. Nyrop. 1991. “Anaesthetic Equipment for a Developing Country.” British Journal of Anaesthesia 66: 264–70.

Madhi, S. A., K. Petersen, A. Madhi, M. Khoosal, and K. P. Klugman. 2000. “Increased Disease Burden and Antibiotic Resistance of Bacteria Causing Severe Community Acquired Lower Respiratory Tract Infections in Human Immunodeficiency Virus 1 Infected Children.” Clinical Infectious Diseases 31: 170–76. Madhi, S. A., K. Petersen, A. Madhi, A. Wasas, and K. P. Klugman. 2000. “Impact of Human Immunodeficiency Virus Type 1 on the Disease Spectrum of Streptococcus pneumoniae in South African Children.” Pediatric Infectious Disease Journal 19 (12): 1141–47.

Peiris, J. S., W. C. Yu, C. W. Leung, C. Y. Cheung, W. F. Ng, J. M. Nicholls, and others. 2004. “Re-emergence of Fatal Human Influenza A Subtype H5N1 Disease.” Lancet 363 (9409): 617–19. Perkins, B. A., J. R. Zucker, J. Otineo, H. S. Jafari, L. Paxton, S. C. Redd, and others. 1997. “Evaluation of an Algorithm for Integrated Management of Childhood Illness in an Area of Kenya with High Malaria Transmission.” Bulletin of the World Health Organization 75 (Suppl. 1): 33–42.

Makela, P. H., M. Sibakov, E. Herva, J. Henrichsen, J. Luotonen, M. Timonen, and others. 1980. “Pneumococcal Vaccine and Otitis Media.” Lancet 2 (8194): 547–51.

Quiambao, B. P., E. A. Simoes, E. Abucejo-Ladesma, L. S. Gozum, S. P. Lupisan, L. T. Sombrero, and P. J. Ruutu (ARIVAC Consortium). Forthcoming. “Serious Community Acquired Pediatric Infections in Rural Asia (Bohol Island, Philippines).” Pediatric Infectious Disease Journal.

Management Sciences for Health. 2005. International Drug Price Indicator Guide. Cambridge, MA: Management Sciences for Health.

Redd, S. 1994. “Diagnosis and Management of Acute Respiratory Infections in Lesotho.” Health Policy and Management 5: 255–60.

McCullers, J.A., and K. C. Bartmess. 2003.“Role of Neuraminidase in Lethal Synergism between Influenza Virus and Streptococcus pneumoniae.” Journal of Infectious Diseases 187: 1000–9.

Riley, I. D., F. A. Everingham, D. E. Smith, and R. M. Douglas. 1981. “Immunization with a Polyvalent Pneumococcal Vaccine: Effect of Respiratory Mortality in Children Living in the New Guinea Highlands.” Archives of Disease in Childhood 56 (5): 354–57.

Monto, A. S., and B. M. Ullman. 1974. “Acute Respiratory Illness in an American Community: The Tecumseh Study.” Journal of the American Medical Association 227 (2): 164–69. Mulholland, E. K., E. A. Simoes, M. O. Castales, E. J. McGrath, E. M. Manalac, and S. Gove. 1992. “Standardized Diagnosis of Pneumonia in Developing Countries.” Pediatric Infectious Disease Journal 11: 77–81. Mulholland, K., S. Hilton, R. Adegbola, S. Usen, A. Oparaugo, C. Omosigho, and others. 1997. “Randomised Trial of Haemophilus influenzae Type-B Tetanus Protein Conjugate Vaccine for Prevention of Pneumonia and Meningitis in Gambian Infants.” Lancet 349 (9060): 1191–97. Mulholland, K., S. Usen, R. Adegbola, and M. Weber. 1998. “Use of Pneumococcal Polysaccharide Vaccine in Children.” Lancet 352 (9127): 575–76. Nathoo, K. J., F. K. Nkrumah, D. Ndlovu, D. Nhembe, J. Pirie, and H. Kowo. 1993. “Acute Lower Respiratory Tract Infection in Hospitalized Children in Zimbabwe.” Annals of Tropical Paediatrics 13: 253–61.

Riley, I. D., D. Lehmann, and M. P. Alpers. 1991. “Pneumococcal Vaccine Trials in Papua New Guinea: Relationships between Epidemiology of Pneumococcal Infection and Efficacy of Vaccine.” Reviews of Infectious Diseases 13 (Suppl. 6): S535–41. Rudan, I., L. Tomaskovic, C. Boschi-Pinto, and H. Campbell (WHO Child Health Epidemiology Reference Group). 2004. “Global Estimate of the Incidence of Clinical Pneumonia among Children under Five Years of Age.” Bulletin of the World Health Organization 82 (12): 895–903. Santosham, M., M. Wolff, R. Reid, M. Hohenboken, M. Bateman, J. Goepp, and others. 1991. “The Efficacy in Navajo Infants of a Conjugate Vaccine Consisting of Haemophilus influenzae Type B Polysaccharide and Neisseria meningitidis Outer-Membrane Protein Complex.” New England Journal of Medicine 324 (25): 1767–72. Sazawal, S., and R. E. Black. 2003. “Pneumonia Case Management Trials Group: Effect of Pneumonia Case Management on Mortality in


Neonates, Infants, and Preschool Children—A Meta-analysis of Community-Based Trials.” Lancet Infectious Diseases 3: 547–56. Schellenberg, J. A., C. G. Victora, A. Mushi, D. de Savigny, D. Schellenberg, H. Mshinda, and others. 2003. “Inequities among the Very Poor: Health Care for Children in Rural Southern Tanzania.” Lancet 361 (9357): 561–66.

Wall, R. A., P. T. Corrah, D. C. Mabey, and B. M. Greenwood. 1986. “The Etiology of Lobar Pneumonia in The Gambia.” Bulletin of the World Health Organization 64 (4): 553–58.

Schneider, G. 2001.“Oxygen Supply in Rural Africa: A Personal Experience.” International Journal of Tuberculosis and Lung Disease 5 (6): 524–26.

Weber, M. W., E. K. Mulholland, S. Jaffar, H. Troedsson, S. Gove, and B. M. Greenwood. 1997. “Evaluation of an Algorithm for the Integrated Management of Childhood Illness in an Area with Seasonal Malaria in The Gambia.” Bulletin of the World Health Organization 75 (Suppl. 1): 25–32.

Schumacher, R., E. Swedberg, M. O. Diallo, D. R. Keita, H. Kalter, and O. Pasha. 2002. Mortality Study in Guinea: Investigating the Causes of Death in Children under Five. Arlington, VA: Save the Children and the Basic Support for Institutionalizing Child Survival Project.

Wenger, J. D., J. DiFabio, J. M. Landaverde, O. S. Levine, and T. Gaafar. 1999. “Introduction of Hib Conjugate Vaccines in the Nonindustrialized World: Experience in Four ‘Newly Adopting’ Countries.” Vaccine 18 (7–8): 736–42.

Shann, F. 1986. “Etiology of Severe Pneumonia in Children in Developing Countries.” Pediatric Infectious Disease 5 (2): 247–52.

Wenger, J. D., and M. M. Levine, eds. 1997. Epidemiological Impact of Conjugate Vaccine on Invasive Disease Caused by Haemophilus influenzae Type B. New York: Marcel Dekker.

Shann, F., M. Gratten, S. Germer, V. Linnemann, D. Hazlett, and R. Payne. 1984. “Aetiology of Pneumonia in Children in Goroka Hospital, Papua New Guinea.” Lancet 2 (8402): 537–41. Shann, F., K. Hart, and D. Thomas. 1984. “Acute Lower Respiratory Tract Infections in Children: Possible Criteria for Selection of Patients for Antibiotic Therapy and Hospital Admission.” Bulletin of the World Health Organization 62: 749–51. Simoes, E. A. 1999. “Respiratory Syncytial Virus Infection.” Lancet 354 (9181): 847–52. Simoes, E. A., T. Desta, T. Tessema, T. Gerbresellassie, M. Dagnew, and S. Gove. 1997. “Performance of Health Workers after Training in Integrated Management of Childhood Illness in Gondar, Ethiopia.” Bulletin of the World Health Organization 75 (Suppl. 1): 43–53. Sloyer, J. L. J., J. H. Ploussard, and V. M. Howie. 1981. “Efficacy of Pneumococcal Polysaccharide Vaccine in Preventing Acute Otitis Media in Infants in Huntsville, Alabama.” Reviews of Infectious Diseases 3 (Suppl.): S119–23. Stensballe, L. G., J. K. Devasundaram, and E. A. Simoes. 2003. “Respiratory Syncytial Virus Epidemics: The Ups and Downs of a Seasonal Virus.” Pediatric Infectious Disease Journal 22 (2 Suppl.): S21–32. Strauss, W. L., S. A. Qazi, Z. Kundi, N. K. Nomani, and B. Schwartz (Co-trimoxazole Study Group). 1998. “Antimicrobial Resistance and Clinical Effectiveness of Co-trimoxazole versus Amoxycillin for Pneumonia among Children in Pakistan: Randomised Controlled Trial.” Lancet 352: 270–74.

Whitney, C. G., M. M. Farley, J. Hadler, L. H. Harrison, N. M. Bennett, R. Lynfield, and others. 2003. “Decline in Invasive Pneumococcal Disease after the Introduction of Protein-Polysaccharide Conjugate Vaccine.” New England Journal of Medicine 348 (18): 1737–46. WHO (World Health Organization). 1990. “Antibiotics in the Treatment of Acute Respiratory Infections in Young Children.” Unpublished document WHO/ARI/90.10, available on request from the Division of Child Health and Development, formerly the Division of Diarrhoeal and Acute Respiratory Disease Control, WHO, Geneva. . 1991. “Management of the Young Child with an Acute Respiratory Infection. Supervisory Skills Training Module.” Unpublished document, available on request from the WHO Division of Child Health and Development, formerly the Division of Diarrhoeal and Acute Respiratory Disease Control, WHO, Geneva. . 1993. “Oxygen Therapy for Acute Respiratory Infections in Young Children in Developing Countries.” Geneva, WHO. http://www. who.int/child-adolescent-health/New_Publications/CHILD_ HEALTH/WHO_ARI_93.28.htm. . 2002. The Multicountry Evaluation of IMCI Effectiveness, Cost and Impact (MCE): Progress Report, May 2001–April 2002. WHO/FCH/CAH/02.16. Geneva: Division of Child and Adolescent Health and Development, WHO. . 2003. Consultative Meeting on Management of Children with Pneumonia and HIV Infection, 30–31 Jan. 2003, Harare, Zimbabwe. WHO/FCH/CAH/03.4. Geneva: WHO.

Temple, K., B. Greenwood, H. Inskip, A. Hall, M. Koskela, and M. Leinonen. 1991. “Antibody Response to Pneumococcal Capsular Polysaccharide Vaccine in African Children.” Pediatric Infectious Disease Journal 10 (5): 386–90.

. 2004a. “Review Panel on Haemophilus influenzae Type B (Hib) Disease Burden in Bangladesh, Indonesia, and Other Asian Countries, Bangkok, 28–29 January 2004.” Weekly Epidemiological Record 79 (18): 173–75.

Tupasi, T. E., M. G. Lucero, D. M. Magdangal, N. V. Mangubat, M. E. Sunico, C. U. Torres, and others. 1990. “Etiology of Acute Lower Respiratory Tract Infection in Children from Alabang, Metro Manila.” Reviews of Infectious Diseases 12 (Suppl. 8): S929–39.

. 2004b. “WHO/UNICEF Joint Statement: Management of Pneumonia in Community Settings.” WHO/FCH/CAG/04.06. WHO, Geneva.

UNAIDS (Joint United Nations Programme on HIV/AIDS). 2002. AIDS Epidemic Update. Geneva: UNAIDS. Usen S., M. Weber, K. Mulholland, S. Jaffar, A. Oparaugo, C. Omosigho, and others. 1999. “Clinical Predictors of Hypoxaemia in Gambian Children with Acute Lower Respiratory Tract Infection: Prospective Cohort Study.” British Medical Journal 318 (7176): 86–91. Van den Hoogen, B. G., J. C. de Jong, J. Groen, T. Kuiken, R. de Groot, R. A. Fouchier, and A. D. Osterhaus. 2001. “A Newly Discovered Human Pneumovirus Isolated from Young Children with Respiratory Tract Disease.” Nature Medicine 7: 719–24. von Mutius, E. 2001. “Pediatric Origins of Adult Lung Disease.” Thorax 56: 153–57.

WHO (World Health Organization) and Child Adolescent Health. Forthcoming. Report on the Methodology and Assumptions Used to Estimate Costs of Scaling Up Selected Child Health Interventions to 95% in Order to Reduce Under-Five Mortality. Geneva: WHO. Williams, B. G., E. Gouws, C. Boschi-Pinto, J. Bryce, and C. Dye. 2002. “Estimates of Worldwide Distribution of Child Deaths from Acute Respiratory Infections.” Lancet Infectious Diseases 2: 25–32. World Bank. 2002. World Development Indicators. CD-ROM. Washington, DC: World Bank. Zwi, K. J., J. M. Pettifior, and N. Soderlund. 1999. “Paediatric Hospital Admissions at a South African Urban Regional Hospital: The Impact of HIV, 1992–1997.” Annals of Tropical Paediatrics 19: 135–42.

Vuori-Holopainen, E., and H. Peltola. 2001. “Reappraisal of Lung Tap: Review of an Old Method for Better Etiologic Diagnosis of Childhood Pneumonia.” Clinical Infectious Diseases 32 (5): 715–26. Acute Respiratory Infections in Children | 497 ©2006 The International Bank for Reconstruction and Development / The World Bank 103


Chapter 27

Newborn Survival Joy E. Lawn, Jelka Zupan, Geneviève Begkoyian, and Rudolf Knippenberg

The second half of the 20th century witnessed impressive reductions in the risk of under-five child mortality, which was halved between 1960 and 1990. The greatest reduction was for children after the first month of life, with relatively little decrease in the neonatal period (the first 28 days of life). Neonatal deaths, estimated at approximately 4 million annually, now account for 38 percent of the world’s deaths of children under five. The fourth Millennium Development Goal (MDG) aspires to a global target, by 2015, of reducing the under-five mortality rate by two-thirds, which implies approximately 30 deaths per 1,000 live births for children under five. Currently, there are an estimated 30 deaths per 1,000 live births in the neonatal period alone. Thus, the fourth MDG cannot be achieved without substantial reduction in neonatal deaths (Lawn, Cousens, and Zupan 2005). Addressing neonatal mortality requires links within the continuum of care from maternal health through pregnancy, childbirth, and early neonatal care, and into child health programs. Such services can be delivered through a combination of care at the family-community level, outreach, and clinical care (figure 27.1). Yet neither child survival nor safe motherhood programs have adequately addressed newborn deaths. The first week of life, when 75 percent of neonatal and 50 percent of maternal deaths occur, is associated with low health care coverage, particularly in poor communities. Investing in maternal, neonatal, and child health (MNCH) services will improve the survival of newborns and reduce stillbirths and maternal and child deaths. The first weeks of life are also a time of behavioral transition, representing an opportunity to promote healthy behaviors that have benefit beyond the neonatal period.

This chapter provides an overview of neonatal deaths, presenting the epidemiology as a basis for program priorities and summarizing the evidence for interventions within a health systems framework, providing cost and impact estimates for packages that are feasible for universal scale-up. The focus of the chapter is restricted to interventions during the neonatal period. The priority interventions identified here are largely well known, yet global coverage is extremely low. The chapter concludes with a discussion of implementation in country programs with examples of scaling up, highlighting gaps in knowledge.

NEONATAL DEATHS One reason neonatal survival has received little attention relative to the huge number of deaths is the invisibility of those deaths. Most deaths during the neonatal period occur at home and are often unregistered even in transition countries (Lumbiganon and others 1990). Social invisibility is linked to an expectation of high mortality; many traditional societies do not name newborns for up to six weeks. Data presented here are derived from full-coverage vital registration for 72 countries, which cover less than 4 percent of all neonatal deaths; demographic and health surveys, which cover 75 percent of global neonatal deaths; and statistical modeling, for the 20 percent of neonatal deaths in countries without data (WHO forthcoming). Population-based data on neonatal morbidity or longterm disability in low- and middle-income countries (LMICs) are scarce. The World Health Organization (WHO) has estimated that three conditions (birth asphyxia, prematurity, 531


Clinical care Outreach services Familycommunity

Packages of care by service delivery strategy

Family planning

Skilled obstetric and immediate newborn care including resuscitation

Emergency newborn care for illness, especially sepsis management

Emergency obstetric care to manage complications such as obstructed labor and hemorrhage

Extra care of very low birth weight babies including kangaroo mother care

Prenatal care package

Postnatal care to support healthy practices Early detection and referral of complications

Prepregnancy Counseling and preparation for health and newborn care and breastfeeding nutrition Emergency preparedness

Epidemiological terms

Prepregnancy health

Clean delivery Simple early newborn care

Healthy home care including breastfeeding promotion, hygienic cord and skin care, thermal care, promotion of demand for quality care Interventions such as extra care of small babies and case management of pneumonia depending on local situation

Pregnancy care Early fetal period

Postnatal and newborn care

Birth

Late fetal period

wks

Infant and child care

Neonatal period Early

Late

Perinatal I (22 weeks gestation to 7 days after birth) Perinatal II (28 weeks gestation to 7 days after birth)

Note: International Classification of Diseases version 10 recommends perinatal I for national data collection. The World Health Organization recommends perinatal II for international comparisons of data.

Figure 27.1 The Continuum of Care for Mothers, Newborns, and Children, Showing Epidemiological Terms around the Time of Birth and Packages of Care Relevant to Newborn Health, According to Service Delivery Level

and “other perinatal causes”), collectively termed perinatal causes, contribute to 6.3 percent of global disability-adjusted life years (WHO 2003a). Although these causes represent only part of the neonatal burden, the WHO estimate is more than triple that of HIV, yet receives remarkably little attention. Where Do Newborns Die? Only 1 percent of neonatal deaths occur in high-income countries. These countries have average neonatal mortality rate (NMR) of 4 per 1,000 live births, whereas in LMICs the average NMR is 33 per 1,000 live births, with a range of 2 to 70 (table 27.1). The highest number of neonatal deaths occur in South Asia because of the large populations of this region. The six countries with the highest numbers of neonatal deaths in 2000 include the populous nations of India (1.09 million neonatal deaths annually), China (416,000), Pakistan (298,000), Nigeria (247,000), Bangladesh (153,000), and Ethiopia (147,000). Of the 20 countries with the highest NMRs, 80 percent are in Sub-Saharan Africa. The highest rates occur in countries there that have experienced recent civil unrest, such as Liberia (65 per 1,000 live births), Sierra Leone

(60 per 1,000 live births), Mozambique (55 per 1,000 live births), and Ethiopia (52 per 1,000 live births). When Do Newborns Die? Each year 3 million newborns die during their first seven days of life, accounting for 75 percent of all neonatal deaths. At least 1 million babies die during their first 24 hours of life (Lawn, Cousens, and Zupan 2005). If mortality rates during the first five years of life are adjusted to rates per week, the risk in the first week of life is massively higher than during any other time of life: 24 per 1,000 in the first week compared with 3 per week for the rest of the first month and only 0.12 per week after the first year of life. Yet the first week is the very period in the continuum of care when services are most likely to be lacking, particularly in poor communities, where most deaths occur. Time Trends in Neonatal Mortality As shown in figure 27.2, the disparity in NMRs between LMICs and high-income countries is increasing over time, especially during the early neonatal period, which saw an almost 60 percent reduction in high-income countries between 1983 and

532 | Disease Control Priorities in Developing Countries | Joy E. Lawn, Jelka Zupan, Geneviève Begkoyian, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 106

Table 27.1 NMRs and Neonatal Deaths by Region for 2000, and Variation in NMR by Income Quintile and by Region

Region World

Poorest quintile

Richest quintile

Number (percentage) of neonatal deaths (thousands)

Percentage of deaths during the neonatal period among children under five

—

—

3,998 (100)

38

Median NMR by income quintile by region

NMR per 1,000 live births (range across countries) 30

High-income countries

4 (1–11)

—

—

33 (2–70)

—

—

3,956 (99)

38

Africa

44 ( 9–70)

48

34

1,128 (28)

24

Americas

12 ( 4–34)

35

18

195 (5)

48

Eastern Mediterranean

40 ( 4–63)

38

28

603 (15)

40

Europe

11 ( 2–38)

—

—

116 (3)

49

South Asia

38 (11–43)

50

28

1,442 (36)

50

Western Pacific

19 ( 1–40)

28

17

514 (13)

56


42 (1)

63

Region

Source: Authors’ calculations, based on NMRs and under-five mortality, WHO and UNICEF estimates; NMR by income quintile based on analysis of demographic and health survey data for 50 countries, 1995–2002. — not available.

NMR per 1,000 live births 100 Postneonatal period Late neonatal period Early neonatal period

80 44 60 35 29 40

16 12

8

24

25

20 28

5 2

9

0 1980

1995 LMICs

2000

6

1980

1995

1 1 4

1 1 2000


Source: Authors’ calculations, based on UNICEF, various years; WHO 1998c; and WHO forthcoming.

Figure 27.2 Trends in Early and Late Neonatal and Postneonatal Mortality, by Country Income Levels

2000, compared with about a 15 percent reduction in LMICs. There has been no measurable decline in the regional average NMR for sub-Saharan Africa. However some regions have made significant progress in reducing NMRs, particularly Latin America and the Western Pacific. Some low-income countries such as Bangladesh, Indonesia, and Sri Lanka have achieved NMR reductions of 40 to 50 percent. In South Asia and SubSaharan Africa, the decline in late neonatal deaths was influenced by the halving of neonatal tetanus deaths that occurred during the 1990s as a result of increased tetanus toxoid protection and clean delivery practices. By 2000, two-thirds of LMICs had eliminated neonatal tetanus and an additional 22 countries were nearing this goal.

Historical data also show more rapid reductions in postneonatal mortality, steady reductions in late neonatal mortality, and slower reductions in early neonatal deaths. In England, the NMR fell from more than 30 per 1,000 live births in 1940 to 10 per 1,000 in 1975. This fall occurred before intensive care, which was introduced only when the NMR had fallen below 15 per 1,000. The greatest reduction of NMR coincided with the introduction of free prenatal care, high coverage of skilled childbirth care, and the availability of antibiotics. Although the number of postneonatal and late neonatal deaths is amenable to public health interventions (such as immunization and improved hygiene and nutrition), larger reduction of early neonatal deaths and of maternal deaths requires a system that provides effective clinical care—particularly during childbirth, which is more challenging. Direct Causes of Neonatal Death Fewer than 3 percent of the world’s neonatal deaths occur in countries that have vital registration data that are reliable enough to use in cause-of-death analysis. Population-based information in high-mortality settings often depends on verbal autopsy tools of variable quality. The Child Health Epidemiology Reference Group undertook an extensive exercise to derive global estimates for program-relevant causes of neonatal death, including preterm birth, asphyxia, sepsis/pneumonia, neonatal tetanus, diarrhea, and other causes, with the latter including specific but less prevalent causes such as jaundice. For low-mortality countries, vital registration data from 45 countries with full vital registration coverage (cumulative sample size of 96,797) were included. For high-mortality countries, studies were identified through extensive systematic searches, and a meta-analysis was performed after applying inclusion criteria Newborn Survival | 533


and using standard case definitions (56 studies, cumulative sample size of 13,685). Models were developed to simultaneously estimate the seven selected causes of death by country (Lawn, Cousens, and Wilczynska forthcoming). Three causes of death—infections (pneumonia, diarrhea, and tetanus) (36 percent), preterm birth (28 percent), and asphyxia (23 percent)—account for the majority of neonatal deaths. Causes of death vary between the early and late neonatal periods, with deaths caused by preterm birth, asphyxia, and congenital defects occurring predominantly during the first week of life and infection being the major cause of neonatal deaths thereafter. Neonatal tetanus, a totally preventable condition, still accounts for more than a quarter of a million deaths, even after the second global elimination deadline has passed. Most neonatal tetanus deaths occur in 20 countries in South Asia and Sub-Saharan Africa, all of which have very high NMRs. Variation in causes of neonatal death is seen between and within countries, closely associated with the NMR level. Where the NMR is high (more than 45 per 1,000 live births), more than half of neonatal deaths are due to infections; where the NMR is low, prematurity and congenital abnormalities are the major causes of death (Lawn, Cousens, and Zupan 2005). Hence, information regarding the local epidemiology is important in prioritizing interventions. Indirect Causes of Neonatal Death An estimated 20 million low birthweight (LBW) infants (that is, weighing less than 2,500 grams), are born each year— 25 percent of them in South Asia (Blanc and Wardlow 2005). Although globally only 16 percent of newborns have LBW, 60 to 80 percent of neonatal deaths occur in LBW infants (Lawn, Cousens, and Wilczynska forthcoming). LBW is due to short gestation (preterm birth), intrauterine growth restriction (IUGR), or both. Globally, almost one-third of neonatal deaths are directly attributable to preterm birth. In contrast, an analysis of vital registration data for 45 countries and of five population-based studies suggests that a maximum of 1 to 2 percent of neonatal deaths are directly attributable to IUGR in full-term neonates (Lawn, Cousens, and Wilczynska forthcoming). Prematurity and full-term IUGR are also indirect causes or risk factors for neonatal deaths, particularly deaths resulting from infection. The relative risk among preterm infants is much higher than for full-term IUGR infants (Yasmin and others 2001). Complex technology is not necessary to avoid most deaths in moderately preterm newborns. Extra attention to warmth and feeding and to prevention or early treatment of infections is crucial (Lawn, McCarthy, and Ross 2001). Maternal health and health care are important determinants of neonatal survival. Neonatal outcomes are affected by female health throughout the life cycle, from child, through adolescence, and into pregnancy (Pojda and Kelley 2000). In general, intrapartum risk factors are associated with greater increases in

risk of neonatal death than factors identified during pregnancy, which are in turn associated with greater increases in risk than prepregnancy factors (Lawn, Cousens, and Zupan 2005). Obstructed labor and malpresentation present the highest risk and require skilled intervention. The mother’s death substantially increases the risk of death for her child. Greenwood and others (1987) report that of mothers who died in labor (N 8), all the babies died within one year. Delays in access to care for severely ill young infants are common. Peterson and others (2004), in a study in Uganda, find that almost 80 percent of the caregivers of severely ill young infants did not comply with recommended referrals to a health facility. The reason given in 90 percent of the cases was lack of money, underscoring the need for pro-poor financing mechanisms and promotion of community demand for care. This recalls the “three delays” model for maternal deaths, which outlines delays in recognition of illness and in access to care and provision of care once at a health facility (Thaddeus and Maine 1994). Poverty is the root cause of many maternal and neonatal deaths, either because it increases the prevalence of risk factors such as maternal infections or because it reduces access to care. An analysis of 50 demographic and health surveys between 1995 and 2002 reveals that, within regions, the poorest quintiles have an NMR that is, on average, 20 to 50 percent higher than that for the highest income quintile (table 27.1). Deliberate programmatic focus is required to ensure that care reaches poor families. Applying Lessons from Epidemiology to Programs There are almost 4 million neonatal deaths annually. Given that the proportion of child deaths that occur during the neonatal period (currently 38 percent) will increase over time, the MDG for child survival cannot be met without a significant reduction in the NMR. Most neonatal deaths are in Sub-Saharan Africa and South Asia and are due to preventable causes. Historical data demonstrate that the NMR can be reduced to 15 per 1,000 without intensive care. Priority should be given to two main gaps in the provision of care. The first is the continuum of care by time. The period through pregnancy and childbirth into infancy contains a gap at childbirth and during the first week of life, when most neonatal deaths—and also most maternal deaths—occur. Addressing this gap will involve strengthening safe motherhood and child survival services and institutionalizing links at the subnational, national, and global levels. The second gap is between levels of care (figure 27.1)—particularly with the family-community level, since poor and rural communities account for the majority of neonatal and maternal deaths. Approaches are needed to better link homes and health care, supplying care closer to such communities, increasing demand for skilled care, and empowering communities, including poor communities, to make healthful decisions.


INTERVENTIONS We undertook literature searches and categorized interventions by time period (during pregnancy, and intrapartum and postnatal or neonatal periods) (table 27.2). We focus on interventions delivered during the neonatal period that are likely to reduce neonatal deaths, as opposed to those delivered during the neonatal period that yield later benefits (for example, prevention of mother to child transmission of HIV). Although rigorous evaluation of evidence is vital, evidence is not available for some well-established interventions. In the case of neonatal resuscitation, for example, a randomized controlled trial is impossible for ethical reasons, yet the intervention is a cornerstone of neonatal care in high-income settings. Some important practices, such as cleanliness, have undergone little rigorous evaluation but are obviously beneficial (Bhutta and others 2005). On the basis of level of evidence and feasibility of implementation, we grouped interventions into three categories: • Universally applicable interventions are selected on the basis of mortality impact, cost, and feasibility. Some of these interventions are feasible only after skilled care is available. Other interventions are feasible immediately, even in the absence of skilled care. A particular example is improved family care practices. Interventions may apply to different newborns as follows: — essential newborn care for all babies at all levels — extra newborn care for babies with specific risk factors, such as LBW — emergency newborn care for babies who are ill, particularly those with infections. • Additional interventions should apply where neonatal mortality is lower and capacity is greater. These interventions are more complex, requiring more skilled staff members and additional commodities, and therefore cost more for less reduction in mortality. Universal scaling up cannot be recommended at present, but these interventions become important for further reduction of mortality and disabilities after universal care packages are in place. • Situational interventions are necessary because of locally prevalent risk factors, such as HIV or malaria. The packages of newborn care selected for universal scale-up are summarized in table 27.3 and discussed in the following subsections, starting with family-community interventions and followed by essential, extra, and emergency newborn care packages.

and afterward (WHO 2003c). Cleanliness (for example, cord care and hand washing), warmth provision, and exclusive breastfeeding reduce neonatal illnesses, especially infection. Implementation of this package will depend on the setting, the coverage of facility delivery, and the availability of community workers or other channels but is feasible even in poorly developed health systems (Knippenberg and others 2005). The role and value of the mother are central. Although much has been written to describe traditional newborn care practices, few studies assess behavior change. An exception is the study by Meegan and others (2001) of the Masai in Kenya, where behavioral messages about cord care practices were associated with the virtual elimination of neonatal tetanus—with no increase in tetanus toxoid immunizations. The Warmi Project in rural Bolivia demonstrated that raising community awareness of maternal, fetal, and neonatal health issues through women’s community groups increased familyplanning coverage, attendance at prenatal and postnatal services, and the presence of trained traditional birth assistants at childbirth, resulting in a 62 percent reduction of perinatal mortality (O’Rourke, Howard-Grabman, and Seoane 1998). A cluster randomized trial in rural Nepal, where 90 percent of women deliver at home, also used female facilitators working with women’s groups. Comparing the 12 intervention villages with their paired villages showed a 30 percent reduction in the NMR (mainly late NMRs) mediated through increased health seeking and improved home behaviors (such as doubling the rates of practices such as hand washing and use of clean delivery kits) and strengthening of the health system (Manandhar and others 2004). A family-community package promoting good home care of the newborn—particularly cleanliness, warmth, and exclusive breastfeeding—would have an expected reduction in the NMR of 10 to 40 percent, varying with the baseline NMR and the potential for accessing care. The effect might be greater if the package successfully addressed harmful local practices. The effect of early care seeking for illness will depend on the capacity of the primary and referral health care levels to manage neonatal illness. Thus, community-level interventions with no supply-side strengthening will have only a limited effect. Many questions remain about how best to work with families and communities, given widely differing cultures and behaviors and the varying capacities of existing community health workers (Darmstadt and others 2005), and about the wider application of demand subsidies.

Essential Newborn Care at the Time of Birth Family-Community Care of the Newborn Family care of the newborn is important for all newborns. It includes promoting positive behaviors such as breastfeeding and demand for health care throughout the neonatal period

WHO (2003d) defines essential newborn care as the care of the newborn at birth, including cleaning, drying, and warming the infant; initiating exclusive breastfeeding early; and caring for the cord. Essential care of the newborn is necessary for all Newborn Survival | 535


Table 27.2 Interventions to Reduce Fetal and Neonatal Mortality by Timing of Intervention and by Scalability of Intervention

Period

Interventions for universal coverage (priority interventions for high-mortality settings)

Prepregnancy

Family planning [B]: • delay age of first pregnancy to after 18 • space births by two to three years • provide opportunity for women to reduce births

to their desired number and to avoid pregnancy after age 45 Prevention, identification, and management of sexually transmitted diseases [A]

Additional interventions (where the health care system has additional capacity and the NMR is lower; for example, transition countries) Rubella immunization either of girls only or of all population if regular coverage can be maintained at more than 80 percent of the population [A] Periconceptual or preconceptual provision of folate [A] Information counseling and support for • smoking [RF A]

Situational interventions (where specific conditions are prevalent) HIV prevalent: • primary prevention strategies [B] • voluntary counseling and testing

and option of antiretroviral therapy [A] High prevalence of recessive conditions (such as sickle cell disease) or high rates of consanguineous marriages: offer genetics counseling [RF A]

Micronutrient deficiency prevention strategies

• alcohol and drug abuse [RF A]

• iodination of salt [B]

• women experiencing violence [RF A]

During pregnancy

Four-visit prenatal care package, including • two tetanus immunizations [A]

Identification and treatment of bacteriuria [A]

HIV prevalent:

• Essential for all

• iron and folate supplements [B]

Information counseling and support for

• voluntary counseling and testing

• syphilis screening and treatment [A]

• smoking cessation [RF A]

• identification and referral of multiple

• alcohol and drug abuse [RF A]

pregnancies

pregnancy, abnormal lie, preeclampsia [B] • birth planning and emergency preparedness [C]

• Extra care for

those at risk of complications

• primary prevention strategies [B]

and option of antiretroviral therapy [A]

• healthy diet and avoidance of

unhelpful dietary taboos [C]

• prenatal counseling and preparation for breastfeeding [C]

• women experiencing violence [RF A]

Extra prenatal care (more frequent visits, more skilled caregiver) if

External cephalic version for breech presentation at 36 weeks [A]

• multiple pregnancy or abnormal lie (breech or

Fetal growth monitoring [A]

transverse) [RF A]

Malaria endemic: • intermittent presumptive treatment

monthly after 20 weeks [A] • insecticide-treated bednets [B based

on effect on LBW, not on NMR]

• pregnancy-induced hypertension or

preeclampsia [RF A]

Hookworm infestation prevalent:

• diabetes [RF A]

• presumptive treatment with

• severe anemia [RF A]

mebendazole [B]

• previous fetal or neonatal death [RF A] • Emergency for

those with complications (first referral level and above)

Management of emergencies, including • preeclampsia or eclampsia [A]

In utero transfer of high-risk pregnancies [B]

Iodine deficiency prevalent: • iodine supplementation [B]

• bleeding in pregnancy [A*]

Famine:

• uterine infection [RF A]

• targeted food supplementation [B]

Group B streptococcus prevalent: • screening and treatment [A]

Birth

Skilled care in labor, including

• Essential

• monitoring progress of labor (partograph),

Supportive companion in labor [A]

maternal and fetal well-being [A] • infection control [A*]

Newborn resuscitation if required [A*]


Mother HIV positive: • antiretroviral therapy [A]


Period

Interventions for universal coverage (priority interventions for high-mortality settings)

• Extra care

Extra care if • preterm (37 weeks) or prolonged (18 hours)

rupture of membranes or evidence of chorioamnionitis; give antibiotics to woman [A]

Additional interventions (where the health care system has additional capacity and the NMR is lower; for example, transition countries) Tocolytics in preterm labor and transfer to higher-level care if available [A] If preterm labor, then give prenatal steroid injection to mother [A]

Situational interventions (where specific conditions are prevalent) Maternity waiting home if limited access to emergency obstetric care, high-risk condition identified, and culturally acceptable [B]

• failure to progress in labor including instrumen-

tal vaginal delivery (vacuum) if required [RF A] Newborn resuscitation if required [A*] • Emergency

Emergency obstetric care for acute intrapartum emergencies: [A*] • obstructed labor and fetal distress • bleeding, infections, or eclampsia

Neonatal resuscitation if required [A*] Postnatal and newborn

Essential newborn care for all newborns, including

Trained breastfeeding counselors undertaking home visits [A]

• Essential

• early and exclusive breastfeeding [B]

Vitamin K (cost-effective as prophylaxis for all babies in transition countries) [B]

• warmth provision and avoidance of bathing

during first 24 hours [C] • infection control, including cord care and

hygiene [B] • postpartum vitamin A provided to mother [B]

Routine newborn screening programs for sickle cell disease, glucose 6 phosphate dehydrogenase deficiency [B]

Hepatitis B prevalent: • give hepatitis B immunization

early [A] Mother HIV positive: • provide counseling and support for

feeding choices [C]

• eye antimicrobial provided to prevent

ophthalmia [A] • information and counseling for home care and

emergency preparedness [C] • Extra care

Extra care for small babies (preterm or term IUGR) and multiple births, severe congenital abnormalities:

Provide special or intensive care for preterm babies [A]

Mother with tuberculosis: • keep baby with mother and give

izoniazid prophylaxis

• extra attention to warmth, feeding support, and

Mother with syphilis:

early identification and management of complications [B]

• treat the baby even if asymptomatic

[A*]

• kangaroo mother care [A: morbidity not

mortality data] • vitamin K injection [B] • Emergency

Emergency care providing specific and supportive care according to evidence-based guidelines for the following:

Provide special care for sick and small babies using skilled nurses and a higher nurse-to-patient ratio [B]

• severe infections [A] • neonatal encephalopathy (following acute

intrapartum insult) • severe jaundice or bleeding [A*] • neonatal tetanus Source: Authors, based on extensive literature review. References detailed on http://www.fic.nih.gov/dcpp/. Note: A rigorous meta-analysis or at least one good randomized controlled trial exists, RF A evidence regarding risk is strong, B well-conducted clinical studies exist but no randomized controlled trial done, C some descriptive evidence and expert committee consensus exists, A* unethical to test rigorously and widely practiced as standard (for example, blood transfusion, neonatal resuscitation). Bold text signifies priority packages or interventions considered in detail in this chapter.

Newborn Survival | 537 ©2006 The International Bank for Reconstruction and Development / The World Bank 111

Table 27.3 Packages for Universal Scale-up of Newborn Care

Intervention package Contents

Number of target population per year (millions)

Familycommunity care of the newborn at home after birth

Healthy home care practices (exclusive breastfeeding, warmth protection, clean cord care, care seeking for emergencies); if birth outside a facility, then clean delivery kit.

Essential newborn care at the time of birth

Immediate drying, warmth, All newborn early breastfeeding, hygiene infants: maintenance, and infection World 130 prevention South Asia and Sub-Saharan Africa 63

Neonatal resuscitation

Resuscitation after birth if required

All newborn infants: World 130 South Asia and Sub-Saharan Africa 63

Newborns not breathing at birth:

Implementation strategy

Estimated current Reduction coverage (percent) in allcause SubSouth Saharan NMR (percent) Comments on evidence Asia Africa

Women’s groups and 36 community health workers doing postnatal visits, with links to the formal health care system, including support for referral. If appropriate, extra care of moderately small babies at home and community-based management of acute respiratory infections.

28

10–40

Mortality reduction based on studies in high NMR settings with weak health systems. Extra care of LBW infants and community management of acute respiratory infections not included in range shown.

Skilled attendant, or if no skilled attendant available, some simple postnatal practices are feasible at home with other cadres of workers.

11

14

20–30

Based on conservative combining of single interventions (for example, breastfeeding) in the package.

Skilled attendant.

3

3

10–25

Limited studies, mainly from lower NMR settings with high percentage of asphyxia deaths, so range from studies was reduced.

Facility-based care for severely preterm babies. Community-based care is effective for moderately preterm babies.

10

10

20–40

Most studies are nonrandomized controlled trials at the community level in settings with extremely high LBW rates. Effect depends on baseline NMR and LBW rates.

Facility-based care with antibiotics and supportive care. Community-based management with oral antibiotics for acute respiratory infections.

20

20

20–50

Meta-analysis of effect on the NMR of oral antibiotic management of acute respiratory infections in the community in high-mortality settings.

Supply of care throughout pregnancy, childbirth, and postnatal period with increased demand and improved referral systems.

5

5

—

No study data identified. Marginal budgeting for bottlenecks tool suggests 58 percent in South Asia and 71 percent in Sub-Saharan Africa.

World 6.5 South Asia and Sub-Saharan Africa 3.2 Extra care of small newborns

Extra support for warmth (kangaroo mother care), feeding, and illness identification and management

LBW neonates:

Emergency care of ill newborns

Management of ill infants, especially those with neonatal infections

Neonates with illnesses:

World 20.0 South Asia and Sub-Saharan Africa 10.7

World 13.0 South Asia and Sub-Saharan Africa 6.3

Neonatal packages plus MCH package

Neonatal packages as above, in addition to family planning, prenatal care, and comprehensive obstetric care packages

All newborn infants: World 130 South Asia and Sub-Saharan Africa 63

Source: Local data or Darmstadt and others 2005; Knippenberg and others 2005; Lawn, Cousens, and Zupan 2005. Note: The range of reduction of all-cause NMRs given for each package is independent of the others; hence, the total is greater than 100 percent.


infants and is ideally provided by a skilled attendant, but in the absence of skilled care, many of the tasks can be carried out at home by alternative cadres of workers. WHO’s essential care package includes resuscitation, which we consider separately because the skill level required is more complex. Clean care of the umbilical cord (clean blade and tie) is important in reducing the incidence of neonatal tetanus and umbilical sepsis, but evidence for topical treatment of the cord remains unclear (Zupan and Garner 2000). Hand washing is important at all levels of care. Hypothermia is an important and preventable contributor to morbidity and mortality, especially in preterm babies. The so-called warm chain involves ensuring that childbirth takes place in a warmed room, drying the newborn, encouraging skin-to-skin contact between the newborn and the mother, and avoiding bathing for at least 12 hours (Lawn, McCarthy, and Ross 2001). In hospitals in LMICs, many newborns are hypothermic, and staff knowledge and practices could be improved (Dragovich and others 1997). The effects of exclusive breastfeeding have been intensively studied, and the positive effect on infant mortality is unequivocal, although studies often do not specify the effect on neonatal mortality and morbidity. The WHO collaborative trial found the risk of mortality in nonbreastfed neonates to be 2.5 to 7.0 times greater than for breastfed neonates (WHO Collaborative Group 2000). The practice of keeping well babies close to their mothers and allowing feeding on demand increases breastfeeding rates, reducing both hypothermia and nosocomial infections (WHO 1998b). Unfortunately, as exemplified by the low proportion of hospitals that are certified as baby friendly, this practice is poorly implemented. Supportive policy, such as the International Code of Marketing of Breastmilk Substitutes, is also important at the national level. The effect of essential newborn care has not been formally tested as a package, although exclusive breastfeeding, cleanliness, infection control measures, and hypothermia avoidance all individually reduce neonatal mortality and morbidity.

Nevertheless, only 11 percent of babies in South Asia and 14 percent in Sub-Saharan Africa are exclusively breastfed to three months. The Bellagio group estimated a 15 percent reduction in the NMR through 99 percent coverage of exclusive breastfeeding and an 11 percent impact reduction through clean delivery (Jones and others 2003). Conservatively, an essential newborn care package may result in a 10 to 25 percent reduction in the NMR, but field trials of a combined package are still required. No economic assessments were identified.

Newborn Resuscitation Approximately 5 to 10 percent of newborns do not breathe spontaneously and require stimulation. About half of those have difficulty initiating breathing, requiring resuscitation (WHO 1998a). The major reasons for failure to breathe include preterm birth and acute intrapartum events resulting in hypoxic brain injury. Basic resuscitation using a self-inflating bag and air is effective for the majority of these newborns, although some may be too premature or have already experienced severe hypoxic brain injury and die despite resuscitation. Monitoring labor and providing effective obstetric care can reduce the need for resuscitation (Dujardin, Sene, and Ndiaye 1992), but resuscitation may be required even with good obstetric care. Therefore, every skilled attendant should be competent in newborn resuscitation (box 27.1). For most babies who do not breathe at birth, ventilation with a self-inflating bag and mask is lifesaving, and the time to first breath differs little between use of a self-inflating bag and mask and use of endotracheal intubation. Evidence is growing that most newborns can be successfully resuscitated without the use of oxygen (Saugstad 2001), although a small proportion of infants require such advanced resuscitation techniques as endotracheal intubation, oxygen, chest compression, or drugs. Such advanced resuscitation is appropriate only in institutions that provide ventilation. In the 1980s, the high cost of a self-inflating

Box 27.1

Institutionalizing a Neonatal Resuscitation Program in a Chinese Province A hospital-based study from China reports baseline surveillance of 1,722 newborns followed by a two-year prospective assessment of 4,751 newborns, while instituting standardized resuscitation guidelines. Previous traditional resuscitation involved infusing central stimulants plus vitamin C and 50 percent glucose; wiping the baby with alcohol; and pressing the philtrum. Health professionals recognized that asphyxia was the leading cause of

neonatal death and the second leading cause of infant death nationally. They also recognized that child survival goals could not be met unless asphyxia was addressed. They developed and implemented an evidence-based neonatal resuscitation program, training staff in using the new guidelines. The early NMR fell significantly—by 66 percent, to 3.4 per 1,000.

Source: Zhu and others 1997.


bag and mask led to the development of a prototype mouthto-mask device operated by blowing expired air. A study by Massawe and others (1996) in two teaching hospitals, one in Tanzania and the other in India, found that resuscitators using this device could maintain a maximum of only 20 breaths per minute, one-third of the recommended rate. Low-cost (less than US$5) versions of the bag and mask are now available, and it is the recommended device for resuscitation. Although small-scale studies show that nonprofessional cadres can learn the technique of resuscitation (Bang and others 1999; Kumar 1995), a significant effect on mortality has not been demonstrated, and the feasibility of maintaining competency and the cost-effectiveness of training such cadres have yet to be ascertained. If traditional birth assistants attend, say, 20 deliveries a year, they would encounter a baby requiring resuscitation an average of only once a year, so the effect would be lower, and the cost per life saved higher, compared with a facility-based midwife who does 200 or more deliveries a year. Thus, more research is required before home resuscitation by traditional birth assistants can become a widespread policy. In the meantime, it should be ensured that where skilled attendants exist, they have the skills and equipment to perform neonatal resuscitation. Because a randomized controlled trial would be considered unethical, the studies identified apply a before-and-after comparison. No cost assessments were identified. Achieving wider coverage of resuscitation is a challenge, especially for the 47 percent of the world’s babies born at home. Extra Care for Small Babies Because 60 to 80 percent of neonatal deaths occur in LBW babies, targeting this group for additional preventive and early curative care is a logical approach to mortality reduction. Addressing deaths among severely preterm infants (fewer than 32 weeks of gestation) is more complex, but most preterm infants are moderately preterm (33.0 to 36.9 weeks). Excess mortality from acquired infections and other complications can largely be prevented or managed without intensive care. A number of community-based studies have undertaken simplified identification of small babies and provided extra care at home, especially feeding (including the use of a dropper or cup feeding if required), warmth promotion, and cord cleanliness. The reported NMR reductions range from 25 percent (Pratinidhi and others 1986) to 42 percent (Daga and others 1988). Datta (1985) applied a comprehensive approach, including weighing all babies and providing extra home support to LBW infants through feeding counseling and early recognition of and referral for illness, alongside strengthening of local health systems. Compared with a control area, the NMR was reduced by more than 30 percent, with the greatest reduction among the group of 1,500- to 2,500-gram babies. In Bang and others’ (1999) study, 90 percent of neonatal deaths were in LBW

infants, and all LBW babies were targeted for increased home visits. Special sleeping bags were provided for warmth, and support was given for breastfeeding and early treatment of possible infections. The NMR fell by 87 percent in the moderately preterm group (35 to 37 weeks) (Bang and others 1999). So-called kangaroo mother care involves continuous skinto-skin contact between mother and baby to provide thermal stability and promote exclusive breastfeeding for clinically stable preterm infants. The published evidence relates to facility-based care with or without kangaroo mother care after discharge. Mortality impact data for kangaroo mother care are lacking, but a review by Conde-Agudelo, Diaz-Rossello, and Belizan (2000) that included three randomized controlled trials found that serious morbidity was reduced by about 60 percent at the six-month follow-up visit. Although cost has not been formally evaluated, it must be considerably less than for incubator care. The lack of assessments of kangaroo mother care at community level is a research gap. A few studies in health facilities in LMICs have reported increased survival of LBW infants with improved care. One from Papua New Guinea demonstrated a 56 percent reduction in the NMR with the introduction of standards for care and of basic technology (Duke, Willie, and Mgone 2000). Data from Ghana showed a 28 percent reduction in mortality for LBW infants with support for breastfeeding, attention to warmth, and early management of infections and jaundice using standard protocols (Lawn, McCarthy, and Ross 2001). The reported effect for extra care of LBW babies in the community varies between 20 and 40 percent, excluding Bang and others’ (1999) study because additional interventions were involved. Given the high LBW prevalence in these studies, the effect may be less in other settings with a lower LBW prevalence. Data from facilities that do not offer intensive care suggest a similar or slightly larger effect. Cost-effectiveness assessments were not identified. Emergency Care for Ill Newborns For many of the world’s 4 million neonatal deaths, the immediate cause is a neonatal illness presenting as an emergency either soon after birth (such as complications of preterm birth and asphyxia) or later (because of neonatal tetanus or communityacquired infections). Other important but less prevalent conditions include jaundice and hemorrhagic disease of the newborn. Long-term disability follows many neonatal conditions, but it is poorly documented. Many serious neonatal problems present with similar signs: inability to feed, breathing difficulty, and temperature instability. All those conditions have high fatality rates, particularly neonatal tetanus (Institute of Medicine 2003) and neonatal encephalopathy (Ellis and others 1999), and preventive interventions may be the most realistic option in those conditions. Early phototherapy for jaundice reduces both mortality and chronic disability subsequent to


kernicteris and is feasible in facilities (WHO 2003b). We focus on the clinical neonatal management of infection, which is the most prevalent neonatal illness and the most feasible to scale up. A meta-analysis of community-based trials of case management of pneumonia in Africa and Asia yields a summary estimate for NMR reduction of 27 percent (Sazawal and Black 2003). The antibiotic regime used was mainly oral cotrimoxazole, although two studies included injectable penicillins. Bang and others’ (1999) study in rural India reports a 62 percent reduction in the NMR with a home-based package for neonatal sepsis that included injectable gentamicin, although this reduction may be related to a number of simultaneously introduced interventions in addition to the gentamicin. The effect of emergency care on neonatal sepsis can be assumed to be similar to the range in Sazawal and Black’s (2003) meta-analysis: 20 to 60 percent. Published cost data were not identified apart from the Bang and others (1999) study, which indicated a cost of US$5.30 per neonate treated. This cost estimate includes the time of community health workers and the cost of equipment and drugs, but not associated supervision or system costs.

Because newborn health depends on services in the continuum of care for mother, newborn, and child, a vertical program would be duplicative, expensive, and inappropriate (Tinker and others 2005). Hence costing and impact estimates will be based on marginal additions of neonatal-specific packages to existing maternal and child health (MCH) services (table 27.4). This scenario reflects the reality in many South Asian and SubSaharan African contexts, where MCH services exist but do not yet include newborn interventions. We will cost packages, because packages are more cost-effective than single interventions, and the emphasis is on the packages described for universal scale-up (table 27.3). The benefits take into account only neonatal deaths averted, whereas many of the interventions will also reduce maternal deaths, stillbirths, and childhood morbidity and disability—and therefore the benefits underestimate gains for both the fourth and the fifth MDGs. Costing and impact simulations are provided using the “marginal budgeting for bottlenecks” tool, a prioritization tool developed by the United Nations Children’s Fund (UNICEF), the World Bank, and WHO. The inputs for the analysis presented here are as follows:

neonatal estimates by country (Lawn, Cousens, and Wilczynska forthcoming). • Baseline coverage estimates for the neonatal packages presented in table 27.3 are taken from local data, if available (for example, exclusive breastfeeding prevalence), or drawn from coverage estimates in the Lancet newborn series (Darmstadt and others 2005; Knippenberg and others 2005; Lawn, Cousens, and Zupan 2005). • Impact estimates for neonatal mortality are from the literature, as presented in this chapter. The range uses the 95 percent confidence interval, rounded to the nearest 5 percent where available (table 27.3). If the data were from an efficacy trial or a before-and-after trial, the range in the literature was reduced to reflect the expected effectiveness, based on expert opinion. Cause-specific mortality was used to allow combinations of effects across packages, and the assumptions applied were aligned with those used in the Lancet neonatal series (Darmstadt and others 2005)— although the packages here differ, because this chapter is restricted to the neonatal period. The assumptions for cause-specific impact are detailed at http://www.fic.nih. gov/dcpp. The effect for outcomes other than neonatal ones was based on data in the marginal budgeting for bottlenecks tool, primarily from the Lancet Bellagio series (Jones and others 2003) and Cochrane reviews. Effects are combined in a residual manner; for example, deaths averted by preventive strategies are removed from the pool before curative approaches are applied, and hence the total effect is less than the sum of the effects. Years of life lost were calculated using local average life expectancy discounted at 3 percent per year. This measure equates to the fatal outcome component of disability-adjusted life years, as described in chapter 15. • Specific costs of adding the intervention packages are calculated on the basis of the cadre of worker, additional personnel time, in-service training, supervision, performance incentives, travel and subsistence costs for referral care, drugs, and equipment. Demand promotion and community mobilization are included. The costs of time, training, and incentives are based on national salary levels, using real country data or World Bank databases. The costs of commodities are based on the UNICEF supply system (http://www.supply.unicef.dk/Catalogue/). The cost of strengthening health systems, including improving management and logistics, constructing new facilities, and deploying and training new cadres of workers, is included in the comprehensive MCH package.

• Baseline epidemiology uses NMRs from the latest demographic and health surveys by country or state and recent local relevant demographic data, such as crude birth rates. • Cause-specific neonatal mortality estimates by country are from the Child Health Epidemiology Reference Group’s

Table 27.4 presents the estimated NMR effects and per capita costs, in selected Indian states and Sub-Saharan African countries, of strengthening health systems to increase coverage with existing MCH packages (without neonatal care after birth). It then presents the additional specific costs of including

MARGINAL IMPACT AND COST OF SCALING UP UNIVERSAL NEONATAL PACKAGES


542 | Disease Control Priorities in Developing Countries | Joy E. Lawn, Jelka Zupan, Geneviève Begkoyian, and others


13–26

0–9

3–8

12–12

Scenario 1

27–58

0–22

5–15

27–27

Scenario 2

11–23

1–9

2–6

11–11

Scenario 1

24–46

3–22

6–14

24–24

Scenario 2

Sub-Saharan Africa

b

2.40

0.04

0.30

2.00

Scenario 1

India

5.50

0.10

0.60

4.80

2.80

0.11

0.23

2.40

Scenario 1

5.70

0.23

0.37

5.10

Scenario 2

Sub-Saharan Africab

Cost per capita (US$) Scenario 2

a

244–516 (average 380)

11–265

100–257

480

Indiaa

282–583 (average 432)

25–360

100–270

506

Sub-Saharan Africab

Additional cost per neonatal YLL averted for 20 percent increase in coverage for lower and upper efficacy ranges (US$)

Source: Estimates by authors, using the “marginal budgeting for bottlenecks” tool as detailed in the text. YLL years of life lost. YLL includes neonatal fatal outcomes only and is based on local life expectancy discounted at 3 percent per year. Scenario 1: increasing coverage by 20 percent. Scenario 2: meeting fourth MDG, necessitating about 45–60 percent NMR reduction, depending on the percentage of under-five mortality that is neonatal. Note: No specific neonatal outreach package is shown, because this is in prenatal care as part of the MCH package or home postnatal visits in the family-community package a. Five states in India are represented: Gujarat, Madhya Pradesh, Orissa, Rajasthan, and West Bengal. b. Five countries in Sub-Saharan Africa are represented: Benin, Ethiopia, Madagascar, Mali, and Rwanda. c. The MCH package consists of family planning, prenatal and obstetric care, and child health services (comprehensive integrated management of infant and childhood illness including prevention and community activities) and includes system strengthening costs. d. Includes interventions listed in table 27.3 under family-community package plus extra care of moderately small babies at home and community-based management of acute respiratory infections. e. Includes clinical care packages listed in table 27.3 (essential newborn care, neonatal resuscitation, extra care of small newborns, and emergency care of ill newborns).

Total impact or cost with combined MCH and neonatal-specific packages

Clinical packages

e

Family-community packaged

Marginal impact or cost of adding neonatal packages to the MCH package

MCH package (no neonatal care after birth)c

Package

India

a

NMR reduction 2004–15 (range of lower and upper efficacy, percent)

Table 27.4 Estimated Marginal Effect and Cost of Adding Neonatal Packages to Existing MCH Packages for Three Scenarios in Selected Indian States and Sub-Saharan African Countries

neonatal packages at the family-community level and in clinical services and, finally, the combined costs for comprehensive MNCH. Results are shown for two coverage scenarios: • Scenario 1: increasing coverage of the interventions by 20 percent from the baseline • Scenario 2: increasing coverage to the level required to meet the fourth MDG, necessitating about a 45 to 60 percent reduction in NMR, depending on the baseline percentage of under-five mortality that is neonatal. Table 27.4 shows that the addition of neonatal packages will reduce neonatal deaths at an average cost of about US$0.50 per capita per year for up to a 15 percent reduction in NMR at the family-community level and about US$0.20 per capita for a 22 percent NMR reduction at the clinical care level. Although the cost per capita is low for clinical care, the cost per case treated is higher, and the lag time to scale up is longer. The familycommunity neonatal package in India is estimated to cost US$100 to US$257 per year of life saved (table 27.4), which corresponds to about US$2,800 to US$7,800 per death averted. That is similar to the results of US$3,442 per neonatal death averted or US$111 per life year saved in a community participatory package in Nepal (US$4,397 and US$142, respectively, with health system strengthening) (Manandhar and others 2004). The comprehensive MNCH package (the MCH package plus integrated neonatal packages) is more expensive than the neonatal packages alone: US$2.40 to US$2.80 per capita and per year for a 20 percent increase in coverage, and US$5.50 to US$5.70 to achieve the mortality reduction necessary to meet the fourth MDG (including the health system strengthening and demand-side approaches required). However, the effect of the MNCH packages on the NMR is more than double that of the neonatal packages alone—for example, a reduction of up to 58 percent in NMRs in Africa, compared with up to 22 percent using interventions in the neonatal period only. This finding emphasizes the advantages of a comprehensive approach across the continuum of care. Hence, the average cost per year of life saved is still low at US$380 (India) and US$432 (SubSaharan Africa) for a 20 percent increase in coverage, including costs of system strengthening. If the coverage of the MCH plus neonatal packages were to reach 90 percent, those packages would avert up to 71 percent of neonatal deaths in the African countries and up to 76 percent in the Indian states. In settings where the current coverage of skilled care is low, opportunities exist to start with family care and extra care of LBW babies while building toward more challenging clinical packages. Some clinical care packages—such as simple extra care of the small baby or the provision of oral antibiotics for pneumonia later in the neonatal period—can be adapted for delivery through community health systems. Varying the cadres of worker involved or the level of health system at which

the package is delivered may reduce the cost of the package, but it also necessitates extra supervision and attention to links with the formal health system. Box 27.2 describes the projected effect and cost of various packages in Ethiopia for a 12-year program to improve maternal and child survival targeted at achieving the fourth MDG by 2015. Outreach services such as prenatal care alone have an effect of about 10 percent on NMRs, but when they are combined with a family package using community health promoters, an additional 30 percent reduction in the NMR is projected in Ethiopia. Outreach and family care options are more feasible initially. Yet if commitment toward moving to strengthen the clinical care system is lacking, the potential reduction in NMRs over time from those options is limited, and the cost per death averted is higher. Although the estimated cost (averaged over 12 years, with gradually increasing amounts) is low, the input is higher than the current government and donor health expenditure of the countries examined. Thus, spending in India would have to be doubled, and in some African countries probably tripled. Considerable new funding is required at the national and international levels, as well as more efficient allocation and absorption of existing funds (Martines and others 2005).

IMPLEMENTATION Effective interventions exist and are low cost, especially when added to existing programs, but current coverage is low, especially for the poor, who have the highest mortality risk. Approximately 53 percent of women worldwide deliver with a skilled attendant: fewer than 30 percent in the poorest countries and more than 98 percent in the richest countries. In Sub-Saharan Africa, average coverage with skilled care has increased at only 0.2 percent per year in the past decade; without faster progress, coverage of skilled attendance will still be less than 50 percent in 2015. Analysis in 50 low-income countries showed that the richest 20 percent of women were, on average, almost five times as likely to use a skilled attendant as the poorest 20 percent (Knippenberg and others 2005). Hence, coverage is low, progress is slow, and inequity is high. Each country or decision-making unit starts with a different epidemiology and varying coverage and capacity in its health system. No single recipe for strengthening newborn care in health systems is available. Scaling up MNCH care will involve systematic steps to assess local situations and opportunities, improve care within current constraints, and overcome supply and demand constraints—especially for the poor. No country or program can achieve multiple new interventions at once, and scaling up human resources takes time. Therefore, phasing approaches is essential not only to allow faster approaches to reach the poor soon, but also to allow consistent strengthening of the health system (Knippenberg and others 2005). Newborn Survival | 543


Box 27.2

Steps to Increase Coverage of Key MNCH Interventions in Ethiopia Ethiopia is one of the poorest countries in the world, with gross national income of US$100 (in 2000), less than half the average for Sub-Saharan Africa. Neonatal deaths of some 135,000 a year account for 29 percent of child deaths. According to a 2000 demographics and health survey, coverage of care is extremely low: only 6 percent of women deliver with a skilled attendant present and only 8 percent receive postnatal care within 48 hours of delivery. The poor and those in rural areas have even lower coverage. Health professionals are in short supply. At the same time, obstetric services may be unused even when accessible because of issues of affordability and acceptability (most health workers are male). In 2004, the government and major stakeholders held a national partnership conference to develop a national plan for scaling up child survival interventions. The government decided on a health extension package that would deploy two female health extension workers to each kebele (commune of 5,000 inhabitants). Those workers are mainly responsible for MNCH interventions, such as immunization, micronutrient supplementation, and family planning, but they also have other public health and some clinical responsibilities. In addition, one primary

school graduate per 50 families will be trained to promote healthy family behaviors. Estimates based on the marginal budgeting for bottlenecks tool suggest that, during the first eight years, progressive scaling up of the health extension and health promoters packages, together with some upgrading of clinical services, will cost an additional US$4 per person per year. That effort could result in a 30 percent reduction in the NMR, attributable mostly to improved behaviors, such as clean delivery and exclusive breastfeeding, and to increased demand for care. Increased coverage with family planning and tetanus toxoid vaccination through the health extension package accounts for about 10 percent of the NMR reduction. By the end of the 12-year period, an additional 30 percent reduction in NMR is expected from strengthening clinical services.A comprehensive package of family-based, outreach, and clinical services is projected to reduce the NMR by nearly 50 percent, associated with a 25 percent reduction in the maternal mortality ratio—as compared with a less than 5 percent reduction in the maternal mortality ratio with family and outreach care alone. The incremental annual cost of almost US$10 per person is more than three times current public spending on health of US$2.70.

Source: Knippenberg and others 2005.

Step 1: Assess the Situation and Advocate for Action for Newborn Health Careful examination of local data is required (Lawn, McCarthy, and Ross 2001). Newborn health should be included in general health sector and public sector planning—for instance, for education and transportation. When governments set mortality reduction targets for children under five, they should consider setting simultaneous targets for reducing NMRs (Martines and others 2005). The level of participation— involving multiple stakeholders, including women and communities—and the political will to implement and finance such plans are also crucial to success. Reaching every pregnant woman and every newborn with effective care involves everyone: the family and community provide home care and advocate for access to preventive and curative care; the health system supplies care during normal pregnancy, childbirth, and postnatal care, along with emergency obstetric and young infant care services if required; and the government and global policy makers provide supportive policy and resources, in particular to ensure that there are enough health care providers, such as

midwives. National champions can be effective in promoting progress. Global partnerships may also play a role in facilitating broad national plans and promoting donor convergence in implementation (Tinker and others 2005). The government of Nepal recently held a series of stakeholder meetings and developed a plan for a national newborn health strategy. Representatives from such diverse backgrounds as neonatology, safe motherhood programs, and community mobilization efforts met over a five-month period to create an operational plan for newborn care through 2017 (Khadka, Moore, and Vikery 2003). Step 2: Achieve Optimal Newborn Care within the Constraints of the Current Health System Because situations vary even within countries, data-driven prioritization and good leadership are crucial to using resources well (Lawn, McCarthy, and Ross 2001). Program areas related to newborn health include safe motherhood, child survival, immunization, family planning, and nutrition, along with management of sexually transmitted diseases, prevention of


Box 27.3

Adding Newborns to IMCI in India An estimated 1.1 million neonatal deaths occur annually in India—approximately 28 percent of the world’s total. Between 1960 and 1990, India achieved a 50 percent reduction in infant mortality, but in the 1990s, the decline in the infant mortality rate slowed, partially because of the increasing proportion of infant deaths during the neonatal period. The government looked for ways to add to existing programs and to increase coverage of services, especially given that most neonatal deaths occur in the first few days of life in home settings. Two major adaptations have been made to the standard IMCI approach: • Integrated management of neonatal illness was introduced into the global generic guidelines for IMCI, which do not cover illness in the first week of life. • Focus on outreach services and family care, taking the program into communities to achieve higher coverage, is being promoted through a variety of strategies, namely: — three home visits in 10 days for normal weight babies, with a further three in the subsequent three

weeks if the infant is LBW, to provide essential newborn care, extra care of the LBW infant, and early identification and referral for sepsis — improved coordination between auxiliary nursemidwives and community health workers to assist with the integration of health and nutrition services at household levels. The marginal cost of adding N (for neonatal) into IMCI in relation to clinical care is estimated at less than US$0.10 per person, given the existence of traditional IMCI programs. Training the health and nutrition workers (2 per 1,000 population) and providing home visits is estimated to cost US$0.22 per person. In 2002, the government began to test the integrated management package in 50 districts of United Nations Children’s Fund areas of programming. This initiative has prompted policy makers to scale up implementation throughout the country during the 2005–10 phase of its Reproductive and Child Health Program.

Source: Adapted from K. Suresh, M. Babille, and V. K. Paul, personal communication, April 2004.

maternal-child transmission of HIV, and prevention of malaria during pregnancy. The reality is that such interventions have not reached most women and children and that existing services fail to coordinate along the continuum of care. This situation results in gaps in service and missed opportunities. In Africa, for example, the regional average for prenatal care coverage is 64 percent, yet coverage of tetanus toxoid immunization is 42 percent (Knippenberg and others 2005). Syphilis treatment is another opportunity that frequently is missed during prenatal care (Gloyd, Chai, and Mercer 2001). Including the newborn in transport and funding programs that currently address only maternal emergencies may be of little marginal cost for significant benefit. In India, where integrated management of infant and childhood illness (IMCI) is being scaled up, the marginal cost of adding selected neonatal conditions to the clinical care component of IMCI is low, estimated at less than US$0.10 per capita (box 27.3). In many settings in South Asia and Sub-Saharan Africa, even where midwives are in place they do not have the skills required for newborn care. Competency-based training in neonatal resuscitation is a rarity and must be incorporated into preservice as well as in-service training (box 27.1). India’s National Neonatology Forum identified birth asphyxia as a leading

cause of neonatal deaths and launched the Neonatal Resuscitation Program, developing a course with standard guidelines and certification of competency (Deorari and others 2001). Between 1990 and 1992, more than 12,000 physicians and nurses were trained. The effect of the program was evaluated in 14 teaching hospitals in India. Changes in resuscitation practices were noted, and asphyxia-related mortality fell significantly. The prevalence of survivors with disabilities was not assessed. An alternative model of skill strengthening has been tested in South Africa, where significant improvements in knowledge and skills have been documented as a result of the Perinatal Education Programme, a distance-run self-taught course (Woods and Theron 1995). More than 30,000 midwives in South Africa have passed the examinations, and the program’s manuals are used in many undergraduate medical and nursing schools. Numerous publications have detailed suboptimal hospital management of women in labor or newborns, variously reported as contributing to 10 to 75 percent of all perinatal deaths (Lawn and Darmstadt forthcoming). Thus, there is scope for improving outcomes and client satisfaction in virtually all settings. For example, in much of Sub-Saharan Africa, a Newborn Survival | 545


Box 27.4

South Africa and the Perinatal Problem Identification Programme: Locally Owned Data for Decision Making Care for pregnant women and newborns in South Africa ranges from unattended childbirth in rural mud huts to advanced obstetric and intensive neonatal care. National perinatal mortality is estimated at 40 per 1,000 live births, with regional and racial disparities. During the 1990s, growing awareness of the importance and preventability of newborn deaths resulted in the development of the Perinatal Problem Identification Programme. Under the program, basic data are entered into a computer program that calculates perinatal mortality, supporting the identification of avoidable factors to aid the prioritization of actions to address key problems. More than 44 sites across the country use the Perinatal Problem Identification Programme, covering almost 80,000 births annually, or approximately 10 percent of deliveries, with 3,045 perinatal deaths (2000). Avoidable factors were identified in 83 percent of deaths, with half of these being patient related, such as a delayed response to complications. A

further 14 percent of avoidable factors were administrative and, in particular, were related to transportation and lack of staff members. About 25 percent of the avoidable factors involving health workers pertained to intrapartum care, especially poor monitoring (not using the partograph) and inadequate response to problems identified during labor. Half of the cesarean sections were delayed by an hour or more. The program identified the following national priorities to reduce perinatal deaths: • reducing intrapartum asphyxia, especially in rural areas—for instance, using maternity waiting homes and addressing transport delays • improving intrapartum management by means of protocols (partograph and effective monitoring), competencybased training, and ongoing audit • implementing syphilis screening and treatment more effectively.

Source: Authors, based on data from Pattinson 2002.

significant proportion of women deliver in facilities that collect data that could be used to identify achievable improvements in care (box 27.4).

Step 3: Phase the Systematic Scaling-Up of Newborn Care Although some resource-poor countries have succeeded in building functional systems (box 27.5), the process, especially for clinical care, takes time. Professional care during childbirth and childhood illnesses is the ideal, but significant costs are involved in increasing the numbers of professionals and retaining them, especially in rural posts. Even maintaining current staff presents challenges, given low pay and high frustration. To markedly increase coverage requires new commitment now to a massive expansion in the number of midwives and to innovative approaches to retain staff, especially in hard-toserve areas. Supply constraints must be systematically identified and targeted—notably, human resources, accessibility to facilities, financial barriers, and supply of commodities and drugs (Knippenberg and others 2005). Demand-side strategies are also important, including consideration of subsidies for preventive care or transport for emergency care. In the meantime, most neonatal deaths continue to occur in underserved and poor communities that will wait the longest for access to skilled care. Each year, 60 million women deliver without skilled care present. There is a moral imperative to

reach those women now. Feasible strategies to reduce NMRs exist (for example, efforts to improve family behaviors, tetanus toxoid immunization campaigns, and community-based management of acute respiratory infections) and have been demonstrated in poorly developed health care systems. Interim strategies are available, such as linking a group of traditional birth attendants with skilled attendants (Koblinsky, Campbell, and Heichelheim 1999) or medical assistants to perform cesarean sections. Policy conflicts between skilled and community approaches are not helpful. Both approaches are required. With phased program planning, community services can be used now while professional care is being strengthened. The community services can then promote demand for skilled care (Knippenberg and others 2005).

Step 4: Monitor Coverage and Measure Effect and Cost In most high-mortality countries, NMRs are measured only intermittently (typically every five years through demographic and health surveys). Tracking of coverage indicators, and especially equity of coverage, is important for managing program decision making. Information is lacking, and the information that is available is often not used to improve care. Governments must be encouraged to report funding, coverage, and outcomes related to national plans for maternal, neonatal, and child survival. Donors should also be accountable for reporting funding


Box 27.5

Reducing Newborn Deaths Is Possible in Low-Income Countries Sri Lanka achieved neonatal mortality of 11 per 1,000 live births in 2000 despite a low gross national product per capita of US$800 and less than US$1.50 per capita per year of health spending on maternal and neonatal health. In 1959, maternal and neonatal mortality were high, with an NMR of 50 per 1,000 live births, and gross national product per capita was US$290. Maternal and infant mortality were halved by 1980 because skilled childbirth care was scaled up and because prenatal, childbirth, and postnatal and newborn care services were provided close to commu-

nities and without user charges. The period 1980–2000 saw a further 50 percent reduction in the NMR without the use of intensive care, apart from one unit in the capital. Malaysia also followed a policy of rapid scale-up of the coverage of skilled care at birth. It trained large numbers of midwives and encouraged collaboration with traditional birth attendants to promote a gradual transition to skilled care over several decades. The NMR is now 6 per 1,000 live births, and 95 percent of women deliver with a skilled attendant.

Source: Adapted from Koblinsky 2003.

flows and ensuring that commitments are kept (Martines and others 2005).

RESEARCH PRIORITIES The overwhelming priority in newborn health research remains how to reach underserved populations. This effort involves demonstrating the effect, cost, and scaling up process for packages of interventions. The processes of adapting effective packages to different settings using various cadres of health workers and of identifying indicators of successful implementation that are replicable are all basic to scaling up yet have been little studied. Costing of newborn health interventions is a major gap. Virtually no published examinations of the marginal benefits and costs of adding neonatal interventions to existing programs aimed at safe motherhood, IMCI, HIV/AIDS, malaria, and sexually transmitted diseases are available. A demonstration of such synergies will help influence policy makers to incorporate neonatal issues into these and other programs. Testing innovative approaches to protect poor families from user costs is also important. Given that preterm birth accounts for almost 30 percent of neonatal deaths and contributes indirectly to many more deaths, reducing the incidence of preterm birth and decreasing deaths among preterm infants are important areas for study. Low-tech extra care of small babies has the potential to reduce deaths significantly, but the effectiveness of various home and facility packages, including the potential of emollients for preventing infections, needs to be tested. A large industry is developing high-tech devices for newborn care to address the 2 percent of neonatal deaths in rich countries. Yet there is little investment in the development and testing of low-cost, simple, robust devices in the settings where most fetal and neonatal deaths occur.

Understanding is lacking of the effects of maternal infections, particularly of synergies between HIV, malaria, and sexually transmitted diseases (Ticconi and others 2003) as well as the potential synergy between maternal infections and apparent asphyxial injury to neonates (Peebles and Wyatt 2002). Incidence and intervention data regarding neonatal morbidity and disability at the population level are entirely lacking in LMICs. Improved tools for assessing cause-specific mortality and morbidity outcomes are required to advance answers to many of these questions (Lawn, Cousens, and Wilczynska forthcoming).

CONCLUSIONS Reductions in neonatal mortality are necessary to meet the fourth MDG. High-impact, low-cost, feasible interventions are available. They could avert approximately 70 percent of the world’s 4 million neonatal deaths, according to analysis presented here, an estimate similar to the estimates in the Lancet neonatal series (Darmstadt and others 2005). Large gains in neonatal survival are linked to other health gains, such as reduced childhood morbidity and disability, prevention of stillbirths, and improved maternal survival, thus contributing also to the achievement of the fifth MDG. The success of some low-income countries is encouraging, but in South Asia and Sub-Saharan Africa, coverage is generally low, progress is slow, and inequity is high. While countries continue to move toward a more comprehensive health care system, simpler approaches at family-community level and through outreach services can save many lives now, even in the poorest settings. Well-known interventions, such as neonatal resuscitation and case management of infections, can be added to other programs, particularly safe motherhood and IMCI Newborn Survival | 547


programs, at low marginal cost. However, to reach the MDGs, skilled care is required. Scaling up coverage to ensure professional midwives reach those in underserved areas will require major new investment to generate and retain more skilled staff members, along with the necessary supportive infrastructure. This investment will involve increased spending, which—as shown here—may double current national health expenditures per capita in Asia and triple them in many African countries. Even if poor countries spend more and spend better, outside funding will be required. Current investment in MNCH by most national governments and international donors is utterly inadequate compared with investment in conditions that have higher profiles yet lower mortality rates. The deaths of 10,000 newborns each day are unconscionable when most could be saved now at relatively low cost if the political will to do so existed.

Deorari, A. K., V. K. Paul, M. Singh, and D. Vidyasagar. 2001. “Impact of Education and Training on Neonatal Resuscitation Practices in 14 Teaching Hospitals in India.”Annals of Tropical Paediatrics 21 (1): 29–33. Dragovich, D., G. Tamburlini, A. Alisjahbana, R. Kambarami, J. Karagulova, O. Lincetto, and others. 1997. “Thermal Control of the Newborn: Knowledge and Practice of Health Professionals in Seven Countries.” Acta Paediatrica 86 (6): 645–50. Dujardin, B., H. Sene, and F. Ndiaye. 1992. “Value of the Alert and Action Lines on the Partogram.” Lancet 339 (8805): 1336–38. Duke, T., L. Willie, and J. M. Mgone. 2000. “The Effect of Introduction of Minimal Standards of Neonatal Care on In-Hospital Mortality.” Papua New Guinea Medical Journal 43 (1–2): 127–36. Ellis, M., N. Manandhar, P. S. Shrestha, L. Shrestha, D. S. Manandhar, and A. M. Costello. 1999. “Outcome at One Year of Neonatal Encephalopathy in Kathmandu, Nepal.” Developmental Medicine and Child Neurology 41 (10): 689–95. Gloyd, S., S. Chai, and M. A. Mercer. 2001. “Antenatal Syphilis in SubSaharan Africa: Missed Opportunities for Mortality Reduction.” Health Policy and Planning 16 (1): 29–34. Greenwood, A. M., B. M. Greenwood, A. K. Bradley, K. Williams, F. C. Shenton, S. Tulloch, and others. 1987. “A Prospective Survey of the Outcome of Pregnancy in a Rural Area of The Gambia.” Bulletin of the World Health Organization 65 (5): 635–43.

ACKNOWLEDGMENTS The following individuals are gratefully acknowledged for reviewing this chapter: Gary Darmstadt, Affette Mccaw-Binns, Barbara Stoll, and Anne Tinker. We thank Saving Newborn Lives, especially Julia Ruben, for editing assistance. Joy E. Lawn was supported by the Bill & Melinda Gates Foundation through a grant to Save the Children/USA for the Saving Newborn Lives initiative.

Institute of Medicine. 2003. Improving Birth Outcomes: Meeting the Challenge of the Developing World. Washington, DC: National Institutes of Science.

REFERENCES

Khadka, N., J. Moore, and C. Vikery. 2003. “Nepal’s Neonatal Health Strategy: A Policy Framework for Program Development.” In Shaping Policy for Maternal and Neonatal Health: A Compendium of Case Studies, ed. S. Crump, 47–52. Washington, DC: JHPIEGO. http://www.mnh.jhpiego.org/resources/shapepolicy.asp.

Bang, A. T., R. A. Bang, S. B. Baitule, M. H. Reddy, and M. D. Deshmukh. 1999. “Effect of Home-Based Neonatal Care and Management of Sepsis on Neonatal Mortality: Field Trial in Rural India.” Lancet 354 (9194): 1955–61. Bhutta, Z., G. L. Darmstadt, B. Hasan, and R. Haws. 2005. “CommunityBased Interventions for Improving Perinatal and Neonatal Outcomes in Developing Countries: A Review of the Evidence.” Pediatrics 115 (2): 520–603. Blanc, A., and T. Wardlow. 2005. “Monitoring Low Birth Weight: An Evaluation of International Estimates and an Updated Estimation Procedure.” Bulletin of the World Health Organization 83 (3): 178–85. Conde-Agudelo, A., J. L. Diaz-Rossello, and J. M. Belizan. 2000. “Kangaroo Mother Care to Reduce Morbidity and Mortality in Low Birthweight Infants.” Cochrane Database of Systematic Reviews (2) CD00277 [PMID:]. Daga, S. R., A. S. Daga, S. Patole, S. Kadam, and Y. Mukadam. 1988. “Foot Length Measurement from Foot Print for Identifying a Newborn at Risk.” Journal of Tropical Pediatrics 34 (1): 16–19. Darmstadt, G. L., Z. A. Bhutta, S. N. Cousens, T. Adam, L. de Bernis, and N. Walker. 2005. “Evidence-Based, Cost-Effective Interventions That Matter: How Many Newborns Can We Save and at What Cost?” Lancet 365 (9463): 977–88. Datta, N. 1985. “A Study of Health Problems of Low Birth Weight Babies in a Rural Community and the Feasibility of Intervention Package Likely to Improve Their Health Status.” Ph.D. dissertation, Postgraduate Institute of Medical Education and Research, Chandrigarh, India.

Jamison, D. T., S. Shahid-Salles, J. S. Jamison, J. Lawn, and J. Zupan. 2006. “Incorporating Deaths Near the Time of Birth into Estimates of the Global Burden of Disease.” In Global Burden of Disease and Risk Factors, eds. Alan Lopez, Colin Mathers, Majid Ezzati, Dean Jamison, and Christopher Murray. New York: Oxford University Press. Jones, G., R. W. Steketee, R. E. Black, Z. A Bhutta, and S. S. Morris. 2003. “How Many Child Deaths Can We Prevent this Year?” Lancet 362 (9377): 65–71.

Knippenberg, R., J. E. Lawn, G. L. Darmstadt, G. Bekyorian, H. Fogstadt, N. Waleign, and V. Paul. 2005. “Systematically Scaling Up Newborn Care in Countries.” Neonatal Series Paper 3. Lancet 365: 1087–98. Koblinsky, M. A., ed. 2003. Reducing Maternal Mortality: Learning from Bolivia, China, Egypt, Honduras, Indonesia, Jamaica, and Zimbabwe. Washington, DC: World Bank. http://www-wds.worldbank.org/ servlet/WDSContentServer/WDSP/IB/2003/06/06/000094946_030528 0402518/Rendered/PDF/multi0page.pdf. Koblinsky, M. A., O. Campbell, and J. Heichelheim. 1999. “Organizing Delivery Care: What Works for Safe Motherhood?” Bulletin of the World Health Organization 77 (5): 399–406. Kumar, R. 1995. “Birth Asphyxia in a Rural Community of North India.” Journal of Tropical Pediatrics 41 (1): 5–7. Lawn, J. E., S. N. Cousens, and K. Wilczynska. Forthcoming. Estimating the Cause of Death for 4 Million Neonates in the Year 2000. Lawn, J. E., S. N. Cousens, and J. Zupan. 2005. “Four Million Neonatal Deaths: When? Where? Why?” Neonatal Series Paper 1. Lancet 365 (9462): 891–900. Lawn, J. E., and G. L. Darmstadt. Forthcoming. “A Review of Strategies to Address Birth Asphyxia Especially for the Poor.” Journal of Perinatology (Suppl.). Lawn, J. E., B. McCarthy, and S. R. Ross. 2001. The Healthy Newborn: A Reference Guide for Program Managers. Atlanta: Centers for Disease


Control and Prevention and CARE. http://www.cdc.gov/reproductivehealth/health_newborn.htm. Lumbiganon, P., M. Panamonta, M. Laopaiboon, S. Pothinam, and N. Patithat. 1990.“Why Are Thai Official Perinatal and Infant Mortality Rates So Low?” International Journal of Epidemiology 19 (4): 997–1000. Manandhar, D. S., D. Osrin, B. P. Shrestha, N. Mesko, J. Morrison, K. M. Tumbahangphe, and others. 2004. “Effect of a Participatory Intervention with Women’s Groups on Birth Outcomes in Nepal: Cluster-Randomised Controlled Trial.” Lancet 364 (9438): 970–79. Martines, J., V. K. Paul, Z. A. Bhutta, M. Koblinsky, A. Soucat, N. Walker, and others. 2005. “Increasing Newborn Survival: A Call to Action.” Lancet 365 (9465): 1189–97. Massawe, A., C. Kilewo, S. Irani, R. J. Verma, A. B. Chakrapam, T. Ribbe, and others. 1996. “Assessment of Mouth-to-Mask Ventilation in Resuscitation of Asphyctic Newborn Babies: A Pilot Study.” Tropical Medicine and International Health 1 (6): 865–73.

Sazawal, S., and R. E. Black. 2003. “Effect of Pneumonia Case Management on Mortality in Neonates, Infants, and Preschool Children: A Meta-analysis of Community-Based Trials.” Lancet Infectious Diseases 3 (9): 547–56. Thaddeus, S., and D. Maine. 1994. “Too Far to Walk: Maternal Mortality in Context.” Social Science and Medicine 38 (8): 1091–110. Ticconi, C., M. Mapfumo, M. Dorrucci, N. Naha, E. Tarira, A. Pietropolli, and others. 2003. “Effect of Maternal HIV and Malaria Infection on Pregnancy and Perinatal Outcome in Zimbabwe.” Journal of Acquired Immune Deficiency Syndrome 34 (3): 289–94. Tinker A., P. ten Hoope-Bender, S. Azfar, F. Bustreo, and R. Bell. 2005. “A Continuum of Care to Save Newborn Lives.” Lancet 365 (9462): 822–52. WHO (World Health Organization). 1998a. Basic Newborn Resuscitation: Practical Guide. WHO/RHT/MSM/98.1, 1–32. Geneva: WHO. ———. 1998b. Evidence for the Ten Steps to Successful Breastfeeding. WHO/CHD/98.9, 1–118. Geneva: WHO.

Mathers C. D., C. J. L. Murray, and A. D. Lopez. 2006. “The Burden of Disease and Mortality by Condition: Data, Methods and Results for the Year 2001.” In Global Burden of Disease and Risk Factors, eds. Alan Lopez, Colin Mathers, Majid Ezzati, Dean Jamison, and Christopher Murray. New York: Oxford University Press.

———. 2003b. Pregnancy, Childbirth, Postpartum, and Newborn Care: A Guide for Essential Practice. Geneva: WHO.

Meegan, M. E., R. M. Conroy, S. O. Lengeny, K. Renhault, and J. Nyangole. 2001. “Effect on Neonatal Tetanus Mortality after a Culturally-Based Health Promotion Programme.” Lancet 358 (9284): 640–41.

———. Forthcoming. Neonatal and Perinatal Mortality, Estimates for 2000. Geneva: WHO.

O’Rourke, K., L. Howard-Grabman, and G. Seoane. 1998. “Impact of Community Organization of Women on Perinatal Outcomes in Rural Bolivia.” Revista Panamericana de Salud Pública 3: 9–14.

WHO (World Health Organization) Collaborative Group. 2000. “Effect of Breastfeeding on Infant and Child Mortality Due to Infectious Diseases in Less Developed Countries: A Pooled Analysis.” Lancet 355: 451–55.

Pattinson, R. C., ed. 2002. Saving Babies 2001: Second Perinatal Care Survey of South Africa. Pretoria: MRC Unit for Maternal and Infant Health Care Strategies. Peebles, D. M., and J. S. Wyatt. 2002. “Synergy between Antenatal Exposure to Infection and Intrapartum Events in Causation of Perinatal Brain Injury at Term.” British Journal of Obstetrics and Gynaecology 109 (7): 737–39. Peterson, S., J. Nsungwa-Sabiiti, W. Were, X. Nsabagasani, G. Magumba, J. Nambooze, and G. Mukasa. 2004. “Coping with Paediatric Referral— Ugandan Parents’ Experience.” Lancet 363 (9425): 1955–56. Pojda, J., and L. M. Kelley, eds. 2000. Low Birth Weight: Report of a Meeting in Dhaka, Bangladesh, 14–17 June 1999. Nutrition Policy Paper 18. Geneva: United Nations Subcommittee on Nutrition. Pratinidhi, A., U. Shah, A. Shrotri, and N. Bodhani. 1986. “Risk-Approach Strategy in Neonatal Care.” Bulletin of the World Health Organization 64: 291–97.

———. 2003a. Global Burden of Disease, 2000. Version c. Geneva: WHO.

———. 2003c. Working with Individuals, Families, and Communities. Geneva: WHO.

Woods, D. L., and G. B. Theron. 1995. “The Impact of the Perinatal Education Programme on Cognitive Knowledge in Midwives.” South African Medical Journal 85 (3): 150–53. Yasmin, S., D. Osrin, E. Paul, and A. Costello. 2001. “Neonatal Mortality of Low-Birth-Weight Infants in Bangladesh.” Bulletin of the World Health Organization 79 (7): 608–14. Zhu, X. Y., H. Q. Fang, S. P. Zeng, Y. M. Li, H. L. Lin, and S. Z. Shi. 1997. “The Impact of the Neonatal Resuscitation Program Guidelines (NRPG) on the Neonatal Mortality in a Hospital in Zhuhai, China.” Singapore Medical Journal 38 (11): 485–87. Zupan, J., and P. Garner. 2000. “Topical Umbilical Cord Care at Birth.” Cochrane Database of Systematic Reviews (3) CD001057 [DOI:10.1002/14651858].

Saugstad, O. D. 2001. “Resuscitation of Newborn Infants with Room Air or Oxygen.” Seminars in Neonatology 6 (3): 233–39.



Chapter 28

Stunting, Wasting, and Micronutrient Deficiency Disorders Laura E. Caulfield, Stephanie A. Richard, Juan A. Rivera, Philip Musgrove, and Robert E. Black

Undernutrition and micronutrient deficiencies contribute substantially to the global burden of disease (Ezzati and others 2002). Impoverished communities experience high rates of undernutrition and increased exposure to infectious diseases caused by crowding and inadequate sanitation. Women of reproductive age and children experience devastating health consequences as a result of limited resources, cultural influences, and biological vulnerabilities. Undernutrition and infectious diseases exist in a baleful synergy: undernutrition reduces immunological capacity to defend against diseases, and diseases deplete and deprive the body of essential nutrients. Undernutrition and infectious diseases further exacerbate poverty through lost wages, increased health care costs, and— most insidiously—impaired intellectual development that can significantly reduce earning potential. Health experts have recently recognized the long-term effects of early undernutrition and inadequate infant feeding for obesity and chronic diseases, including diabetes and cardiovascular diseases. This chapter summarizes the problems of undernutrition and vitamin A, iron, zinc, and iodine deficiencies in young children and current programmatic efforts to prevent and treat them.

NATURE, CAUSES, AND BURDEN OF UNDERNUTRITION The following section describes the magnitude, distribution, and etiology of growth faltering and specific micronutrient deficiencies in young children.

Growth Faltering Because nutritional inputs are necessary for children’s growth, undernutrition is generally characterized by comparing the weights or heights (or lengths) of children at a specific age and sex with the distribution of observed weights or heights in a reference population of presumed healthy children of the same age and sex and then calculating z-scores, that is, the difference between a child’s weight or height and the median value at that age and sex in the reference population, divided by the standard deviation (SD) of the reference population. A child whose height-for-age is less than 2 SD is considered stunted, because the chances of the child’s height being normal are less than 3 percent. A child whose weight-for-age is less than 2 SD is considered underweight, and one whose weight-for-height is less than 2 SD is deemed wasted. Stunting results from chronic undernutrition, which retards linear growth, whereas wasting results from inadequate nutrition over a shorter period, and underweight encompasses both stunting and wasting. Typically, growth faltering begins at about six months of age, as children transition to foods that are often inadequate in quantity and quality, and increased exposure to the environment increases their likelihood of illness. Although knowledge about the prevalence of stunting and wasting is preferred, information about underweight is more available globally. The high correlation between stunting and underweight and the low prevalence of wasting mean that the prevalence of underweight directly describes the magnitude of the problem of growth faltering and stunting in young children. About 130 million children under the age of five are 551


underweight, with the highest prevalences in South Asia and Sub-Saharan Africa (table 28.1). The prevalence of stunting, underweight, and wasting is decreasing in most areas of the world; however, in most of Africa, stunting is increasing. Childhood malnutrition diminishes adult intellectual ability and work capacity, causing economic hardships for individuals and their families. Malnourished women tend to deliver premature or small babies who are more likely to die or suffer from suboptimal growth and development (Allen and Gillespie 2001). Poor early nutrition leads to poor school readiness and performance, resulting in fewer years of schooling, reduced productivity, and earlier childbearing. Thus, poverty, undernutrition, and ill-health are passed on from generation to generation. Undernutrition impedes economic progress in all developing countries. Undernutrition raises the likelihood that a child will become sick and will then die from the disease. Morbidity and mortality are highest among those most severely malnourished; however, given the high prevalence of mild to moderate underweight, the mildly or moderately underweight individuals experience

the greatest total burden of disease (Fishman and others 2004). Children whose weight-for-age is less than 1 SD are also at increased risk of death, and undernutrition is responsible for 44 to 60 percent of the mortality caused by measles, malaria, pneumonia, and diarrhea. Overall, eliminating malnutrition would prevent 53 percent of deaths in young children, with most of those deaths occurring in South Asia and Sub-Saharan Africa (table 28.2). Morbidity attributable to undernutrition depends on the nature of the illness. Susceptibility to a highly infectious disease such as measles is unlikely to be affected by nutritional status: all individuals are equally likely to become infected if they are unvaccinated and naive. However, 5 to 16 percent of pneumonia, diarrhea, and malaria morbidity is attributable to moderate to severe underweight (Fishman and others 2004). As table 28.3 shows, the number of disability-adjusted life years (DALYs) attributable to undernutrition is high and, as with mortality, is concentrated in South Asia and Sub-Saharan Africa. The tremendous costs associated with the care and treatment of childhood diseases that could be partially

Table 28.1 Estimated Prevalence of Selected Nutritional Deficiencies in Children Ages Birth through Four, by Region (percent) Weight-for-age less than 2 SD

Weight-for-age 2 SD through less than 1 SD

Vitamin A deficiency

Iron deficiency anemia

Zinc deficiency

18

29

11

40

7

Eastern Europe and Central Asia

6

21

1

22

10


6

23

15

46

33


21

35

18

63

46

South Asia

46

44

40

76

79

Sub-Saharan Africa

32

38

32

60

50

2

14

0

7

5

Region East Asia and the Pacific


Sources: Underweight: Fishman and others 2004; vitamin A: Rice, West, and Black 2004; iron: Stoltzfus, Mullany, and Black 2004; zinc: Caulfield and Black 2004.

Table 28.2 Estimated Deaths of Children Ages Birth through Four Attributable to Selected Nutritional Deficiencies by Region (thousands) Region East Asia and the Pacific Eastern Europe and Central Asia Latin America and the Caribbean Middle East and North Africa South Asia Sub-Saharan Africa High-income countries

Weight-for-age less than 1 SDa


Iron deficiency anemiab

Zinc deficiency

125

11

18

15

14

0

3

4

22

6

10

15

305

70

10

94

870

157

66

252

1,334

383

21

400

0

0

6

0

Sources: Underweight: Fishman and others 2004; vitamin A: Rice, West, and Black 2004; iron: Stoltzfus, Mullany, and Black 2004; zinc: Caulfield and Black 2004. a. In high-income countries, the percentage of children at each weight-for-age criterion are those expected in a healthy population. b. Considers only deaths directly attributable to iron deficiency anemia in children. Does not include perinatal deaths attributable to maternal iron deficiency anemia.

552 | Disease Control Priorities in Developing Countries | Laura E. Caulfield, Stephanie A. Richard, Juan A. Rivera, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 126

Table 28.3 Estimated DALYs Lost by Children Ages Birth through Four Attributable to Selected Nutritional Deficiencies by Region (thousands) Region East Asia and the Pacific Eastern Europe and Central Asia Latin America and the Caribbean Middle East and North Africa

Weight-for-age less than 1 SD


Iron deficiency anemiaa

Zinc deficiency

Iodine deficiency

5,777

994

241

1,004

66

489

1

66

149

409

725

218

109

587

83

10,308

2,403

109

3,290

381

South Asia

27,879

4,761

704

8,510

366

Sub-Saharan Africa

45,131

13,552

596

14,094

748

0

0

40

2

2


Sources: Underweight: Fishman and others 2004; vitamin A: Rice, West, and Black 2004; iron: Stoltzfus, Mullany, and Black 2004; zinc: Caulfield and Black 2004. a. Only considers DALYs directly attributable to iron deficiency anemia. Not included are DALYs due to perinatal deaths attributable to maternal iron deficiency anemia.

prevented through improvements in child nutrition have not been quantified. Evidence is accumulating that early malnutrition increases the risk of numerous chronic diseases later (Caballero 2001; Gluckman and Hanson 2004). Associations of early undernutrition with diabetes, hypertension, renal disease, and cardiovascular disease mean that child undernutrition also leads to high adult health care costs.

Vitamin A Deficiency Vitamin A deficiency (VAD) is a common cause of preventable blindness and a risk factor for increased severity of infectious disease and mortality (Rice, West, and Black 2004). One of the first symptoms of marginal VAD is night blindness. If VAD worsens, additional symptoms of xerophthalmia arise, eventually resulting in blindness. A child who becomes blind from VAD has only a 50 percent chance of surviving the year. Even if children survive, blindness severely diminishes their economic potential. VAD may cause anemia in some regions, but it does not appear to impair children’s growth (Ramakrishnan and others 2004). Increased mortality is associated with VAD, most likely because of the detrimental effects on the immune system, which result in increased severity of illness (Sommer and West 1996). According to Rice, West, and Black (2004), VAD is responsible for almost 630,000 deaths each year from infectious disease (table 28.2), accounting for 20 to 24 percent of the mortality from measles, diarrhea, and malaria (Rice, West, and Black 2004). Attributable fractions are highest where VAD is prevalent and mortality is high. Linking morbidity with VAD is far more difficult. Vitamin A supplementation decreases the severity of diarrhea and complications from measles, but in some trials, supplementation has been associated with increased lower respiratory infections. VAD results from inadequate intakes of vitamin A because of low intakes of animal foods; inadequate intakes of nonanimal sources of carotenoids that are converted to vitamin A; and

inadequate intakes of fat, which facilitates the absorption of carotenoids. Dietary sources of preformed vitamin A include liver, milk, and egg yolks. Dark green leafy vegetables such as spinach, as well as yellow and orange noncitrus fruits (mangoes, apricots, papayas) and vegetables (pumpkins, squash, carrots), are common sources of carotenoids (vitamin A precursors), which are generally less bioavailable than preformed vitamin A but tend to be more affordable. Table 28.1 shows recent estimates of the prevalence of VAD in young children (Rice, West, and Black 2004). Of those affected, 250,000 to 500,000 each year will lose their sight as a result. The overall prevalence of VAD is decreasing markedly because of increased awareness of VAD as a public health problem and increased measles immunization and vitamin A supplementation or fortification programs. However, the prevalence of VAD is increasing or is unknown in some regions because of political instability, high rates of infectious disease, and increasing poverty.

Iron Deficiency More than 2 billion people, mostly women and young children, are thought to be iron deficient (Stoltzfus and Dreyfuss 1998). Iron is found in all plant foods but is more plentiful and bioavailable in meat. Deficiency results from insufficient absorption of iron or excess loss. Absorption is tightly regulated in the intestines, depending on the iron status of the individual, the type of iron, and other nutritional factors. Once iron is absorbed, it is well conserved. Iron is depleted primarily through blood loss, including from parasitic infections such as schistosomiasis and hookworm. Mainly found in hemoglobin, iron is essential for the binding and transport of oxygen, as well as for the regulation of cell growth and differentiation (Beard 2001). Iron deficiency is the primary cause of anemia, although vitamin A deficiency, folate deficiency, malaria, and HIV also result in anemia. Iron deficiency anemia is most prevalent in South Asia and Sub-Saharan Stunting, Wasting, and Micronutrient Deficiency Disorders | 553


Africa, but it is not limited to developing countries (table 28.1). Iron deficiency results in neurological impairment, which may not be fully reversible (Grantham-McGregor and Ani 1999). Finally, iron deficiency is known to decrease immune function, but some investigators have also hypothesized that deficiency protects against infectious disease or that iron supplementation increases infectious disease (Caulfield, Richard, and Black 2004). Iron deficiency and anemia do not appear to contribute to growth faltering (Ramakrishnan and others 2004). Stoltzfus, Mullany, and Black (2004) find that iron deficiency anemia was an underlying factor in 841,000 deaths per year resulting from maternal and perinatal causes, and it directly causes the deaths of 134,000 young children annually (table 28.2). Worldwide, iron deficiency is a substantial contributor to DALY losses (table 28.3). Iodine Deficiency Iodine is necessary for the thyroid hormones that regulate growth, development, and metabolism and is essential to prevent goiter and cretinism. Inadequate intake can result in impaired intellectual development and physical growth. A range of impairments resulting from iodine deficiency are referred to as iodine deficiency disorders (IDD) (Hetzel 1983) and can include fetal loss, stillbirth, congenital anomalies, and hearing impairment. The vast majority of deficient individuals experience mild mental retardation. This decrease in mental ability and work capacity may have significant economic consequences. Iodine deficiency has not, however, been associated with the incidence or severity of infectious disease, and studies implicating deficiency as an underlying cause of mortality are limited. Because of this, few child deaths can be attributed to iodine deficiency, but the directly attributable DALY losses remain considerable (table 28.3). The prevalence of iodine deficiency is often estimated from the prevalence of palpable goiter, but this method is not sensitive to milder expressions of deficiency. Iodine deficiency is thought to be a public health problem in a community if goiter is detected in more than 5 percent of the school-age population. A prevalence greater than 30 percent means that the deficiency is severe. According to World Health Organization (WHO) estimates, goiter rates among school-age children exceed 5 percent in 130 countries, putting 2,225,000 people at risk of IDD. A high prevalence of IDD occurs in Eastern Europe and Central Asia, the Eastern Mediterranean and North Africa, South Asia, and Sub-Saharan Africa (WHO 1999). Iodized salt programs are decreasing iodine deficiency in many regions; however, this reduction is offset by apparent increases in other regions, where public health officials are now aware of the problem because of increased surveillance. Switzerland and the United States embarked on iodine fortification programs in earnest in the early 1920s. Success resulted in enthusiastic political and financial support for increased

global coverage, and control of IDD through salt iodation represents a great achievement in international public health. Nevertheless, significant numbers of people remain at risk. Zinc Deficiency Zinc is ubiquitous within the body and is vital to protein synthesis, cellular growth, and cellular differentiation. Studies in children have demonstrated important roles for zinc in relation to immune function, growth, and development (Brown and others 2002; Shankar and Prasad 1998). Zinc deficiency results from inadequate intakes and, to some extent, increased losses. Only animal flesh, particularly oysters and shellfish, is a good source of zinc, and fiber and phytates inhibit absorption. Thus, as with iron deficiency, populations consuming a primarily plant-based diet are susceptible. Deficiency can also result from losses during diarrheal illness. Consensus is currently lacking on how to measure zinc deficiency in individuals. The International Zinc Nutrition Consultative Group recommended using serum or plasma zinc concentrations to identify the risk of deficiency at the population level. In addition, the group used information on absorbable zinc in the food supplies of 176 countries to estimate the proportion of each national population at risk of inadequate intake (table 28.1). This information was used to calculate the burden of disease (table 28.2) associated with zinc deficiency in young children. Prevalence is not expected to decrease unless the implementation of zinc-related interventions increases substantially (Caulfield and Black 2004). The health consequences of severe zinc deficiency have been elucidated over the past 40 years, whereas the health risks of mild to moderate deficiency have been described only recently. Clinical presentations of severe deficiency include growth retardation, impaired immune function, skin disorders, hypogonadism, anorexia, and cognitive dysfunction. Mild to moderate deficiency increases susceptibility to infection, and the benefits of zinc supplementation on the immune system are well documented (Shankar and Prasad 1998). Zinc can prevent and palliate diarrhea and pneumonia (Zinc Investigators’ Collaborative Group and others 1999, 2000) and also may reduce malaria morbidity in young children (Caulfield, Richard, and Black 2004). Improvements in growth have been demonstrated (Brown and others 2002), which may operate directly or indirectly through increased immune function and decreased infectious disease. Zinc deficiency is estimated to be responsible for about 800,000 deaths annually from diarrhea, pneumonia, and malaria in children under five (table 28.2). Sub-Saharan Africa, the Eastern Mediterranean, and South Asia bear the heaviest attributable burden of pneumonia and diarrhea, with SubSaharan Africa accounting for nearly the entire attributable malaria burden.


INTERVENTIONS Clearly, growth faltering and micronutrient deficiency disorders are prevalent, have deleterious consequences for children’s health and development, and are primary contributors to the global burden of disease. Economic development is not the only path to solving childhood undernutrition. Improvements in family income may not translate into increased food intakes because the income elasticity for caloric intake is relatively low. The effects on micronutrient deficiencies might be greater if the food sources of those nutrients (meat, seafood, eggs, fortified food products) were more sensitive to income increases and if children had access to those foods. Price subsidies may reduce undernutrition in young children if targeted to foods consumed by them; the potential contribution of price subsidies to family nutrition is discussed elsewhere (see chapter 11). This chapter focuses on specific public health measures that are intended to address the problems directly. Progress has been made in some areas, but the current magnitude of the problems and of the associated disease burden underscore the need for more investment in nutritional interventions. Growth Faltering and Childhood Stunting Infants and young children falter in their growth because of inadequate dietary intakes and recurrent infectious diseases, which reduce appetite, increase metabolic requirements, and increase nutrient loss. Even though this problem is understood, progress to reduce malnutrition has been slow. Over time, thinking on how to reduce growth faltering and childhood stunting has shifted. Whereas previous efforts focused almost exclusively on identifying and rehabilitating severely malnourished children, current efforts emphasize prevention through combined nutritional and disease prevention and treatment interventions. Initially, these efforts to prevent undernutrition focused on diseases rather than on improved child feeding practices as such. However, according to Becker, Black, and Brown (1991), despite the devastating effects of illness on nutritional status, improving dietary intakes is more effective than disease prevention efforts in reducing undernutrition. Because of dramatic reductions in appetite during illness, efforts to improve dietary intakes initially focused on maintaining energy intakes despite anorexia and on increasing intakes during recuperation, when appetite may be normal or high. More recent interventions aim at feeding healthy children optimal diets, which includes paying attention to dietary quality. Finally, some have argued that, for nutritional advice to be effective, it needs to be provided alongside growth monitoring and promotion; however, it is increasingly recognized that messages for prevention are largely universal and that integrated growth monitoring and promotion are not the only model for service delivery.

Promotion of Optimal Feeding of Infants and Young Children. Much of the early focus on optimal feeding was on breastfeeding, which should be immediate and exclusive until six months of age. At that time nutritious and safe foods should be added to a diet that is still based on breast milk until early in the second year of life. A consensus has been reached that six months is the recommended duration of exclusive breastfeeding (WHO 2002) and that the total duration is a decision left to the mother. Multiple approaches exist to promote the initiation of breastfeeding and to prolong exclusive breastfeeding—health education; professional support; lay support; health sector changes (for example, infant friendly hospitals); and media campaigns—through health facilities and community programs. A recent Cochrane review estimates the potential effectiveness of these approaches (Sikorski and others 2002). Women who received any form of support for breastfeeding were 22 percent less likely to stop exclusive breastfeeding, and women who received lay support, in particular, were 34 percent less likely to stop exclusive breastfeeding. Substantial evidence indicates that interventions can be effective in prolonging breastfeeding and exclusive breastfeeding and that operational research is needed for program implementation and sustainability. If such programs were fully successful, they would reduce deaths in children under five by 13 percent (Jones and others 2003). Complementary feeding is the process of introducing other foods and liquids into the child’s diet when breast milk alone is no longer sufficient to meet nutritional requirements. According to Brown, Dewey, and Allen (1998), complementary feeding practices are suboptimal from several perspectives: • Complementary foods are introduced too early or too late. • Foods are served too infrequently or in insufficient amounts, or their consistency or energy density is inappropriate. • The micronutrient content of foods is inadequate to meet the child’s needs, or other factors in the diet impair the absorption of foods. • Microbial contamination may occur. In addition, because children often do not eat all the food offered to them, interaction between the caregiver and the child, along with other psychosocial aspects of care during feeding, requires attention. The amount of complementary food a child needs depends on breast milk intake. Guidelines are available for determining energy and nutrient intakes from complementary foods, given breast milk intakes (Dewey and Brown 2003). Several reviews of the multiple approaches to improving infant and young child feeding practices are available (Allen and Gillespie 2001; Caulfield, Huffman, and Piwoz 1999; Dewey 2002; Hill, Kirkwood, and Edmond 2004; Swindale and others 2004). Caulfield, Huffman, and Piwoz (1999) review Stunting, Wasting, and Micronutrient Deficiency Disorders | 555


16 programs in 14 countries to improve dietary intakes of infants 6 to 12 months of age. The programs were designed to promote exclusive breastfeeding and appropriate feeding during illness up to age three, and the content and approaches reflected current thinking regarding nutrition and behavior change. The approaches employed included using the mass media to reach both caregivers and the population as a whole to change cultural norms about complementary feeding and using one-on-one or small group interactions with community health workers to provide individualized information and support. Most of the projects achieved good coverage (50 to 70 percent), with rates varying depending on the communication strategy. They resulted in large shifts in maternal knowledge and attitudes and changes in infant feeding practices. In the few programs assessing dietary intakes, intakes improved by 70 to 165 kilocalories per day. Differences in nutritional status at 12 months indicated weight-for-age and height-for-age gains of 0.24 to 0.87 SD. Even with a 50 percent overestimation of the effects, the effect of such programs could translate into tangible reductions in malnutrition and attributable mortality. In addition, these calculations do not consider the cumulative reduction in malnutrition from programs that benefit children’s growth into the second and third years of life. Jones and others (2003) use the results of the analysis, along with knowledge of the relationship between underweight and child mortality, to estimate that programs to promote complementary feeding could reduce by 6 percent the deaths of children under five in developing countries. Many programs provide supplemental food to participants either to provide them an incentive for participating in other activities (to offset time costs and increase consumer demand for preventive services) or to rehabilitate severely malnourished children. Although the latter approach is traditionally considered for supplemental food programs, the former approach is more common. Indeed, India’s Integrated Child Development Services Program, the world’s largest supplemental food program, plans to shift from rehabilitation to the use of supplemental food as a “magnet” for providing other integrated child development services (Kapil 2002). No consensus exists on when or how to include supplemental food to reduce undernutrition, and inefficient targeting is frequently a key constraint to effectiveness. Swindale and others’ (2004) review of the effectiveness of food-assisted child survival programs concludes that such programs are reducing malnutrition by 2.0 to 2.5 percent per year. Despite evidence of the effectiveness of nutritional interventions in improving feeding practices and preventing undernutrition, few programs take a comprehensive approach toward optimizing infant feeding, perhaps because of a lack of consensus on the key components of a comprehensive strategy. In 2002, participants at a WHO consultation developed 10 guiding

principles for optimal feeding of the breastfed child (PAHO and WHO 2003). These principles, outlined in box 28.1, build on lessons from previous programmatic efforts such as those reviewed here and provide a basis for designing comprehensive programs to reduce malnutrition. The international public health community faces the challenge of implementing and evaluating these approaches. Disease Control and Prevention. Interventions to prevent or decrease malnutrition or infectious disease are expected to decrease child mortality, and interventions that accomplish both will have the greatest effect (Pelletier, Frongillo, and Habicht 1993). This subsection considers the potential for disease control and prevention efforts to reduce undernutrition in young children. Malaria is responsible for a large portion of childhood mortality in Sub-Saharan Africa. The effect of undernutrition on susceptibility to malaria has been discussed at length elsewhere (Caulfield, Richard, and Black 2004), but the nutritional deficiencies resulting from malaria have been insufficiently explored. Insecticide-treated bednets have been shown to prevent clinical episodes of malaria and decrease the prevalence of anemia in children (Lengeler 2003). Improvements in growth have also been documented. Water, sanitation, and hygiene interventions decrease childhood malnutrition primarily by preventing diarrheal disease (Checkley and others 2004). Hand-washing interventions can reduce the risk of diarrheal diseases by about 45 percent. Handwashing interventions can be included in water and sanitation programs or can exist as a single intervention, and they are both effective and cost-effective (Borghi and others 2002).

Vitamin A Deficiency Even though the consequences of VAD had been defined by 1920, it was 1986 when vitamin A interventions were rigorously studied in a large, controlled community trial (Sommer and West 1996). A number of other community trials soon also demonstrated a significant decrease in child mortality with vitamin A supplementation (Beaton and others 1993). Supplementation can alleviate acute VAD quickly, whereas long-term strategies incorporate fortification and dietary diversification. Supplementation can be either a curative or a preventive measure. If an individual presents with ocular symptoms of VAD, supplementation is part of the usual standard of care. Beyond the use of supplementation for symptoms that result directly from deficiency, its use as part of the treatment regimen for measles or severe malnutrition can improve health outcomes. In deficient areas, high-dose oral supplementation is recommended every four to six months for children under five and is highly efficacious in reducing ocular effects as well as


Box 28.1

Guiding Principles for Complementary Feeding of the Breastfed Child 1. Practice exclusive breastfeeding from birth to six months of age and introduce complementary foods at six months of age (180 days) while continuing to breastfeed. 2. Continue frequent, on-demand breastfeeding until two years of age or beyond. 3. Practice responsive feeding, applying the principles of psychosocial care. Specifically, do the following: • Feed infants directly and assist older children when they feed themselves, being sensitive to their hunger and satiety cues. • Feed slowly and patiently; encourage children to eat, but do not force them. • Experiment with different food combinations, tastes, textures, and methods of encouragement if children refuse many foods. • Minimize distractions during meals if the child loses interest easily. • Remember that feeding times are periods of learning and love, and talk to children during feeding, including making eye contact. 4. Practice good hygiene and proper food handling: • Wash hands before food preparation and eating (both caregivers and children). • Store foods safely and serve foods immediately after preparation. • Use clean utensils to prepare and serve food. • Use clean cups and bowls when feeding children. • Avoid the use of feeding bottles, which are difficult to keep clean. 5. Start at six months of age with small amounts of food and increase the quantity as the child gets older, while maintaining frequent breastfeeding. According to average breast milk intakes in developing countries, infants’ needs from complementary foods are approximately 200 kilocalories per day at 6 to 8 months, 300 kilocalo-

6.

7.

8.

9.

10.

ries per day at 9 to 11 months, and 550 kilocalories per day at 12 to 23 months. Increase food consistency and variety gradually as the infant gets older, adapting to the infant’s requirements and abilities. Infants can eat pureed, mashed, and semisolid foods beginning at six months. By eight months most infants can also eat finger foods—that is, snacks that they can eat unaided. By 12 months, most children can eat the same types of foods that the rest of the family consumes, keeping in mind the need for nutrient-dense foods. Avoid foods that cause choking. Increase the frequency with which the child is fed complementary foods as he or she gets older. The appropriate number of feedings depends on the energy density of local foods and the usual amounts consumed at each feeding. For the average healthy, breastfed infant, meals should be provided two or three times a day at 6 to 8 months of age and three or four times a day at 9 to 23 months of age, with additional snacks. Feed a variety of foods to ensure that nutrient needs are met. The child should eat meat, poultry, fish, or eggs daily, or as often as possible. Vegetarian diets cannot meet nutrient needs at this age unless nutrient supplements or fortified products are used. Use fortified complementary foods or vitamin and mineral supplements for the infant, as needed. In some populations, breastfeeding mothers may also need vitamin and mineral supplements or fortified products for their own health and to ensure normal concentrations of certain nutrients in their breast milk. Increase fluid intake during illness, including more frequent breastfeeding, and encourage the child to eat soft, varied, appetizing, favorite foods. After illness, give food more often than usual, and encourage the child to eat more.

Source: PAHO and WHO 2003.

mortality (Sommer and West 1996). A meta-analysis of controlled trials in children demonstrated a 23 percent reduction in mortality (Beaton and others 1993). High-dose vitamin A supplements are considered safe for infants younger than six months. Several studies suggest that giving vitamin A within 48 hours of birth reduces mortality in the first three months by 21 to 74 percent (D. Ross 2002).

A variety of foodstuffs have been fortified with vitamin A, including oil, monosodium glutamate, butter, wheat flour, sugar, and rice. Fortified white sugar has been successful in reducing VAD prevalence in Central America. In El Salvador and Guatemala, where fortified sugar is the primary source of vitamin A, it accounts for approximately 30 percent of the recommended dietary intake (RDI). Fortification of monosodium Stunting, Wasting, and Micronutrient Deficiency Disorders | 557


glutamate with vitamin A has been demonstrated to be biologically efficacious. Even though program implementation was flawed by unacceptable cost, discoloration of the monosodium glutamate, and packaging problems, indicators of VAD declined significantly during periods of fortification in both Indonesia and the Philippines (Dary and Mora 2002). Vitamin A intakes can also be improved through dietary diversification, either by educating communities about important sources of vitamin A and beta-carotene that are available in the local diet or by increasing economic prosperity so that individuals have additional funds to spend on a wider variety of food. Education alone has not been demonstrated to affect the degree of VAD in a community, but it can be a powerful tool when incorporated in a broader strategy that also includes supplementation and fortification (Sommer and West 1996).

Iron Deficiency Despite the public health community’s enduring interest in preventing and treating iron deficiency anemia, little evidence suggests that the problem has been reduced. Indeed, in some regions the opposite may be true. From the 1970s to the 1980s, the iron density of people’s diets decreased in every region except the Near East and North Africa as iron-poor cereals displaced legumes. During much of this period, iron deficiency anemia increased in South Asia and Sub-Saharan Africa, where the problem is most severe (Stoltzfus, Mullany, and Black 2004). Goals for reducing iron deficiency anemia were articulated for the 1990s at the 1990 World Summit for Children, and many countries adopted policies for providing supplementation for young children; however, few large programs have been developed to eliminate the problem. The explanations for this failure to act include doubts among both scientific program planners and policy makers about the causes and consequences of iron deficiency and anemia; lack of political commitment; inadequate program planning, including mobilization and training of health staff members; insufficient community involvement; and, in particular, inherent difficulties with prolonged adherence to daily supplementation (Stoltzfus, Mullany, and Black 2004). Despite this bleak picture, guidelines for supplementation have been formulated for children ages 6 to 24 months and for low birthweight infants beginning at 2 months (Stoltzfus and Dreyfuss 1998). Also, various scientific documents synthesize and communicate current knowledge about the consequences of iron deficiency anemia and programming efforts. Ample evidence indicates that iron deficiency is the principal cause of anemia in children; that iron supplements are efficacious in preventing and treating iron deficiency anemia, increasing hemoglobin concentrations by about 1 gram per deciliter on average in controlled trials; and that supplements reduce severe anemia even in malarious areas. The contribution of parasitic

infections such as malaria and hookworm to anemia does not negate the usefulness of iron supplements; rather it underscores the need for multiple inputs to prevent severe anemia, given the risks of transfusion. Although current recommendations indicate daily supplements, less frequent delivery, such as intermittently or weekly, is commanding interest. Beaton and McCabe’s (1999) meta-analysis concludes that both daily and weekly supplementation are efficacious if adherence is good. In many countries, iron fortification of foods is the principal strategy for reducing iron deficiency and anemia. Fortified foodstuffs include wheat and maize flours, noodles, sugar, condiments, and complementary foods and milk for infants and children. Efficacy studies indicate the potential of fortification to increase iron intakes and reduce anemia, and effectiveness trials in Chile (dry milk for infants), Ghana (complementary food for young children), Guatemala (sugar), India (salt), Mexico (fortified weaning food and dry milk), and República Bolivariana de Venezuela (maize and wheat) have found improvements in hemoglobin concentration or reductions in anemia prevalence (Allen and Gillespie 2001; Rivera and others 2004). Nevertheless, few national iron fortification programs have evaluation results that are without controversy. Yip and Ramakrishnan (2002) argue that the strongest examples of the potential for fortification are found in the Chilean program of fortified dry milk for infants and in the U.S. program of ironfortified infant cereals. A randomized trial in Mexico of a poverty alleviation program that distributes a complementary food fortified with multiple micronutrients, including iron, found positive effects on anemia rates (Rivera and others 2004). Evaluations of newly implemented iron fortification programs should gauge their contribution to anemia prevention. Newer strategies, such as sprinkles (powders), spreads, or foodlets (a hybrid of a food and a tablet), appear promising, particularly for regions where the infrastructure will not support more traditional forms of fortification (Zlotkin and others 2003). Processed complementary foods and beverages offer additional vehicles for reducing iron and other micronutrient deficiencies and promoting well-being (Solon and others 2003). Implementing such strategies and documenting their cost-effectiveness are important activities for the next few years. In many settings, promoting iron-rich organ meats and animal products and undertaking other food-based strategies may increase iron intakes and contribute to anemia reduction. Such approaches have been promoted for many years, but research is still needed to document their efficacy and effectiveness (Ruel and Levin 2000).

Iodine Deficiency Disorders Interventions to diminish iodine deficiency using either supplementation or fortification are both efficacious and inexpensive, and WHO, the United Nations Children’s Fund, and


the International Council for the Control of Iodine Deficiency Disorders have pledged to eliminate iodine deficiency and the spectrum of IDD. For regions with severe endemic iodine deficiency, highdose iodine supplementation is indicated while longer-term solutions are put into place. Iodized oil and iodide tablets are the most common means of direct administration. Injections of iodized oil have been used with much success to decrease the prevalence of IDD and have been shown to be effective for three to four years, depending on the dosage (Hetzel 1989). Although injected oil is effective, it is also expensive, requires trained personnel to administer, and carries the risk of infectious disease transmission from contaminated needles. Because of those drawbacks, researchers began exploring oral administration as an alternative. Oral administration of iodized oil in liquid and tablet form has been successful in the long-term correction of clinical deficiency, and in Indonesia, oral administration was associated with a reduction in infant mortality (Cobra and others 1997). Iodized or iodated salt is the primary strategy for correcting iodine deficiency because of the nearly universal consumption of salt regardless of socioeconomic status; the lack of an effect on consistency, color, or taste from the addition of iodine; and the limited number of producers in many countries. Large-scale salt fortification has been highly successful in many countries, and of the 130 countries with iodine deficiency, 75 percent have laws mandating salt iodization. The goal of universal salt iodization for consumption by both humans and livestock in all countries with endemic iodine deficiency was set at the 1990 World Summit for Children (WHO, UNICEF, and ICCIDD 2001). Some populations do not easily embrace salt iodization because of cultural preferences or because they have an ample supply of unprocessed salt, so other means of fortification are needed. One promising option is to add potassium iodate to irrigation water.

Zinc Deficiency Although zinc deficiency is likely widespread and even mild deficiency probably has significant health consequences, few interventions have been developed to combat it in developing countries. Possible interventions include supplementation, fortification, and dietary diversification or modification. The strong evidence that the use of zinc supplements given during and for a short time after diarrhea improves the outcome of that episode and prevents future episodes has led to the recommendation that zinc, along with increased fluids and continued feeding, be used to treat all episodes of acute diarrhea (WHO and UNICEF 2004). Substantial efforts are under way to initiate programs in developing countries. Prophylactic zinc supplementation also improves growth and reduces diarrhea incidence (International Zinc Nutrition Consultative Group 2004).

Fortification interventions include the traditional method of adding zinc to a commercial food, consumer fortification using sprinkles, and plant-breeding techniques. For example, Mexico has introduced several large-scale programs, including the fortification of maize and wheat flours and the distribution of fortified complementary food and fortified milk to lowincome children (Rivera and Sepulveda 2003). Researchers are investigating the possibility of home fortification of food using sprinkles containing iron and zinc (Zlotkin and others 2003), but further research is needed to determine whether sprinkles are a viable option. Through plant breeding and genetic engineering, staple crops may be made to contain more zinc or less phytate, resulting in increased zinc bioavailability (Ruel and Bouis 1998). Other dietary strategies target food preparation techniques, such as fermentation of unrefined flour to increase zinc bioavailability.

INTERVENTION COSTS AND COST-EFFECTIVENESS Multiple strategies exist for preventing malnutrition in young children in the short and long term. This section considers the costs and cost-effectiveness of these interventions for preventing malnutrition or deaths attributable to each nutritional problem. Table 28.4 presents a compendium of cost information, including, where possible, the costs of preventing a child death or saving a DALY. Horton and others (1996) use data from Brazil, Honduras, and Mexico to estimate the costs and cost-effectiveness of hospital-based programs to promote breastfeeding. Using standard costing methods, they examine the costs of breastfeeding promotion activities in each program and the additional inputs, as well as the savings. Savings accrued from the removal of infant formula where it was currently used. Using data on infant feeding practices and morbidity and mortality from Brazil, they estimated the costs of the programs per birth, per diarrhea case averted, and per death averted. As table 28.4 shows, the costs of such programs range from US$0.30 to US$0.40 per child, and from US$100 to US$200 per death averted, making them comparable in cost-effectiveness to measles and rotavirus vaccination. Assuming that deaths would otherwise have occurred around age one, and using average Latin American life expectancy at that age, yields a cost per DALY gained of only US$3 to US$7. In many community-based strategies, multiple organizations work through a variety of communication channels to promote exclusive breastfeeding. Two studies in Ghana and Madagascar provide costs estimates for such programs (Chee, Makinen, and Sakagawa 2002; Chee and others 2003). The programs cost US$4 to US$16 per child, and given the effect on mothers’ practices, the cost ranged from US$5 to Stunting, Wasting, and Micronutrient Deficiency Disorders | 559


Table 28.4 Costs and Cost-Effectiveness of Nutrition Interventions Costs (US$) Type of deficiency and intervention

Source

Year

Country

Per child or per outcome

Per death averted

Per DALY gained

Breastfeeding support

Horton and others 1996

1996

Brazil, Honduras, Mexico

0.30–0.40 per birth; 0.65–1.10 per diarrhea case averted

100–200

3–7


Ross, Loening, and Mbele 1987

1987

Mali

2–3 per child

282

11


Chee, Makinen, and Sakagawa 2002

2002

Ghana

16 per child; 5–58 per adopter of exclusive breastfeeding

203a

7.80

Chee and others 2003

2003

Madagascar

4.41 per child; 10–17 per adopter of exclusive breastfeeding

—

—

J. Ross 1997; WHO 2002

1997

Across programs

76–101 per undernourished child averted

1,200

41–43

Underweight

Child survival program with nutrition component Nutrition programs Less intensive More intensive

2–5 per child 5–10 per child Fiedler 2003

2003

Honduras

4 per child; 20 per undernourished child averted

240–320b

8–11

Capsule distribution

Rassas, Hottor, and others 2004 Rassas, Nakamba, and others 2004 Fiedler 2000 Fiedler and others 2000

2004 2004 2000 1994

Ghana Zambia Nepal

0.90 per child 1.23 per child 1.25 per child

277 162 327

11 6–7 11–12

Fortification Sugar Other

Institute of Medicine 1998; World Bank 1994

Guatemala

0.17 per child 0.05–0.15 per child

1,000

33–35

3.17–5.30 per child

—

—

Growth monitoring and counseling Vitamin A deficiency

Iron deficiency Supplements Fortification Salt Sugar Cereal Iodine deficiency


1994

World Bank 1994 World Bank 1994 World Bank 1994

1994 1994

India Guatemala

0.12 per child 0.20–1.00 per child 0.09 per child

—

—

— 2,000

— 66–70

1994

Peru Zaire

2.75 per child 0.80 per child 1.25 per child

— — —

— — —

Indonesia Italy India

0.05 per child 0.02–0.05 per child 0.05 per child

1,000 —

34–36 —

n.a.

0.47 per child

2,100

73


Oil injection

Fortification Water Salt Salt Zinc deficiency Supplements with oral rehydration salts

Robberstad and others 2004

2004

— Source did not include data from which to estimate deaths averted (and DALYs gained). Note: Deaths prevented by promoting or supporting breastfeeding are assumed to occur around age one. Deaths prevented by other programs to reduce underweight and all programs to reduce micronutrient deficiency are assumed to occur between ages one and five. Authors’ estimates of costs per DALY (in parentheses) using region-specific life expectancies at ages one and five, reflect this range. a. Assumes that all the DALY gains come from preventing deaths. b. Assumes that an undernourished child has a chance of 1 in 16 to 1 in 12 (6 to 8 percent) of dying before age five, the same as estimated for child survival programs.


US$58 per adopter of exclusive breastfeeding. In Ghana, an estimated 883 deaths were averted, yielding a program cost of US$7.80 per DALY gained or US$203 per death prevented. The range of costs within each program depended on the baseline prevalence of the behavior, the population density, and the characteristics of the implementing organizations themselves. Programs will be more cost-effective when the baseline prevalence is lower; the population density is higher; and the organizations involved are focused, highly motivated, and well organized. Less information is available on the costs of communitybased nutrition programs to prevent growth faltering, to control morbidity, and to improve survival. The costs of a program in Mali (Ross, Loening, and Mbele 1987), which included promotion of breastfeeding, counseling, and education on optimal child feeding; prevention of diarrheal disease; and growth monitoring, were estimated to be US$282 per death averted and US$11 per DALY gained. This estimate is consistent with others that nutrition programs cost US$2 to US$10 per child, depending on the intensity of nutrition counseling, including Fiedler’s (2003) study of the Integrated Community Child Care Program in Honduras, which had an estimated cost of US$4 per child. (For a fuller analysis of such programs, including contextual and programmatic characteristics that affect outcomes, see chapter 56.) In the past five years, investigators have undertaken several cost analyses of national programs to distribute vitamin A capsules. Two reports from Ghana and Zambia are particularly informative (Rassas, Hottor, and others 2004; Rassas, Nakamba, and others 2004). As table 28.4 shows, such programs cost US$0.90 to US$1.23 per child, with the costs per death averted ranging from US$162 to US$277. (Deaths from micronutrient deficiencies are assumed to occur between ages one and five, and estimates of cost per DALY ranging from US$6 to US$11 reflect this range, as well as region-specific life expectancies at those ages.) These costs are comparable with estimates of a vitamin A program in Nepal that cost US$1.25 per child and US$327 per death averted (Fiedler 2000). Ching and others (2000) examine the costs of incorporating vitamin A capsule distribution into immunization campaigns in 50 countries in 1998 and 1999. Their analysis finds that the total costs per death averted ranged from about US$150 to US$600, with the incremental costs for vitamin A distribution amounting to only about US$30 to US$150 per death averted. The costs per death averted depended on the country setting, the program’s coverage, the delivery of vitamin A (one or two doses), and the underlying level of mortality. The incremental cost per DALY gained could be as low as US$1 or as high as US$6. Fewer examples of vitamin A fortification programs are available, with the only clear example being sugar fortification

in Central America. In 1994, estimates indicated that a program in Guatemala cost US$0.17 per child, and US$1,000 per death averted. Counting only the losses from mortality, the cost of saving a DALY was US$33 to US$35. However, for each death prevented, there were probably several cases of eye damage prevented and of improved general health; thus, taking full account of nonfatal effects would reduce the cost per DALY somewhat. Iron supplementation is more costly than distribution of vitamin A capsules, as it involves a daily supplement over an extended period. Estimates indicate that such programs cost US$3.17 to US$5.30 per child. Numerous cost estimates are available for iron fortification programs, because these programs have been the principal strategy to prevent and control iron deficiency anemia. Such programs have traditionally cost US$0.09 to US$1.00 per child, depending on the country and the vehicle for fortification. These estimates are based on elemental iron as the fortifier. Even though this is the cheapest form available, critics have questioned the bioavailability of elemental iron, and many researchers now advocate using other forms of iron. Iodine fortification programs cost little, about US$0.02 to US$0.05 per child. Iodized oil injections are more costly at US$0.80 to US$2.75 per beneficiary, but these programs may be recommended for settings where people consume little commercialized and easily fortified food. Currently, no examples of zinc intervention programs are available from which to estimate cost-effectiveness. However, Robberstad and others’ (2004) simulation analysis examines the potential costs and cost-effectiveness of providing zinc as an adjunct to oral hydration salts in treating diarrhea in young children. Providing zinc as part of case management carries an estimated incremental cost of US$0.47 per treatment, ranging from US$0.33 to US$0.62. Given the relationship between zinc provision and mortality risk, this addition to current management programs would cost, on average, US$2,100 per death adverted and US$73 per DALY gained. Despite the enormity of the nutritional problems, the associated loss of DALYS, and the existence of programs to combat malnutrition, surprisingly little data on the costs or cost-effectiveness of nutritional programs are available. This problem represents a serious gap in information for health planning, implementation, and advocacy. Nonetheless, considerable evidence indicates that when programs to promote breastfeeding or child growth or to correct micronutrient deficiencies are delivered to populations with a relatively high prevalence of malnutrition, the cost per participating child is usually so low that deaths can be averted at a cost per DALY that is less than US$100, and often less than US$10, even in regions with low life expectancy. Few health interventions are comparably cost-effective.

Stunting, Wasting, and Micronutrient Deficiency Disorders | 561 ©2006 The International Bank for Reconstruction and Development / The World Bank 135

ECONOMIC BENEFITS OF INTERVENTION The previous sections outlined the costs to society in terms of deaths and disabilities resulting from growth faltering and micronutrient malnutrition, as well as the costs and costeffectiveness of options for their alleviation and prevention; however, DALYs do not capture the full range of potential benefits to society from effective nutrition programs. For example, even though the effect of iron deficiency on mental retardation in children contributes to the attributable DALYs (Stoltzfus, Mullany, and Black 2004), the negative effects of iron deficiency on cognition that do not constitute retardation are not considered. Other effects of malnutrition on cognitive and physical functioning that ultimately affect labor productivity are also not considered, nor are other long-term health consequences of child undernutrition. Finally, because undernutrition increases the frequency and severity of disease, undernutrition is associated with considerable health care costs, which are also not captured in burden estimates.

Malnutrition and Human Capital Formation Researchers have studied cognitive function using global measures of development and intelligence, such as IQ, along with school performance and more narrowly defined intellectual, psychomotor, and behavioral skills. A large body of research has examined whether undernutrition causes lasting cognitive deficits in later life and whether potential deficits are amenable to subsequent nutritional interventions. Acute malnutrition is associated with negative neuroanatomical, emotional, and behavioral effects on children’s development. After recovery, results of behavioral and developmental tests generally improve, but the long-term developmental implications remain unclear. Many studies find IQ scores 8 to 18 points lower in children who suffered from severe malnutrition (Fishman and others 2004). Studies of chronic undernutrition also report deficits in IQ and school performance with stunting during early childhood. Evidence from nutritional interventions among high-risk or undernourished children suggests that early supplementary feeding (but no sooner than two years of age) improves developmental scores during the intervention, with some evidence of long-term benefits. For example, followup of Guatemalan children exposed to prenatal and early postnatal supplementation demonstrated long-term cognitive benefits even after adjusting for socioeconomic factors and educational experience (Pollitt and others 1995). These results argue strongly for preventing acute severe malnutrition and generalized growth faltering that leads to stunting in children. Nutritional interventions may preserve or improve cognitive function through mechanisms other than preventing growth faltering or acute malnutrition. For example, breastfeeding confers some cognitive benefits. Anderson, Johnstone,

and Remley’s (1999) meta-analysis estimates gains of 3.5 IQ points, adjusting for important covariates. Iron deficiency has long been associated with developmental delays, and iron supplementation studies have demonstrated improvements in cognitive function. Whether the negative effects of iron deficiency and anemia on development are reversible remains controversial, which implies the need for strong preventive measures. More research is needed to learn about the effects of iron deficiency on development and to develop measures for evaluating programs that provide iron. Multiple lines of evidence indicate that zinc influences development (Black 1998). Despite a clear biological role, epidemiological studies provide insufficient evidence to draw conclusions on the gain in human capital if zinc deficiency were reduced through public health interventions. Research to address this gap is under way. The public health community has long recognized that iodine deficiency is the most common cause of preventable mental retardation. Even though the problem of maternal iodine deficiency and cretinism in the offspring is well recognized, evidence also suggests that deficiency in children is negatively associated with cognitive abilities. Bleichrodt and Born’s (1994) meta-analysis finds losses of 13.5 IQ points in those with iodine deficiency. Some of these effects occur in the absence of goiter, the hallmark of IDD. More research is needed to fully understand the human consequences of milder forms of iodine deficiency that are probably still prevalent in developing countries. Malnutrition and Loss of Productivity Abundant evidence demonstrates that both anemia and iron deficiency decrease fitness and capacity for aerobic work by decreasing oxygen transport and respiratory efficiency in muscles. The consequences of iron deficiency are thus measurable in terms of loss of economic productivity. Aguayo, Scott, and Ross’s (2003) case study in Sierra Leone estimates that anemia among women is associated with agricultural productivity losses of US$19 million per year. For children, the economic costs are not as clear, but those costs may be substantial depending on the children’s ages and the types of work they perform. Growth faltering that leads to stunting in early childhood translates into shortened adult stature. Adult height is related not only to total food consumption but also to protein intake (Jamison, Leslie, and Musgrove 2003), which reinforces the importance of dietary quality. Multiple levels of evidence link adult stature and worker productivity (Martorell 1996). Haddad and Bouis (1991) estimate that a 1 percent decrease in adult stature is associated with a 1.4 percent decrease in productivity. Others find that a 1 percent increase in adult stature is associated with a 2.0 to 2.4 percent increase in wages or earnings. Other things being equal, current programs to prevent


stunting in early childhood can deliver about a third to a half of that 1 percent increase in adult stature. Thus, a lifetime of economic loss results from a failure to prevent stunting in early childhood and accompanying deficits in adult stature, and strategies to reduce this tremendous loss are available. In addition, the impacts of malnutrition on cognitive development translate indirectly into deficits in productivity in adulthood. Children who are malnourished are more likely to start school late, to perform less well, and to stay in school for a shorter time (Behrman, Alderman, and Hoddinott 2004). Studies suggest that improvements in nutrition within the current range of benefits of programs for young children can lead to substantial increases in rates of school initiation and to more years of schooling (Alderman, Hoddinott, and Kinsey 2003; Alderman and others 2001; Behrman and others 2003). Both years of schooling and school performance affect wages and economic productivity. Alderman, Hoddinott, and Kinsey (2003) calculate that the effects of malnutrition during early childhood, with the accompanying effects on schooling, lead to a 12 percent reduction in lifetime earnings in Zimbabwe. Current programming could restore a significant proportion of those lost wages.

Resource Allocation Malnutrition increases the likelihood that a child will be sick and, when sick, will become seriously ill. Thus, resources must be allocated to health care services to deal with the increased frequency and severity of illness caused by undernutrition and micronutrient deficiencies. To our knowledge, this increase in likelihood and severity of illness has never been quantified, but it is likely to be high, considering not only the costs of health care infrastructure, but also the time costs and costs of lost wages or schooling borne by the family for each episode of illness. Furthermore, to the extent that undernutrition or micronutrient deficiencies lead to deficits in cognitive development, resources need to be allocated to special education, rehabilitation, and vocational services. The costs associated with not providing such services are ultimately paid in mortality and economic statistics. Adult Disease and Disability In the past 10 years, a growing literature has identified associations between small size at birth; early patterns of postnatal growth; and adult conditions as diverse as diabetes, cardiovascular disease, and schizophrenia. More research is needed to provide evidence of causality for such associations and to create the evidence base for attributing those effects to malnutrition in burden-of-disease calculations. Given current knowledge, health care budgets in developing countries will likely be strained to deal with the burden of chronic diseases of adulthood caused by the failure to prevent maternal and child undernutrition.

PROGRAM IMPLEMENTATION: LESSONS OF EXPERIENCE For decades, countries have implemented programs to alleviate growth faltering and micronutrient deficiencies in children; therefore, it is timely to consider what has been accomplished and what can be learned from successes and failures. The task is difficult, because nutrition programs are diverse, ranging from the simple fortification of salt with iodine to multifaceted programs to improve dietary intakes and prevent growth faltering. Nonetheless, some general statements about the state of programming in this area are possible. Success in conceptualizing and implementing programs to reduce growth faltering by combining disease control strategies with the promotion of breastfeeding and optimal complementary feeding has been demonstrable. The focus has shifted away from growth monitoring and promotion (counseling) strategies to population-based assessment with more generalized dissemination of key messages for behavior change. Available data suggest high cost-effectiveness for such programs. Key challenges involve scaling up and sustainability, as well as strengthening of monitoring and evaluation systems. A gap in this knowledge concerns optimal feeding in the presence of HIV infection, and testing options and designing programs in such settings are of the highest priority. Iodine fortification has been a clear success over decades, which underscores the need for continued and consistent funding and advocacy for such programs. Even when universal access to iodine becomes a reality, policy and programmatic supports will be necessary to maintain it. The success of iodine fortification contrasts with other examples of fortification that have made slow and uneven progress. Fortification of foodstuffs with vitamin A is limited geographically, and even though many countries have embarked on iron fortification, these programs lag because of controversies about the effectiveness of existing programs, the evaluation methods used, and the lack of infrastructure for fortification in some settings. Concerted efforts to address the controversies and to provide evidence of the effectiveness of fortification in controlling iron deficiency are under way. In addition, recognition that fortification should address multiple micronutrient deficiencies, chiefly the B vitamins and zinc, has grown. Programs to distribute vitamin A capsules twice a year are a reality in many areas characterized by VAD. Jones and others (2003) estimate that current coverage of supplementation for children living in areas with VAD is 55 percent. In the past few years, studies have provided solid data on the costs and costeffectiveness of such programs in diverse settings. In contrast, despite concerns about the health and developmental consequences of iron deficiency and anemia, few examples are available of even small-scale iron supplementation programs for young children. Supply and adherence continue to Stunting, Wasting, and Micronutrient Deficiency Disorders | 563


constrain progress, with adherence depending on program workers’ and families’ perceptions of benefits and their reluctance to continue the long-term use in children of what are often considered to be medicines. Similar constraints apply to programs to provide iron supplements to pregnant women, but operational research has overcome many obstacles, and the hope is that the lessons learned can inform the design and implementation of iron supplementation programs for young children. Food-based strategies, particularly dietary diversification and the promotion of specific food groups for preventing micronutrient malnutrition, are less advanced than other programs. In part, this lack of advancement reflects the diverse nature of the behaviors to be changed and of the available options. Given this diversity and the fact that such strategies are more setting specific than, for example, capsule distribution, the lack of summary estimates of effectiveness is not surprising. Consensus is growing that improving dietary intakes through agricultural innovations and dietary diversification represents long-term answers to micronutrient malnutrition, but progress is slow because of the urgency of alleviating deficiencies in the short term. More research is needed to define the policies that will promote these strategies. Research over the past decade has articulated a strong case for interventions to prevent zinc deficiency, with supplementation and fortification identified as important approaches. Experiences with zinc supplementation or fortification programs are needed to provide estimates of costs and cost-effectiveness. If the costs of providing zinc supplements to young children are in line with those reported earlier, then such programs would be highly cost-effective, considering the prevalence and burden of disease associated with zinc deficiency. Child malnutrition results from multiple factors, and even though each context has its own unique features, the etiology has many more commonalities. Thus, for program planners and policy makers intent on alleviating malnutrition to begin designing and implementing programs in their particular settings from scratch is strikingly inefficient. In the past decade, this point has been recognized, and documents that articulate processes for program implementation and evaluation have mushroomed. These “road maps” permit policy makers and program planners to capitalize rapidly on interest in addressing nutrition problems. The road maps also communicate a sense of feasibility by streamlining the complex processes of program design and evaluation. Thus, their use can reduce the likelihood that programs will be diffuse (too many inputs), will be culturally inappropriate, will have unrealistic expectations, and will have no possibility of sustainability and no plans for process or impact evaluation. Demonstrating that nutrition programs are effective is key to translating scientific findings into policies and programs as well as to ensuring the continuity and expansion of funding.

Despite decades of nutrition programs, with identifiable successes, uncertainty about their effectiveness persists. The value of publishing solid process and outcome evaluations in the scientific literature in addition to project reports has only recently been recognized and cannot be overstated. Whereas outcome evaluations provide data on program effects, process evaluations provide key information to maintain quality assurance and to support the plausibility of key outcomes. Consensus is growing on the need to evaluate a package of services rather than use complex strategies to tease apart the effects of specific program elements. Well-designed programs with process evaluation efficiently provide this information. Although following standard scientific approaches to establish program effectiveness has enabled progress in many interventions, alternative designs can and should be used for this purpose. Scientists traditionally argue that randomized controlled trials are needed to establish causal evidence of effectiveness and that multiple trials are needed in diverse settings, perhaps followed by pooled or meta-analyses to provide summary estimates. Others argue that designs that provide plausible evidence of program effects or adequate information to support continued funding should be recognized as valid by funders and publishers in refereed journals and should be implemented more broadly (Victora, Habicht, and Bryce 2004).

RESEARCH AND DEVELOPMENT AGENDA Despite progress, much work remains unfinished. Other chapters focus on research and development needs in relation to packaging services, scaling up, and ensuring sustainability. Here the focus is on research for strengthening the database for policy making. Gaps in knowledge remain with respect to recognized strategies for intervention programs. Often information on intervention efficacy exists, yet little scientific literature on program effectiveness is available. Key gaps include the following: • evaluation of the effectiveness of national iron fortification programs to reduce iron deficiency anemia • implementation and evaluation of the effectiveness of iron supplementation programs for young children • evaluation of the effect on child mortality of multifaceted programs to reduce child undernutrition • evaluation of the effectiveness of programs based on the new guiding principles for reducing undernutrition and micronutrient malnutrition in young children • implementation and evaluation of the effectiveness of foodbased strategies to reduce micronutrient malnutrition • implementation and evaluation of the effectiveness of early postnatal vitamin A supplementation to reduce infant mortality.


Costing studies should accompany the evaluations to allow estimates of cost-effectiveness for decision making. Because of the logistical difficulties in developing fortification approaches in settings with little industry infrastructure, alternative fortification approaches are needed, such as micronutrient sprinkles or foodlets. In addition, operational research is needed to develop, implement, and evaluate programs to improve zinc status. Never has so much evidence been amassed on the consequences of a deficiency disorder without programmatic application. The challenge now is to develop and implement programs for preventing and treating zinc deficiency and to evaluate their effectiveness for child growth, health, and survival. The International Zinc Nutrition Consultative Group (2004) has laid out a research agenda with these aims in mind.

CONCLUSIONS Undernutrition is a major cause of death and disability in young children. When ranked among other causes, growth faltering and micronutrient deficiencies figure prominently, both because they are prevalent and because their consequences are devastating. Not included in the numbers, however, are the losses of lifetime productivity associated with early malnutrition and the resources that must be allocated to confront the developmental and morbidity consequences of child malnutrition, which last a lifetime. Success has been achieved in preventing and controlling iodine deficiency, and palpable progress has been made in the past 20 years in correcting vitamin A deficiency and promoting breastfeeding; however, for iron, articulated goals have not been translated into programs, and the problem has remained the same or worsened. Zinc deficiency is now recognized as an important new challenge. As shown here, solid evidence shows that nutrition programs can be effective at addressing nutritional problems in young children. Increasingly available cost data, when combined with outcome evaluations, demonstrate that nutritional interventions rank favorably in terms of cost-effectiveness when compared with competing interventions. The case that further investment in nutrition interventions is warranted is thus compelling.

REFERENCES Aguayo, V. M., S. Scott, and J. Ross. 2003. “Sierra Leone: Investing in Nutrition to Reduce Poverty—A Call for Action.” Public Health Nutrition 6 (7): 653–57. Alderman, H., J. Behrman, D. Ross, and R. Sabot. 2001. “Child Health and School Enrollment: A Longitudinal Analysis.” Journal of Human Resources 36 (1): 185–205. Alderman, H., J. Hoddinott, and B. Kinsey. 2003. Long Term Consequences of Early Childhood Malnutrition. Washington, DC: World Bank.

Allen, L., and S. Gillespie. 2001. What Works? A Review of the Efficacy and Effectiveness of Nutrition Interventions. Geneva: United Nations, Administrative Committee on Coordination and Subcommittee on Nutrition in collaboration with the Asian Development Bank. Anderson, J. W., B. M. Johnstone, and D. T. Remley. 1999. “Breast-Feeding and Cognitive Development: A Meta-Analysis.” American Journal of Clinical Nutrition 70 (4): 525–35. Beard, J. L. 2001. “Iron Biology in Immune Function, Muscle Metabolism, and Neuronal Functioning.” Journal of Nutrition 131 (2 Suppl. 2): S568–79. Beaton, G. H., R. Martorell, K. J. Aronson, B. Edmonston, G. McCabe, A. C. Ross, and others. 1993.“Effectiveness of Vitamin A Supplementation in the Control of Young Child Morbidity and Mortality in Developing Countries.” Geneva: United Nations, Administrative Committee on Coordination and Subcommittee on Nutrition. Beaton, G. H., and G. McCabe. 1999. “Efficacy of Intermittent Iron Supplementation in the Control of Iron Deficiency Anaemia in Developing Countries: An Analysis of Experience—Final Report to the Micronutrient Initiative.” Montreal: Micronutrient Initiative. Becker S., R. E. Black, and K. H. Brown. 1991. “Relative Effects of Diarrhea, Fever, and Dietary Energy Intake on Weight Gain in Rural Bangladeshi Children.” American Journal of Clinical Nutrition 53 (6): 1499–503. Behrman, J., H. Alderman, and J. Hoddinott. 2004. Hunger and Malnutrition. Copenhagen: Copenhagen Consensus. Behrman, J., J. Hoddinott, J. A. Maluccio, A. Quisumbing, R. Martorell, and A. D. Stein. 2003. The Impact of Experimental Nutritional Interventions on Education into Adulthood in Rural Guatemala: Preliminary Longitudinal Analysis. Philadelphia: University of Pennsylvania; Atlanta: Emory University; Washington, DC: International Food Policy Research Institute. Black, M. M. 1998. “Zinc Deficiency and Child Development.” American Journal of Clinical Nutrition 68 (Suppl. 2): S464–69. Bleichrodt, N., and M. Born. 1994. “A Meta-Analysis of Research into Iodine and Its Relationship to Cognitive Development.” In The Damaged Brain of Iodine Deficiency, ed. J. B. Stanbury, 195–200. New York: Communication Corporation. Borghi, J., L. Guinness, J. Ouedraogo, and V. Curtis. 2002. “Is Hygiene Promotion Cost-Effective? A Case Study in Burkina Faso.” Tropical Medicine and International Health 7 (11): 960–69. Brown, K. H., K. G. Dewey, and L. H. Allen. 1998. Complementary Feeding of Young Children in Developing Countries: A Review of Current Scientific Knowledge. WHO/NUT/98.1. Geneva: World Health Organization. Brown, K. H., J. M. Peerson, J. Rivera, and L. H. Allen. 2002. “Effect of Supplemental Zinc on the Growth and Serum Zinc Concentrations of Prepubertal Children: A Meta-Analysis of Randomized Controlled Trials.” American Journal of Clinical Nutrition 75 (6): 1062–71. Caballero, B. 2001. “Early Nutrition and Risk of Disease in the Adult.” Public Health Nutrition 4 (6A): 1335–36. Caulfield, L. E., and R. E. Black. 2004. “Zinc Deficiency.” In Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors, ed. M. Ezzati, A. D. Lopez, A. Rodgers, and C. J. L. Murray, vol. 1, 257–9. Geneva: World Health Organization. Caulfield, L. E., S. L. Huffman, and E. G. Piwoz. 1999. “Interventions to Improve the Complementary Food Intakes of 6–12 Month Old Infants in Developing Countries: Impact on Growth, Prevalence of Malnutrition, and Potential Contribution to Child Survival.” Food and Nutrition Bulletin 20 (2): 183–200. Caulfield, L. E., S. A. Richard, and R. E. Black. 2004. “Undernutrition as an Underlying Cause of Malaria Morbidity and Mortality in Children.” American Journal of Tropical Medicine Hygiene 71 (Suppl. 2): S55–63. Stunting, Wasting, and Micronutrient Deficiency Disorders | 565


Checkley, W., P. R. Gilman, P. R. Black, L. D. Epstein, L. Cabrera, P. C. Sterling, and L. H. Moulton. 2004. “Effect of Water and Sanitation on Childhood Health in a Poor Peruvian Peri-Urban Community.” Lancet 363 (9403): 112–18. Chee, G., M. Makinen, and B. Sakagawa. 2002. Cost and Effectiveness Analysis of LINKAGES’ Breastfeeding Interventions in Ghana. Bethesda, MD: Abt Associates. Chee, G., K. Smith, M. Makinen, and Z. Rambeloson. 2003. Cost and Effectiveness Analysis of LINKAGES’ Infant and Young Child Feeding Program in Madagascar. Bethesda, MD: Abt Associates. Ching, P., M. Birmingham, T. Goodman, R. Sutter, and B. Loevinsohn. 2000. “Childhood Mortality Impact and Costs of Integrating Vitamin A Supplementation into Immunization Campaigns.” American Journal of Public Health 90 (10): 1526–29.

Horton, S., T. Sanghvi, M. Phillips, J. Fiedler, R. Perez-Escamilla, C. Lutter, and others. 1996. “Breastfeeding Promotion and Priority Setting in Health.” Health Policy and Planning 11 (2): 56–68. Institute of Medicine. 1998. Prevention of Micronutrient Deficiencies: Tools for Policy Makers and Public Health Workers. Washington, DC: National Academy Press. International Zinc Nutrition Consultative Group. 2004. “Developing Zinc Intervention Programs.” Food and Nutrition Bulletin 24 (1): 163–86. Jamison, D. T., J. Leslie, and P. Musgrove. 2003. “Malnutrition and Dietary Protein: Evidence from China and from International Comparisons.” Food and Nutrition Bulletin 24 (2): 145–54. Jones, G., R. W. Steketee, R. E. Black, Z. A. Bhutta, and S. S. Morris. 2003. “How Many Child Deaths Can We Prevent This Year?” Lancet 362 (9377): 65–71.

Cobra, C., Muhilal, K. Rusmil, D. Rustama, Djatnika, S. S. Suwardi, and others. 1997. “Infant Survival Is Improved by Oral Iodine Supplementation.” Journal of Nutrition 127 (4): 574–78.

Kapil, U. 2002. “Integrated Child Development Services (ICDS) Scheme: A Program for Holistic Development of Children in India.” Indian Journal of Pediatrics 69 (7): 597–601.

Dary, O., and J. O. Mora. 2002. “Food Fortification to Reduce Vitamin A Deficiency: International Vitamin A Consultative Group Recommendations.” Journal of Nutrition 132 (Suppl. 9): S2927–33.

Lengeler, C. 2004. “Insecticide-Treated Bednets and Curtains for Preventing Malaria.” Cochrane Library (2) CD000363.

Dewey, K. G. 2002. “Successful Intervention Programs to Promote Complementary Feeding.” In Public Health Issues in Infant and Child Nutrition, Nestle Nutrition Workshop Series Pediatric Program, ed. R. E. Black and K. F. Michaelsen, vol. 48, 199–216. Philadelphia: Lippincott, Williams, and Wilkins. Dewey, K. G., and K. H. Brown. 2003. “Update on Technical Issues Concerning Complementary Feeding of Young Children in Developing Countries and Implications for Intervention Programs.” Food and Nutrition Bulletin 24 (1): 5–28. Ezzati, M., A. D. Lopez, A. Rodgers, S. Vander Hoorn, C. J. Murray, and Comparative Risk Assessment Collaborating Group. 2002. “Selected Major Risk Factors and Global and Regional Burden of Disease.” Lancet 360 (9343): 1342–43. Fiedler, J. L. 2000. “The Nepal National Vitamin A Program: Prototype to Emulate or Donor Enclave?” Health Policy Planning 15 (2): 145–56. ———. 2003. A Cost Analysis of the Honduras Community-Based Integrated Child Care Program. Washington, DC: World Bank. Fiedler, J. L., D. R. Dado, H. Maglalang, N. Juban, M. Capistrano, and M. V. Magpantay. 2000. “Cost Analysis as a Vitamin A Program Design and Evaluation Tool: A Case Study of the Philippines.” Social Science and Medicine 51 (2): 223–42. Fishman, S., L. Caulfield, M. de Onis, M. Blossner, A. Hyder, L. Mullany, and R. Black. 2004. “Childhood and Maternal Underweight.” In Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors, ed. M. Ezzati, A. D. Lopez, A. Rodgers, and C. J. L. Murray, . vol. 1, 39–162. Geneva: World Health Organization. Gluckman, P. D., and M. A. Hanson. 2004. “Living with the Past: Evolution, Development, and Patterns of Disease.” Science 305 (5691): 1733–36. Grantham-McGregor, S. M., and C. C. Ani. 1999. “The Role of Micronutrients in Psychomotor and Cognitive Development.” British Medical Bulletin 55 (3): 511–27. Haddad, L. J., and H. E. Bouis. 1991. “The Impact of Nutritional Status on Agricultural Productivity: Wage Evidence from the Philippines.” Oxford Bulletin of Economics and Statistics. 53: 45–68. Hetzel, B. S. 1983. “Iodine Deficiency Disorders (IDD) and Their Eradication.” Lancet 2 (8359): 1126–29. ———. 1989. “The Prevention and Control of Iodine Deficiency Disorders.” Nutrition Policy Discussion Paper 3, United Nations, New York. Hill, Z., B. Kirkwood, and K. Edmond. 2004. Family and Community Practices That Promote Child Survival, Growth, and Development: A Review of the Evidence. Geneva: World Health Organization.

Martorell, R. 1996. “The Role of Nutrition in Economic Development.” Nutrition Reviews 54 (4 Part 2): S66–71. PAHO and WHO (Pan American Health Organization and World Health Organization). 2003. Guiding Principles for Complementary Feeding of the Breastfed Child. Washington, DC: PAHO and WHO. Pelletier, D. L., E. A. Frongillo Jr., and J. P. Habicht. 1993. “Epidemiologic Evidence for a Potentiating Effect of Malnutrition on Child Mortality.” American Journal of Public Health. 83 (8): 1130–33. Pollitt, E., K. S. Gorman, P. L. Engle, J. A. Rivera, and R. Martorell. 1995. “Nutrition in Early Life and the Fulfillment of Intellectual Potential.” Journal of Nutrition 125 (Suppl. 4): S1111–18. Ramakrishnan, U., N. Aburto, G. McCabe, and R. Martorell. 2004. “Multimicronutrient Interventions but Not Vitamin A or Iron Interventions Alone Improve Child Growth: Results from Three MetaAnalyses.” Journal of Nutrition 134 (10): 2592–602. Rassas, R., J. K. Hottor, O. A. Anerkai, M. M. Kwame, M. M. Agble, A. Nyaku, and T. Taylor. 2004. Cost Analysis of the National Vitamin A Program in Ghana. Arlington, VA: International Science and Technology Institute. Rassas, R., P. M. Nakamba, C. M. Mwela, R. Mutemwa, B. Mulenga, W. Siamusantu, and T. Taylor. 2004. Cost Analysis of the National Vitamin A Program in Zambia. Arlington, VA: International Science and Technology Institute. Rice, A. L., K. P. West Jr., and R. E. Black. 2004. “Vitamin A Deficiency.” In Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors, ed. M. Ezzati, A. D. Lopez, A. Rodgers, and C. J. L. Murray, vol. 1, 211–56. Geneva: World Health Organization. Rivera, J. A., and A. J. Sepulveda. 2003. “Conclusions from the Mexican National Nutrition Survey 1999: Translating Results into Nutrition Policy.” Salud Publica Mexico. 45 (Suppl. 4): S565–75. Rivera, J. A., D. Sotres-Alvarez, J. P. Habicht, T. Shamah, and S. Villalpando. 2004. “Impact of the Mexican Program for Education, Health, and Nutrition (Progresa) on Rates of Growth and Anemia in Infants and Young Children: A Randomized Effectiveness Study.” Journal of the American Medical Association 291 (21): 2563–70. Robberstad, B., T. Strand, R. E. Black, and H. Sommerfelt. 2004. “CostEffectiveness of Zinc as Adjunct Therapy for Acute Childhood Diarrhea in Developing Countries.” Bulletin of the World Health Organization 82 (7): 523–31. Ross, D. A. 2002. “Recommendations for Vitamin A Supplementation.” Journal of Nutrition 132 (Suppl. 9): S2902–6. Ross, J. S. 1997. Cost-Effectiveness of the Nutrition Communication Project in Mali. Washington, DC: Academy for Educational Development.


Ross, S. M., W. E. Loening, and B. E. Mbele. 1987.“Breast-Feeding Support.” South African Medical Journal 72 (5): 357–58. Ruel, M. T., and H. E. Bouis. 1998. “Plant Breeding: A Long-Term Strategy for the Control of Zinc Deficiency in Vulnerable Populations.” American Journal of Clinical Nutrition 68 (Suppl. 2): S488–94. Ruel, M. T., and C. Levin. 2000. Assessing the Potential for Food-Based Strategies to Alleviate Vitamin A and Iron Deficiencies: A Review of Recent Evidence. Discussion paper 92, International Food Policy Research Institute, Washington, DC. Shankar, A. H., and A. S. Prasad. 1998. “Zinc and Immune Function: The Biological Basis of Altered Resistance to Infection.” American Journal of Clinical Nutrition 68 (Suppl. 2): S447–63. Sikorski, J., M. J. Renfrew, S. Pindoria, and A. Wade. 2002. “Support for Breastfeeding Mothers.” Cochrane Database System Reviews (1): CD001141. Solon, F. S., J. N. Sarol, A. B. I. Bernardo, J. A. A. Solon, H. Mehansho, L. E. Sanchez-Fermin, and others. 2003. “Effect of a Multiple-Micronutrient Fortified Fruit Powder Beverage on the Nutrition Status, Physical Fitness, and Cognitive Performance of Schoolchildren in the Philippines.” Food and Nutrition Bulletin 24 (Suppl. 4): S129–40. Sommer, A., and K. P. West. 1996. Vitamin A Deficiency Health, Survival, and Vision. New York: Oxford University Press. Stoltzfus, R. J., and M. L. Dreyfuss. 1998. Guidelines for the Use of Iron Supplements to Prevent and Treat Iron Deficiency Anemia. Washington, DC: ILSI Press. Stoltzfus, R. J., L. Mullany, and R. E. Black. 2004. “Iron Deficiency Anemia.” In Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors, ed. M. Ezzati, A. D. Lopez, A. Rodgers, and C. J. L. Murray, vol. 1, 163–209. Geneva: World Health Organization. Swindale, A., M. Deitchler, B. Cogill, and T. Marchione. 2004. “The Impact of Title II Maternal and Child Health and Nutrition Programs on the Nutritional Status of Children.” Occasional Paper 4, Academy for Educational Development, Washington, DC.

Victora, C. G., J. P. Habicht, and J. Bryce. 2004. “Evidence-Based Public Health: Moving Beyond Randomized Trials.” American Journal of Public Health 94 (3): 400–5. WHO (World Health Organization). 1999. Progress Towards Elimination of Iodine Deficiency Disorders. WHO/NHD/99.4. Geneva: WHO. ———. 2002. World Health Report 2002: Reducing Risks, Promoting Healthy Life. Geneva: WHO. WHO and UNICEF (United Nations Children’s Fund). 2004. WHO/UNICEF Joint Statement on the Clinical Management of Acute Diarrhea. WHO/FCH/CAH/04.7. Geneva: WHO and UNICEF. WHO, UNICEF, and ICCIDD (International Council for the Control of Iodine Deficiency Disorders). 2001. Assessment of the Iodine Deficiency Disorders and Monitoring Their Elimination. WHO/NHD/01.1. Geneva: WHO. World Bank. 1994. Enriching Lives: Overcoming Vitamin and Mineral Malnutrition in Developing Countries. Washington, DC: World Bank. Yip, R., and U. Ramakrishnan. 2002. “Experiences and Challenges in Developing Countries.” Journal of Nutrition 132 (Suppl. 4): S827–30. Zinc Investigators’ Collaborative Group, Z. A. Bhutta, S. M. Bird, R. E. Black, K. H. Brown, J. M. Gardner, and others. 2000. “Therapeutic Effects of Oral Zinc in Acute and Persistent Diarrhea in Children in Developing Countries: Pooled Analysis of Randomized Controlled Trials.” American Journal of Clinical Nutrition 72 (6): 1516–22. Zinc Investigators’ Collaborative Group, Z. A. Bhutta, R. E. Black, K. H. Brown, J. M. Gardner, S. Gore, and others. 1999. “Prevention of Diarrhea and Pneumonia by Zinc Supplementation in Children in Developing Countries: Pooled Analysis of Randomized Controlled Trials.” Journal of Pediatrics 135 (6): 689–97. Zlotkin, S., P. Arthur, C. Schauer, K. Y. Antwi, G. Yeung, and A. Piekarz. 2003. “Home-Fortification with Iron and Zinc Sprinkles or Iron Sprinkles Alone Successfully Treats Anemia in Infants and Young Children.” Journal of Nutrition 133 (4): 1075–80.

Stunting, Wasting, and Micronutrient Deficiency Disorders | 567 ©2006 The International Bank for Reconstruction and Development / The World Bank 141


Chapter 38

Oral and Craniofacial Diseases and Disorders Douglas Bratthall, Poul Erik Petersen, Jayanthi Ramanathan Stjernswärd, and L. Jackson Brown

The oral cavity is an essential part of the body and contributes to total health and well-being. Recent research indicates that poor oral health affects general health and that some systemic diseases can affect oral health. A variety of diseases involve the oral cavity; the two main oral diseases present worldwide and lead to tooth destruction or tooth loss: • dental caries, the disease that leads to cavities in the teeth • periodontal disease, which leads to loosening of teeth. Both diseases are preventable, and strong efforts have been made to control them. Other diseases and conditions are much less prevalent, yet serious, and sometimes even life threatening: oral precancer and cancer, oral manifestations of HIV and AIDS, noma, developmental disorders, and fluorosis of teeth.

DENTAL CARIES Dental caries develops by the localized dissolution of the tooth hard tissues, caused by acids that are produced by bacteria in the biofilms (dental plaque) on the teeth and eventually lead to “cavities.” The biofilm consists of microorganisms, including the highly cariogenic mutans streptococci, and a matrix made up mainly of extracellular polysaccharides. The destructive acids are produced when fermentable carbohydrates (sugars) reach these biofilms, each episode resulting in tooth damage (attack). If this process does not occur frequently, then the natural capacity of the body (through saliva) to remineralize will

prevent formation of a cavity. Thus, the main risk factors include presence of cariogenic biofilms and frequent consumption of fermentable carbohydrates. Exposure to fluorides in optimum concentrations reduces the risk, and normal saliva flow and saliva protective systems are also important to counteract the cariogenic factors. Untreated caries can give rise to infection of the tooth pulp, which can spread to the supporting tissues and the jaws, culminating in advanced disease conditions that are often painful. For example, in Thailand, recent surveys of a sample of 12-year-old children revealed that 53 percent had suffered from pain or discomfort from teeth over the past year (Petersen and others 2001). The corresponding figures in China were 34 percent for 12-year-olds (Peng, Petersen, Fan, and others 1997) and 74 percent for adults (Petersen, Peng, and Tai 1997). Tooth decay is a public health problem worldwide. According to the U.S. Surgeon General’s report (U.S. Public Health Service 2000), dental caries is the single most common chronic childhood disease in the United States. Epidemiological data for almost 200 countries are available in the World Health Organization (WHO) Country/Area Profile Programme (CAPP) oral health database (http://www.whocollab.od.mah. se/index.html) (see table 38.1 for examples). Caries prevalence of permanent teeth is expressed by the decayed, missing, and filled teeth (DMFT) index (calculated by counting the number of DMFT of individuals and taking the mean for the group examined). One indicator age group used for international comparisons is 12-year-old children. The WHO oral health goal was to achieve three DMFT or fewer among 12-year-olds


Table 38.1 Mean DMFT and SiC Index of 12-Year-Olds for Some Countries, by Ascending Order of DMFT Country

Mean DMFT

SiC Index

Year

Sample size

Australia

0.8

2.4

1999

29,130

Nepal

0.8

2.5

2000

623

Sweden

0.9

2.6

2001

71,896

Jamaica

1.0

2.8

1995

362

China

1.0

3.0

1996

23,452

Senegal

1.2

2.8

1994

Sri Lanka

1.4

3.6

1994–95

2,003

300

England, U.K. (Northwest)

1.4

3.2

2000–1

12,029

United States

1.4

3.6

1988–91

176

Portugal

1.5

3.6

1999

800

Germany

1.7

4.1

1997

1,043

Reference Armfield, Roberts-Thomson, and Spencer 2003 Data from WHO, courtesy P. E. Petersen Sundberg 2002 Data from PAHO, courtesy E. D. Beltran and S. Estupinan-Day Data from WHO, courtesy P. E. Petersen Sembene, Kane, and Bourgeois 1999 Abayaratna and Krishnarasa 1997 Pitts and others 2002 Data from PAHO, courtesy E. D. Beltran and S. Estupinan-Day Data from WHO, courtesy P. E. Petersen Micheelis and Reich 1999

Israel

1.7

4.1

2002

1,327

Courtesy S. P. Zusman, Division of Dental Health, Israel

South Africa

1.7

4.3

1988–89

1,571

van Wyk 1994

Greece (Northeastern province) (11-year-olds)

1.8

4.2

2001

2,217

Demertzi and Topitsoglou 2002

Scotland (U.K.)

1.8

4.3

1996–97

6,165

Data from K. Woods from the study Pitts, Evans, and Nugent 1998

France

2.0

4.7

1998

6,000

Hescot and Roland 2000

Thailand

2.4

4.9

2001

1,116

Data from WHO, courtesy P. E. Petersen

Mexico (state of Mexico)

2.5

5.0

1997

1,138

Irigoyen and Sanchez-Hinojosa 2000

Uruguay

2.5

5.3

1999

596

Sector Público 1999

Comoros

2.6

6.1

2000

142


Belarus

2.7

5.4

1999

2,537


Romania

2.7

5.8

2001

785


Nicaragua

2.8

5.7

1997

365

Data from PAHO, courtesy E. D. Beltran and S. Estupinan-Day

Greenland

3.5

7.0

2002

236


Latvia

3.8

7.1

1998

416


Poland

3.9

7.2

1997

1,732


Honduras

4.0

7.5

1997

307


Bolivia

4.7

8.8

1995

389


Slovak Republic

5.9

14.3

1998

1,589


Costa Rica

8.5

13.7

1988

1,349


Source: Authors. PAHO Pan American Health Organization; SiC Significant caries.

by 2000. According to the CAPP database, 70 percent of the countries had achieved three DMFT or fewer by 2001, representing 85 percent of the world population. Several developing economies, however, have reported a trend toward higher levels of dental caries. A detailed analysis of caries data for many countries, both industrial and developing, shows skewed distributions of the disease—that is, a proportion of a population of children showing a high or very high number of caries and the rest showing a low number of caries or none. Expressing caries prevalence as mean DMFT may, therefore, not accurately describe the disease

level in populations with skewed distribution. The Significant Caries (SiC) Index was proposed to bring attention to those hidden high caries groups (Bratthall 2000). The SiC Index is calculated by simply taking the mean DMFT of the one-third of the group having the highest DMFT in a population (figure 38.1). Table 38.1 shows several countries having fewer than three mean DMFT but high SiC Index values, thus illustrating the hidden caries burden for children (Nishi and others 2002). Dental caries is found not only in children and young adults but also in all age groups. The elderly, in particular those with exposed tooth root surfaces, constitute a special risk

724 | Disease Control Priorities in Developing Countries | Douglas Bratthall, Poul Erik Petersen, Jayanthi Ramanathan Stjernswärd, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 144

• Individuals with poor oral hygiene and frequent sugar intake are at increased risk. • Individuals not exposed to fluorides—for example, from fluoridated water or toothpastes—are at increased risk of caries. • Persons with individual risk factors, such as reduced saliva flow or exposed tooth root surfaces, or with certain general diseases are also at increased risk of caries.

SiC

DMFT 10 9 8 7 6 5 4

Caries Intervention Programs

3 2 1 0 0

6

12

18

24

30

36

42 48 55 61 67 Percentage of group

73

79

85

91

97

Source: Adyatmaka and others 1998. Note: The mean DMFT is 2.3. The Significant Caries Index is 5.4. Arrow indicates the proportion of individuals who are included in the calculation of the index. West Kalimantan is one of the most caries-affected provinces in Indonesia.

Figure 38.1 DMFT for 331 12-Year-Olds, West Kalimantan, Indonesia

population (Barmes 2000). A Swedish study reported DMFT values of 21.4 and 24.4 for 50- and 70-year-olds, respectively, indicating that nearly all teeth were affected in these age groups (Hugoson and others 1995). Thomson (2004), reviewing longitudinal studies of older adults (age 50+), found an incidence of root surface caries varying from 29 to 59 percent and concluded that older people are a caries-active group, experiencing new caries at a rate comparable to that of adolescents. With increasing numbers of people becoming 50 years of age or older in some developing countries, root surface caries may become a significant problem. When we consider the global epidemiology of dental caries, the main patterns seem to be the following: • Countries with low mean sugar consumption (less than 10 to 15 kilograms of sugar per person per year) generally have low mean caries prevalence. • Countries with high mean sugar consumption (more than 20 to 25 kilograms of sugar per person per year) and without effective preventive programs generally have high mean caries prevalence. • Countries with high mean sugar consumption (more than 20 to 25 kilograms of sugar per person per year) using effective preventive programs have been able to reduce the caries prevalence. If we consider the prevalence of caries within a population, the main patterns seem to be as follows: • Disadvantaged or poor population groups have higher dental caries experience than advantaged groups.

Since the discovery of the caries-preventive effect of fluorides in the 1930s, different forms of fluoride administration programs have been implemented, often with remarkable cariesreducing effects. Fluoride has been added to different vehicles, such as water, salt, toothpaste, and milk. Fluoride tablets and fluoride mouth rinsing have been used among young children and in schools, and more recently even among adults at high caries risk (Petersen 1989, 1990). For individual use, fluoride in high concentrations has been added to various forms of gels and varnishes to be applied on the teeth. Furthermore, fluoride in chewing gum is available in some countries. When a group of international experts on cariology were asked in a study to identify the main causes of the caries decline seen in several Western countries during recent decades, practically all the experts pointed to fluoride dentifrice as the most significant factor (Bratthall, Hänsel-Petersson, and Sundberg 1996). According to WHO (1994), community water fluoridation is safe and cost-effective in preventing dental caries in every age group, benefiting all residents served by the community water regardless of their social or economic status (Burt 2002; Petersen and Lennon 2004; White, Antczak-Bouckoms, and Weinstein 1989). Examples of countries with fluoridated water supplies for significant parts of the populations are Argentina, Brazil, Brunei Darussalam, Canada, Chile, Ireland, New Zealand, the United Kingdom, and the United States. In many developing countries, lack of community water supplies makes water fluoridation impossible. Effective fluoride toothpastes have been available for about 40 years (WHO 1994). They have been tested in numerous studies, in particular in school-based programs. The most commonly used concentrations are 1,000 or 1,500 parts per million (ppm). Because most studies have been conducted in developed countries, WHO launched a program testing a socalled “affordable fluoridated toothpaste” in developing countries. In the West Kalimantan Province of Indonesia, a supervised school-based toothbrushing program was implemented over a period of three years, resulting in a reduction of 12 to 40 percent of caries incidence in the study groups when compared to control groups (Adyatmaka and others 1998). Domestic salt fluoridation is another method of automatic fluoridation. In the early 1950s, Switzerland and Austria Oral and Craniofacial Diseases and Disorders | 725


introduced this approach by offering their populations fluoridated salt for the table and for cooking. The fluoride concentration in the salt originally was 90 ppm and was later increased to 250 ppm. Fluoridated salt is now available in several countries in Europe and in South and Central America. A comparison of caries data for Jamaica in 1984 (before salt fluoridation) and 1995 (after salt fluoridation) showed a reduction of caries experience of 69 percent, 84 percent, and 87 percent among 15-, 12-, and 6-year-olds, respectively (Estupinan-Day and others 2001). Milk fluoridation projects are being conducted in several countries, including Bulgaria, China, the Russian Federation, Thailand, and the United Kingdom. In Bulgaria, a milk fluoridation project resulted in a 79 percent lower DMFT in those children who had participated in the full five years of the program than in the control children (Pakhomov and others 1995). Fluoride tablets and fluoride mouth-rinsing programs under supervision in schools have been implemented in several countries, including the Scandinavian countries, the United Kingdom, and the United States. The requirement that teachers and students be motivated has limited such approaches. In recent years, many national fluoride programs have been adjusted as the additional caries-reducing effects of topical applications with daily use of fluoridated toothpaste have been questioned (Petersen and Torres 1999).

Oral Health Education and Promotion Programs The WHO Global Oral Health Programme has developed a manual for integration of oral health with school health programs (WHO 2003). In many industrial countries, school health education programs have included oral health, and researchers have shown that children’s self-care capacity improved in regard to regular toothbrushing with the use of fluoridated toothpaste (Flanders 1987; Honkala, Kannas, and Rise 1990; Petersen and Torres 1999; Sogaard and Holst 1988; Wang and others 1998). Examples also exist from school oral health education in developing countries. Some programs have been organized within the context of the WHO Health Promoting Schools Initiative. In Madagascar, the evaluation of program outcomes has shown remarkably good results in reducing dental caries risk, improving self-care capacity of children and mothers, and introducing higher levels of dental knowledge and attitudes (Razanamihaja and Petersen 1999). Other successful examples are available from Tanzania (Petersen and others 2002; van Palenstein Helderman and others 1997), Zimbabwe (Frencken and others 2001), and Namibia (Priwe 1998). In China, principles from the WHO Health Promoting Schools Initiative have been applied in certain provinces; positive effects of programs were obtained regarding health-related knowledge and behavior, but the clinical outcome measures were less evident (Petersen and others 2004; Tai and others

2001). The Chinese health authorities have emphasized preventive oral care and oral health education since the late 1980s. The nationwide mass campaign “Love Teeth Day” has been conducted annually since 1989, and the effective transmission of oral health messages to the public has shown improved oral health knowledge and behavior in children as well as in adults (Peng, Petersen, Tai, and others 1997). In addition, various dental organizations (Cohen 1990) and private companies have developed and carried out successful oral health programs worldwide. For example, toothpaste manufacturers have donated toothpastes, toothbrushes, and educational material promoting oral health in several countries. Effectiveness of the Oral Health Programs In countries with systematic national oral disease prevention programs, the total cumulative effect of these programs is reflected in the epidemiological figures demonstrating caries decline (table 38.2) and in the growing proportions of cariesfree individuals. However, singling out the effects of specific activities or methods of programs is difficult because several program components often operate simultaneously. For example, in industrial countries, practically all individuals use fluoridated toothpaste, and removing this preventive measure from a group of individuals just to evaluate the effect of another fluoride program would be unethical. In addition, other factors affect caries reduction, such as changing lifestyles, changing patterns of sugar consumption, and improving living conditions. The current trend in clinical health care and public health is to base recommendations on evidence derived from systematic reviews of the literature and critical assessment of the quality of results (U.S. Public Health Service 2000). The office of the U.S. Surgeon General (U.S. Public Health Service 2000) and the Swedish Council on Technology Assessment in Health Care (SBU 2002) are examples of entities that have attempted to determine the effectiveness in public health of evidence-based approaches and technologies. Oral Health in America, the U.S. Surgeon General’s report (U.S. Public Health Service 2000), reviewed experiences from the administration of fluorides. Primarily based on U.S. studies, the report had these conclusions: • Strong evidence exists supporting the effectiveness of water fluoridation in preventing crown and root caries in children and adults. • Strong evidence exists of the effectiveness of the schoolbased fluoride supplement (tablets) program. The program, with motivated supervising personnel, such as teachers, is recommended for children at high risk for caries. • Evidence supports the effectiveness of school-based fluoride (0.2 percent sodium fluoride) mouth-rinsing programs conducted before 1985 (before the introduction of fluoride


Table 38.2 Declining Caries Experience in Some Countries Country

Year

DMFT in 12-year-olds

1996

1.8

Guinan and others 1999

1993

2.6

Data from Oral Health Programme, WHO

1997

1.3

Petersen and Kaka 1999

1992

1.5


1988

1.7

Woodward and Walker 1994

1998

2.3

Data from PAHO

1984

4.8


1999

2.3

Data from PAHO

1996

4.8

Data from Ministry of Health

1993

4.9

Data from PAHO

1995

1.3

Beltran-Aguilar, Estupinan-Day, and Baez 1999

1983

2.7


2000

1.0

Data from PAHO

1994

2.2

Data from PAHO

1997

3.7


1987

5.7


1995

1.1


1984

6.7


1997

2.8


1983

6.9


1997

3.6


1989

4.2


Reference

African region Côte d’Ivoire

Niger

American region Colombia

Costa Rica

Guyana

Haiti

Honduras

Jamaica

Nicaragua

Panama

United States

Venezuela, R. B. de

1992–94

1.28

NHANES III, Courtesy D. Bruce

1988–91

1.4


1986–87

1.8


1997

2.1


1986

3.6

Data from PAHO

1995

1.7


1991

2.1


1995

1.6

Nithila and others 1998

1993

2.0


2000

2.7

Leous and Petersen 2002

1994

3.8

Leous and Petersen 2002

2002

0.9

Data from National Board of Health, Denmark

1995

1.2


1980

5.0


Middle Eastern region Saudi Arabia

United Arab Emirates

European region Belarus

Denmark


Oral and Craniofacial Diseases and Disorders | 727 ©2006 The International Bank for Reconstruction and Development / The World Bank 147

Table 38.2 Continued Country

Year

DMFT in 12-year-olds

France

1998

1.9


1993

2.1


1990

3.0


1996

3.8

Szoke and Petersen 2000

1991

4.3


1985

5.0


Hungary

Israel

Latvia

Norway

Poland

Portugal

Romania

Sweden

United Kingdom

Reference

2002

1.66

Data from Dr S. P. Zusman, Division of Dental Health, Israel

1989

3.0

Zadik, Zusman, and Kelman 1992

2000

3.9

Latvia, State Dentistry Centre 2000

1998

4.2

Latvia, State Dentistry Centre 2000

2000

1.5

Data from Norwegian Board of Health

1992

2.2

von der Fehr 1994

1986

3.1

Haugejorden 1994

2000

3.8

Wierzbicka and others 2002

1991

5.1

Wierzbicka and others 2002

1999

1.5

de Almeida and others 2003

1990

3.2


1984

3.7


2000

2.7

Petersen and Rusu 2002

1990

3.9

Petersen and others 1994

2001

0.9

Sundberg 2002

1995

1.4

Sundberg 2002

1985

3.1

Sundberg 2002

1996–97

1.1

Pitts, Evans, and Nugent 1998

1983

3.1

Downer 1994

2000

1.0

Ullah 2001

1981

1.5


1994–95

1.4

Abayaratna and Krishnarasa 1997

1983–84

1.9

Sri Lanka, Ministry of Health 1985

1999

0.8

Armfield, Roberts-Thomson, and Spencer 2003

1990

1.4

Armfield, Roberts-Thomson, and Spencer 2003

1980

3.6

Carr 1988

2001

0.8

Hong Kong, Department of Health 2003

1986

1.5

Lo, Evans, and Lind 1990

Asian region Bangladesh

Sri Lanka

Western Pacific region Australia

Hong Kong (China)

Japan

Malaysia

1999

2.4

Data from Ministry of Health and Welfare

1993

3.6

Miyazaki and Morimoto 1996

1987

4.9

Miyazaki and Morimoto 1996

1997

1.6

Malaysia, Dental Services Division 1997

1988

2.4

Malaysia, Dental Services Division 1997

Source: Authors. PAHO Pan American Health Organization; NHANES III Third U.S. National Health and Nutritional Examination Survey. Note: Numbers in italics indicate that the country did not achieve the WHO global goal of fewer than three DMFT by 2000 but shows caries decline.


toothpastes) in preventing caries in children. The costeffectiveness of this intervention is reduced with the current decline in prevalence of caries. It is recommended for use in high-risk children consistently over a period of time. • Strong evidence supports the effectiveness of sealants in preventing pits and fissure caries. The report recommends that the programs be limited to high-risk children and highrisk teeth. • Fluoride varnishes were not approved for use in the United States until 1994; hence, investigations are ongoing of the effectiveness of this intervention. The Swedish Council on Technology Assessment in Health Care (SBU 2002) applied strict criteria of evidence of effectiveness; that is, the study had to be randomized and have a sample representing the total population. For permanent teeth, a three-year follow-up was necessary. The number of studies meeting all the criteria was not very high. Here are some conclusions of this review: • Daily use of fluoridated toothpaste is an effective method to reduce caries in permanent teeth among children and adolescents. Daily, weekly, or biweekly fluoride mouth rinsing can reduce caries, but together with daily fluoride toothpaste use, the additional effects are not strong. • Daily fluoride mouth rinsing can reduce root surface caries in the elderly, and professional application of fluoride varnish twice a year has a caries-reducing effect in permanent teeth among youth, as does the use of fluoridated toothpaste. • Fissure sealants have a caries-reducing effect. According to the SBU report, it was difficult to interpret the effect of programs aimed at reducing the intake of sugars or the effect of so-called sugar substitutes. Systematic evaluation of community preventive programs should be carried out in the future, particularly to help identify appropriate alternatives for developing countries.

ASPECTS OF TREATMENT OF CAVITIES AND OF CARIES DISEASE One has to differentiate between treatment of cavities and treatment of the disease process resulting in cavities. The normal treatment of a tooth with a cavity is a filling or, if the cavity is large, a crown. Large cavities may involve “rootfillings” or even extraction of the tooth. A variety of materials are used globally: composites, amalgam, gold, porcelain, and others. Options for replacing extracted teeth include removable prostheses, fixed bridges, or implants. The more complex treatments are costly, and no country has been able to afford to introduce systems in which all dental costs are covered by

public funds. Moreover, a filling does not affect the disease process causing the cavities. Treatment must be directed against the causative factors (described earlier). For the individual case, several options are available in addition to the various fluoride programs mentioned: dietary counseling, sugar substitutes, antimicrobial agents to reduce plaque and specific bacteria, and the use of saliva-stimulating products. In many developing countries, the lack of dental manpower means that carious teeth remain untreated. The ratio of dentists to population is particularly unfavorable in the African region compared with Western European countries. For instance, according to CAPP, the ratio is 1 to 1.2 million in Ethiopia, 1 to 225,000 in Mali, and 1 to 166,000 in Zambia, against about 1 to 1,000 in Scandinavian countries and 1 to 2,100 in the United Kingdom (see http://www.whocollab.od. mah.se/index.html). In India, the ratio is 1 to 27,000 in the urban areas but 1 to 300,000 in the rural areas (Shah 2001). Such ratios mean that neither dental caries disease nor the cavities will receive proper attention. After taking into consideration the high costs for dental treatment and the lack of dentists, atraumatic restorative treatment (ART) was introduced. This approach requires only hand instruments rather than sophisticated electric dental drills, and trained dental auxiliaries can deliver ART. The public dental health services in South Africa adopted the approach as an appropriate and economic means of providing basic restorative care in certain communities. A randomized clinical trial conducted in Tanzania showed no statistically significant differences between the retention of occlusal amalgam (74 percent) and ART occlusal restorations (67 percent) after a six-year follow-up (1992–98) (Mandari, Frencken, and Van’t Hof 2003). A potentially affordable treatment procedure that could prevent untreated carious teeth from being extracted, ART may have relevance to some middle-income countries, although the method is not realistic for most low-income countries, where sustainability of such programs would be low.

PERIODONTAL DISEASES: CHRONIC GINGIVITIS AND CHRONIC PERIODONTITIS Gingivitis, the inflammation of gum tissue caused by bacteria accumulating in the plaque along the gingival margin, precedes chronic periodontitis. The more destructive form of periodontal disease, which breaks down the supporting tissues of the teeth, progressively leading to loosening of teeth and tooth loss, affects 10 to 15 percent of most adult populations (Papapanou 1999). Cigarette smoking and diabetes mellitus (with poorly controlled diabetes) are two major risk factors associated with periodontal disease and appear markedly to affect the initiation and progression of the disease (Genco 1996; Papapanou 1999). Oral and Craniofacial Diseases and Disorders | 729


In recent years there has been a growing awareness of the association between some systemic diseases and oral disease, especially periodontal diseases. For example, a national study in the United States found that the prevalence of diabetes mellitus in patients with periodontitis was significantly greater (twofold) than in nonperiodontal patients (Soskolne and Klinger 2001). Periodontal disease may be considered one of the complications of diabetes. Effective control of periodontal infection in diabetics appears to reduce the levels of advanced glycogen end-products in the serum. Proper oral hygiene practices can prevent both gingivitis and advanced periodontal disease. All intervention programs leading to improved oral hygiene are instrumental in the control of periodontal disease and will reduce risk of future tooth loss. The school-based oral health educational programs previously discussed are effective in preventing gingivitis, but no community-based intervention program addresses periodontal disease, especially among adults. Tobacco cessation programs are also important in the prevention of periodontal diseases. Treatment of periodontal diseases consists of plaque removal, scaling, and sometimes surgery, plus motivation and instruction in oral hygiene. Dental hygienists can perform parts of the treatment program.

ORAL PRECANCER AND CANCER The most frequent form of oral precancerous lesion, leukoplakia, appears as a white patch that cannot be rubbed off, typically in the buccal mucosa, lateral borders of the tongue, and floor of the mouth. The prevalence of leukoplakia among those 15 years old and above ranged from 1.1 percent in Cambodia, to 1.7 percent in Myanmar, to 3.6 percent in Sweden (Axell 1976; Ikeda and others 1995). Malignant transformation varies in different populations; nearly 5 percent of lesions are found to be malignant at first biopsy, and 5 percent develop into malignancy at a later stage. Erythroplakias appear as red patches and are less common but have a higher tendency (90 percent or more) than leukoplakias to transform into malignancies (Sudbo and Reith 2003). Oral cancers affect about 300,000 people worldwide annually (Ferlay and others 2001) and often develop from oral precancerous lesions (Sudbo and Reith 2003). Early detection of oral precancerous lesions, notably oral leukoplakia and erythroplakia, could easily prevent the development of the disfiguring disease oral cancer and premature death. Tobacco use in any form (smoking or chewing) and excessive alcohol consumption remain the primary risk factors in the development of these precancerous lesions (“Early Diagnosis and Prevention of Oral Cancer and Precancer” 1995; Reichart 2001). Factors such as local irritation, Candida albicans infection, and nutritional deficiencies are also associated with the presence of leukoplakia.

Screening populations and routine examination in dental and medical clinics for oral precancer and early cancer lesions would reduce the mortality, morbidity, and cost of treatment associated with oral cancers. Not all oral premalignancies show malignant transformation, and detection of these oral lesions by biopsies are straightforward, not requiring sophisticated equipment. Tobacco cessation programs aimed at younger and older age groups and control of excessive alcohol intake are definitely beneficial in the prevention of oral cancer.

ORAL MANIFESTATIONS OF HIV/AIDS The scarce epidemiological data available on oral manifestations of HIV in developing countries are difficult to interpret because these studies are not standardized (Holmes and Stephan 2002). In the study groups, the prevalence of oral lesions in Africa ranged from 15 percent to more than 90 percent of infected individuals; in India the prevalence was 72 percent; and in Thailand it was 82 percent. Reviews are available on the different studies performed on oral manifestations of HIV and AIDS (Naidoo and Chikte 1999; Patton and others 2002). Candida infections, oral hairy leukoplakia, oral ulcers, and Kaposi’s sarcoma are some of the common oral manifestations of HIV and AIDS. Notably, Kaposi’s sarcomas were never detected in the Asian populations studied in India, Singapore, and Thailand but were seen in South African, Zambian, and Zimbabwean studies (Arendorf and others 1998; Hodgson 1997; Holmes and Stephan 2002; Lim and others 2001; Nittayananta and Chungpanich 1997; Ranganathan and others 2000). The presence of oral candidiasis and hairy leukoplakia alone or at the same time in an apparently healthy individual could be an early indicator of the undetected HIV infection progressing to AIDS. Those signs may be used as indicators during clinical examinations in developing countries where technology for laboratory tests is not available or is too expensive (Greenspan and Greenspan 2002; Holmes and Stephan 2002).

NOMA (CANCRUM ORIS) Noma usually begins as a small ulcer of the gingiva and develops into a rapidly spreading gangrenous condition of the oral and facial tissues. Seen mainly in debilitated and malnourished children, it is disfiguring and deadly. The condition is reported in developing countries in several regions of the world, particularly in Sub-Saharan Africa (Enwonwu, Falkler, and Idigbe 2000; Naidoo and Chikte 2000; Petersen 2003). Noma disappeared from the industrial world in the 20th century except


during World War II. In contrast, risk factors such as poverty, poor hygiene, and malnutrition, eventually in combination with infectious diseases such as HIV and AIDS, may have recently increased the prevalence of this disease in Sub-Saharan Africa (Enwonwu 1995; Naidoo and Chikte 2000). Most important, 90 percent of infected children die without having received any care. Although the specific etiologic factors for noma are not known, poverty has been identified as the single most important risk indicator. Accordingly, improving the overall socioeconomic conditions can prevent noma. Public health approaches such as providing a high-protein diet, clean water, and sanitation and preventing communicable diseases such as diphtheria, dysentery, and tuberculosis would be needed for effective prevention of noma in Africa. Prognosis of noma is considerably better with timely administration of antibiotics.

DEVELOPMENTAL DISORDERS Developmental disorders involve teeth and the craniofacial structures. A few of these disorders are congenital diseases of the enamel or dentin; problems related to the number, size, or shape of teeth; and craniofacial birth defects, such as cleft lip and palate (CL/P). Among the most common congenital malformations seen in humans, cardiovascular malformation is ranked as the first and CL/P as the second. Unilateral CL/P occurs six times more frequently than the bilateral form. Females are more prone to get cleft palates, whereas cleft lip or CL/P is most common in males (U.S. Public Health Service 2000). The incidence of CL/P differs from 0.18 to 3.74 per 1,000 live births, the highest incidence being seen in Native Americans at 3.74 per 1,000, closely followed by the Japanese at 3.36 per 1,000 live births. A fairly uniform incidence of 1 per 600 to 700 live births is reported among Europeans. Overall, the incidence rates appear high among Asians (0.82 to 3.36 per 1,000 live births), intermediate in Caucasians (0.9 to 2.69 per 1,000 live births), and often very low in black Africans (0.18 to 1.67 per 1,000 live births) (Hewson and McNamara 2000; Vanderas 1987; Wantia and Rettinger 2002). The causes of CL/P are complex, involving multiple genetic and environmental risk factors. Not all cases of CL/P are inherited. A number of risk factors, such as folic acid deficiencies, maternal smoking, and maternal age, have been implicated in the formation of clefts (Wantia and Rettinger 2002). Advanced surgery, specific prosthetic appliances, and orthodontic treatment can improve the quality of life for those born with clefts. However, such treatment is not accessible to children of several developing countries. Tobacco cessation programs aimed at pregnant mothers are essential in the prevention of CL/P.

FLUOROSIS OF TEETH Fluorosis of teeth develops during formation of teeth when children are young. Drinking water having more than 1.5 ppm of fluoride can give rise to enamel defects and discoloration of teeth, leading to endemic fluorosis in the population. These effects may vary from mild to severe. For example, in the Great Rift Valley area of East Africa, the ground water has high levels of fluoride, leading to high rates of dental fluorosis—nearly 90 percent in some parts of Kenya (Chibole 1987). Some individuals in developed countries can acquire fluorosis of teeth as a result of the widespread use of different forms of fluorides in the prevention of caries, though the degree of fluorosis often is mild compared with endemic fluorosis. Defluoridation of the central water supplies is possible when naturally occurring fluoride is excessive in the drinking water. However, most developing countries do not have central water distribution systems, and the cost of defluoridation equipment and its maintenance can be high. WHO encourages effective and inexpensive methods that are useful for individual households or community defluoridation of drinking water (WHO 1994). Such methods exist, but a number of operational problems have been identified, requiring further initiatives in this field (Kloos and Haimanot 1999).

COMMON-RISK-FACTOR INTERVENTION PROGRAMS New research is pointing to associations between chronic oral infections—particularly periodontitis—and heart and lung diseases, stroke, osteoporosis, low birthweight, and premature births in addition to diabetes. Such findings strengthen WHO health promotion strategies that are based on the commonrisk-factor approach, which controls essential risk factors that contribute to a large number of chronic diseases (Petersen 2003). Risk behaviors such as smoking; alcohol; diets rich in fats and sugars and low in fiber, fruit, and vegetables; stress; poor hygiene; and sedentary lifestyle are factors leading to such major chronic diseases as cardiovascular diseases, cancers, diabetes, obesity, osteoporosis, dental caries, and periodontal disease. These principal risk factors for major chronic diseases are often seen to cluster in the same individuals. The WHO Global Oral Health Programme recommends the common-risk-factors approach (Petersen 2003), which implies development of integral activities in health promotion and disease prevention, involving health education, community empowerment, and legislative policy development. For example, such programs could aim at reducing the caries levels among preschool children and simultaneously improving general health. Promoting the reduction of sugar consumption would improve not only oral health but also general health Oral and Craniofacial Diseases and Disorders | 731


Table 38.3 Prevention Strategies for Oral Health Disease or condition

Causes

Actions needed and methods

Dental caries

High or frequent sugar consumption, plaque present, highly cariogenic microorganisms, nonuse of fluorides, reduced saliva flow, systemic diseases, and other individual risk factors

Targeted actions against causative factors on community and individual levels

Plaque present, pathogenic bacteria, influence of systemic diseases, tobacco use

Improved oral hygiene, professional cleaning, antibiotics, identification and treatment of systemic diseases

Periodontal diseases

Health education toward self-care capacity, fluoride programs, sugar restriction, actions based on risk assessment of individuals and groups

Elimination of pockets if present and removal of local dental irritants, such as rough fillings Tobacco cessation Oral precancer and cancer

Tobacco and alcohol use; see chapter 29

Tobacco cessation; see chapter 29

Oral manifestations of HIV/AIDS

See chapter 18

See chapter 18. Special oral care

Noma (cancrum oris)

Probably bacterial in connection with severe malnourishment

Antibiotics together with nutritional support; surgery sometimes necessary

Developmental disorders

Various genetic or environmental causes such as tobacco use

Tobacco cessation programs aimed at pregnant mothers

Fluorosis of teeth

Too high concentration of fluoride in drinking waters or from other sources

Identification of water sources and reduction of fluoride or recommendation of other water sources

Source: Authors; partly based on Bratthall and Barmes 1993. Note: This table is by no means complete. Many other oral diseases or conditions are important and need attention. The listed ones are of special relevance for developing countries.

through better quality of children’s diet. Some prevention strategies for oral health, suitable for developing countries are outlined in table 38.3.

RESEARCH AND FUTURE ACTIONS Several promising actions against factors causing the two major oral diseases, caries and periodontal disease, are ongoing: attempts to control the formation of the biofilm with its microflora are of high priority. One research line is to identify pathogenic bacteria and try to replace them with genetically modified, less pathogenic bacteria or to eradicate them by antibiotics or antiseptics. Preventing dental caries by a vaccine is not a new idea, and efforts continue. Among other ideas is the use of plantibodies (plant-derived therapeutic antibodies) or genetically modified bacteria, releasing components targeting pathogens. Functional foods, which include various elements in food, may be another future option to control oral diseases. Although pilot or small-scale studies seem promising, it will be several years before such methods can possibly be of use in populations because large clinical trials have not even started. Saliva is believed to be usable as a diagnostic tool, providing noninvasive assessment of a number of oral and systemic diseases. Devices are being designed to identify in saliva various bacteria and their virulence factors, drugs, metabolic products,

hormones, biomarkers for oral cancer, inflammatory mediators, and more. Future developments may result in other affordable and effective devices. Continuous attempts are being made to assess the sociobehavioral factors in oral health and the information on risk factors. Caries risk assessment models are tested also for the individual cases. Through present knowledge, individuals in need of targeted actions can be identified. Another strong trend is to use evidence-based reviews. This type of research is, of course, not restricted to oral health. Several reviews have already been done, and a frequent conclusion is that the number of randomized clinical trials is limited, in particular for common clinical procedures. This trend will change as the quality of future oral health research improves, but not all research problems can be solved by such studies. Community-based participatory research is another approach that may be used to improve oral health studies (O’Fallon and Dearry 2002). Within the management of dental diseases—in particular, caries—is the “minimally invasive dentistry” approach, which promotes the concept that large restorations (crowns, bridges) are not as necessary as believed. Risk assessment, preventive measures, and improved dental materials with good adhesion capacity are some of the several components in this approach. Research in transfer of knowledge using the Internet or other electronic media is another strongly expanding area, from which developing countries should be able to benefit.


COST-EFFECTIVENESS OF ORAL HEALTH CARE

DMFT 9

Using the evidence available, the U.S. Surgeon General’s report (U.S. Public Health Service 2000) and the report of the Swedish Council on Technology Assessment in Health Care (SBU 2002; see also Kallestal and others 2003) have attempted to determine the cost-effectiveness of oral health intervention programs from developed countries. Among the findings in the U.S. report were the following:

8 7 6 5 4 3

• Water fluoridation costs about a dollar per person per year for water serving most individuals in the United States. Community water fluoridation is believed to be an effective and cost-effective caries preventive method. • Economic analyses of community dental sealant programs suggest that they are cost-effective and may even provide cost savings when used in high-risk populations. The Swedish report (SBU 2002), reviewing original studies on economic evaluation of caries prevention (a total of 17 selected from 1966 to 2003 MEDLINE and manual Internet searches), commented that no conclusion could be drawn owing to the low evidence values and contradictory results. This comment prompted the group to present its own calculation for cost-effectiveness based on Swedish caries prevalence and charges used in Swedish dental care. The group found that the cost-effectiveness for fluoridated toothpaste is extremely good (cost per prevented DMFT very low), which, of course, is not surprising, given the significant caries-reducing results in combination with low cost for society. No clear correlation appears to exist between caries experience and health care investment for individual countries. Some countries with the lowest health care expenditures have values for caries experience (DMFT) that are similar to or even lower than those countries having the highest expenditures on health (figure 38.2). Those low-income countries often have low per capita sugar consumption and, therefore, do not need to install expensive measures for treatment or prevention. It may seem surprising that so few studies are available regarding the cost-effectiveness of caries prevention, or of any other oral disease. In a critical review article, Schwarz (1998) analyzed the issue. He wrote, “Several decades after considerable improvements in the oral disease situation were documented in Scandinavia, doubts are still expressed about whether preventive measures are cost-effective.” In addition, he recommended that four elements be considered when a preventive effect was evaluated: the definition of prevention, the practical perception of effective prevention, the appropriateness of traditional cost-effectiveness analysis, and the time factor. He pointed out that “caries prevention is not uniformly defined by the profession, that dental research is casting doubt

2 1 0 0

1,000

2,000

3,000

4,000

5,000

6,000

7,000

US$

Source: For health expenditure: http://www.who.int/en/; for DMFT: http://www. whocollab.od.mah.se/index.html, both for June 2003. Note: Original data for health expenditures were in international dollars and were converted to U.S. dollars using the exchange rate of US$1 0.70681 (period average June 2003). Because the exchange rate varies over time, the data should be taken as approximate values.

Figure 38.2 DMFT as Related to Health Care Expenditure per Capita for 12-Year-Olds in 149 Countries

on the effectiveness of traditionally accepted preventive measures, that political pressures on health care are motivated by economic pressures.” Finally, he stated that traditional costbenefit and cost-effectiveness analyses have not been able to help the decision makers choose wisely and that the time perspective for the real effects of prevention lies beyond the interests of decision makers. However, without proper prevention, the alternative strategy is restorative dentistry—that is, to make fillings, crowns, and dentures. Is this a feasible alternative for developing countries? Yee and Sheiham (2003) give some examples: In Nepal, a simple amalgam filling would cost about US$4, which does not include the many additional expenses for impoverished rural families, who may have to travel by bus or walk for a day or two to get to the clinic. The total expenses incurred, including dental fees, meals, and lodging but not including lost wages, would amount to US$12, an enormous sum considering the average Nepalese’s earning of US$0.75 per day, and it is enough to buy food for a month. Yee and Sheiham conclude that treating caries with the traditional method of restorative dentistry is beyond the financial capabilities of most low-income nations because three-quarters of these countries do not even have sufficient resources to finance an essential package of health care services for their children. Yee and Sheiham (2003) estimate that treating dental caries by the traditional amalgam restorative dentistry in the permanent dentition of the child population would cost about US$2,000 for 1,000 children of mixed ages from 6 to 18 years, which would require financial Oral and Craniofacial Diseases and Disorders | 733


resources beyond the capabilities of low-income nations. Hence, they propose a public health and health promotion approach to reduce caries burden instead of the restorative approach. Although several studies evaluating the effectiveness of intervention and oral health promotion programs in developing countries are becoming available (Estupinan-Day and others 2001; Pakhomov and others 1995; Petersen and others 2004), a definite need exists for further cost-effectiveness analysis on such programs, which should be addressed in the future. It would also be useful if studies were commenced on intervention programs using the common-risk approach suggested by WHO (Petersen 2003).

Axell, T. 1976. “A Prevalence Study of Oral Mucosal Lesions in an Adult Swedish Population.” Odontologisk Revy 27 (Suppl. 36): 1–103. Barmes, D. E. 2000. “Public Policy on Oral Health and Old Age: A Global View.” Journal of Public Health Dentistry 60: 335–37. Beltran-Aguilar, E. D., S. Estupinan-Day, and R. Baez. 1999. “Analysis of Prevalence and Trends of Dental Caries in the Americas between the 1970s and 1990s.” International Dental Journal 49: 322–29. Bratthall, D. 2000. “Introducing the Significant Caries Index Together with a Proposal for a New Global Oral Health Goal for 12-Year-Olds.” International Dental Journal 50: 378–84. Bratthall, D., and D. E. Barmes. 1993. “Oral Health.” In Disease Control Priorities in Developing Countries, ed. D. T. Jamison, W. H. Mosley, A. R. Measham, and J. L. Bobadilla, 647–59. Washington, DC: World Bank. Bratthall, D., G. Hänsel-Petersson, and H. Sundberg. 1996. “Reasons for the Caries Decline: What Do the Experts Believe?” European Journal of Oral Sciences 104: 416–22. Burt, B. A. 2002. “Fluoridation and Social Equity.” Journal of Public Health Dentistry 62: 195–200.

CONCLUSIONS Dental caries and periodontal diseases are the most known oral diseases, but other conditions can strongly and negatively influence the quality of life. Effective programs to reduce the burden of oral diseases—in particular, caries—are available in principle, but to run these programs in developing countries, new approaches are needed. The WHO strategy of identifying common risk factors seems promising for health promotion. In broad terms, the most important challenges for oral health in the 21st century relate to the transfer of knowledge and experiences in preventive oral care to the poor and disadvantaged population groups in both developing and developed countries.

Carr, L. M. 1988. “Dental Health of Children in Australia, 1977–1985.” Australian Dental Journal 33: 205–11. Chibole, O. 1987. “Epidemiology of Dental Fluorosis in Kenya.” Journal of the Royal Society of Health 107: 242–43. Cohen, L. K. 1990. “Promoting Oral Health: Guidelines for Dental Associations.” International Dental Journal 40: 79–102. de Almeida, C. M., P. E. Petersen, S. J. Andre, and A. Toscano. 2003. “Changing Oral Health Status of 6- and 12-Year-Old Schoolchildren in Portugal.” Community Dental Health 20: 211–16. Demertzi, A., and V. Topitsoglou. 2002. “Caries Prevalence of 11-Year-Olds between 1989–2001.” Abstract. Community Dental Health 19: 203. Downer, M. C. 1994. “The 1993 National Survey of Children’s Dental Health: A Commentary on the Preliminary Report.” British Dental Journal 176: 209–14. “Early Diagnosis and Prevention of Oral Cancer and Precancer: Report of Symposium III.” 1995. Advanced Dental Research 9: 134–37. Enwonwu, C. O. 1995. “Noma: A Neglected Scourge of Children in SubSaharan Africa.” Bulletin of the World Health Organization 73: 541–45.

ACKNOWLEDGMENTS

Enwonwu, C. O., W. A. Falkler, and E. O. Idigbe. 2000. “Oro-Facial Gangrene (Noma/Cancrum Oris): Pathogenetic Mechanisms.” Critical Reviews in Oral Biology and Medicine 11: 159–71.

We acknowledge with great appreciation comments and suggestions from Dr. Lois Cohen, Dr. Kevin Hardwick, Dr. Jeanne C. Sinkford, and Thomas Wall. Sir George Alleyne, our editor, is to be congratulated for his constructive ideas and patience.

Estupinan-Day, S. R., H. Baez, R. Horowitz, R. Warpeha, B. Sutherland, and M. Thamer. 2001. “Salt Fluoridation and Dental Caries in Jamaica.” Community Dentistry and Oral Epidemiology 29: 247–52.

REFERENCES

Ferlay, J., F. Bray, P. Pisani, and D. M. Parkin. 2001. GLOBOCAN 2000: Cancer Incidence, Mortality and Prevalence Worldwide. Version 1.0. IARC CancerBase, International Agency for Research on Cancer, Lyon. http://wwwdep.iarc.fr/globocan/globocan.htm.

Abayaratna, S., and K. Krishnarasa. 1997. National Oral Health Survey 1994–95. Colombo: Ministry of Health. Adyatmaka, A., U. Sutopo, P. Carlsson, D. Bratthall, and G. Pakhomov. 1998. School-Based Primary Preventive Programme for Children: Affordable Toothpaste as a Component in Primary Oral Health Care— Experiences from a Field Trial in Kalimantan Barat, Indonesia. Geneva: World Health Organization. Arendorf, T. M., B. Bredekamp, C. A. Cloete, and G. Sauer. 1998. “Oral Manifestations of HIV Infection in 600 South African Patients.” Journal of Oral Pathology and Medicine 27: 176–79. Armfield, J. M., K. F. Roberts-Thomson, and A. J. Spencer. 2003. The Child Dental Health Survey, Australia 1999: Trends across the 1990s. Adelaide: Australian Institute of Health and Welfare. http://www.cecdo.org/ pages/database%20intro.html.

Flanders, R. A. 1987.“Effectiveness of Dental Health Educational Programs in Schools.” Journal of the American Dental Association 114: 239–42. Frencken, J. E., K. Borsum-Andersson, F. Makoni, F. Moyana, S. Mwashaenyi, and J. Mulder. 2001. “Effectiveness of an Oral Health Education Programme in Primary Schools in Zimbabwe after 3.5 Years.” Community Dentistry and Oral Epidemiology 29: 253–59. Genco, R. J. 1996. “Current View of Risk Factors for Periodontal Diseases.” Journal of Periodontology 67: 1041–49. Greenspan, J. S., and D. Greenspan. 2002. “The Epidemiology of the Oral Lesions of HIV Infection in the Developed World.” Oral Diseases 8 (Suppl. 2): 34–39. Guinan, J. C., R. Bakayoko-Ly, M. Samba, A. L. Kattie, and A. E. Oka. 1999. “Caries Assessment of School Children 12 Years of Age in 1996 in Ivory Coast.” Tropical Dental Journal 22: 48–54.


Haugejorden, O. 1994. “Changing Time Trend in Caries Prevalence in Norwegian Children and Adolescents.” Community Dentistry and Oral Epidemiology 22: 220–25. Hescot, P., and E. Roland. 2000. La santé dentaire en France, 1998. L’Union Française pour la Santé Bucco-Dentaire, Paris. Hewson, A. R., and C. M. McNamara. 2000. “Cleft Lip and/or Palate in the West of Ireland, 1980–1996.” Special Care in Dentistry 20: 143–46. Hodgson, T. A. 1997. “HIV-Associated Oral Lesions: Prevalence in Zambia.” Oral Diseases 3 (Suppl. 1): 46–50. Holmes, H. K., and L. X. G. Stephan. 2002. “Oral Lesions of HIV Infection in Developing Countries.” Oral Diseases 8 (Suppl. 2): 40–43. Hong Kong, Department of Health. 2003. Oral Health Survey 2001. http://www.info.gov.hk/tooth_club/survey_eng.htm. Honkala, E., L. Kannas, and J. Rise. 1990. “Oral Health Habits in 11 European Countries.” International Dental Journal 40: 211–17. Hugoson, A., G. Koch, T. Bergendal, A. L. Hallonsten, C. Slotte, B. Thorstensson, and H. Thorstensson. 1995. “Oral Health of Individuals Aged 3–80 Years in Jönköping, Sweden, in 1973, 1983 and 1993.” Swedish Dental Journal 19: 243–60. Ikeda, N., Y. Handa, S. P. Khim, C. Durward, T. Axell, T. Mizuno, and others. 1995. “Prevalence Study of Oral Mucosal Lesions in a Selected Cambodian Population.” Community Dentistry and Oral Epidemiology 23: 49–54.

Nishi, M., J. Stjernsward, P. Carlsson, and D. Bratthall. 2002. “Caries Experience of Some Countries and Areas Expressed by the Significant Caries Index.” Community Dentistry and Oral Epidemiology 30: 296–301. Nithila, A., D. Bourgeois, D. E. Barmes, and H. Murtomaa. 1998. “WHO Global Oral Data Bank, 1986–96: An Overview of Oral Health Surveys at 12 Years of Age.” Bulletin of the World Health Organization 76: 237–44. Nittayananta, W., and S. Chungpanich. 1997. “Oral Lesions in a Group of Thai People with AIDS.” Oral Diseases 3 (Suppl. 1): S41–45. O’Fallon, L. R., and A. Dearry. 2002. “Community-Based Participatory Research as a Tool to Advance Environmental Health Sciences.” Environmental Health Perspectives 110 (Suppl. 2): 155–59. Pakhomov, G. N., K. Ivanova, I. J. Moller, and M. Vrabcheva. 1995. “Dental Caries-Reducing Effects of a Milk Fluoridation Project in Bulgaria.” Journal of Public Health Dentistry 55: 234–37. Papapanou, P. N. 1999.“Epidemiology of Periodontal Diseases: An Update.” Journal of the International Academy of Periodontology 1: 110–16. Patton, L. L., J. A. Phelan, F. J. Ramos-Gomez, W. Nittayananta, C. H. Shiboski, and T. L. Mbuguye. 2002. “Prevalence and Classification of HIV-Associated Oral Lesions.” Oral Diseases 8 (Suppl. 2): 98–109. Peng, B., P. E. Petersen, M. W. Fan, and B. J. Tai. 1997. “Oral Health Status and Oral Health Behaviour of 12-Year-Old Urban Schoolchildren in the People’s Republic of China.” Community Dental Health 14: 238–44.

Irigoyen, M. E., and G. Sanchez-Hinojosa. 2000. “Changes in Dental Caries Prevalence in 12-Year-Old Students in the State of Mexico after 9 Years of Salt Fluoridation.” Caries Research 34: 303–7.

Peng, B., P. E. Petersen, B. J. Tai, B. Y. Yuan, and M. W. Fan. 1997. “Changes in Oral Health Knowledge and Behaviour 1987–95 among Inhabitants of Wuhan City, PR China.” International Dental Journal 47: 142–47.

Kallestal, C., A. Norlund, B. Soder, G. Nordenram, H. Dahlgren, L. G. Petersson, and others. 2003. “Economic Evaluation of Dental Caries Prevention: A Systematic Review.” Acta odontologica Scandinavica 61: 341–46.

Petersen, P. E. 1989. “Evaluation of a Dental Preventive Program for Danish Chocolate Workers.” Community Dentistry and Oral Epidemiology 17: 53–59.

Kloos, H., and R. T. Haimanot. 1999. “Distribution of Fluoride and Fluorosis in Ethiopia and Prospects for Control.” Tropical Medicine and International Health 4: 355–64. Latvia, State Dentistry Centre. 2000. Annual Report of Dental Health Care in Latvia. Riga: State Dentistry Centre. Leous, P., and P. E. Petersen. 2002. Oral Health Status of Schoolchildren in Belarus, 2000. Copenhagen: WHO Regional Office for Europe. Lim, A. A., Y. S. Leo, C. C. Lee, and A. N. Robinson. 2001. “Oral Manifestations of Human Immunodeficiency Virus (HIV)–Infected Patients in Singapore.” Annals of the Academy of Medicine, Singapore 30: 600–6. Lo, E. C., R. W. Evans, and O. P. Lind. 1990. “Dental Caries Status and Treatment Needs of the Permanent Dentition of 6–12-Year-Olds in Hong Kong.” Community Dentistry and Oral Epidemiology 18: 9–11. Malaysia, Dental Services Division. 1997. Dental Services. Kuala Lumpur: Ministry of Health. Mandari, G. J., J. E. Frencken, and M. A. Van’t Hof. 2003. “Six-Year Success Rates of Occlusal Amalgam and Glass-Ionomer Restorations Placed Using Three Minimal Intervention Approaches.” Caries Research 37: 246–53. Micheelis, W., and E. Reich. 1999. The Third German Oral Health Study (DMS III). Cologne, Germany: Deutscher Aerzte-Verlag. Miyazaki, H., and M. Morimoto. 1996. “Changes in Caries Prevalence in Japan.” European Journal of Oral Sciences 104: 452–58. Naidoo, S., and U. M. Chikte. 1999. “HIV/AIDS—The Evolving Pandemic and Its Impact on Oral Health in Sub-Saharan Africa.” South African Dental Journal 54: 616–30. ———. 2000. “Noma (Cancrum Oris): Case Report in a 4-Year-Old HIV-Positive South African Child.” South African Dental Journal 55: 683–86.

———.1990.“Self-Administered Use of Fluoride among Danish Chocolate Workers.” Scandinavian Journal of Dental Research 98: 189–91. ———. 2003. “The World Oral Health Report 2003: Continuous Improvement of Oral Health in the 21st Century—The Approach of the WHO Global Oral Health Programme.” Community Dentistry and Oral Epidemiology 31 (Suppl. 1): 1–21. Petersen, P. E., I. Danila, A. Delean, O. Grivu, G. Ionita, M. Pop, and A. Samolia. 1994. “Oral Health Status among Schoolchildren in Romania, 1992.” Community Dentistry and Oral Epidemiology 22: 90–3. Petersen, P. E., N. Hoerup, N. Poomviset, J. Prommajan, and A. Watanapa. 2001. “Oral Health Status and Oral Health Behaviour of Urban and Rural Schoolchildren in Southern Thailand.” International Dental Journal 51: 95–102. Petersen, P. E., and M. Kaka. 1999. “Oral Health Status of Children and Adults in the Republic of Niger, Africa.” International Dental Journal 49: 159–64. Petersen, P. E., and M. A. Lennon. 2004. “Effective Use of Fluorides for the Prevention of Dental Caries in the 21st Century: The WHO Approach.” Community Dentistry and Oral Epidemiology 32: 319–21. Petersen, P. E., U. Nyandindi, E. N. Kikiwilu, L. Mabelya, B. S. Lembariti, and V. J. Poulsen. 2002. Oral Health Status and Oral Health Behaviour of Schoolchildren, Teachers, and Adults in Tanzania. Geneva: World Health Organization. Petersen, P. E., B. Peng, and B. J. Tai. 1997. “Oral Health Status and Oral Health Behaviour of Middle-Aged and Elderly People in PR China.” International Dental Journal 47: 305–12. Petersen, P. E., B. Peng, B. Tai, Z. Bian, and M. Fan. 2004. “Effect of a School-Based Oral Health Education Programme in Wuhan City, People’s Republic of China.” International Dental Journal 54: 33–41. Petersen, P. E., and M. Rusu. 2002. Oral Health Status of Romanian Schoolchildren—National Survey 2000. Copenhagen: WHO Regional Office for Europe. Oral and Craniofacial Diseases and Disorders | 735


Petersen, P. E., and A. M. Torres. 1999. “Preventive Oral Health Care and Health Promotion Provided for Children and Adolescents by the Municipal Dental Health Service in Denmark.” International Journal of Paediatric Dentistry 9: 81–91. Pitts, N. B., D. J. Evans, and Z. J. Nugent. 1998. “The Dental Caries Experience of 12-Year-Old Children in the United Kingdom: Surveys Coordinated by the British Association for the Study of Community Dentistry in 1996/97.” Community Dental Health 15: 49–54. Pitts, N. B., D. J. Evans, Z. J. Nugent, and C. M. Pine. 2002.“The Dental Caries Experience of 12-Year-Old Children in England and Wales: Surveys Coordinated by the British Association for the Study of Community Dentistry in 2000/2001.” Community Dental Health 19: 46–53. Priwe, C. 1998. The Smiling School Project: A School Based Oral Health Promotion Programme: Mid-Term Progress Report. Windhoek: Ministry of Health and Social Services. Ranganathan, K., B. V. Reddy, N. Kumarasamy, S. Solomon, R. Viswanathan, and N. W. Johnson. 2000. “Oral Lesions and Conditions Associated with Human Immunodeficiency Virus Infection in 300 South Indian Patients.” Oral Diseases 6: 152–57. Razanamihaja, N., and P. E. Petersen. 1999. “School Based Oral Health Promotion Programmes in Madagascar.” In Health Care Systems in Africa—Patterns and Perspectives, ed. L. Blegvad, 123–29. Copenhagen: University of Copenhagen Press. Reichart, P. A. 2001. “Identification of Risk Groups for Oral Precancer and Cancer and Preventive Measures.”Clinical Oral Investigations 5: 207–13. SBU (Swedish Council on Technology Assessment in Health Care). 2002. Att förebygga karies: En systematisk litteraturöversikt. Gothenburg: Swedish Council on Technology Assessment in Health Care.

Szoke, J., and P. E. Petersen. 2000. “Evidence for Dental Caries Decline among Children in an East European Country (Hungary).” Community Dentistry and Oral Epidemiology 28: 155–60. Tai, B., M. Du, B. Peng, M. Fan, and Z. Bian. 2001. “Experiences from a School-Based Oral Health Promotion Programme in Wuhan City, PR China.” International Journal of Paediatric Dentistry 11: 280–91. Thomson, W. M. 2004. “Dental Caries Experience in Older People over Time: What Can the Large Cohort Studies Tell Us?” British Dental Journal 196: 89–92. Ullah, M. S. 2001. An Epidemiological Oral Health Study on 12-Year-Old Bangladeshi Schoolchildren. Thesis, Faculty of Dentistry, Oslo. U.S. Public Health Service. 2000. Oral Health in America: A Report of the Surgeon General. Washington, DC: U.S. Public Health Service. http://www.nidr.nih.gov/sgr/sgrohweb/TOC.htm. Vanderas, A. P. 1987. “Incidence of Cleft Lip, Cleft Palate, and Cleft Lip and Palate among Races: A Review.” Cleft Palate Journal 24: 216–25. van Palenstein Helderman, W. H., L. Munck, S. Mushendwa, M. A. van’t Hof, and F. G. Mrema. 1997. “Effect Evaluation of an Oral Health Education Programme in Primary Schools in Tanzania.” Community Dentistry and Oral Epidemiology 25: 296–300. van Wyk, P. J. 1994. National Oral Health Survey, South Africa, 1988/89. Pretoria: Department of Health. von der Fehr, F. R. 1994. “Caries Prevalence in the Nordic Countries.” International Dental Journal 44 (Suppl. 1): 371–78.

Schwarz, E. 1998. “Is Caries Prevention Cost-Effective? Does Anybody Care?” Acta odontologica Scandinavica 56: 187–92.

Wang, N. J., C. Kalletstal, P. E. Petersen, and I. B. Arnadottir. 1998. “Caries Preventive Services for Children and Adolescents in Denmark, Iceland, Norway and Sweden: Strategies and Resource Allocation.” Community Dentistry and Oral Epidemiology 26: 263–71.

Sector Público. 1999. Encuesta de salud bucal, En escolares de 11 a 14 años. Montevideo: Ministry of Public Health.

Wantia, N., and G. Rettinger. 2002. “The Current Understanding of Cleft Lip Malformations.” Facial Plastic Surgery 18: 147–53.

Sembene, M., A. W. Kane, and D. Bourgeois. 1999. “Caries Prevalence in 12-Year-Old Schoolchildren in Senegal in 1989 and 1994.” International Dental Journal 49: 73–75. Shah, N. 2001. “Geriatric Oral Health Issues in India.” International Dental Journal 51: 212–18. Sogaard, A. J., and D. Holst. 1988. “The Effect of Different School Based Dental Health Education Programmes in Norway.” Community Dental Health 5: 169–84. Soskolne, W. A., and A. Klinger. 2001. “The Relationship between Periodontal Diseases and Diabetes: An Overview.” Annals of Periodontology 6: 91–98.

White, B. A., A. A. Antczak-Bouckoms, and M. C. Weinstein. 1989. “Issues in the Economic Evaluation of Community Water Fluoridation.” Journal of Dental Education 53: 646–57.

Sri Lanka, Ministry of Health. 1985. National Oral Health Survey, 1983–84. Colombo: Ministry of Health. Sudbo, J., and A. Reith. 2003. “Which Putatively Pre-Malignant Oral Lesions Become Oral Cancers? Clinical Relevance of Early Targeting of High-Risk Individuals.” Journal of Oral Pathology and Medicine 32: 63–70. Sundberg, H. 2002. Tandhälsan hos barn och ungdomar 1985–2001. Newsletter. Swedish National Board of Health and Welfare, Stockholm.

WHO (World Health Organization). 1994. Fluorides and Oral Health. Technical Report Series No. 846. Geneva: WHO. ———. 2003. School Oral Health Promotion. WHO School Health Information Series 11. Geneva: WHO. Wierzbicka, M., P. E. Petersen, F. Szatko, E. Dybizbanska, and I. Kalo. 2002. “Changing Oral Health Status and Oral Health Behaviour of Schoolchildren in Poland.” Community Dental Health 19: 243–50. Woodward, M., and A. R. Walker. 1994. “Sugar Consumption and Dental Caries: Evidence from 90 Countries.” British Dental Journal 176: 297–302. Yee, R., and A. Sheiham. 2003. “Is Treating Caries in Children in Developing Countries by the Restorative Approach a Rational Objective?” Developing Dentistry 3: 10–17. Zadik, D., S. P. Zusman, and A. M. Kelman. 1992. “Caries Prevalence in 5and 12-Year-Old Children in Israel.” Community Dentistry and Oral Epidemiology 20: 54–55


Chapter 39

Unintentional Injuries Robyn Norton, Adnan A. Hyder, David Bishai, and Margie Peden

This chapter examines the issue of unintentional injuries and focuses on a selected number of cause-specific unintentional injuries. Injuries have traditionally been defined as damage to a person caused by an acute transfer of energy (mechanical, thermal, electrical, chemical, or radiation) or by the sudden absence of heat or oxygen. Unintentional injuries consist of that subset of injuries for which there is no evidence of predetermined intent. The cause-specific unintentional injuries examined here include those that the World Health Organization (WHO) routinely analyzes and publishes data on and that individually account for the greatest unintentional injury burden in terms of mortality and disability-adjusted life years (DALYs). These include road traffic injuries (RTIs), poisonings, falls, burns, and drowning (figure 39.1).

BURDEN AND CAUSES OF UNINTENTIONAL INJURIES This section provides a brief outline of the burden of unintentional injuries and then reviews the available evidence about known and potential causes of such injuries.

Burden of Unintentional Injuries Worldwide, unintentional injuries accounted for more than 3.5 million deaths in 2001, or about 6 percent of all deaths and 66 percent of all injury deaths. Unintentional injuries were also responsible for more than 113 million DALYs in 2001, or about 8 percent of all DALYs and some 70 percent of all injury DALYs. More than 90 percent of unintentional injury deaths occurred in low- and middle-income countries (LMICs),

accounting for around 7 percent of all deaths in those countries. Similarly, more than 90 percent of DALYs that were attributed to unintentional injuries occurred in LMICs, accounting for about 8 percent of all DALYs in those countries. Injury death rates per 100,000 population were higher in LMICs (62 per 100,000) than globally (57 per 100,000). Males accounted for almost two-thirds of the deaths attributed to unintentional injuries in LMICs in 2001, with rates of both injury death and DALY losses higher among males than females (table 39.1). Compared with other age groups, young people age 15 to 29 accounted for the largest proportion of deaths from unintentional injuries in LMICs (figure 39.2). RTIs accounted for the greatest burden of deaths from unintentional injuries in LMICs in 2001, or about 34 percent of the total burden, and the greatest burden of DALYs from unintentional injuries in LMICs in 2001, accounting for 28 percent of the burden (figure 39.1). Whereas young people age 15 to 29 years accounted for the highest proportion of all unintentional injuries, those age 45 to 59 accounted for the highest proportion of injuries from poisonings, while those age 70 to 79 accounted for the highest proportion of injuries from falls (figure 39.2). Economic Burden of Unintentional Injuries. Estimates of the burden of unintentional injuries as measured in terms of economic costs are almost nonexistent. The best estimates available are for RTIs. Using road crash costs from 21 developed and developing countries, the Transport Research Laboratory Ltd. finds that the average annual cost of road crashes was equivalent to about 1.0 percent of gross national product in developing countries, 1.5 percent in transition countries, and 2.0 percent in highly motorized countries. The annual burden 737


Table 39.1 Cause-Specific Death Rates and DALYs Lost because of Unintentional Injuries, by Gender, Worldwide and in LMICs, 2001

a. Deaths Other unintentional injuries 26%

Road traffic injuries 34%

Global Category

LMICs

Total Males Females Total Males Females

Deaths (per 100,000 population) Drowning 11% Fires 9%

Poisonings 10%

Falls 10% b. DALYs

All unintentional injuries

57

75

41

61

80

44

RTIs

19

28

11

20

30

11

Poisonings

6

7

4

6

8

5

Falls

6

8

5

6

8

5

Fires

5

4

6

6

4

7

Drowning

Other unintentional injuries 37%

Other unintentional injuries

Road traffic injuries 28%

Poisonings 6% Falls 12%

Fires 9%

9

4

7

10

5

19

11

16

20

11

14

22

28

16

DALY losses (per 1,000 population) All unintentional injuries

Drowning 8%

6 15

Source: Authors.

Figure 39.1 Distribution of Unintentional Injuries, Low- and MiddleIncome Countries, 2001

20

25

RTIs

6

8

3

6

9

4

Poisonings

1

2

1

1

2

1

Falls

2

3

2

3

3

2

Fires

2

1

2

2

2

2

Drowning

2

2

1

2

2

1

Other unintentional injuries

7

9

5

8

10

6

Source: Authors. Note: All figures are rounded to the nearest 1,000.

Percentage 35 30 25 20 15 10 5 0 All unintentional injuries

Road traffic injuries

Poisonings

Falls

Fires

Drowning

Other

Type of injury 0–4 years

5–14 years

15–29 years

30–44 years

45–59 years

60–69 years

Source: Authors.

Figure 39.2 Distribution of Unintentional Injuries by Type of Injury and Age Group, LMICs, 2001 738 | Disease Control Priorities in Developing Countries | Robyn Norton, Adnan A. Hyder, David Bishai, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 158

70–79 years

80 + years

of road crash costs is about US$518 billion globally and about US$65 billion in LMICs, exceeding the total annual amount these countries receive in development assistance (Jacobs, Aeron-Thomas, and Astrop 2000).

Causes of Unintentional Injuries in LMICs As in the case of most diseases, unintentional injuries are caused by multiple factors. The traditional epidemiological paradigm of host, vector, and environmental factors that in combination contribute to the incidence of disease has been adapted and applied in determining the causes of unintentional injury. However, this paradigm has been extended to consider each factor in relation to the time of the injury—that is, factors operating before, during, and after the injury that might be associated with both its incidence and its severity (Haddon 1968). Although the matrix, called the Haddon matrix, was initially developed to address the problem of RTIs only, it provides a comprehensive framework in which researchers can consider the multitude of factors that may play a role in the causal injury pathway, as outlined in table 39.2. In the past two decades, the evidence base for the identification of risk factors for unintentional injuries in high-income countries (HICs) has increased dramatically as the number of injury researchers and research institutions has increased. However, because of the paucity of injury researchers and research institutions in LMICs, the evidence base for the identification of risk factors for unintentional injuries in these countries is growing more slowly. Although knowledge about risk factors for injuries in HICs may also be relevant for LMICs, the material presented in the following section focuses on information that has been obtained from studies in LMICs. However, the section also

considers the extent to which information obtained from studies conducted in HICs may be relevant. Risk Factors for Road Traffic Injuries. The increasing volume of traffic is one of the main factors contributing to the increase in RTIs in LMICs. Motorization rates rise with income (Kopits and Cropper 2005), and a number of LMICs experiencing growth have seen a corresponding increase in the number of motor vehicles (Ghaffar and others 1999). In some LMICs, this growth has been led by an increase in motorized two-wheeled vehicles, one of the least safe forms of travel, which has resulted in concurrent increases in related injuries (Zhang and others 2004). The rapid growth in motor vehicles in many LMICs has not been accompanied by improvements in facilities for these road users or by facilities that respond to the continued predominance of nonmotorized traffic (Khayesi 2003). Many of the technical aspects of planning, highway design, traffic engineering, and traffic management that are the hallmarks of transportation systems in many HICs are absent in LMICs, which need to plan for a level of heterogeneity in traffic that HICs do not encounter (Tiwari 2000). Studies undertaken primarily in HICs show a strong relationship between the increase in vehicle speeds and increased risk of crash and injury, both for motor vehicle occupants and for vulnerable road users, particularly pedestrians (European Road Safety Action Program 2003). This relationship is likely to be true for LMICs, and indeed, data obtained from routinely collected police reports in a number of LMICs show that speed is listed as the leading cause of road traffic crashes, accounting for up to 50 percent of all crashes (Afukaar 2003; Odero, Khayesi, and Heda 2003; Wang and others 2003). Several case-control studies in HICs have confirmed the role of alcohol in the increasing risk of road crashes (Peden and

Table 39.2 The Haddon Matrix as Applied to Road Traffic Injuries Factors Phase

Nature of intervention

Human

Vehicles and equipment

Environment

Precrash

Crash prevention

Information

Roadworthiness

Road design

Attitudes

Lighting

Road layout

Impairment

Braking

Speed limits

Police enforcement

Handling

Pedestrian facilities

Speed management Crash

Injury prevention during crash

Use of restraints

Occupant restraints

Impairment

Other safety devices

Forgiving roadside (for example, crash barriers)

Crash-protective design Postcrash

Life sustaining

First-aid skill

Ease of access

Rescue facilities

Access to medical personnel

Fire risk

Congestion

Source: Authors.

Unintentional Injuries | 739 ©2006 The International Bank for Reconstruction and Development / The World Bank 159

others 2004). Studies conducted in LMICs showed that drivers had consumed alcohol in 33 to 69 percent of crashes in which drivers were fatally injured and in 8 to 29 percent of crashes in which drivers were not fatally injured (Odero and Zwi 1995). Alcohol consumption by pedestrians also increases their risk of injuries in HICs; moreover, in at least some LMICs, more than 50 percent of fatally injured pedestrians had consumed alcohol (Peden and others 1996). Other factors that increase the risks of road crashes in HICs include fatigue, use of hand-held mobile telephones, and inadequate visibility of vulnerable road users (Peden and others 2004), all of which are equally likely to increase risks in LMICs. Indeed, a recent case-control study from China shows that the risks of a crash doubled with chronic sleepiness on the part of the driver (G. F. Liu and others 2003), and surveys of commercial and public road transport in a number of African countries have shown that drivers often work long hours and go to work exhausted (Mock, Amegashi, and Darteh 1999; Nafukho and Khayesi 2002). Studies in Malaysia clearly show that motorcyclists who use daytime running lights have a crash risk about 10 to 29 percent lower than those who do not because of their greater visibility (Radin Umar, Mackay, and Hills 1996). Road- and vehicle-related factors may also increase the risk of crash involvement. Specific factors related to road planning include traffic passing through residential areas, conflicts between pedestrians and vehicles, schools located on busy roads, lack of median barriers to prevent dangerous passing on two-lane roads,and lack of barriers to prevent pedestrian access onto highspeed roads, although few studies have specifically examined the risks associated with those factors (Ross and others 1991). Although the severity of crash injuries is related to invehicle crash protection, evidence indicates that many engineering advances found in vehicles in HICs are not present in vehicles in LMICs (Odero, Garner, and Zwi 1997). Perhaps one of the most important factors contributing to injury severity relates to crash protection for vulnerable road users. However, few HICs, let alone LMICs, require the fronts of cars or buses to be designed in a way that would protect vulnerable road users (Mohan 2002). A significant risk factor for increased severity of injuries of users of motorized two-wheeled vehicles is riders’ failure to use motorcycle helmets (B. Liu and others 2004). Studies in a number of Asian countries have shown that failure to use helmets, use of nonstandard helmets, and use of improperly secured helmets are not uncommon, even in countries with mandatory helmet laws (Conrad and others 1996; Kulanthayan and others 2000). Failure to wear helmets is also a risk factor for increased injury severity among bicyclists (Attewell, Glase, and McFadden 2001). Although the failure to use seat belts is a significant risk factor associated with injury severity among vehicle occupants, many LMICs have no requirements for seat belts to be fitted or used (Peden and others 2004).

Studies in HICs suggest that roadside hazards, such as trees, poles, and road signs, may contribute to between 18 and 42 percent of road crashes and increase injury severity (Kloeden and others 1998), although the extent to which this is also true in LMICs has not been determined. Risk Factors for Poisonings. The literature on poisonings in LMICs includes comprehensive information about intentional poisonings; significant information about occupation-related poisonings, especially pesticide poisonings; and a growing body of information about lead poisoning. Each of these types of poisoning is covered elsewhere in this book. This chapter focuses on risk factors for other types of poisoning in LMICs, and, in particular, focuses on risk factors for poisonings in young children. The literature’s focus on risk factors for childhood poisoning probably reflects the fact that child poisoning victims are seen more often than adults in most hospital settings (Ellis and others 1994; Nhachi and Kasilo 1992). This fact is in stark contrast to the data presented earlier, which clearly show that middle-aged individuals sustain the vast majority of deaths and DALYs from poisonings in LMICs. Those numbers no doubt reflect the importance of work-related poisonings. Young males consistently appear to be at higher risk of poisonings than females (Ellis and others 1994; Fernando and Fernando 1997; Soori 2001). The most common agents involved in childhood poisonings are paraffin (or kerosene) and other household chemicals; pesticides; and various plants or animals, including snakes (Fernando and Fernando 1997). Several case-control studies in LMICs indicate the importance of a number of sociodemographic risk factors, including young parents, residential mobility, and limited adult supervision of children (Azizi, Zulkifli, and Kasim 1993; Soori 2001). The studies also suggest that previous poisoning may be a risk factor (Soori 2001). Another important factor seems to be storage, including the number of storage containers used in the residence; the use of nonstandard containers for storage (for example, beverage bottles for storing kerosene); and the storage of poisons at ground level (Azizi, Zulkifli, and Kasim 1993; Chatsantiprapa, Chokkanapitak, and Pinpradit 2001; Soori 2001). Risk Factors for Fall-Related Injuries. Risk factors for fallrelated injuries in older people are generally considered in terms of risk factors for falling, risk factors associated with the severity of the impact following the fall, and risks factors associated with low levels of bone mineral density—insofar as almost all fall-related injuries in older people involve broken bones. The risk factors associated with the latter two categories are generally related to aspects of the aging process and, as a consequence, are considered in more detail in chapter 51.

740 | Disease Control Priorities in Developing Countries | Robyn Norton, Adnan A. Hyder, David Bishai, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 160

Analytical studies conducted in a variety of LMICs have tended to show that risk factors for fall-related injuries, especially hip fractures, are consistent with the risk factors identified in HICs. Those risk factors include low bone density; poor nutritional status and low body mass index; low calcium intake; comorbid conditions, such as hypertension and diabetes; poor performance in activities of daily living; low levels of engagement in physical activity; poor cognitive function; poor perceived health status; poor vision; environmental factors affecting balance or gait; family history of hip fracture; and alcohol consumption (Boonyaratavej and others 2001; Clark and others 1998; Jitapunkul, Yuktananandana, and Parkpian 2001). Some studies have identified other factors that may be more relevant in the context of LMICs. For example, studies in Thailand suggest that factors associated with poor socioeconomic status may increase risk—for example, not having electricity in the house and living in Thai-style houses or huts (Jitapunkul, Yuktananandana, and Parkpian 2001). The literature specifically identifying risk factors for falls in younger people in LMICs is sparse, but the information there is indicates that such falls usually occur in and around the home, with a significant proportion being associated with falls from heights, including rooftops and trees (Adesunkanmi, Oseni, and Badru 1999; Bangdiwala and Anzola-Perez 1990; Kozik and others 1999; Raja, Vohra, and Ahmed 2001). However, falls other than from heights predominate and are frequently related to engagement in vigorous levels of physical activity. Risk Factors for Burn-Related Injuries. Despite the focus of WHO’s data on burn-related injuries sustained as a result of fires, a number of country-specific surveys conducted in medical facilities suggest that scalds from hot water may be equally important or more important causes of burn-related injuries (Chan and others 2002; Delgado and others 2002; Forjuoh, Guyer, and Smith 1995; Rossi and others 1998). However, in some countries, including China and particularly India, firerelated injuries clearly outweigh scald-related injuries (Ahuja and Bhattacharya 2002; Jie and Ren 1992). Overall, women are at greater risk of fire-related burn injuries than are men; however, data from population-based and medical center surveys suggest that in some settings (excluding India), males may be at greater risk of burns than are females (Chan and others 2002; Zhu, Yang, and Meng 1988). In many studies, burn-related injuries account for a much higher proportion of injuries in young children compared with other age groups (Jie and Ren 1992; E. H. Liu and others 1998). Rural location appears to be a consistent risk factor for burn-related injuries (Courtright, Haile, and Kohls 1993; Zhu, Yang and Meng 1988), as is the home (Delgado and others 2002; Forjuoh, Guyer, and Smith 1995; E. H. Liu and others 1998).

Investigators have undertaken case-control studies aimed at identifying risk and protective factors for burn-related injuries in Africa, Asia, and South America, and all focus on identifying risk factors for children. Environmental risk factors that have been identified include lack of a water supply, storage of a flammable substance in the home, cooking equipment in the kitchen within reach of children, and housing that is located in slums and congested areas. Persons with personal and socioeconomic risk factors included children who were not the first born, who had a pregnant mother, whose mother recently was dismissed from a job, who had recently moved, who had a preexisting impairment, whose sibling died from a burn or had a history of burn, whose parents lacked alertness to burns, whose clothing was made of synthetic fabrics, whose parents were illiterate, and whose parents were of low economic status. Protective factors included the presence of a living room, better maternal education, and a history of previous injury among males who lived in good environmental conditions (Daisy and others 2001; Delgado and others 2002; Forjuoh and others 1995; Werneck and Reichenheim 1997). Risk Factors for Drowning. Most drowning incidents in LMICs are not associated with recreation or leisure, as is commonly the case in HICs, but instead are associated with everyday activities near bodies of water, including rivers, wells, and buckets (Celis 1997; Hyder and others 2003; Kobusingye, Guwatudde, and Lett 2001). As noted earlier, men account for a higher proportion of drowning incidents than women, and children age one to four and young people appear to be at greatest risk, with drowning accounting for a high proportion of injury-related deaths in those age groups (Celis 1997; Kibel and others 1990; Kozik and others 1999; Tan, Li, and Bu 1998). Some surveys also suggest that older people may be at particularly high risk (Tan, Li, and Bu 1998). Descriptive surveys indicate that those living in rural areas are at greater risk than those living in urban areas (Kobusingye, Guwatudde, and Lett 2001), probably indicating greater exposure to unprotected water surfaces. A number of studies find that most adult drowning incidents appear to be associated with positive blood alcohol tests (Carlini-Cotrim and da Matta Chasin 2000; Celis 1997). Case-control studies of drowning in young children have identified both sociodemographic risk factors and risk factors associated with proximity to bodies of water. Ahmed, Rahman, and van Ginneken’s (1999) study in Bangladesh shows that the risk of drowning increased with the age of the mother and increased much more sharply the larger the number of children in the family. Celis’s (1997) case-control study in Mexico finds that the risk of drowning associated with having a well at home was almost seven times that for children in homes without a well. Unintentional Injuries | 741


INTERVENTIONS Interventions to prevent unintentional injuries have traditionally been considered in terms of the three E’s—education, enforcement, and engineering—and within the framework of the Haddon matrix. That is, interventions are considered in terms of preventing the occurrence of the injury, minimizing the severity of injury at the time of the injury, and minimizing the severity of injury following the injury event. Although randomized controlled trials are the gold standard for assessing the effectiveness of injury interventions, such trials are still relatively rare in relation to injuries, and in many cases such trials may be impractical to implement. Studies comparing the incidence of injury before and after the implementation of an intervention, sometimes with reference to a control population in which the intervention has not been introduced, more commonly provide the only evidence of effectiveness. In some areas, findings from observational studies, such as case-control studies, provide the best available evidence. However, randomized controlled trials are clearly not needed for some interventions because their benefits are

obvious. Other interventions, particularly those that may have modest but important benefits, may require rigorous evaluation methods. Evidence of the effectiveness of interventions in LMICs, as opposed to HICs, is also relatively uncommon. Although the proven efficacy of some interventions in HICs does not require replication in LMICs—for example, the use of motorcycle helmets—strategies that may be effective in increasing the rates of helmet wearing in HICs may not necessarily be appropriate in LMICs. Thus, WHO and others increasingly endorse tailoring interventions found to be effective in HICs to LMICs, followed by rigorous evaluation (Peden and others 2004). Table 39.3 provides a summary of promising and recommended interventions, as well as interventions that have specifically been shown to be effective in LMICs. Road Traffic Injuries Many working to reduce RTIs use the “safer roads, safer vehicles, safer people, and safer systems” motto. A recent augmentation of this motto derives from the recognition of the important

Table 39.3 Promising and Effective Interventions for Injuries in LMICs Injury

Promising interventions

RTIs

Reducing motor vehicle traffic: efficient fuel taxes, changes in land-use policy, safety impact assessment of transportation and land-use plans, provision of shorter and safer routes, trip reduction measures

Interventions shown to be effective in LMICs (references) Increasing the legal age of motorcyclists from 16 to 18 years (Norghani and others 1998)

Making greater use of safer modes of transport Minimizing exposure to high-risk scenarios: restricting access to different parts of the road network, giving priority to higher occupancy vehicles or to vulnerable road users, restricting the speed and engine performance of motorized two-wheelers, increasing the legal age for operating a motorcycle, using graduated driver’s licensing systems Safer roads Safety awareness in planning road networks, safety features in road design, and remedial action in high-risk crash sites: making provisions for slow-moving traffic and vulnerable road users; providing passing lanes, median barriers, and street lighting Traffic calming measures, such as speed bumps

Speed bumps in reducing pedestrian injuries (Afukaar, Antwi, and Ofosu-Amaah 2003)

Speed cameras Safer vehicles Improving the visibility of vehicles, including requiring automatic daytime running lights

Daytime running lights on motorcycles (Radin Umar, Mackay, and Hills 1996; Yuan 2000)

Incorporating crash protective design into vehicles, including installing seat belts Mandating vehicle licensing and inspection Safer people Legislating strategies and increasing enforcement of, for example, speed limits, alcohol-related limits, hours of driving for commercial drivers, seat belt use, bicycle and motorcycle helmet use

Increases in fines and suspension of driver’s licenses (Poli de Figueiredo and others 2001) Legislation and enforcement of motorcycle helmets (Ichikawa, Chadbunchachai, and Marui 2003; Supramaniam, Belle, and Sung 1984).


Table 39.3 Continued Interventions shown to be effective in LMICs (references)

Injury

Promising interventions

Poisonings

Better storage, including positioning and nature of storage vessels Use of child-resistant containers

Free distribution of child-resistant containers (Krug and others 1994)

Warning labels First-aid education Poison control centers Fall-related injuries

Older people Muscle strengthening and balance retraining, individually prescribed Tai chi group exercise Home hazard assessment and modification for high-risk individuals Multidisciplinary, multifactorial screening for health and environmental risk factors Younger people Multifaceted community programs of the Children Can’t Fly type

Burn-related injuries

Fire-related injuries Introducing programs to install smoke alarms Separating cooking areas from living areas Locating cooking surfaces at heights Reducing the storage of flammable substances in households Supervising children more effectively Introducing, monitoring, and enforcing standards and codes for fire-resistant garments Scald-related injuries Separating cooking areas from play areas Improving the design of cooking vessels Fire- and scald-related injuries Increasing awareness of burns prevention Providing first-aid education

Drowning

Limiting exposure to bodies of water close to dwellings, such as by fencing Providing learn-to-swim programs Providing education about risks for drowning Increasing supervision and providing lifeguards at recreational facilities Equipping boats with flotation devices and ensuring their use Legislating and enforcing rules about the numbers of individuals carried on boats Having trained and responsive coast guard services

Source: Authors.

role of appropriate transport and land-use policies in managing exposure to the risk of an RTI (Peden and others 2004). Managing exposure to risk involves strategies aimed at reducing motor vehicle traffic, encouraging the use of safer modes of travel, and minimizing exposure to high-risk scenarios, as outlined in greater detail in table 39.3. Evidence from Malaysia shows that increasing the legal age of motorcyclists from 16 to 18 has been beneficial (Norghani and others 1998), but evidence of the effectiveness of many of the other strategies is not yet available for LMICs.

Safer Roads. Intervention strategies focusing on safer roads should incorporate safety awareness in planning road networks, safety features in road design, and remedial action for high-risk crash sites. HICs have adopted many of these strategies, and though they have not been examined in rigorously controlled studies, such strategies form the basis of best-practice guidelines and manuals now being used in LMICs (Ross and others 1991). Traffic calming measures are among the strategies recommended for incorporating safety features into road design. Unintentional Injuries | 743


Although evidence from randomized controlled trials is not yet available (Bunn and others 2003), a before-and-after study conducted in Ghana suggested that speed bumps were effective in reducing traffic injuries, especially pedestrian injuries (Afukaar, Antwi, and Ofosu-Amaah 2003). A recent summary of research findings also suggests that automated speed enforcement virtually eliminates speeding (ICF Consulting Ltd. and Imperial College Centre for Transport Studies 2003). Safer Vehicles. Strategies focusing on safer vehicles include improving the visibility of vehicles, incorporating crash protective design into vehicles, and promoting further development of “intelligent” vehicles. However, in LMICs, strategies that simply ensure regular maintenance of older vehicles or removal of vehicles in poor condition from the roads, as well as vehicle licensing and inspection, have the potential to be cost-effective (Peden and others 2004). Meta-analyses of the effects of automatic daytime running lights on cars consistently show that they reduce road crashes (Elvik and Vaa 2004). Studies in both Malaysia and Singapore show similar positive effects for daytime running lights on motorcycles (Radin Umar, Mackay, and Hills 1996; Yuan 2000). Although the fitting of seat belts—probably the most well-known and effective safer vehicle strategy—is covered by technical standards worldwide and is mandatory in most countries, anecdotal evidence suggests that vehicles in many LMICs lack functioning seat belts (Forjuoh 2003). Safer People. Intervention strategies aimed at improving road user behavior are increasingly focusing on the introduction and enforcement of relevant legislation rather than on educational efforts. For example, Poli de Figueiredo and others’ (2001) research in Brazil indicates that increasing fines and suspending drivers’ licenses immediately reduced RTIs and deaths. A large body of research, although little of it conducted in LMICs, shows that setting and enforcing speed limits reduces RTIs by up to 34 percent. It also shows that RTIs are reduced in varying magnitudes by setting and enforcing legal blood alcohol limits and minimum drinking-age laws, using alcohol checkpoints, and running mass media campaigns aimed at reducing drinking and driving (Peden and others 2004). The introduction and enforcement of mandatory seat belt and child restraint laws reduces occupant deaths and injuries by up to 25 percent; however, such laws have not been introduced in all LMICs (Peden and others 2004). Both bicycle and motorcycle helmets reduce head injuries among riders by up to 85 percent. Though education may be effective in increasing helmet use, the effect is greater when combined with legislation and enforcement, as demonstrated in Malaysia and Thailand (Ichikawa, Chadbunchachai, and Marui 2003; Supramaniam, Belle, and Sung 1984).

Poisonings The prevention of unintentional poisonings includes consideration of both occupational and nonoccupational poisonings; however, chapter 60 provides a fuller discussion of effective interventions in relation to work-related poisonings, so these are not discussed here. Suggested interventions to reduce exposure to nonoccupational poisonings include better storage of poisons in terms of both the location and the nature of the storage vessels used. Specific interventions include storing poisons outside the home and above children’s head height and reducing the use of secondhand household containers—for example soda bottles—along with introducing and enforcing legislation to prohibit the sale of poisons in such containers (Nhachi and Kasilo 1994). The efficacy of child-resistant containers in preventing access to poisons has been demonstrated, and data from a controlled before-and-after study in South Africa suggest that free distribution of child-resistant containers is a highly effective means of preventing poisoning in children (Krug and others 1994).

Fall-Related Injuries Interventions proven effective for preventing falls by older people in HICs include muscle strengthening and balance retraining that is individually prescribed at home by a trained health professional; tai chi group exercise; home hazard assessment and modification that is professionally prescribed for older people with a history of falling; and multidisciplinary, multifactorial health and environmental risk factor screening and intervention programs, both for community-dwelling older people in general and for older people with known risk factors (Chang and others 2004). In relation to fall-related injuries among young children, other than general recommendations about increased supervision of children and the importance of height reductions and appropriate ground surfacing to prevent playground injuries, only one intervention provides evidence of effectiveness that may be relevant for LMICs. The Children Can’t Fly Program has four major components, which include surveillance and follow-up, media campaigns, community education, and the provision of free, easily installed window guards to families with young children living in high-risk areas (Spiegel and Lindaman 1977). The program has been shown to be effective in reducing falls in low-income areas.

Burn-Related Injuries Evidence of the effectiveness of interventions to prevent firerelated injuries is limited. A randomized controlled trial of a smoke detector giveaway program in inner London was unable


to show evidence of the program’s effectiveness on the incidence of fires and fire-related injuries (DiGuiseppi and others 2002). However, a more recent study suggests that installation programs may be more effective in increasing the use of these alarms than giveaway programs alone (Harvey and others 2004). Interventions that have been proposed but whose effectiveness has not yet been proven include separating cooking areas from living areas (including efforts to reduce the use of indoor fires for cooking), ensuring that cooking surfaces are at heights, reducing the storage of flammable substances in households, and supervising young children more effectively (Forjuoh 2004). The introduction, monitoring, and enforcement of standards and codes for and the wearing of fire-retardant garments have also been proposed (Bawa Bhalla, Kale, and Mohan 2000). Evidence of the effectiveness of interventions to prevent scald injuries is minimal but promising, although such interventions primarily focus on education, legislation, and enforcement of efforts to regulate the temperature of water flowing from household taps (Macarthur 2003). Finally, interventions directed at increasing awareness of burn prevention have been proposed, largely because of the success of safe community interventions involving a multitude of strategies (Ytterstad and Sogaard 1995).

Drowning Evidence for the effectiveness of interventions to prevent drowning is almost nonexistent. The only available data come from case-control studies undertaken in HICs that suggest that fencing domestic swimming pools reduces the risks of drowning (Thompson and Rivara 2000). Extrapolation of those findings to a low-income setting suggests that covering wells with grills, fencing nearby lakes or riverbanks, and building flood control embankments might be effective in reducing drowning.

COSTS, COST-EFFECTIVENESS, AND ECONOMIC BENEFITS OF INTERVENTION Data on effective interventions for preventing unintentional injuries in LMICs and on the economic costs of these injuries are limited. As a result, published data on the costs, costeffectiveness, and economic benefits of interventions to prevent unintentional injuries in LMICs are virtually nonexistent. The economic evaluation of interventions and the measurement of the economic costs of injuries therefore remain a high research priority. Some data are available from HICs on the costs and, in particular, the net economic benefits of interventions for RTIs. Also, a body of evidence suggests that many of the interventions designed to provide safer roads and vehicles, and to improve driver behavior, have clear net economic benefits

(Peden and others 2004). Some data are also starting to emerge from HICs with respect to the cost-effectiveness of fall-related injury prevention programs for older people. However, data on either the costs or the cost-effectiveness of interventions to prevent poisonings, burns, or drownings are limited. Cost-effectiveness studies done in HICs can only be suggestive for LMICs, because the costs of property losses, disability, and medical care are so vastly different. Furthermore, basic efficacy is not always guaranteed when a control strategy that worked in a modern city is exported to a poor LMIC village. Consequently, the ability to extrapolate from high-income to low-income countries is severely limited. Yet as middle-income countries progress, they will begin to consider interventions that have already been proven. Despite the methodological challenges, we modeled the cost-effectiveness of five potential interventions to prevent unintentional injuries using information presented earlier on known effective interventions in LMICs. In each case, the evidence for effectiveness in an LMIC setting was strong. However, because so few interventions have been evaluated in LMICs, we had to make certain assumptions to extrapolate findings about costs and effectiveness in one LMIC setting to other settings (for an outline of the assumptions associated with this modeling, see Bishai and Hyder 2004). Our economic analyses are highly generalized and indicative of what might be achieved with the interventions considered. For the analyses, we present all cost estimates in local currency converted to U.S. dollars (2001 exchange rates). We adopt a societal perspective for each intervention, but if appropriate, we comment on cost-effectiveness from a government perspective. The time horizon for each intervention is one year of sustaining the intervention. Costs are annualized so that a typical year of operating the intervention is known. As with any intervention, annual operating costs may fall as those involved learn ways to carry out their tasks more efficiently. Each year of program operation prevents an estimated number of deaths and injuries. In each case, we present estimates of the raw numbers of deaths and the undiscounted numbers of life years they represent. However, from an economic perspective, the life years and DALYs of those who sustain nonfatal injuries count less than the deaths. For comparability with other economic estimates, and in accordance with the economic analysis guidelines provided to authors, we discount estimates of DALYs using both a 3 percent and a 6 percent discount rate. The 3 percent discount rate is standard for economic evaluations in HICs; however, a higher discount rate may be appropriate in LMICs.

Increased Penalties for Speeding and Other Effective Road Safety Regulations Poli de Figueiredo and others (2001) provide evidence from Brazil on the effectiveness of an intervention to publicize and Unintentional Injuries | 745


enforce traffic speed and other road safety regulations. This intervention required three components—legislation to impose stiffer penalties, media coverage of the new regime, and better enforcement—and achieved a 25 percent reduction in traffic fatalities between 1997 and 1998. On the basis of a model of the costs of media coverage and of better police enforcement, we estimate that implementing such an intervention in a population of 1 million people might range from as low US$8,100 in South Asia to US$196,000 in LMICs in Europe and Central Asia (table 39.4). Those intervention costs are incremental costs that assume that the population already has 50 percent of the necessary police strength. We define adequacy as one officer for every 5,000 vehicles and use regional data on vehicles per 1 million people to estimate the number of police officers and amount of equipment needed to enforce traffic laws. The assumption is that after the intervention the population will have enough officers to issue citations to one-third of their beat’s 5,000 vehicles each year. This effort would require them to write about 7 to 10 citations per workday. Using the estimates of traffic injury burdens in the regions listed in the table and the potential to lower traffic deaths by 25 percent, as reported in the Brazilian study, we estimate potential DALY reductions and cost per DALY averted (table 39.4; for details of the calculations see Bishai and Hyder 2004). The cost estimates shown in table 39.4 do not include potential cost offsets from savings derived by preventing expenditures on medical care or vehicle repair. Including those potential savings would lower the societal cost and enhance the estimated cost-effectiveness. Those cost offsets will vary widely by region. To demonstrate the importance of cost offsets, we use data from Bangladesh, for which the Transport Research Laboratory Ltd. (2003) has estimated the medical and property costs of traffic crashes. On the basis of these estimates, we calculate 1 fatality, 8 serious injuries, and 28 slight injuries occur for every fatal crash in Bangladesh. Each serious injury is associated with US$2,016 in costs for property, administration, lost output, medical care, and pain and suffering, and each slight

injury incurs US$929 in similar costs (Bishai and Hyder 2004). Thus, if we associate 1 prevented traffic fatality with preventing 8 serious injuries worth US$16,128 (8 US$2,016) and 28 slight injuries worth US$26,012 (28 US$929), then total additional cost savings would amount to US$42,140. If intervention costs in Bangladesh were close to the US$8,105 shown in table 39.4 for South Asia, then the intervention would save society more than it cost if it prevented only one death and the expected proportion of nonfatal injuries. If an enforcement intervention in Bangladesh were as effective as the one documented in Brazil, it could lower fatalities by 25 percent. With 83 traffic fatalities per 1 million population, the intervention could prevent 21 deaths and lead to net savings of US$876,835—or (21 US$42,140) US$8,105— for every million population receiving this intervention.

Speed Bumps A study in Ghana (Afukaar, Antwi and Ofosu-Amah 2003) showed that road traffic fatalities fell by more than 50 percent following the introduction of speed bumps. Because speed bumps are usually most effective when installed at the most hazardous junctions or near pedestrian crossings, planners need to know which junctions are the most hazardous. We assumed that half of a city’s crashes occur at junctions and that cities have different numbers of treatable junctions. A few junctions would have multiple fatalities per year, but most would have one or zero fatalities per year. We assumed that the number of fatalities per junction would be distributed as a negative exponential to calculate how many junctions might lack effective speed control modifications and could thereby be targeted as those responsible for 10 percent or 25 percent of a city’s preventable fatalities. Assuming a 10-year useful life for a speed bump and using regionalized estimates of speed bump construction costs, we modeled the annualized cost of constructing speed bumps at junctions responsible for 10 percent or 25 percent of fatalities. As before, we lacked an evidence

Table 39.4 Costs, DALYs, and Costs per DALY of an Intervention to Improve and Publicize Traffic Enforcement by Region (2001 US$) Present value of annual DALYs averted

Cost per DALY averted

Cost to intervene in a population of 1,000,000 for 1 year a

Discounted at 3 percent per year


11,817

1,517

956

8

12


195,971

1,433

903

137

217

Latin American and the Caribbean

225,513

1,333

840

169

268


114,915

2,166

1,365

53

84

Region

South Asia Sub-Saharan Africa




8,105

1,528

963

5

8

24,518

2,003

1,370

12

18

Source: Authors’ calculations. a. Costs do not include cost offsets from prevented medical care and prevented vehicle repair.


Table 39.5 Annualized Costs and DALYs of an Intervention to Build Speed Bumps for the Top 10 Percent of the Most Lethal Junctions in a City of 1 Million, by Region Present value of annual DALYs averted (2001 US$)

Cost to intervene in population of 1,000,000 for 1 yeara



725

167


708

158

299 1,070

Region

Latin American and the Caribbean Middle East and North Africa


Cost per DALY averted (2001 US$) Discounted at 3 percent per year


105

4.34

6.89

99

4.48

7.11

147

92

2.04

3.23

238

150

4.49

7.12

South Asia

324

168

106

1.93

3.06

Sub-Saharan Africa

498

220

151

2.26

3.30

Source: Authors’ calculations. a. Annual costs in local currency converted to US$ around 2001. Costs do not include cost offsets from prevented medical care and prevented vehicle repair.

base from which to estimate cost offsets from prevented medical care or vehicle repair and could not include those potential savings. Table 39.5 presents the costs of DALYs saved and costs per DALY saved by building speed bumps at the top 10 percent of the most lethal junctions in a city of 1 million people. We assumed the speed bumps could lower injuries by 50 percent, as observed in the Ghana study. Given the low costs per DALY averted and the typical high expenditures for medical care for crash victims, we are confident that the medical savings to society would more than offset the intervention’s costs, but we lack the data to prepare complete estimates.

Bicycle Helmet Legislation and Enforcement Thompson, Rivara, and Thompson’s (1989) case-control study indicates that the effectiveness of a bicycle helmet for a single rider is 85 percent. The effect on lives saved and DALYs averted depends on how many people in a population ride bicycles and the roadway environment for riders. Although the degree of energy transferred to the brain in a crash and the clinical efficacy of helmets may be the same worldwide, few data are available on exposure and the bicycle crash burden in LMICs. Thus, in modeling the effects of bicycle helmet legislation, we were limited to assessing the case of the one country with adequate data on bicycle injury epidemiology: China. In China, bicycle-related deaths kill 22 people per 1 million population per year (Li and Baker 1997). Given estimates of the annualized cost of helmet acquisition for all the bicyclists in a Chinese population of 1 million and of the enforcement costs of penalizing unhelmeted riders, we estimate that protecting bicyclists with helmets would cost US$265,000. Assuming that China could convert from zero to 100 percent adherence to helmet use, it could achieve an 85 percent reduction in head injuries from this intervention and would avert

2,478 DALYs at a 3 percent discount rate and 1,562 DALYs at a 6 percent discount rate. Thus, the cost-effectiveness of going from zero to 100 percent helmet use in China would be US$107 (US$265,000/2,478) per DALY at a 3 percent discount rate or US$170 (US$265,000/1,562) per DALY at a 6 percent discount rate.

Motorcycle Helmet Legislation and Enforcement As with bicycles, we have epidemiological data for China, where motorcycle-related deaths kill 16 people per 1 million population per year (Zhang and others 2004). We assume that a population of 1 million in China has 125,000 regular motorcyclists, which will require the equivalent of half the time of a police officer to cite 1 percent of them for helmet violations. At Chinese salary levels, this effort would cost the equivalent of US$7,500 per year. The helmets for this population would cost US$250,000 at US$2 per year of helmet use. Thus, the total cost of the intervention would be US$257,500. Assuming a mean age of injury of 20 years and a disability weight of 0.4 for head injury, we estimate the DALYs averted by motorcycle helmet legislation as 589 at a 3 percent discount rate and 357 at a 6 percent discount rate. This intervention therefore costs US$437 (US$257,500/589) per DALY based on a 3 percent discount rate or US$721 (US$257,500/357) per DALY based on a 6 percent discount rate.

Childproof Paraffin Containers The use of childproof paraffin containers is relevant primarily in Sub-Saharan Africa, where households use paraffin as a cooking fuel and frequently store it in bottles previously used to store beverages. Studies from South Africa have significantly enhanced our understanding of the cost-effectiveness of distributing child-resistant containers. According to Krug and others’ Unintentional Injuries | 747


(1994) findings, a population of 1 million who used paraffin regularly in South Africa experienced 1,040 poisonings a year. After child-resistant containers were distributed, the incidence dropped to 540, indicating that 500 poisonings per year had been prevented. We therefore assume that (a) in a population of 1 million, child-resistant containers would need to be distributed to 200,000 households; (b) each child-resistant container costs R 0.85 (US$0.33), including the costs of distribution; and (c) total direct costs would be US$66,000 (200,000 US$0.33). The average cost of treating a poisoned child in a South African hospital was R 256.13 (US$100). Thus, indirect cost savings would be US$50,000 (500 US$100), which would partially offset the US$66,000 in direct costs, leading to a net cost of US$16,000 to intervene. The mean age of children who suffered poisoning in South Africa was 12 to 24 months. Although no deaths were reported among children in the South African study, the most common figure in the literature is a 2 percent case fatality rate (Krug and others 1994), suggesting that the prevention of 500 poisonings averted 10 deaths among children around two years old. Life tables provided to the authors for Sub-Saharan Africa show life expectancy at age 2 is 49 years; thus, the US$16,000 intervention could save 490 life years. Therefore, a rough estimate of the cost-effectiveness of child-resistant containers as a way of preventing paraffin poisoning in South Africa would be US$1,600 (US$16,000/10) per death averted. Most survivors of paraffin poisoning do not suffer permanent disability, and because we lack any objective means for assigning disability weights to those who are disabled, we neglect years lived with a disability in calculating DALYs. The investment of US$16,000 thus results in 10 children surviving for 49 more years. Undiscounted, this is 490 (10 49) life years. The impact is 263 DALYs averted at a 3 percent discount rate or 166 DALYs averted at a 6 percent discount rate. The cost-effectiveness is US$61 (US$16,000/263) per DALY at a 3 percent discount rate or US$96 (US$16,000/166) per DALY at a 6 percent discount rate.

Summary Estimated costs per DALY from the interventions considered here range from negative (that is, savings) to a few hundred U.S. dollars per DALY. The order of magnitude of the costs per DALY averted using these injury countermeasures suggests that they could be categorized as highly cost-effective (Murray and others 2000). Our estimates of intervention costs neglect the potential savings from prevented medical spending but still appear quite promising. Although our estimates provide some indicative information about the economic properties of counterinjury interventions, these findings point primarily to the lack of information about the global economic burden of injury that could enable more comprehensive estimates.

IMPLEMENTATION OF PREVENTION AND CONTROL STRATEGIES Investments in the health sector to address specific problems are a critical indicator of political commitment, sectoral efforts, and priorities at the national and international levels. In some cases, investments are so low that they provide a useful reference point for assessing the returns on additional investments in the future. Such a situation has been described as a null point in health systems, and current expenditures on injury prevention and control in LMICs approximate this concept (Murray and others 2000). This concept can be illustrated by considering investments in preventing RTIs, which are responsible for the majority of the burden of unintentional injuries and about which much is known regarding effective interventions, even though such interventions have not been examined in the context of rigorously controlled studies in LMICs (see box 39.1). Peden and others (2004) recognize that, despite the global burden of RTIs, the levels of investment are pitifully small, largely because of a lack of awareness of the scale of the problem and a lack of awareness that interventions can prevent and reduce the levels of harm. As a consequence, the report directs a number of recommendations at governments and communities in the hope that these recommendations will enable countries, particularly LMICs, to begin a sustainable process that will eventually lead to the adaptation and implementation of effective preventive strategies. The recommendations include the following: • Identify a lead government agency to guide the national road safety effort. • Assess the problems, policies, and institutional settings relating to RTIs and the capacity for preventing RTIs in each country. • Prepare a national road safety strategy and plan of action. • Allocate financial and human resources to address the problem. • Implement specific actions to prevent crashes, minimize injuries and their consequences, and evaluate the effect of those actions. • Support the development of national capacity and international cooperation. Although few data are available to show the levels of investment in other areas of unintentional injury prevention, those levels are no doubt considerably lower than for RTIs. With increases in the proportions and numbers of older people in many LMICs, the burden of fall-related injuries is likely to increase significantly in the coming years. Recognition of the changing demographics in countries such as China, Mexico, and Thailand plus a growing body of evidence on effective


Box 39.1

Implementation: Case Study of RTIs Bishai and others (2003) quantify the magnitude of government investment in road safety and the extent of RTIs in Pakistan and Uganda. They estimate that Pakistan spent $0.07 per capita, or 0.015 percent of gross domestic product (GDP) per capita, on road safety in 1998 and that Uganda spent $0.09 per capita, or 0.02 percent of GDP per capita. This type of evidence stands in stark contrast with the high burden of RTIs in these countries. These findings occur in the context of public expenditure on health of 1.8 percent of GDP by Pakistan and 1.6 percent by Uganda (UNDP 1998). Per capita health spending by households in Uganda was $7.70 in 1995/96, and public spending on health at the district level was $4.84 per capita in 1997/98 (Hutchinson 1999). Public spending on road safety amounts to about 1 percent of public spending on health in each country. It is equivalent to 0.2 percent of military spending in Pakistan and 1.1 percent of Uganda’s military budget. A review of road safety initiatives in Benin, Côte d’Ivoire, Kenya, Tanzania, and Zimbabwe found similar underinvestment in road safety and attributes this insuffi-

cient investment to conflicts between government ministries, inefficient civil services, and corruption rather than to a lack of knowledge about possible road crash countermeasures (Assum 1998). RTIs have an inverted U-shaped relationship to economic development—injuries rise early during development, then plateau with investments in road safety, and then fall as appropriate interventions succeed (van Beeck, Borsboom, and Mackenbach 2000). This biphasic pattern is known as a Kuznets curve. Attempts to estimate a Kuznets curve for road fatalities suggest that the inflection point at which fatalities begin to decline occurs at GDP per capita in the range of $5,000 to $10,000 (Bishai and others, forthcoming; Kopits and Cropper 2005). This relationship, although based on historical records from HICs, has an important lesson for LMICs: they do not need to experience massive death and disability from RTIs provided that they undertake safety investments now. Waiting for overall economic development before implementing specific interventions will result in the needless loss of millions of lives.

Note: All dollars in box 39.1 are 1998 international dollars.

interventions to prevent falls suggest that investments in this area could lead to significant benefits. Similarly, increasing recognition of the significance of the burden of drowning in children is leading to growing awareness of the need to invest in that area. However, the absence of any effective evidencebased interventions may be a barrier to further investment, suggesting that research into the burden of drowning must be a priority. Investment in prevention and control activities in other areas of unintentional injuries is minimal in most LMICs, in large part because the burden of those injuries is unrecognized and because evidence of effective interventions is lacking. Therefore, there is clearly a need to consider the development, implementation, and evaluation of prevention strategies in combination, so that effective interventions can be identified and promulgated and so that ineffective interventions can be identified and discarded.

RESEARCH AND DEVELOPMENT AGENDA The Global Forum for Health Research (2002) estimates that of the US$73.5 billion spent on health research globally in 1998,

less than 10 percent was spent on addressing problems related to 90 percent of the world’s population. Analyses revealed that RTIs were a highly neglected area for investment compared with the burden of disease RTIs represented as measured in U.S. dollars per DALY. As a result, increasing the level of investment for research and development (R&D) on RTIs and other injuries should be a focus of global advocacy efforts, and investment is critical for promoting an R&D agenda on injuries in LMICs. Developing and prioritizing a global R&D agenda for unintentional injuries, though, is challenging, and such an exercise may be more useful at national or large subnational levels. However, a number of issues requiring R&D are likely to be common across a range of LMICs. Epidemiological research to describe the existing burden, causes, and distribution of unintentional injuries in LMICs is still needed. Often the data are most limited for areas with the greatest potential burden of injuries. Assessing the loss of health and life from unintentional injuries—whom they affect, how, and under what specific circumstances—is thus a continuing research agenda for LMICs. Problems of underreporting and other biases in available data also need to be addressed. Unintentional Injuries | 749


The lack of intervention research in LMICs is a huge gap in global health research. For the most part, no scientific trials of injury interventions have been conducted in LMICs, and existing and new interventions need to be modified, adapted, and tested in those specific settings. Three broad domains should be the foci of intervention research:

a major health problem. They cause preventable loss of life and health, and they have major economic implications. As a result, R&D investments are a health and economic imperative for developing countries and donor organizations.

• R&D to enhance the efficiency of currently available efficacious interventions. For example, increasing the use of helmets would prevent motorcycle injuries in East Asia. • R&D to enhance the cost-effectiveness of interventions that are currently not being implemented or that could be used more widely. For example, seat belts and child restraints are known effective interventions, and reducing the cost of such interventions might enhance their wide-scale implementation in LMICs. • R&D to develop new interventions for unintentional injuries and to respond to that proportion of the burden that is not currently being addressed. For example, childhood falls from rooftops in South Asia have been recognized as an issue, but a locally derived intervention is currently unavailable.

Unintentional injuries are an important contributor to global death and disability burdens, especially in LMICs. However, the significance of the burden is not matched by substantive knowledge about risk factors or effective interventions in LMICs. Nevertheless, the models outlined in this chapter indicate that several interventions for preventing unintentional injuries are highly cost-effective and in some cases could result in significant cost savings. Recent evidence shows that public efforts in injury control, such as traffic safety, are poorly funded in developing countries (Bishai and others 2003). The low expenditure compares unfavorably with expenditure on other health conditions and with expenditures in more developed nations, where government efforts in relation to such issues as traffic safety are well funded. Even adjusting for the 20-fold to 30-fold difference in gross domestic product per capita between HICs and LMICs, the investment disparities suggest that LMICs attach a low priority to injury prevention. Given the current low level of investment, initial investments in safety, if chosen with care, could turn out to be extremely beneficial to public health and welfare. If, in the first instance, investments were to be made only in the interventions modeled here, then injury reductions would likely be significant. The next step would be to modify other interventions that have proven effective in HICs and to combine the introduction of such interventions with evaluations of their effects. Policy makers will be concerned that many of the cost-effective interventions are not low-cost interventions. They save many lives but require an extensive upfront investment. Using costeffectiveness analyses of these interventions to document high returns would encourage financing of these interventions and widespread replication efforts. Policy makers would be unwise to wait for advanced stages of economic development to attend to the problem of road safety or other unintentional injuries. Indeed, given the limited but growing knowledge that low-cost, effective interventions exist, for governments not to intervene would be unethical. Even though institutional obstacles are formidable in developing countries, governments routinely overcome them to address other perceived threats to public well-being—such as crime, terrorism, and war—that disrupt fewer lives than unintentional injuries. The real enigma is that such a profound loss of life can take place each year in LMICs without an outcry that would trigger sustained and effective political commitment by governments and civil society.

Although some might argue that intervention research should be the priority in most LMICs, unless the basic underpinning research on the burden and determinants of unintentional injuries has been undertaken, the political and financial support for such research will not be forthcoming. The dearth of economic and policy analysis of unintentional injuries in LMICs is an embarrassment for the global health research community. A recent review of economic analysis of road traffic interventions found a complete absence of any detailed studies from the developing world (Waters, Hyder and Phillips 2004). This gap in health systems research would need to be addressed to develop and implement successful injury prevention programs. Defining a research agenda is necessary but is not by itself sufficient to conduct research or to implement the results. Two key conditions are required for moving forward: a critical mass of people to conduct research and appropriate funds to support R&D. Developing human resources for all aspects of injury prevention and control in the developing world should be a high priority. Individuals need to be trained and institutions supported and empowered to conduct quality scientific research in their own countries and on issues relevant to their locations, which would then be used within their countries. This approach involves paying attention to the issue of strengthening the capacity for research, a major cross-cutting theme for the health sector in the developing world. Funding is and always will be a limiting factor for research; however, the mismatch between the burden of injuries and R&D investments can be corrected. Unintentional injuries are

CONCLUSIONS: PROMISES AND PITFALLS


ACKNOWLEDGMENTS We would like to acknowledge the assistance of Kristina McDaid and Kylie Monro of the George Institute for International Health in preparing this chapter. We would also like to acknowledge useful comments on the initial draft of the chapter provided by David Sleet of the Centers for Disease Control and Prevention, National Center for Injury Prevention and Control, and by Tony Bliss of the World Bank.

REFERENCES Adesunkanmi, A. R., S. A. Oseni, and O. S. Badru. 1999. “Severity and Outcome of Falls in Children.” West African Journal of Medicine 18 (4): 281–85. Afukaar, F. K. 2003. “Speed Control in LMICs: Issues, Challenges, and Opportunities in Reducing Road Traffic Injuries.” Injury Control and Safety Promotion 10 (1–2): 77–81. Afukaar, F. K., P. Antwi, and S. Ofosu-Amaah. 2003. “Pattern of Road Traffic Injuries in Ghana: Implications for Control.” Injury Control and Safety Promotion 10 (1–2): 69–76. Ahmed, M. K., M. Rahman, and J. van Ginneken. 1999. “Epidemiology of Child Deaths Due to Drowning in Matlab, Bangladesh.” International Journal of Epidemiology 28 (2): 306–11. Ahuja, R. B., and S. Bhattacharya. 2002. “An Analysis of 11,196 Burn Admissions and Evaluations of Conservative Management Techniques.” Burns 28 (6): 555–61. Assum, T. 1998. “Road Safety in Africa: Appraisal of Road Safety Initiatives in Five African Countries.” Sub-Saharan Africa Transport Policy Program. Working Paper 33, World Bank, Washington, DC. Attewell, R. G., K. Glase, and M. McFadden. 2001.“Bicycle Helmet Efficacy: A Meta-Analysis.” Accident Analysis and Prevention 33 (3): 345–52. Azizi, B. H., H. I. Zulkifli, and M. S. Kasim. 1993. “Risk Factors for Accidental Poisoning in Urban Malaysian Children.” Annals of Tropical Paediatrics 13 (2): 183–88. Bangdiwala, S. I., and E. Anzola-Perez. 1990. “The Incidence of Injuries in Young People: II. Log-Linear Multivariable Models for Risk Factors in a Collaborative Study in Brazil, Chile, Cuba, and Venezuela.” International Journal of Epidemiology 19 (1): 125–32. Bawa Bhalla, S., S. R. Kale, and D. Mohan. 2000. “Burn Properties of Fabrics and Garments Worn in India.” Accident Analysis and Prevention 32 (3): 407–20. Bishai, D., and A. Hyder. 2004. “Modeling the Cost Effectiveness of Injury Interventions in Lower and Middle Income Countries.” Disease Control Priorities Working Paper 29, Johns Hopkins Bloomberg School of Public Health, Baltimore. Bishai, D., A. A. Hyder, A. Ghaffar, R. H. Morrow, and O. Kobusingye. 2003. “Rates of Public Investment for Road Safety in Developing Countries: Case Studies of Uganda and Pakistan.” Health Policy and Planning 18 (2): 232–35. Bishai, D., A. Qureshi, P. James, and A. Ghaffar. Forthcoming. “National Road Fatalities and Economic Development.” Health Economics. Boonyaratavej, N., P. Suriyawongpaisal, A. Takkinsatien, S. Wanvarie, R. Rajatanavin, and P. Apiyasawat. 2001. “Physical Activity and Risk Factors for Hip Fractures in Thai Women.” Osteoporosis International 12 (3): 244–48. Bunn, F., T. Collier, C. Frost, K. Ker, I. Roberts, and R. Wentz. 2003. “AreaWide Traffic Calming for Preventing Traffic-Related Injuries.” Cochrane Database of Systematic Reviews (1) CD003110.

Carlini-Cotrim, B., and A. A. da Matta Chasin. 2000. “Blood Alcohol Content and Death from Fatal Injury: A Study in Metropolitan Area of São Paulo, Brazil.” Journal of Psychoactive Drugs 32 (3): 269–75. Celis, A. 1997. “Home Drowning among Preschool Age Mexican Children.” Injury Prevention 3 (4): 252–56. Chan, K. Y., O. Hairol, H. Imtiaz, M. Zailani, S. Kunar, S. Somasundaram, and others. 2002. “A Review of Burns Patients Admitted to the Burns Unit of Hospital Universiti Kebangsaan Malaysia.” Medical Journal of Malaysia 57 (4): 418–25. Chang, J. T., S. C. Morton, L. Z. Rubinstein, W. A. Mojica, M. Maglione, M. J. Suttorp, and others. 2004. “Interventions for the Prevention of Falls in Older Adults: Systematic Review and Meta-Analysis of Randomised Clinical Trials.” British Medical Journal 328 (7441): 653–54. Chatsantiprapa, K, J. Chokkanapitak, and N. Pinpradit. 2001. “Host and Environment Factors for Exposure to Poisons: A Case Control Study of Preschool Children in Thailand.” Injury Prevention 7 (3): 214–17. Clark P., F. de la Pena, F. Gomez Garcia, J. A. Orozco, and P. Tugwell. 1998. “Risk Factors for Osteoporotic Hip Fractures in Mexicans.” Archives of Medical Research 29 (3): 253–57. Conrad, P., Y. S. Bradshaw, R. Lamsudin, N. Kasniyah, and C. Costello. 1996. “Helmets, Injuries, and Cultural Definitions: Motorcycle Injury in Urban Indonesia.” Accident Analysis and Prevention 28: 193–200. Courtright, P., D. Haile, and E. Kohls. 1993. “The Epidemiology of Burns in Rural Ethiopia.” Journal of Epidemiology and Community Health 47 (1): 19–22. Daisy, S., A. K. Mostaque, T. S. Bari, R. R. Kahn, and Q. Quamruzzaman. 2001. “Socioeconomic and Cultural Influence in the Causation of Burns in the Urban Children of Bangladesh.” Journal of Burn Care and Rehabilitation 22 (4): 269–73. Delgado J., M. E. Ramirez-Cardich, R. H. Gilman, R. Lavarello, N. Dahodwala, A. Bazan, and others. 2002. “Risk Factors for Burns in Children: Crowding, Poverty, and Poor Maternal Education.” Injury Prevention 8 (1): 38–41. DiGuiseppi, C., I. Roberts, A. Wade, M. Sculpher, P. Edwards, C. Godward, and others. 2002. “Incidence of Fires and Related Injuries after Giving Out Free Smoke Alarms: Cluster Randomized Controlled Trial.” British Medical Journal 325 (7371): 995. Ellis, J. B., A. Krug, J. Robertson, I. T. Hay, and U. MacIntyre. 1994.“Paraffin Ingestion—The Problem.” South African Medical Journal 84 (11): 727–30. Elvik, R., and T. Vaa. 2004. Handbook of Road Safety Measures. Amsterdam: Elsevier. European Road Safety Action Program. 2003. Halving the Number of Road Accident Victims in the European Union by 2010: A Shared Responsibility. Brussels: European Commission. Fernando, R., and D. N. Fernando. 1997. “Childhood Poisoning in Sri Lanka.” Indian Journal of Pediatrics 64 (4): 457–60. Forjuoh, S. N. 2003. “Traffic-Related Injury Prevention Interventions for Low Income Countries.” Injury Control and Safety Promotion 10 (1–2): 109–18. . 2004. “Preventing Burns in Low and Middle-Income Countries.” Disease Control Priorities Working Paper. Forjuoh S. N., B. Guyer, and G. S. Smith. 1995. “Childhood Burns in Ghana: Epidemiological Characteristics and Home-Based Treatment.” Burns 21 (1): 24–28. Forjuoh S. N., B. Guyer, D. M. Strobino, P. M. Keyl, M. Diener-West, and G. S. Smith. 1995. “Risk Factors for Childhood Burns: A Case-Control Study of Ghanaian Children.” Journal of Epidemiology and Community Health 49 (2): 189–93. Ghaffar, A., A. A. Hyder, M. I. Mastoor, and I. Shaikh. 1999. “Injuries in Pakistan: Directions for Future Health Policy.” Health Policy and Planning 14 (1): 11–17.


Global Forum for Health Research. 2002. The 10/90 Report on Health Research 2001–2002. Geneva: Global Forum for Health Research.

Liu, B., R. Ivers, R. Norton, S. Blows, and S. K. Lo. 2004. “Helmets for Preventing Injury in Motorcycle Riders.” Cochrane Database of Systematic Reviews (4) CD004333.

Haddon, W. Jr. 1968. “The Changing Approach to the Epidemiology, Prevention, and Amelioration of Trauma: The Transition to Approaches Etiologically Rather Than Descriptively Based.” American Journal of Public Health and the Nation’s Health 58 (8): 1431–38.

Liu, E. H., B. Khatri, Y. M. Shakya, and B. M. Richard. 1998. “A 3 Year Prospective Audit of Burns Patients Treated at the Western Regional Hospital of Nepal.” Burns 24 (2): 129–33.

Harvey, P. A, M. Aitken, G. W. Ryan, L. A. Demeter, J. Givens, R. Sundararaman, and others 2004. “Strategies to Increase Smoke Alarm Use in High-Risk Households.” Journal of Community Health 29 (5): 375–85. Hutchinson, P. 1999. “Health Care in Uganda.” Discussion Paper 404, World Bank, Washington, DC. Hyder, A. A., S. Arifeen, N. Begum, S. Fishman, S. Wali, and A. H. Baqui. 2003. “Death from Drowning: Defining a New Challenge for Child Survival in Bangladesh.” Injury Control and Safety Promotion 10 (4): 205–10. ICF Consulting Ltd. and Imperial College Centre for Transport Studies. 2003. “Cost-Benefit Analysis of Road Safety Improvements.” Final report. London: ICF Consulting Ltd. and Imperial College Centre for Transport Studies. Ichikawa, M., W. Chadbunchachai, and E. Marui. 2003. “Effect of the Helmet Act for Motorcyclists in Thailand.” Accident Analysis and Prevention 35 (2): 83–89.

Liu, G. F., S. Han, D. H. Liang, F. Z. Wang, X. Z. Shi, J. Yu, and others. 2003. “Driver Sleepiness and Risk of Car Crashes in Shenyang, a Chinese Northeastern City: Population-Based Case-Control Study.” Biomedical and Environmental Sciences 16 (3): 219–26. Macarthur, C. 2003. “Evaluation of Safe Kids Week 2001: Prevention of Scald and Burn Injuries in Young Children.” Injury Prevention 9 (2): 112–16. Mock, C., J. Amegashi, and K. Darteh. 1999. “Role of Commercial Drivers in Motor Vehicle Related Injuries in Ghana.” Injury Prevention 5 (4): 268–71. Mohan, D. 2002. “Road Safety in Less-Motorized Environments: Future Concerns.” International Journal of Epidemiology 31 (3): 527–32. Murray, C. J. L., D. B. Evans, A. Acharya, and B. Baltussen. 2000. “Development of WHO Guidelines on Generalized Cost-Effectiveness Analysis.” Health Economics 9 (3): 235–51.

Jacobs, G., A. Aeron-Thomas, and A. Astrop. 2000. “Estimating Global Road Fatalities.” TRL Report 445, Transport Research Laboratory, Crowthorne, U.K.

Nafukho, F. M., and M. Khayesi. 2002. “Livelihood, Conditions of Work, Regulation, and Road Safety in the Small-Scale Public Transport Sector: A Case of the Matatu Mode of Transport in Kenya.” In Urban Mobility for All: Proceedings of the Tenth International CODATU Conference, Lomé, Togo, 12–15 November 2002, ed. X. Godard and I. Fatonzoun, 241–45. Lisse, the Netherlands: AA Balkema.

Jie, X., and C. B. Ren. 1992. “Burn Injuries in the Dong Bei Area of China: A Study of 12,606 Cases.” Burns 18 (3): 228–32.

Nhachi, C. F., and O. M. Kasilo. 1992. “The Pattern of Poisoning in Urban Zimbabwe.” Journal of Applied Toxicology 12 (6): 435–38.

Jitapunkul, S., P. Yuktananandana, and V. Parkpian. 2001. “Risk Factors of Hip Fracture among Thai Female Patients.” Journal of the Medical Association of Thailand 84 (11): 1576–81.

Nhachi, C. F., and O. M. Kasilo. 1994. “Household Chemicals Poisoning Admissions in Zimbabwe’s Main Urban Centres.” Human and Experimental Toxicology 13 (2): 69–72.

Khayesi, M. 2003. “Liveable Streets for Pedestrians in Nairobi: The Challenge of Road Traffic Accidents.” In The Earthscan Reader on World Transport Policy and Practice, ed. J. Whitelegg and G. Haq, 35–41. London: Earthscan.

Norghani, M., A. Zainuddin, R. S. Radin Umar, and H. Hussain. 1998. Use of Exposure Control Methods to Tackle Motorcycle Accidents in Malaysia. Research Report 3/98. Serdang, Malaysia: Road Safety Research Center, University Putra Malaysia.

Kibel, S. M., F. O. Nagel, J. Myers, and S. Cywes. 1990. “Childhood Near-Drowning—A 12-Year Retrospective Review.” South African Medical Journal 78 (7): 418–21.

Odero, W., P. Garner, and A. B. Zwi. 1997. “Road Traffic Injuries in Developing Countries: A Comprehensive Review of Epidemiological Studies.” Tropical Medicine and International Health 2 (5): 445–60.

Kloeden, C. N., A. J. McLean, M. R. J. Baldock, and A. J. T. Cockington. 1998. “Severe and Fatal Car Crashes Due to Roadside Hazards: A Report to the Motor Accident Commission.” Adelaide, Australia: National Health and Medical Research Council Road Accident Research Unit, University of Adelaide.

Odero W., M. Khayesi, and P. M. Heda. 2003. “Road Traffic Injuries in Kenya: Magnitude, Causes, and Status of Intervention.” Injury Control and Safety Promotion 10 (1–2): 53–61.

Kobusingye, O., D. Guwatudde, and R. Lett. 2001. “Injury Patterns in Rural and Urban Uganda.” Injury Prevention 7 (1): 46–50. Kopits, E., and M. Cropper. 2005. “Traffic Fatalities and Economic Growth.” Accident Analysis and Prevention 37 (1): 169–78. Kozik, C. A., S. Suntayakorn, D. W. Vaughn, C. Suntayakorn, R. Snitbhan, and B. L. Innis. 1999. “Causes of Death and Unintentional Injury among Schoolchildren in Thailand.” Southeast Asian Journal of Tropical Medicine and Public Health 30 (1): 129–35. Krug, A., J. B. Ellis, I. T. Hay, N. F. Mokgabudi, and J. Robertson. 1994. “The Impact of Child-Resistant Containers on the Incidence of Paraffin (Kerosene) Ingestion in Children.” South African Medical Journal 84 (11): 730–34. Kulanthayan, S., R. S. Umar, H. A. Hariza, M. T. Nasir, and S. Harwant. 2000. “Compliance of Proper Safety Helmet Usage in Motorcyclists.” Medical Journal of Malaysia 55 (1): 40–44. Li, G., and S. P. Baker. 1997. “Injuries to Bicyclists in Wuhan, People’s Republic of China.” American Journal of Public Health 87 (6): 1049–52.

Odero, W. O., and A. B. Zwi. 1995. “Alcohol-Related Traffic Injuries and Fatalities in LMICs: A Critical Review of Literature.” In Proceedings of the 13th International Conference on Alcohol, Drugs, and Traffic Safety, Adelaide, 13–18 August 1995, ed. C. N. Kloeden and A. J. McLean, 713–20. Adelaide, Australia: Road Accident Research Unit. Peden, M., D. Knottenbelt, J. Van der Spuy, R. Oodit, M. J. Scholtz, and J. M. Stokol. 1996. “Injured Pedestrians in Cape Town: The Role of Alcohol.” South African Medical Journal 86 (9): 1103–5. Peden, M., R. Scurfield, D. Sleet, D. Mohan, A. A. Hyder, E. Jarawan, and others, eds. 2004. World Report on Road Traffic Injury Prevention. Geneva: World Health Organization. Poli de Figueiredo, L. F., S. Rasslan, V. Bruscagin, R. Cruz, and M. Rocha e Silva. 2001. “Increases in Fines and Driver Licence Withdrawal Have Effectively Reduced Immediate Deaths from Trauma on Brazilian Roads: First-Year Report on the New Traffic Code.” Injury 32 (2): 91–94. Radin Umar, R. S., G. M. Mackay, and B. L. Hills. 1996. “Modelling of Conspicuity-Related Motorcycle Accidents in Seremban and Shah Alam, Malaysia.” Accident Analysis and Prevention 28 (3): 325–32.


Raja, I. A., A. H. Vohra, and M. Ahmed. 2001. “Neurotrauma in Pakistan.” World Journal of Surgery 25 (9): 1230–37.

UNDP (United Nations Development Programme). 1998. Human Development Report 1998. New York: Oxford University Press.

Ross, A., C. Baguley, V. Hills, M. McDonald, and D. Silcock. 1991. Towards Safer Roads in Developing Countries: A Guide for Planners and Engineers. Crowthorne, U.K.: Transport Research Laboratory.

van Beeck, E. F., G. J. Borsboom, and J. P. Mackenbach. 2000. “Economic Development and Traffic Accident Mortality in the Industrialized World, 1962–1990.” International Journal of Epidemiology 29 (3): 503–9.

Rossi, L. A., E. C. Braga, R. C. Barruffini, and E. C. Carvalho. 1998. “Childhood Burn Injuries: Circumstances of Occurrences and Their Prevention in Ribeirão Preto, Brazil.” Burns 24 (5): 416–19. Soori, H. 2001. “Developmental Risk Factors for Unintentional Childhood Poisoning.” Saudi Medical Journal 22 (3): 227–30. Spiegel, C. N., and F. C. Lindaman. 1977 “Children Can’t Fly: A Program to Prevent Childhood Morbidity and Mortality from Window Falls.” American Journal of Public Health 67 (12): 1143–47. Supramaniam, V., V. Belle, and J. Sung. 1984. “Fatal Motorcycle Accidents and Helmet Laws in Peninsular Malaysia.” Accident Analysis and Prevention 16 (3): 157–62. Tan, Z., X. Li, and Q. Bu. 1998. “Epidemiological Study on Drowning in Wujin, Jiangsu, 1997.” Zhonghua Liu Xing Bing Xue Za Zhi 19 (4): 208–10. Thompson, D. C., and F. P. Rivara. 2000. “Pool Fencing for Preventing Drowning in Children.” Cochrane Database of Systematic Reviews (2) CD001047. Thompson, R. S., F. P. Rivara, and D. C. Thompson. 1989. “A Case-Control Study of the Effectiveness of Bicycle Safety Helmets.” New England Journal of Medicine 320 (21): 1361–67. Tiwari, G. 2000. “Traffic Flow and Safety: Need for New Models for Heterogeneous Traffic.” In Injury Prevention and Control, ed. D. Mohan and G. Tiwari, 71–88. London: Taylor and Francis. Transport Research Laboratory Ltd. 2003. Guidelines for Estimating the Cost of Road Crashes in Developing Countries. Department for International Development, Project R7780. London: Babtie, Ross, Silcock.

Wang, S., G. B. Chi, C. X. Jing, X. M. Dong, C. P. Wu, and L. P. Li. 2003. “Trends in Road Traffic Crashes and Associated Injury and Fatality in the People’s Republic of China, 1951–1999.” Injury Control and Safety Promotion 10 (1–2): 83–87. Waters, H. R., A. A. Hyder, and T. L. Phillips. 2004. “Economic Evaluation of Interventions for Reducing Road Traffic Injuries—A Review of Literature with Applications to Low and Middle-Income Countries.” Asia Pacific Journal of Public Health 16 (1): 23–31. Werneck, G. L., and M. E. Reichenheim. 1997. “Paediatric Burns and Associated Risk Factors in Rio de Janeiro, Brazil.” Burns 23 (6): 478–83. Ytterstad, B., and A. J. Sogaard: 1995. “The Harstad Injury Prevention Study: Prevention of Burns in Small Children by a Community-Based Intervention.” Burns 21 (4): 259–66. Yuan, W. 2000. “The Effectiveness of the ‘Ride Bright’ Legislation for Motorcycles in Singapore.” Accident Analysis and Prevention 32 (4): 559–63. Zhang, J., R. Norton, K. C. Tang, S. K. Lo, J. Zhuo, and W. Geng. 2004. “Motorcycle Ownership and Injury in China.” Injury Control and Safety Promotion 11 (3): 159–63. Zhu, Z. X., H. Yang, and F. Z. Meng. 1988. “The Epidemiology of Childhood Burns in Jiamusi, China.” Burns, Including Thermal Injury 14 (5): 394–96.



Chapter 49

Learning and Developmental Disabilities Maureen S. Durkin, Helen Schneider, Vikram S. Pathania, Karin B. Nelson, Geoffrey C. Solarsh, Nicole Bellows, Richard M. Scheffler, and Karen J. Hofman

Learning and developmental disabilities (LDDs) include functional limitations that manifest in infancy or childhood as a result of disorders of or injuries to the developing nervous system (Institute of Medicine Committee on Nervous System Disorders in Developing Countries 2001). These limitations range from mild to severe and can affect cognition, mobility, hearing, vision, speech, and behavior. The known causes of LDD are numerous and include genetic factors, nutritional factors, infections, toxic exposures, trauma, perinatal factors, and multifactorial conditions (table 49.1). Selected causes of LDD that are not addressed in detail in this chapter are described in box 49.1. Although information on the prevalence and impact of disabilities in low- and middle-income countries (LMICs) is scarce, five considerations support the conclusion that LDDs are a public health priority in LMICs today: • Prevalence. Although each individual cause is relatively rare, taken together, LDD affects a large proportion of children. In high-income countries, 10 to 20 percent of children have an LDD (Benedict and Farel 2003). With improvements in child survival in LMICs, it is not known whether the prevalence of disabilities among children is increasing, as has been seen in wealthier countries (Winter and others 2002), but the few data available from LMICs suggest that the prevalence of specific causes and types of LDD may be even higher than in high-income countries. Examples include cognitive disabilities associated with prenatal iodine deficiency, brain infections, and blindness associated with vitamin A deficiency (Durkin 2002). The prevalence of childhood disabilities in LMICs is not well established, but it is likely higher than in high-income countries.

• Lifelong duration. By definition, LDDs have an early onset, with the causes frequently occurring in the prenatal period. These effects are typically lifelong,affecting learning and other neurological functions, educational achievement, quality of life, earning potential, and productivity across the life span. • Costs. The extensive costs include the direct costs of acute care, outpatient health care services, long-term care, rehabilitation, and special education, as well as the indirect costs of morbidity and increased mortality (Waitzman, Romano, and Scheffler 1994). Additionally, the costs and effects extend beyond the individuals affected to include entire families. Health, careers and employment of parents, family disposable income, health and adaptation of siblings, and family interaction are adversely affected when a family member has an LDD (Stein and Jessop 2003). It is difficult to comprehend the extent of these effects, just as it is difficult to measure them and develop economic models that account for them. • Education and work. As societies and economies become increasingly information-oriented and dependent on educated and literate workers, the impact of disabilities affecting cognition and learning becomes greater (Institute of Medicine Committee on Nervous System Disorders in Developing Countries 2001). • Proven interventions. The prospects for preventing LDD and for improving outcomes are considerable and can be achieved, to some extent, by implementing interventions that have been shown to be effective and cost-effective elsewhere but that are not being implemented in LMICs. This chapter provides an overview of the range of interventions likely to improve child development and educational 933


Table 49.1 Categories of Causes of LDD Category

Examples

Genetic Chromosomal

Down syndrome, chromosomal rearrangements

Segmental autosomal syndromes

Prader-Willi syndrome, Angelman syndrome

Sex-linked, single gene

Fragile X syndrome, Rett syndrome

Autosomal recessive

Phenylketonuria, Tay–Sachs disease

Autosomal dominant

Neurocutaneous syndromes, such as neurofibromatosis

Multifactorial Genetic and nutritional

Neural tube defects

Nutritional Prenatal: maternal iodine deficiency

Developmental iodine deficiency disorder

Childhood: vitamin A deficiency

Xerophthalmia, night blindness

Infections Prenatal or perinatal

Toxoplasmosis, rubella, cytomegalovirus, herpes, gonorrhea, syphilis, group B streptococcus, chlamydia, trichomonas vaginalis, bacterial vaginosis, herpes simplex virus, HIV

Postnatal or childhood

Encephalitis, meningitis, varicella, cerebral malaria, polio, trachoma, otitis media

Toxic exposures Prenatal

Alcohol, lead, mercury, antimicrobials (such as sulfonamides, isoniazid, ribavirin), anticonvulsants (such as phenytoin, carbamazepine), and other drugs (such as accutane, thalidomide)

Postnatal or childhood

Lead, mercury

Other maternal disorders Thyroid disease

Cerebral palsy

Other perinatal complications Brain injuries associated with premature birth, birth asphyxia

Cerebral palsy, cognitive disabilities, seizure disorders

Injury Traumatic brain injuries and other disabling injuries from vehicle crashes, child abuse and neglect, falls, burns, warfare, and so forth

Cognitive, motor, speech, vision, hearing, seizure, and behavioral disabilities

Poverty, economic disadvantage Social and cognitive deprivation

Mild mental retardation

Unknown

LDD of unknown cause

outcomes for children in LMICs. Evidence of cost-effectiveness is considered in some detail for three selected interventions. An overview of other key risk factors and conditions that result in LDD is provided. A research agenda is outlined for advancing knowledge of how to prioritize cost-effective interventions and how best to devote resources for the prevention of LDD in LMICs.

LDD AND THE GLOBAL BURDEN OF DISEASE Estimates for disability-adjusted life years (DALYs) (Mathers 2006) are not available to convey the full range of LDDs or their

risk factors. Attempts have been made to estimate the DALYs associated with specific causes of LDDs. For example, it is estimated that 9.8 million DALYs, or nearly 1 percent of the global burden of disease, are due to one relatively minor form of LDD, namely, mild mental retardation (MR) caused by lead ingestion from environmental sources (Fewtrell and others 2004). Since only a small fraction—probably much less than 10 percent—of LDD worldwide can be attributed to lead-induced mild MR, this estimate suggests that LDD as a whole must account for a large proportion, perhaps more than 10 percent of the global burden of disease. Where DALY estimates are available, we use them as a basis for economic analysis to estimate the costs of

934 | Disease Control Priorities in Developing Countries | Maureen S. Durkin, Helen Schneider, Vikram S. Pathania, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 176

Box 49.1

Interventions for the Prevention of Childhood Neurological Disabilities Attention Deficit Hyperactivity Disorder Attention deficit hyperactivity disorder (ADHD) is the most common neurological disorder in children in the United States, with an estimated prevalence of 3 to 11 percent. The prevalence is not known in LMICs, but as schooling increasingly becomes the norm, ADHD is likely to become more obvious. The burden of ADHD in settings of large class sizes will likely pose an increasing challenge. In addition to its major impact on school performance, ADHD affects family relationships and social competence, with lasting consequences. Children with ADHD are also at higher risk for injury, depression, and substance abuse. Worldwide, with the growing use in school settings of stimulants to control this chronic disorder, the impact on health care costs is potentially huge. Although there are a paucity of data on this topic, in one study, the cost of medicating children for ADHD was close to an average of US$500 or more per child per year, and this figure is considered a substantial underestimate (Chan, Zhan, and Homer 2002).

Autism Spectrum Disorders All autism spectrum disorders (ASDs) are characterized by varying degrees of impairment in communication skills and social interactions and in restricted, repetitive patterns of behavior or interests. Although only 50 percent of children in the United States with ASDs are diagnosed before six years of age, this group of disorders can reliably be diagnosed by three years of age and in some cases by as early as 18 months. ASDs range from a severe form called autistic disorder to a milder form known as Asperger syndrome. Prevalence studies of ASDs in Asia, Europe, and North America estimate that 2 to 6 out of every 1,000 children have an ASD. Screening instruments using responses from children and parents are available. Evidence indicates that early intervention (ideally in optimal educational settings for at least two years during preschool) results in improved outcomes. Individuals with ASDs generally respond well to highly structured, specialized programs. A variety of medications is used to treat associated depression, anxiety, ADHD, seizures, and other behavioral symptoms. Adults with severe ASDs require intensive and constant supervision. Little information is available regarding the parental and service costs of ASDs. In a 2001 study in the United Kingdom, the lifetime cost

for a person with autistic disorder exceeded UK £12.4 million, with most of the expense related to living support and daily activities. Infection Numerous prenatal, perinatal, and postnatal infections can damage the developing nervous system or sensory pathways and cause long-term disabilities in children. The relative contribution of these infections to the burden of LDD is likely to vary by country. It will be influenced by overall infant mortality, postneonatal contribution to infant mortality, and regional difference in the distribution of the infections known to be associated with neurological sequelae during different periods in the early life cycle. A few of the most important infections that may result in LDD include the following: • Congenital rubella (chapter 20). This disease is a major global cause of preventable hearing impairment, blindness, and intellectual disability. The incidence of congenital rubella syndrome has been variably set at 0.5 to 2.2 out of every 1,000 live births in LMICs during epidemics, which occur every four to seven years (Cutts and others 1997). Though some LMICs have set elimination goals and vaccination has been noted to be costeffective, only 28 percent of LMICs routinely vaccinate against rubella (Robertson and others 1997). • HIV/AIDS infection (chapter 18). Neurological problems in HIV-infected children vary in different parts of the world but may be as high as 40 to 50 percent (Bobat and others 1998). The developmental trajectory of infected children is confounded by maternal, social, and biological risk factors during pregnancy and early childhood. Maternal substance and drug abuse, more common in HIV-infected women, have an independent adverse effect on brain growth and neurodevelopmental outcome. Low birthweight and prematurity, poverty, protein calorie malnutrition, and micronutrient deficiencies—more frequently seen in HIV-infected children and particularly in LMICs—may similarly compromise early child development (Brouwers and others 1996). • Malaria (chapter 21). In Sub-Saharan Africa, malaria is the leading cause of childhood mortality and morbidity. Cerebral malaria is a well-known complication and

Learning and Developmental Disabilities | 935 ©2006 The International Bank for Reconstruction and Development / The World Bank 177

Box 49.1

(Continued) may result in neurological sequelae in survivors, contributing significantly to the burden of LDD. • Bacterial meningitis (chapter 20). This disease results in long-term sequelae for many children, including approximately 40 percent of children who survive Haemophilus influenza meningitis, 50 percent who survive pneumococcal meningitis, and 10 percent who survive meningococcal meningitis. Cost-effective immunization can prevent meningitis from all these causes.

screening tools for high-risk drinkers, who include women in prisons, drug rehabilitation centers, hospital emergency facilities, and sexually transmitted disease clinics (Sokol, Delaney-Black, and Nordstrom 2003). Little is known about the costs around the world. Annual costs for all individuals with fetal alcohol syndrome in the United States during 1998 was estimated at US$4 billion, with lifetime care per person, for individuals requiring such care, at US$1.4 million (Lupton, Burd, and Harwood 2004). Environmental Exposures

Alcohol Prenatal alcohol exposure resulting in fetal alcohol syndrome may be the most common single preventable cause of MR worldwide (Viljoen 1999), but substantial challenges remain in diagnosing and preventing this disorder (see chapter 47). In addition to growth retardation and congenital heart disease, effects include ADHD, memory deficits, and mood disorders. Adults continue to have attention and social difficulties and higher rates of alcohol, nicotine, and drug dependence. Children exposed to even small amounts of alcohol (half a drink per day) in utero have poor outcomes, suggesting that abstinence should be recommended during conception and throughout pregnancy (Sokol, Delaney-Black, and Nordstrom 2003). Although tools are available to help providers identify women who consume alcohol, detection of maternal alcohol exposure is a challenge. The overall rate of fetal alcohol syndrome for LMICs has been placed at 1 to 4.8 out of every 1,000 population (Sampson and others 1997) and is higher among low socioeconomic populations and subpopulations with particularly high alcohol intakes. If individuals with the full spectrum of fetal alcohol syndrome–related effects are included, this rate may be as high as 1 in every 100 births. A prevalence rate of 40.5 to 46.4 out of every 1,000 children in South Africa, the highest rate worldwide, is attributable to particular historical and social conditions (May and others 2000). Public health measures to prevent prenatal alcohol exposure have had limited success, and rates have not changed over the past decade in the United States (Floyd and Sidhu 2004). These measures include putting warning labels on alcoholic beverages and broadcasting public messages about alcohol dangers during pregnancy. Improved outcomes might result from targeting the use of

Children are more susceptible to environmental factors, including unsafe home environments, road traffic, and chemicals (see chapters 42 and 43). Even in high-income countries in Europe, mild MR resulting from lead exposure accounted for 4.4 percent of DALYs among children zero to four years of age. Legislative efforts are under way to eliminate lead from gasoline and other environmental sources of lead exposure in LMICs (Khan and Khan 1999; Alliance to End Childhood Lead Poisoning 2002). In the 0 to 19 years age group, injuries from all causes accounted for 19 percent of DALYs. The poor and vulnerable road users—pedestrians, cyclists, and motorcyclists—bear the greatest burden of road injuries. Nearly 25 percent of all nonfatally injured victims requiring hospitalization sustain a traumatic brain injury as a result of motor vehicle crashes (Peden and others 2004). Although the effectiveness of bicycle helmets for road safety is high, their use in LMICs is low (Thompson, Rivara, and Thompson 1999). Interventions aimed at reducing children’s exposure to environmental factors and injuries could result in substantial gains. Targeted action by region, even within a single country, is likely to prove most productive (Valent and others 2004). Nutritional Deficiency Iodine deficiency from inadequate quantities of iodine in soil, water, and food affects 13 percent of the world’s population, and an additional 30 percent are at risk (see chapter 28). Maternal iodine deficiency during pregnancy may result in an average loss of 15 IQ points in offspring, making it a leading preventable cause of MR. Iodine deficiency can be prevented with adequate consumption of iodized salt, which is now consumed by about 70 percent of households worldwide.


prevention of LDD. In this chapter, we estimated only costs of the interventions for Down syndrome (DS), neural tube defects (NTDs), and congenital hypothyroidism.

IMPAIRMENT, DISABILITY, AND PARTICIPATION Quantifying the impacts of LDD and their preventive interventions is complicated by the fact that these disorders can exist and be measured at multiple levels, including three levels distinguished by the World Health Organization (WHO) in International Classification of Functioning, Disability, and Health (WHO 2001): • impairment, which refers to physiological or psychological defects or abnormalities, such as failure of the neural tube to close • function or disability, which refers to the ability of an individual to perform a task, such as walking, seeing, hearing, learning language, and reading • participation, which refers to the degree to which an individual participates in school, employment, social role, and recreational activities. A given impairment may be associated with a range of functional outcomes. Some but not all of these may be recognized as disability. Disability is context specific and may vary from culture to culture. For example, conditions such as dyslexia, attention deficit and hyperactivity disorder (ADHD), and mild MR may be especially disabling in school but not as noticeable in nonacademic settings and environments where schooling is optional. Environmental factors and social stigma may determine the participation of people with disabilities more than do the functional deficits themselves. Some interventions may be designed to enhance participation (for example, ramps, accessible public toilets, inclusive education), whereas others may target impairment and disability (for example, nutritional fortification, surgery, rehabilitation, special education, newborn screening, and early treatment).

THREE LEVELS OF PREVENTION Prevention of LDD involves primary, secondary, and tertiary prevention activities: • Primary prevention includes efforts to control the underlying cause or condition that results in disability. Examples include (a) maternal antiretroviral therapy to reduce the risk of mother-to-child transmission of HIV and (b) fortification of the food supply to prevent birth defects such as spina bifida and iodine deficiency disorders. • Secondary prevention aims at preventing an existing illness or injury from progressing to long-term disability. Examples include newborn screening for metabolic disorders followed

by dietary restrictions to prevent damage to the nervous system and effective emergency medical care for head injury. • Tertiary prevention refers to rehabilitation and special educational services to mitigate disability and improve functional and participatory or social outcomes once disability has occurred.

UNINTENDED CONSEQUENCES OF SUCCESSFUL OR PARTIALLY SUCCESSFUL INTERVENTIONS Interventions to reduce mortality and morbidity may be followed by increases in the prevalence of LDD. Examples include the following: • Improved survival of very low birthweight infants at high risk for LDD may cause the prevalence of disability in the population to increase at the same time that it increases the absolute number of survivors without disabilities. • Rubella vaccination programs with less than optimal coverage will prevent infections in those vaccinated but leave unvaccinated girls at risk for acquiring rubella infection during their childbearing years (rather than during childhood, as might be expected in the absence of a vaccination program), thereby increasing the risk of congenital rubella infection and disability in the population. • Newborn screening and treatment for phenylketonuria in infancy and childhood prevent MR, but phenylalanine dietary restriction for women with phenylketonuria during their childbearing years is essential to prevent prenatal neurological damage and MR in their offspring.

OTHER FACTORS LEADING TO INCREASES IN MEASURED PREVALENCE Progress in the field of LDD may result in increases in the recognized prevalence of disability and in social and economic costs, as in the following examples: • Increased availability of services may increase the number of children with recognized disabilities. Just as it is ethically problematic to screen for disorders for which no services can be offered, expansion of case finding becomes justified and ethically demanded as services become available, with the potential result of increasing the measured prevalence of disability. • As educational expectations and awareness of LDD increase, the prevalence of recognized disability may increase. In consideration of these trends and relationships between public health advances and increases in disability, it may not be realistic to expect short-term control of disability or cost savings following interventions that reduce mortality, even if those Learning and Developmental Disabilities | 937


Conception Nutritional supplementation Treatment of infections Prenatal screening and obstetric care

Alcohol

Nutrition

Genetics

Infections

Drugs

Hypertension

Smoking

Positron emission tomography

Delivery Congenital abnormalities

Low birthweight Perinatal asphyxia

Meningitis Head injury

Congenital infections

Diarrhea

Neonatal screening

HIV/AIDS

Immunization

Pneumonia

Growth monitoring and nutrition education

Undernutrition

Developmental screening

Poverty

Deworming and micronutrient supplementation

Poor maternal education

Maternal education and support

Inadequate stimulation

Early child stimulation and education Social welfare support Interventions

Abnormal development and disability

Risk factors

Source: Authors.

Figure 49.1 Causal Pathways for LDD

interventions have a net positive effect on public health. The costs of disability and its prevention may increase initially in the wake of interventions that successfully reduce mortality. Figure 49.1 summarizes the causal pathways and potential interventions for the prevention of LDD.

prevention of disability. The vertical axis distinguishes four levels of evidence for cost-effectiveness:

INTERVENTIONS IN LOW- AND MIDDLE-INCOME COUNTRIES

The literature indicates that the economic outcomes of a given intervention may vary widely for two reasons:

Numerous interventions are effective in preventing LDD. Table 49.2 provides a summary of these interventions classified on two axes. The horizontal axis distinguishes whether the intervention would accomplish primary, secondary, or tertiary

• Variations exist across populations, even within the same country, in the prevalence of the disorder, the cost of health care, and the existing infrastructure available to implement the intervention.

• evidence available for LMICs • evidence available for high-income countries only • evidence for cost-effectiveness not available, but costeffectiveness can be estimated from existing data • evidence not available, but potential for benefits exists.


Table 49.2 Classification of Interventions to Prevent LDD Primary (prevention of condition that can lead to disability) Evidence for cost-effectiveness available for LMICs

Tertiary (rehabilitation or prevention of further disability once disability has occurred)

Secondary (prevention of disability once condition has occurred)

Food fortification (folic acid and iodinea) Rubella vaccinea Hemophilus vaccine Removal of lead from paint and fuel Vitamin A supplementation (vision) Measles vaccine

Evidence for cost-effectiveness available for high-income countries only

Evidence for cost-effectiveness not available, but cost-effectiveness can be estimated from existing data

Prenatal screening for DS and prevention of DS births Newborn screening for metabolic disorders followed by interventions to prevent disability Malaria preventionb

Early detection and care of neonatal jaundice

Special education

Management of malaria

Braille

Prosthetics

Treatment for otitis media

Sign language

Prevention and treatment of neonatal complications through emergency obstetric and pediatric services

Occupational, physical, and speech therapies

Eyeglasses

Residential care

Hearing aids

Assistive devices

Surgery

Detection and treatment of maternal thyroid disorders Evidence for cost-effectiveness not available, but potential for benefits exists

Fetal alcoholism prevention

Dehydration/diarrhea treatment

Trauma prevention (bicycle helmets, burns)

Postnatal combined cognitive stimulation and nutritional intervention

Prevention of shaken baby syndrome and child abuse

Therapeutic stimulants for treatment of ADHD

Community-based rehabilitation

Note: Italicized text represents somewhat detailed consideration of cost-effectiveness included in this chapter. a. Covered in chapter 56, but chapter emphasis is not on implications for preventing developmental disabilities. b. Covered in detail in chapter 21.

• Differences between studies exist in analytical methods used, such as the willingness to pay versus the human capital approach to valuation, and in cost categories, such as whether to include parental time costs. Though these differences make cross-population comparisons difficult, the overall evidence of cost-effectiveness is demonstrated by repeated findings that the benefits of a particular intervention outweigh the costs in a number of different settings.

Too little is known about the fourth type of intervention, community-based rehabilitation, to evaluate it. There is a paucity of knowledge and a history of failed interventions for the prevention of premature birth and the disabilities associated with premature birth.

Current evidence suggests that three interventions are cost saving: folic acid fortification to prevent NTDs, prenatal screening and selective pregnancy termination to prevent DS, and neonatal screening and treatment for congenital hypothyroidism (CH).

NTDs, which are the most common malformation of the central nervous system, result from failure of the neural tube to close during the first month of pregnancy. Anencephaly typically results in pregnancy loss, stillbirth, or neonatal death. Spina bifida (open spine defect) is associated with a range of

Neural Tube Defects: Burden and Cost-Effectiveness of Folic Acid Fortification


functional deficits (requiring multiple surgical and rehabilitative interventions), including paralysis of the lower extremities and often primary enuresis and cognitive disabilities. Large geographic variations in the prevalence of NTDs exist both within and between countries. The burden of disease is highest in South Asia and lowest in LMICs of Europe and Central Asia. Similarly, deaths from NTDs are high in South Asia but lowest in high-income countries. Estimates suggest that almost all NTD disease burden is concentrated in the age group zero to four years (Mathers 2006). Folic Acid. Folate is a vitamin that occurs naturally in green leafy vegetables, legumes, citrus, and other foods. Folic acid (FA) is an easily absorbed synthetic form of folate that can be delivered as a dietary supplement or through FA fortification of flour or other common staple foods. NTDs can be reduced by 70 percent if women consume 400 g of FA daily around the time of conception and until closure of the neural tube. At a population level, either supplementation or fortification of the food supply is necessary to ensure that 400 g of FA is consumed at the critical period of fetal development, as this dose is higher than can reasonably be consumed by relying on naturally occurring folate in foods. Fortification is much more likely than supplementation to reach the population at risk because the benefit of enhanced FA intake occurs early, typically before the pregnancy is recognized. Fortification is of particular value to women who may not receive prenatal care until the third trimester. This section considers only evidence of cost-effectiveness of FA fortification in LMICs with respect to the benefit of preventing NTDs. Additional health benefits can be expected with respect to stroke, heart disease, and cancer. Cost-Effectiveness of Folic Acid Fortification A cost-benefit analysis of grain fortification in the United States (Romano and others 1995) included costs related to the addition of FA to food, to annual testing and surveillance, to a one-time packaging change, and to potential (though not substantiated) adverse health effects associated with undiagnosed vitamin B12 deficiency. Benefits included avoided costs of NTDs, such as mortality costs (particularly for anencephaly) and costs of caring for those with spina bifida. The benefits of fortification outweighed costs with cost-benefit ratios of 1 to 4.3 for low-level fortification and 1 to 6.1 for high-level fortification. Cost-effectiveness relative to status quo of FA fortification depends on several factors: • Costs of food fortification depend on the types and quantity of food that are fortified and the level of fortification. • The proportion of the target population reached by the fortified food is important since, in most LMICs, many people consume food produced on their own farms or within their villages.

• Grains from large mills are relatively cheap to fortify; more resources are required to fortify grains milled in smaller neighborhood mills. • The amount of folate consumed by different populations in the absence of fortification varies. • Prevalence of NTDs varies across populations, and the costeffectiveness increases with prevalence. Costs of food fortification may be lower in high-income countries, where most people consume cereals processed in a few large mills, equipment for fortification is likely to be in place, and quality assurance is facilitated. In contrast, mills in LMICs lack fortification equipment and capital, and running costs are higher in the short run. Costs of Food Fortification For optimal daily consumption, the actual level of food fortification (defined as g of FA per 100 grams of the food item) should be adjusted for storage and other losses so that a daily dose of 400 g is achieved. Food items that should be fortified depend on specific dietary habits. Staples such as rice and flour are obvious choices; salt, sugar, bread, milk, and edible oils are promising candidates. There are economies of scale in FA fortification.It can be and usually is carried out in conjunction with other forms of fortification, such as iron, iodine, and vitamin A fortification. Many food items are already fortified in high-income countries. Other factors to be considered in the choice of food for fortification are items that are centrally processed and allow for quality control. Soy sauce in China is an example: it is consumed on a daily basis by 70 percent of the population and is prepared in a few large factories. The recommended fortification level is thus 240 g per 100 grams of the staple food. This fortification rate is assumed for all regional strata where the per capita staple consumption per day is less than 300 grams. Wheat, rice, maize, or a combination of these foods is the staple in most countries. The recommended level of FA fortification varies from 150 g to 240 g per 100 grams of cereal. So that women receive a daily dose of 400 g, the target cereals for fortification should be those for which daily per capita consumption is at least 200 grams. In Sub-Saharan Africa, daily per capita cereal consumption exceeds 200 grams only if wheat, rice, and maize are considered together. Quality assurance is done through analytic testing of fortified products to confirm FA levels. Quality assurance costs in the United States are estimated at US$0.64 cents per ton of fortified grain in quality assurance costs. The costs of FA fortification include the cost of FA, setup, and analytic testing. The analysis is done using two different cost estimates: US$0.15 and US$0.50 per ton of grain fortified. The cost of FA determines the cost of premix added to the flour. FA is almost never added alone; usually FA, iron, zinc, and niacin are added in combination. The material cost of FA alone is about US$0.10 to US$0.20 per metric ton of milled


wheat. However, a more realistic cost for the premix (including other supplements) is about US$0.50 per metric ton of milled wheat. This higher estimate is conservative and does not account for the health benefits from the other supplements. Either way, the per capita costs are only a few cents in each region. The low per capita cost in high-income countries of US$0.009 assumes that 80 percent of the cereal supply is fortified. In South Asia, where NTDs have the highest burden, the per capita cost is estimated at US$0.067 (Bagriansky n.d.). Benefits of Folic Acid Fortification The cost-effectiveness of FA fortification in terms of its cost per DALY and per death averted assumes that the fortification strategy will reduce the incidence of NTDs by 50 percent. The costs are relatively high because of the high cost of FA. Even a few cents per capita becomes expensive if the per capita prevalence of NTD is very low. Other Costs and Benefits The benefits of FA fortification outweigh the costs. The benefits estimated here are conservative for three reasons: • Strokes and coronary deaths are also prevented by FA fortification and occur more frequently than NTDs. • The percentage of NTDs that can be prevented by FA fortification may be greater than 50 percent, because up to 70 percent of NTDs can be prevented by 400 g of periconceptional FA daily. • These estimates do not take account of the costs of clinical care and management for complications when NTDs are not prevented.

common genetic cause of mental retardation. Identifying a fetus with DS before birth and giving parents the option to terminate the pregnancy early can help decrease the burden of the disease on families and society. During counseling, parents may receive information about the consequences of DS, which will allow them to make an informed decision about the best care for the newborn or about termination of the pregnancy. Prenatal screening services provide an opportunity to profoundly reduce the impact of MR. The cost-effectiveness of prenatal screening for DS is based on two parameters: efficacy (by assessing the false positive rate of screening procedures and the number of fetal losses caused by screening) and financial costs (costs of screening per DS pregnancy averted). On the basis of the evidence, the best screening method is proposed, and sensitivity of the parameters of interest to the LMIC is tested. No formal comparisons are made between the costs of screening and care for a person with DS. The purpose of this analysis is to suggest the most cost-effective way of screening that provides families with information about the health of the child; it is not a cost-benefit analysis of whether a couple should terminate a pregnancy.

Prenatal and Neonatal Screening. Prenatal screening for genetic abnormalities allows parents to determine whether to continue with an affected pregnancy, whereas neonatal screening’s fundamental purpose is to improve the infant’s prognosis through early diagnosis and treatment. A number of LDDs have been screened for in high-income countries since the 1960s, and researchers have conducted economic evaluations of these screening programs, including those for Tay-Sachs disease carriers, DS (Cusick and others 2003), sickle cell disease (Panepinto and others 2000), phenylketonuria (Lord and others 1999), and several other inborn errors of metabolism (Insinga, Laessig, and Hoffman 2002).

Burden. DS is caused by trisomy of chromosome 21—an extra chromosome rather than the usual diploid form—and is a major cause of severe MR (IQ less than 50 with substantial deficits in adaptive behavior). The incidence of DS is higher than the birth prevalence because many fetuses are spontaneously miscarried and, in some cases, selectively terminated. In the absence of prenatal screening and intervention, most DS conceptions (71 percent) result in spontaneous abortion; another 3 percent result in stillbirth, and 26 percent result in live birth with subsequent LDD (Kline, Stein, and Susser 1989). Because the incidence of DS cannot be determined without doing surveillance of all conceptions, the frequency of DS is typically measured in terms of prevalence per 1,000 live births rather than in terms of incidence. Thus, the population prevalence of DS varies depending on the maternal age structure (steep increase after age 35 years) as well as the availability and use of prenatal diagnosis followed by selective termination. Estimates from 10 LMICs range widely, from 0.1 out of every 1,000 live births in Indonesia to 4.4 out of every 1,000 live births in Pakistan (Institute of Medicine 2003). Most studies, in both high-income countries and LMICs, show DS birth prevalence in the range of 1.0 to 1.6 out of every 1,000 births. The birth prevalence of DS is likely higher in LMICs because of a higher proportion of births among women over age 35 (11 to 15 percent) relative to that in high-income countries (5 to 9 percent) (Kline, Stein, and Susser 1989) and possibly because of differential access to prenatal screening for chromosomal abnormalities.

Estimates for Prenatal Screening, Diagnosis, and Selective Pregnancy Termination for Down Syndrome. DS is the most

Life Expectancy and Quality of Life. Life expectancy for children with DS is substantially lower than that of the general

Interventions to Prevent Disability Caused by Down Syndrome Screening programs are critical public health interventions that use universal or targeted screening tests to identify potential causes or cases of LDD, including DS.


Table 49.3 Distribution of DALYs Lost to and Deaths Caused by Down Syndrome, by World Bank Region, 2002 Region East Asia and the Pacific

DALYs

Deaths

4,101,694

1,328


507,723

652

High income countries

199,215

2,113


214,346

1,979


347,898

1,311

2,005,766

11,336

478,851

4,967

South Asia Sub-Saharan Africa Source: Mathers and others 2006.

population. Congenital heart disease occurs in 40 to 60 percent of children with DS and accounts for 30 to 35 percent of deaths. Survival and life expectancy of children with DS have increased dramatically: In a 1940–60 birth cohort in England, only 50 percent of infants with DS survived beyond age two. By comparison, in 1981–85, 90 percent survived beyond age five (McGrother and Marshall 1990). Table 49.3 describes the estimated total deaths caused by DS by region, as well as the estimated total DALYs lost. DS is always associated with cognitive impairment. Disability can range from mild to profound, and most children are affected moderately (IQ 40–55). Early intervention and therapy can improve functional outcomes. Of children with DS, 60 to 80 percent have hearing loss, and approximately 70 percent have ophthalmologic problems. As life expectancy of DS individuals has increased, many grow to adulthood and face an increased risk of early onset Alzheimer’s disease, cataracts, hearing loss, hypothyroidism, and degenerative vascular disease. Costs of Care. Based on 1988 data, the estimated incremental lifetime economic costs of DS are US$410,000 per case or US$647,709 in 2004 dollars (Waitzman, Romano, and Scheffler 1994). In another study, the estimate of per capita incremental costs of DS, converted to 2004 dollars, include net medical costs of US$168,567, developmental services costs of US$80,530, special education costs of US$171,593, and total costs of US$420,690 (Waitzman, Romano, and Scheffler 1994). An estimate of lifetime costs per live born baby with DS— including education, health, and lost productivity costs— ranged from US$137,000 in 1990 to US$515,000 in 1993 (Gilbert and others 2001). Net savings using the annual program of screening, diagnosis, and selective termination was estimated to be US$885, with costs of US$446,000 per 10,000 pregnancies for a program that detects and prevents 9.7 DS births per year and a lower bound estimate of US$137,000 of potential lifetime costs per 9.7 births prevented. The increased life span of individuals with DS and accompanying age-associated morbidity impose heavy demands on

medical care and community services, as well as on sustained support from family members. It is also important to note that dollar costs of care for a DS child in LMICs would be much lower than such costs in high-income countries because of lower prices as well as lower treatment intensity. For example, in some countries, congenital heart disease, which affects 40 to 60 percent of DS children, cannot be treated effectively. This lack of treatment will lower costs of care as well as life expectancy, and cost estimates will vary for each individual area or region. Cost-Effectiveness of Prenatal Screening, Diagnosis, and Selective Pregnancy Termination. Prenatal screening can be implemented to allow selective termination of DS pregnancies and prevention of disability related to DS in the population. This intervention raises ethical, social, and cultural concerns for some individuals and populations that may preclude its applicability. A screening program incorporating maternal serum triple screening in all pregnant women, regardless of maternal age, yields an excellent DS detection rate and is associated with a low false-positive rate (Wald and others 2003). DS pregnancies yield lower levels of alpha-fetoprotein and unconjugated estriol but have elevated levels of human chorionic gonadotropin compared with other pregnancies. Ultrasound evaluation of the fetus neck thickness improves screening sensitivity. It is also useful when used in conjunction with serum screening (Wald and others 2003). A positive screening result is followed by diagnosis using amniocentesis or chorionic villus sampling (CVS). Although both diagnostic procedures are guided by ultrasound to reduce risk, they are invasive, are more expensive than the screening procedure, and carry a small risk of miscarriage of an unaffected pregnancy. Thus, only a select group screening positive for possible trisomy 21 are offered the invasive diagnostic procedures. Amniocentesis, which involves the aspiration of amniotic fluid, is performed between the 14th and 16th weeks of pregnancy. CVS involves aspiration of villi and can be performed between the 10th and 12th weeks of pregnancy. Although CVS can be performed earlier in the pregnancy, amniocentesis is easier to perform and is more widely used in the second trimester. Following diagnostic confirmation of DS, parents are provided with genetic counseling and the option of terminating the pregnancy. Although DS risk increases with maternal age, most births occur in younger women and, therefore, two-thirds of all DS births occur in younger mothers (Ross and Elias 1997). If prenatal diagnosis is available only for mothers 35 years or older, only 33 percent of DS births will be detected. Studies demonstrate that heavy reliance on maternal age to screen for DS may not be desirable in LMICs. Maternal age factor is not so useful in settings where early marriage and motherhood are the norm and most DS pregnancies involve mothers younger than 35 (Gupta and others 2001). Therefore, maternal serum screening


of all pregnant women is important in preventing DS births and achieving cost-effectiveness (Wald and others 2003). Procedure Costs Genetic screening and counseling services are expensive. Even after initial high fixed costs to establish prenatal screening services, provision of high-quality services requires staff training, equipment, and laboratory maintenance. A recent report suggests establishing genetic screening services when other public health interventions have reduced the infant mortality rate to the range of 20 to 40 out of every 1,000 live births (Institute of Medicine 2003). Above this level, other public health interventions may have greater benefits. The breakdown of tasks is as follows: • screening costs, which consist of laboratory expenses (consumables and staff); informing women of results (by mail if negative, by phone if positive); service costs (processing results and monitoring the service); training in ultrasound measurement of neck skin translucency; and overhead expenses • diagnostic costs, which comprise counseling before CVS or amniocentesis, equipment and staff for these procedures, laboratory expenses (consumables and staff), and overhead expenses • costs of termination of selected pregnancies, which include surgical dilation, evacuation (11 to 13 weeks), or medical termination with mifepristone (after 13 weeks). We assume infrastructure exists for prenatal screening, diagnosis, and intervention. We use the following costs: triple serum test, US$70; amniocentesis, US$1,200; genetic counseling, US$100; and termination of pregnancy, US$2,000. These cost estimates have been widely used in the literature (Cusick and others 2003). However, the medical costs can be significantly lower in LMICs and will also vary across and within countries. Cost-Effectiveness and Efficacy We assume that 100 percent of women attend a prenatal clinic between 10 and 14 weeks of gestation and are offered tests in the first trimester,or between 15 and 19 weeks for the tests in the second trimester.We discuss the effect of low uptake of prenatal care and its effect on cost-effectiveness of prenatal screening programs in our sensitivity analysis. In terms of economic considerations, it is desirable to balance the probability of the birth of a DS child with the risk of procedure-related miscarriage. Sensitivity of prenatal screening and the false-positive rates vary widely, depending on the method used. The risk of procedure-related miscarriage can vary from 0.04 to 0.8 percent (Nyberg and others 1998). We use the conservative fetal loss rate of 0.9 percent (Gilbert and others 2001) for both procedures. Efficacy of prenatal screening is defined as the number of unaffected fetuses lost due to prenatal testing per each DS birth

averted (Institute of Medicine 2003). The goal is to minimize this ratio. The efficacy of prenatal screening varies with prevalence, and the primary determinant of variations in prevalence of DS is the age structure of women giving birth. The prevalence of DS and the efficacy of prenatal screening increase with the percentage of births to mothers over the age of 35. In this analysis, a 90 percent rate of selective termination is used (Waitzman, Romano, and Scheffler 1994). On this basis, the number of fetal losses per DS birth avoided varies from 7.13 (for 1 in 10,000 prevalence) to 0.16 (for 44 in 10,000 prevalence). Therefore, in countries with low prevalence of DS, such as Indonesia, more unaffected fetuses are lost than DS births averted because of screening. In areas where the ratio of unaffected fetal losses to DS births avoided is above 1, the efficacy of screening for DS is questionable. Because of higher loss rates for CVS, we use a 1.5 percent fetal loss rate in our sensitivity analysis (Lippman and others 1992). Other costs not considered in this study are the psychological effects of a positive test on the parents, anxiety that may persist from a false-positive test, and potential complications resulting from pregnancy termination. Complications from termination may vary (Stray-Pedersen and others 1991) and may not be the same in LMICs, which should be taken into account. The sensitivity rate for the triple serum test followed by the amniocentesis is 62.3 percent in the clinical trials (Vintzileos and others 2000), and the uptake of amniocentesis is 90 percent for affected mothers and 80 percent for unaffected mothers (Waitzman, Romano, and Scheffler 1994). We assume the false-positive rate of 5 percent. The false-positive rate affects the probability of losing an unaffected fetus as a result of invasive testing that follows serum screening. Financial cost-effectiveness is defined as the screening costs per DS birth averted. It is presented in table 49.4. Costeffectiveness is the highest in countries with high birth prevalence of DS, given that women have access and receive prenatal care. Costs of prenatal screening and termination per DS birth averted vary from US$1,497,390 in Indonesia (for 1 in 10,000 prevalence) to US$37,185 in Pakistan (44 in 10,000 prevalence). A similar relationship is seen between prevalence and cost per DALY. In our analysis, we use costs data that are based on estimates from developed countries. Because costs of care will vary widely across and within countries, cost estimates should be done for individual regions. Lower costs of care will reduce costeffectiveness of prenatal screening for DS. However, even after the cost adjustment, it is unlikely that the benefits will completely go away, because of the large difference between a relatively cheap screening program and high burden of disease of DS. Sensitivity Analysis The results of the analysis above depend on assumptions that may not hold in some LMICs. For example, if many women accept screening but few decide to have an amniocentesis, cost-effectiveness will be adversely affected. The Learning and Developmental Disabilities | 943


Table 49.4 Financial Cost-Effectiveness and Efficacy of Prenatal Screening and Pregnancy Termination for the Prevention of Down Syndrome Births

Representative country

DS births per 100,000 population (birth prevalence)

DS births detected

Cost per 100,000 population (US$)

Cost per DS birth detected (US$)

DS births prevented

Cost of detection and termination (US$)

Cost per DS birth avoided (US$)

US$ per DALY

Unaffected fetal losses

Fetal losses per DS birth prevented

East Asia and the Pacific Indonesia

10

5.61

7,546,188

1,345,851

5.05

7,556,281

1,497,390

14.88

36.0

7.13

56

31.40

7,574,655

241,237

28.26

7,631,174

270,041

38.31

35.98

1.27

67.73

7,614,750

112,433

60.95

7,736,658

126,926

36.09

35.96

0.59

89.71

7,639,014

85,150

80.74

7,800,496

96,612

22.50

35.94

0.45

100

56.07

7,601,884

135,579

50.46

7,702,810

152,643

22.14

35.96

0.71

440

246.71

7,812,290

3,1666

222.04

8,256,364

37,185

4.12

35.84

0.16

210

117.75

7,669,956

65,139

105.9

7,881,901

74,377

16.46

35.92

0.34

Europe and Central Asia Hungary High-income countries Canada

120.79

Latin America and the Caribbean Argentina

160

Middle East and North Africa Israel South Asia Pakistan Sub-Saharan Africa South Africa

public health benefits of screening for DS in socioeconomically deprived areas are small because of low uptake of amniocentesis (Ford and others 1998). With lower uptake rates of amniocentesis, both efficacy and financial cost-effectiveness are adversely affected as a result of low detection rates, and the number of unaffected fetal losses decreases. It is also important to note that, in some countries, many women may not have access to prenatal care or may not seek prenatal care and prenatal testing. In such areas, programs that try to reduce DS prevalence will have limited success, especially if a population at greater risk of DS is not tested. Cost-effectiveness is often measured per DS birth averted since reduction in DS prevalence is the ultimate goal of prenatal testing. In many cultures, an abortion is not an acceptable option. Acceptance of elective termination of pregnancy may also vary across ethnicities and other subgroups within a given country. A study in California found the uptake of termination following the DS diagnosis varied from 47.5 percent for Hispanics to 65.8 percent for whites and 70.8 percent for Asians (Cunningham and Tompkinison 1999). If few families decide to terminate pregnancy to avoid having a child with severe disability, cost-effectiveness per DS birth averted will be adversely affected, and the screening program may fail to reduce the birth prevalence of DS. If a large percentage of families are opposed to induced abortion of fetal DS, the uptake of amniocentesis also will be low.

Because fetal losses following CVS are often higher than those for amniocentesis, efficacy analysis should be conducted assuming a 1.5 percent fetal loss risk attributable to invasive testing in the first trimester. With higher fetal losses, the efficacy of the prenatal screening is adversely affected, although the cost-effectiveness will not change. In addition, assuming a higher false-positive rate of 8.3 percent increases the number of invasive tests on unaffected mothers and the number of unaffected fetal losses, thus adversely affecting the efficacy of the prenatal testing (Vintzileos and others 2000). The analysis presented above is limited to an evaluation of the cost-effectiveness of prenatal screening for DS only. Some serum markers (for example, alpha-fetoprotein) will identify other abnormalities, the benefits of which are not included in this analysis. Equity and Access The desirable policy is that women of similar risk for DS have equal access to diagnostic tests. With limited access to prenatal care, the introduction of the screening programs can have small public health effects. Although the approach used in cost-effectiveness analysis is optimization of societal net benefit, the policies to be recommended for the prevention of disability must also consider individuals’ freedom in decision making at each step of the prenatal diagnosis. Successful policies need to be based on cost-effectiveness


estimates that take into account the needs, sensitivities, and values of individuals and cultures (Institute of Medicine 2003). Interventions to Prevent Disability Caused by Congenital Hypothyroidism For CH, like DS, screening programs are critical public health interventions. Neonatal Screening in Low- and Middle-Income Countries. When considering the costs and benefits associated with a CH screening program, one must first have an estimate of how prevalent CH is in the population so that the avoided costs associated with disability can be calculated. It is important to note that in high-income countries and in several middleincome countries screening is usually done for a series of conditions rather than for a single disorder. This fact is likely to affect the cost. In several of these conditions, the treatment includes dietary modification as well as costly prepared foods and formulas. Policies in countries where this type of screening occurs include labeling of food to alert potentially vulnerable consumers. Several studies have examined the prevalence of CH in specific populations, with substantially varying results. A review of 13 studies reporting findings on CH prevalence identified through individual screening programs found the lowest rate to be 1 case of CH per over 6,000 screened in Thailand (Wasant, Liammongkolkul, and Srisawat 1999). Contrasting this is the highest rate reported: 1 case in 1,000 screened in Pakistan (Lakhani and others 1989). Prevalence can vary not only from one country to the next, but also within countries, depending on different analyses or subpopulations within one country. These variations demonstrate the need for identifying the appropriate population in order to conduct economic evaluations of screening interventions. According to three cost-benefit analyses of CH screening (Layde, Von Allmen, and Oakley 1979; Barden and Kessel 1984), the benefits included savings from institutionalization, special education, medical care, lost parent and child productivity, and slightly decreased life expectancy. The costs included those of the screening program as well as the cost of treating detected cases. Overall, CH screening programs are substantially cost saving, with a cost-benefit ratio as high as 1 to 8.9 in highincome countries (Dhondt and others 1991). Such savings have not yet been evaluated in LMICs. Because the treatment is inexpensive and highly effective, it is anticipated that CH screening would also be substantially cost saving in LMICs. Burden. Congenital hypothyroidism is a common cause of MR that can be prevented by newborn screening and treatment. By the end of the 1970s, neonatal screening programs had been established in many regions of Canada, Europe, Japan, and the United States. Thyroid hormone is required for

normal brain development, and little or no thyroid hormone in the neonatal period results in damage to the nervous system. Various causes of anatomical maldevelopment of the thyroid gland are responsible for CH, and several genes have been implicated. With biochemical newborn screening (best conducted in centralized regional laboratories) using dried blood spots and diagnosis in the first few weeks of life, MR is avoidable. Without appropriate treatment, two-thirds of patients with CH have low IQ, and 30 percent experience severe or profound cognitive disability (Beaulieu 1994). Even with appropriate treatment, some subtle intellectual impairment and behavior deficits may still occur—the mean IQ may be approximately 10 points lower than that of the general population (Tillotson and others 1994). In the United States, infants are screened as newborns and again at two to six weeks of age to detect missed cases. For optimal outcomes, lifelong treatment with thyroid hormone is required, with subsequent monitoring and adjustments recommended every 3 to 12 months until growth and puberty are complete. Many females born with CH are now reaching childbearing age and require increased dosages of thyroid hormone during pregnancy for optimal neuropsychological outcome in their offspring. Costs of Care. Estimated lifetime costs of care for the child with CH include the following (Barden and Kessel 1984): • Institutional care. At the time of the study, 15 percent of congenital hypothyroid individuals were institutionalized from age 5 to 70. • Foster care. About 25 percent of congenital hypothyroid cases received foster care from age 5 to 20. • Residential care. Such care was provided for 40 percent of affected cases. • Special education expenditures. Such expenses varied with the level of MR (15 percent severe, 25 percent moderate, and 40 percent mild). In 2004, estimated lifetime costs of CH care is US$191,000, with a 6 percent discount rate. This estimate of the financial costs of care for an affected person is fairly conservative; it does not take into account lost productivity of the person with CH, a potential loss of income attributable to the time inputs of the family members who are taking care of the affected person, or effects on quality of life. Cost-Effectiveness of Neonatal Screening. Table 49.5 presents cost-effectiveness analysis of neonatal screening for representative countries in the World Bank regions. Screening costs include blood sample collection, laboratory costs, discounted lifetime treatment cost, and costs of care for those missed by the screening. Specimen collection and laboratory costs (Barden and Kessel 1984; OTA 1988) constitute (in 2004 dollars) US$989,000 and US$969,000, respectively, per Learning and Developmental Disabilities | 945


Table 49.5 Cost-Effectiveness of Neonatal Screening for Congenital Hypothyroidism by World Bank Region

Representative country

CH births per 100,000 (birth prevalence)

CH births detected

Program costs for screening and treatment (US$)

Cost per disability averted (US$)

Cost without testing (US$)

Cost savings (US$)

23.94

22.74

2,236,661

98,366

4,342,987

2,106,326

34.97

33.22

2,407,937

72,492

6,344,406

3,936,468

25.00

23.75

2,253,200

94,872

4,536,250

2,283,050

40.7

38.67

2,496,991

64,580

7,385,022

4,888,032

36.25

34.43

2,427,813

70,509

6,576,658

4,148,845

100.00

95.00

3,417,801

35,977

18,145,000

14,727,199

24.13

22.93

2,239,768

97,686

4,379,292

2,139,524

East Asia and the Pacific Thailand Europe and Central Asia Estonia High-income countries United States Latin America and the Caribbean Mexico Middle East and North Africa Saudi Arabia South Asia Pakistan Sub-Saharan Africa South Africa

100,000 children tested. Lifetime discounted (at 6 percent) treatment costs are US$6,292.64 in 2004 dollars (Barden and Kessel 1984). Analysis of costs and benefits in table 49.5 shows that, although screening for the population as a whole requires considerable investment and infrastructure, the burden from the disorder is high and treatment is cheap. Screening all newborns is beneficial compared with the high costs of lifelong care for the affected individuals. Cost savings are positive for all representative countries despite high variance in the prevalence of CH. Even for a low birth prevalence estimate of 4 out of every 100,000 in Thailand (Wasant, Liammongkolkul, and Srisawat 1999), the cost savings would be US$106,326. Effectiveness of the newborn screening in identifying the affected infants depends on the ability of the screening program to collect blood samples from all infants in the first week and to perform tests in time to initiate treatment. This effort may be difficult in some settings, where infants are born at home or released on the first day after birth and do not have contact with the health care system in the first month of their lives (Sack, Feldman, and Kaiserman 1998). The wider the coverage of the screening program, the higher will be the cost savings of screening. Also, follow-up screening for those infants who test as false negative will increase sensitivity to 100 percent and improve cost-effectiveness of the program. In our cost-effectiveness analysis, we assumed the lifetime care and treatment costs to be similar to those estimated for the United States. However, medical costs may vary significantly among and within countries. Such variation is unlikely to alter

the cost-effectiveness analysis, because the difference between program and treatment expenditures and lifetime costs will remain even after we scale the medical costs. The analysis presented above is limited to an evaluation of the cost-effectiveness of neonatal screening for CH. For minimal extra cost, collected blood samples for CH can also be used to identify other inherited disorders, including phenylketonuria, maple syrup urine disease, and other inborn errors of metabolism. Without the benefits of early detection and treatment for these conditions, the result is severe MR.

Community-Based Rehabilitation Community-based rehabilitation is a set of low-cost approaches to providing rehabilitation services such as physical therapy, occupational therapy, prosthetics, and assistive devices for people with disabilities in developing countries. Such rehabilitation also aims to minimize stigmatization of people with disabilities and to support inclusive education and integration of people with disabilities into society. WHO and other organizations have actively promoted community-based models for providing rehabilitation services—including services for children with developmental disabilities—in resource-poor settings (Institute of Medicine Committee on Nervous System Disorders in Developing Countries 2001). Although 80 percent or more of the world’s people with disabilities live in developing countries, only 2 percent have access to rehabilitation services (WHO Community-Based


Rehabilitation 1982). If families of people with disabilities are taken into account, the number of people experiencing the effects of disability is estimated to be up to 25 percent of the world population. Community-based rehabilitation is designed to expand access to rehabilitation services in poor and rural areas by providing training in rehabilitation techniques to individuals with disabilities, their family members, and others in their communities. It also attempts to change negative attitudes toward disability and to remove barriers in the physical environment that prevent people with disabilities from fully participating in society. Costs. In the community-based rehabilitation model, community interventions are shifted from institutions and centers to the homes and communities of people with disabilities and are carried out largely by family members and volunteers. By using volunteer workers and the existing infrastructure in the communities, this form of rehabilitation minimizes costs of delivering services and is assumed to be cost-effective relative to the alternative institution-based rehabilitation (Institute of Medicine Committee on Nervous System Disorders in Developing Countries 2001; WHO Community-Based Rehabilitation 1982; Lagerkvist 1992). Institutional care has higher costs because it relies on paid staff, medical equipment, building maintenance, and medical costs. Some advocate for provision of institutional, center-based, medical, and community-based approaches in a complementary fashion. In a Zimbabwean community-based rehabilitation project twothirds of the patients were referred to hospitals or clinics (Rottier and others 1993). Annual costs for training workshops and salaries of rehabilitation workers amounted to US$60,000 to treat 1,614 individuals with disabilities. Little information is available about the full costs of community-based rehabilitation and how they vary across disabilities, age groups, and societies. The cost-effectiveness of such rehabilitation or whether its costs are lower than alternative rehabilitation models is unknown. It is usually implemented in settings where no other rehabilitation models exist. The costs to consumers in terms of their efforts, time, and money may be substantial (Thomas and Thomas 1998). No formal estimates are available of time costs and opportunity costs to family members involved in community-based rehabilitation. Meeting the needs of a family member with a disability may prohibit or disrupt labor force participation of the caregiver and reduce family income. This need for caregiving may especially affect women (Giacaman 2001). The effectiveness of community-based rehabilitation in improving functional outcomes for children with cerebral palsy in Bangladesh showed no improvement, but researchers unexpectedly found a significant increase in reported stress and symptoms of depression in the mothers of children in the community-based rehabilitation intervention group (McConachie and others 2000).

Efficacy. Other attempts to evaluate community-based rehabilitation in different settings and for a range of outcomes include one for preschool children with disabilities in rural Guyana. The children showed significant improvement after six months in the program, and noticeable improvements in the attitudes of parents and others toward children with disabilities were seen (O’Toole 1988). Community-based rehabilitation programs in the Philippines and Zimbabwe found gains in activities of daily living and communication as well as higher rates of starting school and employment after six months in the program (Lagerkvist 1992). Similarly, people with disabilities participating in a community-based rehabilitation program in Botswana showed high levels of independence in activities of daily living; 20 percent of adults were working, and most school-age children were attending class (Lundgren-Lindquist and Nordholm 1996). Some have questioned the efficacy of community-based rehabilitation and its ability to expand access for people with disabilities. Many people with disabilities do not patronize such programs, and many who do try leave dissatisfied (Kassah 1998). After initial diagnosis, only half of the identified individuals with disabilities continued (Rottier and others 1993). Community-based rehabilitation programs also face the difficulty of working in diverse communities with unique cultural, religious, economic, and social conditions, making it difficult for a single model to meet the needs for rehabilitation services in developing countries (Crishna 1999). Prevention of Premature Birth Premature birth—after 20 weeks but before 37 weeks—is a powerful predictor of death and disability. Infants born before 28 weeks of gestation have a 50-fold increased risk of cerebral palsy (Drummond and Colver 2002) and heightened risk of sensory, cognitive, and educational impairment (Taylor and others 2004). The rate of preterm births in the United State has increased steadily since 1990 (MacDorman and others 2002). Survival of infants born before 34 weeks requires intensive and expensive medical care (Gilbert, Nesbitt, and Danielsen 2003), and the global survival rate differs depending on neonatal care availability (Lorenz and others 2001). Infection or inflammation of the placenta is common in preterm pregnancies (Goldenberg and Culhane 2003), and many deaths attributed to asphyxia may be caused by maternal, placental, or neonatal infection. The cerebral palsy rate is significantly higher in premature infants whose births are monitored electronically (Shy and others 1990).With the exception of magnesium sulfate administered to women in preterm labor (Crowther and others 2003), no specific interventions result in decreased cerebral palsy among premature infants (Crowther and Henderson-Smart 2004). Dietary supplements might decrease the frequency of lowbirthweight births and perhaps the frequency of marked prematurity. In Bangladesh, where the rate of preterm labor Learning and Developmental Disabilities | 947


was high, women who went into labor before term were older, shorter, thinner, less educated, and more disadvantaged economically, with closer spacing of births (Begum, Buckshe, and Pande 2003). Deaths attributable to prematurity in LMICs are seldom due to poor management and are largely related to poor health facilities (Pattinson 2004).

Electronic Fetal Monitoring in Labor For decades most cerebral palsy and a major share of MR, epilepsy, and learning and behavioral disorders of childhood were considered to be due to deprivation of oxygen supply to the fetus during birth. Recent research confirms that only a minority of cerebral palsy cases, as well as associated MR and seizures, are related to markers of birth asphyxia (Nelson and Ellenberg 1986; Torfs and others 1990). Low Apgar scores, the need for respiratory support, and neonatal seizures are more commonly due to etiologies other than asphyxia, most notably intrauterine exposure to infection (Wu and others 2003). So that medical workers could recognize the onset of asphyxia and “rescue” the fetus, continuous electronic fetal monitoring (EFM) of the fetal heart rate during labor was introduced in the 1970s. This intervention was disseminated before being tested in randomized trials to compare continuous electronic monitoring with intermittent observation by stethoscope (auscultation). Since the introduction of EFM, fetal death in labor has decreased, the cesarean section rate has quadrupled (Natale and Dodman 2003), and the rate of cerebral palsy has remained steady. Accordingly, EFM cannot be recommended for use in LMICs. Intermittent auscultation with a stethoscope appears to be the appropriate way to monitor fetal status during labor.

RESEARCH AGENDA FOR PREVENTION OF DISABILITIES IN LOW- AND MIDDLE-INCOME COUNTRIES Research needed as a basis for developing policies and interventions to prevent LDD in low- and middle-income countries includes basic research, epidemiology, and evaluations of early interventions, clinical treatments, prevention strategies, and health services that are culturally appropriate and feasible. Suggested research priorities include the following: • etiology and prevention of adverse pregnancy outcomes associated with LDD, such as low birthweight, preterm birth, intrauterine growth retardation, and related factors • community-based rehabilitation, including effectiveness, cost-effectiveness, and social effects of different models for providing rehabilitation services and special education to children with LDD in LMICs

• methodological and prevalence studies to ensure that the impacts of LDD are effectively measured by DALYs or other international indicators • cost-effectiveness of interventions to prevent specific nutritional, infectious, genetic, and other causes of LDD • impact on child development of multiple insults and risk factors especially common in LMICs, such as neurotoxic exposures, trauma, infectious disease or malnutrition, poverty, maternal illiteracy, and other social factors • health services research related to access to prenatal care and prenatal and newborn screening and evaluation of components of the public health system that might impair or enhance integration of services for patients with LDD • prevalence of ADHD and a cost-benefit analysis of the use of psychotropic medications • prevalence and costs of autism spectrum disorders • strategies to improve interventions for the prevention of fetal alcohol syndrome and to develop effective intervention programs for children affected by prenatal alcohol exposure • evaluation of criteria for newborn screening and effects of new technology on measured incidence, costs, and system effectiveness • evaluation of financing of successful newborn screening and treatment programs • model systems of care for individuals diagnosed through newborn screening from infancy to adulthood.

SUMMARY Many potential interventions exist for the prevention of LDDs, and relatively few are being implemented for the benefit of children in LMICs. The following three interventions are effective and cost-effective in preventing LDD: • Folic acid fortification of the food supply can reduce the occurrence of NTDs by 50 percent or more. This intervention was found to be highly cost-effective in the United States; however, in low-income countries, high capital and running costs may compromise cost-effectiveness, at least in the short run. • Prenatal screening and selective pregnancy termination to prevent DS are highly cost-effective under some conditions but raise ethical, social, and cultural concerns that may preclude their applicability in some LMICs. Screening is not only expensive; it also has negative health outcomes: the false-positive rates and the subsequent anxiety, a risk of miscarriage of an unaffected pregnancy, and the resulting potential complications from pregnancy termination. Another concern is that, where access to prenatal care is limited, the potential for public health benefits of prenatal screening will be small.


• Neonatal screening and treatment for CH is highly costeffective in developed countries, where it provides a lowcost strategy for preventing MR. For minimal extra cost, collected blood samples from newborns can also be used to identify and prevent the disabling effects of other inborn errors of metabolism, such as phenylketonuria and maple syrup urine disease. However, when only a part of the newborn population is reached by screening, high costs will be incurred to care for those missed by the screening, thereby reducing the cost-benefit ratio.

Barden, H. S., and R. Kessel. 1984. “The Costs and Benefits of Screening for Congenital Hypothyroidism in Wisconsin.” Social Biology 31 (3–4): 185–200. Beaulieu, M. D. 1994. “Screening for Congenital Hypothyroidism.” In Canadian Guide to Clinical Preventive Health Care, ed. Canadian Task Force on the Periodic Health Examination. Ottawa: Health Canada. Begum, F., K. Buckshe, and J. N. Pande. 2003.“Risk Factors Associated with Preterm Labour.” Bangladesh Medical Research Council Bulletin 29 (2): 59–66. Benedict, R. E., and A. M. Farel. 2003. “Identifying Children in Need of Ancillary and Enabling Services: A Population Approach.” Social Science and Medicine 57 (11): 2035–47.

For another type of intervention considered, communitybased rehabilitation, costs and benefits have not been quantified sufficiently to allow evaluation. Such rehabilitation is designed to expand access to services in poor and rural areas, to change negative attitudes toward disability, to lower the costs of delivering services, and to enhance the participation of persons with disabilities in society. The benefits of community-based rehabilitation may come at a high cost in terms of time and financial resources of family members. Another intervention, electronic fetal monitoring in labor, has been shown to be unsuccessful in preventing childhood neurological disability associated with premature birth: the risk of cerebral palsy was significantly higher in infants delivered using EFM. Consequently, this intervention is not recommended for use during labor. DALY estimates are not available to convey the full range of LDDs or their risk factors. However, available data are consistent with the possibility that these disabilities account for a large proportion of the global burden of disease. Quantifying the impacts of LDDs and their preventive interventions is complicated by the fact that these disorders can exist at multiple levels and that disability is context-specific, with impacts that may vary across cultures. Several research priorities for improving knowledge and developing policies and interventions to prevent LDD in LMICs are suggested.

Bobat, R., D. Moodley, A. Coutsoudis, H. Coovadia, and E. Gouws. 1998. “The Early Natural History of Vertically Transmitted HIV-1 Infection in African Children from Durban, South Africa.” Annals of Tropical Paediatrics 18 (3): 187–96.

ACKNOWLEDGMENTS

Dhondt, J. L., J. P. Farriaux, J. C. Sailly, and T. Lebrun. 1991. “Economic Evaluation of Cost-Benefit Ratio of Neonatal Screening Procedure for Phenylketonuria and Hypothyroidism.” Journal of Inherited Metabolic Disease 14 (4): 633–39.

The authors thank Emmy Cauthen at the Fogarty International Center for her support.

REFERENCES Alliance to End Childhood Lead Poisoning. 2002. “The Global Lead Initiative: A Proposed Outcome for the World Summit on Sustainable Development.”Alliance to End Childhood Lead Poisoning,Washington, DC. http://www.globalleadnet.org/pdf/GlobalLeadInitiative.pdf. Bagriansky, J. No date. “What Are the Costs for the Premixes?” http://www.sph.emory.edu/wheatflour/Comm/Resource/CDs/Bali/ Bali_files/v3_slide0089.htm.

Brouwers, P., C. Decarli, M. P. Heyes, H. A. Moss, P. L. Wolters, G. TudorWilliams, and others. 1996. “Neurobehavioral Manifestations of Symptomatic HIV-1 Disease in Children: Can Nutritional Factors Play a Role?” Journal of Nutrition 126 (Suppl. 10): S2651–62. Chan, E., C. Zhan, and C. J. Homer. 2002. “Health Care Use and Costs for Children with Attention-Deficit/Hyperactivity Disorder: National Estimates from the Medical Expenditure Panel Survey.” Archives of Pediatrics and Adolescent Medicine 156 (5): 504–11. Crishna, B. 1999. “What Is Community-Based Rehabilitation? A View from Experience.” Child: Care, Health, and Development 25 (1): 27–35. Crowther, C. A., and D. J. Henderson-Smart. 2004. “Vitamin K Prior to Preterm Birth for Preventing Neonatal Periventricular Haemorrhage.” Cochrane Database of Systematic Reviews (4). Crowther, C. A., J. E. Hiller, L. W. Doyle, and R. R. Haslam. 2003. “Effect of Magnesium Sulfate Given for Neuroprotection before Preterm Birth: A Randomized Controlled Trial.” Journal of the American Medical Association 290 (20): 2669–76. Cunningham, G. C., and D. G. Tompkinison. 1999. “Cost and Effectiveness of the California Triple Marker Prenatal Screening Program.” Genetics in Medicine 1 (5): 199–206. Cusick, W., P. Buchanan, T. W. Hallahan, D. A. Krantz, J. W. Larsen Jr., and J. N. Macri. 2003. “Combined First-Trimester versus Second-Trimester Serum Screening for Down Syndrome: A Cost Analysis.” American Journal of Obstetrics and Gynecology 188 (3): 745–51. Cutts, F. T., S. E. Robertson, J. L. Diaz-Ortega, and R. Samuel. 1997. “Control of Rubella and Congenital Rubella Syndrome (CRS) in Developing Countries, Part 1: Burden of Disease from CRS.” Bulletin of the World Health Organization 75 (1): 55–68.

Drummond, P. M., and A. F. Colver. 2002. “Analysis by Gestational Age of Cerebral Palsy in Singleton Births in North-East England 1970–94.” Paediatric and Perinatal Epidemiology 16 (2): 172–80. Durkin, M. 2002. “The Epidemiology of Developmental Disabilities in Low-Income Countries.” Mental Retardation and Developmental Disabilities Research Reviews 8 (3): 206–11. Fewtrell, L. J., A. Pruss-Ustun, P. Landrigan, and J. L. Ayuso-Mateos. 2004. “Estimating the Global Burden of Disease of Mild Mental Retardation and Cardiovascular Diseases from Environmental Lead Exposure.” Environmental Research 94 (2): 120–33. Floyd, R. L., and J. S. Sidhu. 2004. “Monitoring Prenatal Alcohol Exposure.” American Journal of Medical Genetics 127C (1): 3–9. Learning and Developmental Disabilities | 949


Ford, C., A. J. Moore, P. A. Jordan, W. A. Bartlett, M. P. Wyldes, A. F. Jones, and W. E. MacKenzie. 1998. “The Value of Screening for Down’s Syndrome in a Socioeconomically Deprived Area with a High Ethnic Population.” British Journal of Obstetrics and Gynaecology 105 (8): 855–59. Giacaman, R. 2001.“A Community of Citizens: Disability Rehabilitation in the Palestinian Transition to Statehood.” Disability and Rehabilitation 23 (14): 639–44. Gilbert, R. E., C. Augood, R. Gupta, A. E. Ades, S. Logan, M. Sculpher, and J. H. van der Meulen. 2001. “Screening for Down’s Syndrome: Effects, Safety, and Cost Effectiveness of First and Second Trimester Strategies.” British Medical Journal 323 (7310): 423–25. Gilbert, W. M., T. S. Nesbitt, and B. Danielsen. 2003. “The Cost of Prematurity: Quantification by Gestational Age and Birth Weight.” Obstetrics and Gynecology 102 (3): 488–92. Goldenberg, R. L., and J. F. Culhane. 2003. “Infection as a Cause of Preterm Birth.” Clinics in Perinatology 30 (4): 677–700. Gupta, R., R. D. Thomas, V. Sreenivas, S. Walter, and J. M. Puliyel. 2001. “Ultrasonographic Femur-Tibial Length Ratio: A Marker of Down Syndrome from the Late Second Trimester.” American Journal of Perinatology 18 (4): 217–24. Insinga, R. P., R. H. Laessig, and G. L. Hoffman. 2002. “Newborn Screening with Tandem Mass Spectrometry: Examining Its Cost-Effectiveness in the Wisconsin Newborn Screening Panel.” Journal of Pediatrics 141 (4): 524–31. Institute of Medicine. 2003. Reducing Birth Defects: Meeting the Challenge in the Developing World. Washington, DC: National Academies Press. Institute of Medicine Committee on Nervous System Disorders in Developing Countries. 2001. Neurological, Psychiatric, and Developmental Disorders: Meeting the Challenges in the Developing World. Washington, DC: National Academies Press. Kassah, A. K. 1998. “Community-Based Rehabilitation and Stigma Management by Physically Disabled People in Ghana.” Disability and Rehabilitation 20 (2): 66–73. Khan, N. Z., and A. H. Khan. 1999. “Lead Poisoning and Psychomotor Delay in Bangladeshi Children.” Lancet 353 (9154): 754. Kline, J. K., Z. Stein, and M. Susser. 1989. Conception to Birth: Epidemiology of Prenatal Development. New York: Oxford University Press. Lagerkvist, B. 1992. “Community-Based Rehabilitation—Outcome for the Disabled in the Philippines and Zimbabwe.” Disability and Rehabilitation 14 (1): 44–50.

Lupton, C., L. Burd, and R. Harwood. 2004. “Cost of Fetal Alcohol Spectrum Disorders.” American Journal of Medical Genetics 127C (1): 42–50. MacDorman, M. F., A. M. Minino, D. M. Strobino, and B. Guyer. 2002. “Annual Summary of Vital Statistics—2001.” Pediatrics 110 (6): 1037–52. Mathers, C. D., A. D. Lopez, and C. J. L. Murray. “The Burden of Disease and Mortality by Condition: Data, Methods, and Results for 2001.” In Global Burden of Disease and Risk Factors, eds. A. D. Lopez, C. D. Mathers, M. Ezzati, D. T. Jamison, and C. J. L. Murray. New York: Oxford University Press. May, P. A., L. Brooke, J. P. Gossage, J. Croxford, C. Adnams, K. L. Jones, and others. 2000. “Epidemiology of Fetal Alcohol Syndrome in a South African Community in the Western Cape Province.” American Journal of Public Health 90 (12): 1905–12. McConachie, H., S. Huq, S. Munir, S. Ferdous, S. Zaman, and N. Z. Khan. 2000. “A Randomized Controlled Trial of Alternative Modes of Service Provision to Young Children with Cerebral Palsy in Bangladesh.” Journal of Pediatrics 137 (6): 769–76. McGrother, C. W., and B. Marshall. 1990. “Recent Trends in Incidence, Morbidity and Survival in Down’s Syndrome.” Journal of Mental Deficiency Research 34 (Part 1): 49–57. Natale, R., and N. Dodman. 2003. “Birth Can Be a Hazardous Journey: Electronic Fetal Monitoring Does Not Help.” Journal of Obstetrics and Gynaecology Canada 25 (12): 1007–9. Nelson, K. B., and J. H. Ellenberg. 1986. “Antecedents of Cerebral Palsy: Multivariate Analysis of Risk.” New England Journal of Medicine 315 (2): 81–86. Nyberg, D. A., D. A. Luthy, R. G. Resta, B. C. Nyberg, and M. A. Williams. 1998. “Age-Adjusted Ultrasound Risk Assessment for Fetal Down’s Syndrome during the Second Trimester: Description of the Method and Analysis of 142 Cases.” Ultrasound Obstetrics and Gynecology 12 (1): 8–14. O’Toole, B. 1988. “A Community-Based Rehabilitation Programme for Pre-school Disabled Children in Guyana.” International Journal of Rehabilitation Research 11 (4): 323–34. Panepinto, J. A., D. Magid, M. J. Rewers, and P. A. Lane. 2000. “Universal versus Targeted Screening of Infants for Sickle Cell Disease: A CostEffectiveness Analysis.” Journal of Pediatrics 136 (2): 201–8. Pattinson, R. C. 2004. “Are Deaths Due to Prematurity Avoidable in Developing Countries?” Tropical Doctor 34 (1): 7–10.

Lakhani, M., M. Khurshid, S. H. Naqvi, and M. Akber. 1989. “Neonatal Screening for Congenital Hypothyroidism in Pakistan.” Journal of the Pakistan Medical Association 39 (11): 282–84.

Peden, M., R. Scurfiled, D. Sleet, D. Mohan, A. Hyder, E. Jarawan, and C. Mather, eds. 2004. World Report on Road Traffic Injury Prevention. Geneva: World Health Organization.

Layde, P. M., S. D. Von Allmen, and G. P. Oakley Jr. 1979. “Congenital Hypothyroidism Control Programs: A Cost-Benefit Analysis.” Journal of the American Medical Association 241 (21): 2290–92.

Robertson, S. E., F. T. Cutts, R. Samuel, and J. L. Diaz-Ortega. 1997. “Control of Rubella and Congenital Rubella Syndrome (CRS) in Developing Countries, Part 2: Vaccination against Rubella.” Bulletin of the World Health Organization 75 (1): 69–80.

Lippman, A., D. J. Tomkins, J. Shime, and J. L. Hamerton. 1992. “Canadian Multicentre Randomized Clinical Trial of Chorion Villus Sampling and Amniocentesis: Final Report.” Prenatal Diagnosis 12 (5): 385–408. Lord, J., M. J. Thomason, P. Littlejohns, R. A. Chalmers, M. D. Bain, G. M. Addison, and others. 1999. “Secondary Analysis of Economic Data: A Review of Cost-Benefit Studies of Neonatal Screening for Phenylketonuria.” Journal of Epidemiology and Community Health 53 (3): 179–86. Lorenz, J. M., N. Paneth, J. R. Jetton, L. den Ouden, and J. E. Tyson. 2001. “Comparison of Management Strategies for Extreme Prematurity in New Jersey and the Netherlands: Outcomes and Resource Expenditure.” Pediatrics 108 (6): 1269–74. Lundgren-Lindquist, B., and L. A. Nordholm. 1996. “The Impact of Community-Based Rehabilitation as Perceived by Disabled People in a Village in Botswana.” Disability and Rehabilitation 18 (7): 329–34.

Romano, P. S., N. J. Waitzman, R. M. Scheffler, and R. D. Pi. 1995. “Folic Acid Fortification of Grain: An Economic Analysis.” American Journal of Public Health 85 (5): 667–76. Ross, H. L., and S. Elias. 1997. “Maternal Serum Screening for Fetal Genetic Disorders.” Obstetrics and Gynecology Clinics of North America 24 (1): 33–47. Rottier, M. J. N., R. W. Broer, A. Vermeer, and H. J. M. Finkenflügel. 1993. “A Study of Follow Up of Clients in Community-Based Rehabilitation Projects in Zimbabwe.” Journal of Rehabilitation Sciences 6 (2): 35–41. Sack, J., I. Feldman, and I. Kaiserman. 1998. “Congenital Hypothyroidism Screening in the West Bank: A Test Case for Screening in Developing Regions.” Hormone Research 50 (3): 151–54. Sampson, P. D., A. P. Streissguth, F. L. Bookstein, R. E. Little, S. K. Clarren, P. Dehaene, and others. 1997. “Incidence of Fetal Alcohol Syndrome


and Prevalence of Alcohol-Related Neurodevelopmental Disorder.” Teratology 56 (5): 317–26.

Environmental Factors and Injury among Children and Adolescents in Europe.” Lancet 363 (9426): 2032–39.

Shy, K. K., D. A. Luthy, F. C. Bennett, M. Whitfield, E. B. Larson, G. van Belle, and others. 1990. “Effects of Electronic Fetal-Heart-Rate Monitoring, as Compared with Periodic Auscultation, on the Neurologic Development of Premature Infants.” New England Journal of Medicine 322 (9): 588–93.

Viljoen, D. 1999. “Fetal Alcohol Syndrome.” South African Medical Journal 89 (9): 958–60.

Sokol, R. J., V. Delaney-Black, and B. Nordstrom. 2003. “Fetal Alcohol Spectrum Disorder.” Journal of the American Medical Association 290 (22): 2996–99. Stein, R. E., and D. J. Jessop. 2003. “The Impact on Family Scale Revisited: Further Psychometric Data.” Journal of Developmental and Behavioral Pediatrics 24 (1): 9–16. Stray-Pedersen, B., J. Biornstad, M. Dahl, T. Bergan, G. Aanestad, L. Kristiansen, and K. Hansen. 1991. “Induced Abortion: Microbiological Screening and Medical Complications.” Infection 19 (5): 305–8. Taylor, H. G., N. M. Minich, N. Klein, and M. Hack. 2004. “Longitudinal Outcomes of Very Low Birth Weight: Neuropsychological Findings.” Journal of the International Neuropsychological Society 10 (2): 149–63. Thomas, M., and M. J. Thomas. 1998. “Controversies on Some Conceptual issues in Community-Based Rehabilitation.” Asia Pacific Disability Rehabilitation Journal 9 (1): 12–14. Thompson, D. C., F. P. Rivara, and R. Thompson. 1999. “Helmets for Preventing Head and Facial Injuries in Bicyclists.” Cochrane Database of Systematic Reviews (4) CD001855. Tillotson, S. L., P. W. Fuggle, I. Smith, A. E. Ades, and D. B. Grant. 1994. “Relation between Biochemical Severity and Intelligence in Early Treated Congenital Hypothyroidism: A Threshold Effect.” British Medical Journal 309 (6952): 440–45. Torfs, C. P., B. van den Berg, F. W. Oechsli, and S. Cummins. 1990. “Prenatal and Perinatal Factors in the Etiology of Cerebral Palsy.” Journal of Pediatrics 116 (4): 615–19.

Vintzileos, A. M., C. V. Ananth, J. C. Smulian, D. L. Day-Salvatore, T. Beazoglou, and R. A. Knuppel. 2000. “Cost-Benefit Analysis of Prenatal Diagnosis for Down Syndrome Using the British or the American Approach.” Obstetrics and Gynecology 95 (4): 577–83. Waitzman, N. J., P. S. Romano, and R. M. Scheffler. 1994. “Estimates of the Economic Costs of Birth Defects.” Inquiry 31 (2): 188–205. Wald, N. J., C. Rodeck, A. K. Hackshaw, J. Walters, L. Chitty, and A. M. Mackinson. 2003. “First and Second Trimester Screening for Down’s Syndrome: The Results of the Serum, Urine and Ultrasound Screening Study (SURUSS).” Health Technology Assessment 7 (11): 1–77. Wasant, P., S. Liammongkolkul, and C. Srisawat. 1999. “Neonatal Screening for Congenital Hypothyroidism and Phenylketonuria at Siriraj Hospital, Mahidol University, Bangkok, Thailand—A Pilot Study.” Southeast Asian Journal of Tropical Medicine and Public Health 30 (Suppl. 2): 33–37. WHO (World Health Organization). 2001. International Classification of Functioning, Disability and Health. Geneva: WHO. http://www3. who.int/icf/icftemplate.cfm?myurl=homepage.html&mytitle=Home %20Page. WHO Community-Based Rehabilitation. 1982. “Report of a WHO Interregional Consultation.” Colombo, Sri Lanka. Winter, S., A. Autry, C. Boyle, and M. Yeargin-Allsopp. 2002. “Trends in the Prevalence of Cerebral Palsy in a Population-Based Study.” Pediatrics 110 (6): 1220–25. Wu, Y. W., G. J. Escobar, J. K. Grether, L. A. Croen, J. D. Greene, and T. B. Newman. 2003. “Chorioamnionitis and Cerebral Palsy in Term and Near-Term Infants.” Journal of the American Medical Association 290 (20): 2677–84.

Valent, F., D. Little, R. Bertollini, L. E. Nemer, F. Barbone, and G. Tamburlini. 2004. “Burden of Disease Attributable to Selected



Chapter 56

Community Health and Nutrition Programs John B. Mason, David Sanders, Philip Musgrove, Soekirman, and Rae Galloway

Rapid improvements in health and nutrition in developing countries may be ascribed to specific, deliberate, health- and nutrition-related interventions and to changes in the underlying social, economic, and health environments. This chapter is concerned with the contribution of specific interventions, while recognizing that improved living standards in the long run provide the essential basis for improved health. Consideration of the environment as the context for interventions is crucial in determining their initiation and in modifying their effect, and it must be taken into account when assessing this effect. Undoubtedly much change has stemmed from scientific advances, immunization being a prominent case. However, the organizational aspects of health and nutrition protection are equally critical. In the past several decades, people’s contact with trained workers has been instrumental in improving health in developing countries. This factor applies particularly to poor people in poor countries but is relevant everywhere; indeed, it is a reason that social services have essentially eliminated almost all occurrences of child malnutrition in Europe (where, when malnourished children are seen, it is caused by neglect). Community-based programs under many circumstances provide this crucial contact. Their role is partly in improving access to technology and resources, but it is also important in fostering behavior change and, more generally, in supporting caring practices (Engle, Bentley, and Pelto 2000; UNICEF 1990). Such programs may also play a part in mobilizing social demand for services and in generating pressure for policy change. In community-based programs, workers—often volunteers and part-time workers—interact with households to protect

their health and nutrition and to facilitate access to treatment of sickness. Mothers and children are the primary focus, but others in the household should participate. Commonly, people go regularly to a central point in their community—for example, for growth monitoring and promotion—or are visited at home by a health and nutrition worker. The existence, training, support, and supervision of the community worker—based in the community or operating from a nearby health facility—are indispensable features of these programs. Thus community organizations are a key aspect of community-based health and nutrition programs (CHNPs). This chapter focuses on large-scale (national or state) programs. Although these programs are primarily initiated and run at the local level, links with the national level and levels in between are necessary. Both horizontal and vertical organizations are needed. Local organizations make action happen, but they need input and resources, such as training, supervision, and supplies, from more central levels. The experience on which this chapter is based comes from a considerable number of national and large-scale programs. Most of these programs include both nutrition and health activities, aimed particularly at the health and survival of reproductive-age women and children. We draw on these experiences as we try to put forward principles on which future programs can be based—programs that may have broader health objectives for other population groups and diseases. As of 2001, some 19 percent of global deaths were among children—and 99 percent of all child deaths took place in low- and middle-income countries. The disability-adjusted life years (DALYs) lost attributed to zero- to four-year-olds—plus maternal and perinatal conditions, nutrition deficiencies, and endocrine disorders—amount to 42 percent of the total disease 1053


Table 56.1 Estimated Contributions to the Disease Burden in Developing Countries DALYs lost (percentage) Factor General malnutrition Micronutrient deficiencies Total

Direct effect

As risk factor

Total

1.0

14.0

15.0

9.0

8.5

17.5

10.0

22.5

32.5

Source: Mason, Musgrove, and Habicht 2003, table 10.

burden (all ages, both sexes) from all causes for developing regions. CHNPs address about 40 percent of the disease burden. In terms of prevention, Mason, Musgrove, and Habicht (2003) estimated that eliminating malnutrition would remove one-third of the global disease burden. Comparative studies by Ezzati, Lopez, and others (2002) and Ezzati, Vander Hoorn, and others (2003) have reemphasized malnutrition as the predominant risk factor and improvement of nutrition as playing a potentially major role in reducing the burden. Clinical deficiencies contribute directly to malnutrition, but even more, malnutrition is a risk factor for infectious diseases (table 56.1). Furthermore, changes in child malnutrition levels in developing countries are closely related to the countries’ mortality trends (Pelletier and Frongillo 2003). Dealing with women and children’s health and nutrition addresses a substantial part of global health problems. Moreover, the experience of community-based programs linked to nutrition constitutes a significant part of the body of knowledge on ways of improving it. A number of large-scale, sustained health interventions, such as those described by Sanders and Chopra (2004), use a mix of improved access to facilities and community health workers. These interventions include the Comprehensive Rural Health Project, Jamkhed, India; community health projects in Brazil (Ceará, Pelotas); and the work of the Bangladesh Rural Advancement Committee (BRAC). Table 56.2 describes the program experiences drawn on. The evidence is clear that significant differences occur between countries in the rates of change in health and nutritional status. Figure 56.1 shows a comparison of Indonesia, the Philippines, and Thailand. As is common, the indicator used is underweight children, which is likely to reflect broader conditions of health and survival. For Thailand, the figure shows the now-well-known rapid improvement in the 1980s and 1990s. For Indonesia, it shows slower but consistent improvement. The Philippines had little progress until recently, and the start of an improving trend coincided with increases in the number of village health workers and implementation of high-coverage interventions such as iodized salt and vitamin A supplementation (FNRI 2004). A crucial issue is how much of the improvements was caused by interventions that could be replicated— and within that issue is subsumed how much was because of

context, how much was programmatic, and what were the interactions. The contrasts between these three countries are instructive in part because they have several similar contextual factors; for instance, the status of women is relatively good, and social exclusion1 is not extensive (compare both of these in, for example, South Asia). Thus programs may account for a significant part of the differences seen in improvement. The benefits from CHNPs extend well beyond child nutrition (which is used as a summary measure). These benefits have not been quantified but would include improved educability (see chapter 49) and probably increased earning capacity associated with it and with physical fitness.

WHAT IS KNOWN ABOUT EFFICACY AND EFFECTIVENESS The efficacy of health and nutrition interventions in developing countries has been established for decades (for example, Gwatkin, Wilcox, and Wray 1980). Prospective studies in several settings showed that health interventions with or without supplementary foods caused children to thrive and survive better: studies in Narangwal, India (Kielmann and others 1978; Taylor, Kielmann, and Parker 1978); by the Institute for Nutrition for Central America and Panama (Delgado and others 1982); in Jamaica (Waterlow 1992); and in The Gambia (Whitehead, Rowland, and Cole 1976) are examples.2 These studies showed the effect of interventions on growth and (usually) mortality but did not generally factor out the relative contributions of health and nutrition. In fact, results from Narangwal showed similar mortality effects from food or health care; results from The Gambia indicated interaction such that sick children did not grow even with adequate food intake (appetite also playing an important role), and well children did not grow with inadequate food intake (Gillespie and Mason 1991, annex 2). By the early 1980s, the conclusion, based on data at the experimental level (not from routine large-scale programs), was that better health and better nutrition are both required for child survival and development. This conclusion remains generally agreed on today; furthermore, concern exists that health interventions may become less effective unless nutrition is concurrently addressed (Measham and Chatterjee 1999; Pelletier and Frongillo 2003). In their chapter on malnutrition in the first edition of this book, Pinstrup-Andersen and colleagues (1993) drew largely on efficacy findings, with an emphasis on food supplementation. Those studies are not revisited here, but we can continue to build on their conclusions. The efficacy studies were followed by a number of national or other large-scale programs in several countries. Some of those were a direct follow-on; for example, the World Bank Tamil Nadu Integrated Nutrition Program (TINP) followed the

1054 | Disease Control Priorities in Developing Countries | John B. Mason, David Sanders, Philip Musgrove, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 196

Table 56.2 Country Experiences in Community-Based Programs Country and program

Program experience

Africa Tanzania: Iringa

Area program with UNICEF and WHO inputs, 1984–91. After rapid initial drop in child malnutrition, moderate steady improvement. Program not sustained.

Tanzania: Child Survival and Development Program

1985–95, World Bank support. Results similar to Iringa.

Zimbabwe: Supplementary Feeding Programme

Wide-scale program following independence, 1980–90; infant mortality rate (IMR) dropped from 110 to 53 (1988). Not sustained.

Asia Bangladesh: Bangladesh Integrated Nutrition Program and national

BINP: area targeted covering 7 percent of population. Rapid improvement at start (1997); final evaluation not seen.

Bangladesh: Bangladesh Rural Advancement Committee

Community-based health services with village health workers. Wide coverage since 1980s; particular focus on diarrhea.

India: Integrated Child Development Services

Implemented since 1976. Village program with community health (anganwadi) worker. Accelerated improvement reported in some states.

India: Tamil Nadu Integrated Nutrition Program

Implemented 1980 to mid 1990s. Village program in Tamil Nadu with World Bank support; growth monitoring, supplementary feeding, and so on. Substantial improvement in underweight reported.

Indonesia

Massive expansion of village programs 1975–90, covering all villages by 1990. Steady decrease in underweight during this time. Program not sustained in 1990s; now planned to restart.

Philippines: national

No wide CHNPs despite national decree in 1974. No significant improvement in child nutrition.

Thailand

National program from late 1970s; 600,000 village health volunteers trained (1 percent of population). Rapid improvement 1980–90; for example, 36 percent to 13 percent underweight children.

National: program coverage expanding from 2000 on. Substantial improvement in anemia and child underweight seen in Bangladesh starting 1995.

Americas Costa Rica

Expanding rural health services from 1970s following malaria control. Rapid fall in IMR, 1965–80; in stunting, 1979–89.

Jamaica

Expanded health services with community health aides from mid 1970s. Rapid fall in underweight, 1985–89.

Nicaragua

Community health movement, 1979–90, reduced IMR, eliminated polio; about 1 percent of population as village health volunteers.

Source: Authors, from data derived as follows: Tanzania—Gillespie and Mason 1991; Gillespie, Mason, and Martorell 1996; Jennings and others 1991, 117; Kavishe and Mushi 1993; Pelletier 1991; Sanders 1999; Zimbabwe—Sanders 1999; Tagwireyi and Greiner 1994; Werner and Sanders 1997; Bangladesh—BINP and UNICEF 1999; BRAC 2004; Chowdhury 2003; INFS and Department of Economics, University of Dhaka 1998; Mason and others 1999, 2001; Save the Children U.K. 2003; India—Administrative Staff College of India 1997; Mason and others 1999, 2001; Measham and Chatterjee 1999; Reddy and others 1992; Shekar 1989; Indonesia—Berg 1987; Jennings and others 1991, 108; Rohde 1993; Soekirman and others 1992; the Philippines—Guillermo-Tuazon and Briones 1997; Heaver and Hunt 1995; Heaver and Mason 2000; Mason 2003; Thailand—Kachondam, Winichagoon, and Tontisirin 1992; Tontisirin and Winichagoon 1999; Winichagoon and others 1992; Costa Rica—Horwitz 1987; Jennings and others 1991, 77–81; Muñoz and Scrimshaw 1995; Honduras—Fiedler 2003; Jamaica—ACC/SCN 1989, 1996; P. Samuda personal communication, 2004; Robinson personal communication, 2004; Nicaragua—Sanders 1985; Werner and Sanders 1997.

Narangwal study, which was supported by the U.S. Agency for International Development (USAID). A number of overviews and analyses of these programs have been conducted—for example, Allen and Gillespie (2001); Berg (1981, 1987); Gillespie, Mason, and Martorell (1996; includes a summary of overviews, 60); Gillespie, McLachlan, and Shrimpton (2003); Jennings and others (1991); Mason (2000); Sanders (1999); and Shrimpton (1989). These plus some newer examples provide case studies for this chapter, and the sources for the case studies are included in table 56.2. Underweight prevalences are improving at about 0.5 percentage points (ppts) per year except in Sub-Saharan Africa, which is largely static (ACC/SCN 1989, 1992, 1996, 1998, 2004). Programs are needed to accelerate this trend. Cost data

from an earlier study (Gillespie and Mason 1991, 76), combined with the estimated improvements from large-scale programs, led to the assertion that “there seems to be some convergence on around $5 to $10 per head (beneficiary) per year being a workable, common level of expenditure in nutrition programmes, though not generally including supplementary food costs . . . effective programmes, with these levels of expenditure, seem to be associated with reducing underweight prevalences by around 1–2 percentage points per year” (Gillespie, Mason, and Martorell 1996, 69–70). A further important consideration is that the effect is likely to be nonlinearly related to the expenditure, showing the familiar dose-response S-shaped curve. Thus, the first expenditures produce little effect on the outcome, and one needs a minimum Community Health and Nutrition Programs | 1055


Prevalences of underweight children (percent) 50

Indonesia 40

Philippines 30

Thailand

20

10 1970

1980

1990

2000

2010

Sources: ACC/SCN 2004; FNRI 2004; Mason, Rivers, and Helwig 2005. Note: 2 standard deviations NCHS/WHO standards; ages 0–60 months.

Figure 56.1 Comparison of Trends in Underweight Children in Indonesia, the Philippines, and Thailand

input level of resource use before a worthwhile response is achieved (Habicht, Mason, and Tabatabai 1984). This factor generally applies to drawing inferences from cost-effectiveness ratios, which often assume linearity. If the relation is S-shaped, the implication is important: applying too few resources does not simply solve the problem more slowly but does not solve it at all and is a waste. Therefore, program intensity (resources per person) is a critical measure. Effective interventions must include a range of activities relating to health and nutrition. They should be multifaceted, not just for effectiveness but also for organizational efficiency. The structure needed for community-based programs could never make sense or be sustainably set up for single interventions alone. One often-argued case (for example, by Save the Children U.K. 2003) concerns children’s growth monitoring: evidently growth monitoring in isolation from activities that improve children’s growth is not going to achieve anything (or worse, considering the opportunity cost); however, weighing children and charting their weight can be a useful part of broader programs (for example, as growth monitoring and promotion).

COMMUNITY- AND FACILITY-BASED PROGRAMS Protecting and improving health, especially in poor communities, requires a combination of community- and facility-based activities, with support from central levels of organization, as well as some centrally run programs (for example, food fortification). The place of these activities in a strategy is likely to vary, depending on level of development (of infrastructure, health services, and socioeconomic status) and on many local factors. For the poorest societies, the first priorities are basic

preventive services, notably immunization, access to basic drugs, and management of the most serious threats to health, such as some access to emergency care. Moving up the development scale, starting community-based activities may soon become cost effective for prevention, referral, and management of some diseases (notably diarrhea) when coverage of health services is poor. Community-based programs continue to play a key role until health services, education, income, and communications have improved to the point that maternal and child mortality has fallen substantially and malnutrition is much reduced; at this intermediate development level, the needs are less felt, and health services again take on a more prominent role. In this scheme, the widely felt need for better access to emergency obstetric services is problematic, requiring a well-developed human and physical infrastructure, yet arguably being one of the highest priorities. Facility-based programs can be seen either as linking with the community program (referrals, home visits from clinics, and so forth) or as actually being part of the same enterprise. A distinction is that community-based activities take place outside the health facility, in the home or at a community central point, even if they may be supported by health personnel based in health facilities. The local workers in community-based programs may be drawn from the community itself, may be home visitors from a health center or clinic, or may sometimes be volunteers supervised by these home visitors. Many communitybased programs come under the health sector, whatever the exact arrangements with local health services. Regarding specific program components, we return to the relative role of community programs and facilities later. The integrated management of infant and childhood illness (IMCI) program provides guidance mainly on the curative health aspects and contains a number of nutrition activities (for example, administration of vitamin A capsules). Links to local health facilities are essential for the maintenance of the community activities and for referral in cases of illness (see chapter 63). As the IMCI training and implementation progresses, it should integrate directly with CHNPs (in fact, become part of the same exercise), which will add treatment of additional diseases. IMCI addresses diarrhea, acute respiratory infection (ARI), malaria, nutrition, immunization, safe motherhood, and essential drugs (WHO 1997). The 16 key practices for child survival defined in the context of IMCI (Kelley and Black 2001, S115) are exactly those to be promoted within CHNPs, and most are already included (four are nutritional). Decentralization should be considered in this context. Although decentralized systems might be thought to be more effective in supporting CHNPs, the evidence for this assumption is scarce. Decentralization can reduce resources available at the local level if it involves devolving responsibility without the concomitant budgetary resources (Mills 1994). For example, in Kenya, decentralization did not accompany devolving authority


for raising revenue locally. In other cases (for example, the Philippines), decentralization has involved a shifting of resources, but with priorities set in the local government units by locally elected officials (municipal and city mayors), these resources may be used for shorter-term priorities than under previous, centrally decided, policies.

SUCCESS FACTORS A number of useful concepts grew in the 1990s in relation to effective community-based programs. The concept of success factors helped sort out complex interactions: when numerous possibilities exist, understanding the successful pathway to effectiveness is more important than trying to disentangle what did not work. Focusing on successful programs helps simplify complexity and identify success factors, only some of which are

programmatic (directly under the influence of the intervention itself); others are contextual. The importance of context, within which programs are initiated and run, thus emerged as crucial, and priority factors were proposed from studies of community-based programs in Asia (Gillespie, Mason, and Martorell 1996, 67; Jonsson 1997). Sanders (1999) described similar concepts under the headings of community participation and political will. This distinction and interplay between context and program factors is helpful in identifying required supporting policies to improve the context to make programs work. Details are in the later section titled “Contextual Factors.” An overall framework (figure 56.2) for causal links to child survival and nutrition, put forward by the United Nations Children’s Fund (UNICEF 1990), gave a basis for a common language—even if the details might be questioned—revolving

Malnutrition and death

Inadequate dietary intake

Inadequate access to food

Outcomes

Immediate causes

Disease

Inadequate care for mothers and children

Insufficient health services and unhealthy environment

Underlying causes

Inadequate education

Formal and nonformal institutions

Basic causes

Political structure

Economic structure

Potential resources

Source: Redrawn from UNICEF 1990.

Figure 56.2 Conceptual Framework for the Causes of Malnutrition in Society Community Health and Nutrition Programs | 1057 ©2006 The International Bank for Reconstruction and Development / The World Bank 199

around food, health, and care as proximal causes to be addressed through programs. Improving these factors attacks hunger, disease, and neglect, which are the converse of food, health, and care. Basic causes are, like context, open to influence through policy decisions and acting through directly influencing food, health, and care and by modifying the effect of programs. Here malnutrition is seen as the outcome of processes in society, and direct interventions are seen as both shortcutting the needed basic improvements in living conditions and being dependent on these improvements in the long run for sustainability.

COMMUNITY-BASED PROGRAMS—WHAT ARE THEY? Community health and nutrition programs are often initiated and run by the health sector, but sometimes a separate ministry (for example, in India and Indonesia) or service (for example, in Bangladesh) is set up. Attempts to use a national coordinating body appear to be less effective in leading to widespread community programs; an example existed in the Philippines until approximately 2000 (Heaver and Mason 2000). This ineffectiveness stems from the tendency of the coordinating body not to have direct authority over fieldworkers or the budget to create a national program with sufficient coverage and intensity to have a measurable effect. In some other cases, the services linked to poverty alleviation and social welfare programs can play this role (for example, the Samurdhi program in Sri Lanka). Involvement of the health services remains crucial, sometimes as the operational agency responsible for the programs and certainly always for referral. CHNPs have so far been much more relevant to communicable diseases than to noncommunicable diseases in conditions of poverty and where undernutrition is common. (An exception occurs if CHNPs help prevent intrauterine growth retardation with later risks of noncommunicable diseases.) However, in areas where diet-related chronic diseases are developing in conditions of poverty (for example, much of Latin America and the Caribbean) and obesity is rising rapidly, the promotion of behavior change through counseling in CHNPs may become increasingly important. Promoting healthier diets requires access to outlets for fruit and vegetables, often displaced by fast foods, which should be a concern of community activities, as should lifestyle improvements such as use of exercise and recreational facilities. CHNPs often include activities well beyond direct prevention and behavior change. As envisaged with primary health care, water, sanitation, and other aspects of environmental health are frequently included, as well as agricultural interventions (for example, Zimbabwe in the 1980s). In Thailand, the village programs are part of the “Basic Minimum Needs” approach, which includes housing and environment, family

planning, community participation, and spiritual and ethical development. A diagram of the structure, derived from Thailand’s program (figure 56.3), shows the relations between services that provide supervision and contacts with the community (“facilitators”) and with community workers, referred to as “mobilizers.” The activities undertaken in CHNPs—the program content—are familiar and are described here only briefly. Program components, implemented by village workers or in facilities, come under the following headings, which form a menu, with the actual mix depending on local capabilities and conditions (UNICEF 1998, 84; see chapter 24): • Prenatal care includes checking weight gain in pregnancy, prepregnancy weight, anemia, and blood pressure; providing multiple micronutrient supplementation and immunization (tetanus); counseling on diet, workload, breastfeeding; and predicting and arranging for delivery. • Women’s health and nutrition entails counseling on health and nutrition and checkups, promoting improved status and resource allocation in home and outside, promoting improved access to health services, and often offering family-planning services (these services may even be an initiating factor for CHNPs, for example, in Indonesia). • Breastfeeding includes providing knowledge on practices (initial, exclusive, continued); arranging mutual support; building confidence; preventing misinformation and undermining factors; facilitating time for breastfeeding; and providing information along the lines of the infant formula code. • Complementary feeding includes providing knowledge and counseling (timing of introduction, type, energy density, frequency, and so on); sometimes promoting village or urban area production of weaning foods; sometimes marketing inexpensive food; facilitating mother’s time allocation; and promoting technology—storage, preservation, hygiene methods (fermentation, even refrigerators). • Growth monitoring and promotion requires equipment (scales, charts, manuals); training and supervision; needs training of weigher to interpret charts and counsel mother; and a referral system for problems (for treatment, counseling, or other preventive intervention if growth is faltering). Weighing at birth and monthly weighing should be included, if possible, and adequate weight gain (rather than achieved weight or any gain) should be used for guidance on counseling or other intervention. • Micronutrient supplementation should include vitamin A for nonpregnant and pregnant women (low dose weekly, preferably as part of multinutrients); for women within one month of delivery (massive dose to protect infant through breast milk); for infants and children (massive dose at nine months immunization contact and thereafter every six months and when medically indicated). It should also


Services Government, NGO—health, education, agriculture, and so forth

Interface

Facilitators

Community Plan, implement, monitor, …

1:10–20 mobilizers

Supervision, training, information, support

Mobilizers

1:10–20 families

Families Counseling, organization, supplies, and referral for prenatal care, child care practices, growth monitoring, micronutrients … Source: Adapted from Tontisirin (1996, personal communication). NGO = nongovernmental organization

Figure 56.3 General Structure for Community-Based Programs, Based on Thailand’s Program

include vitamin A—daily or weekly, with immunization campaigns, and so forth—and iron—daily or weekly for women (especially during pregnancy) as well as for children and adolescents. Iron is usually provided together with folic acid and may also be provided as part of multiple micronutrient supplementation. Iodine is usually provided by fortification and can be an infrequent (six-monthly) oral supplement, if necessary, but it should be part of multiple micronutrients for pregnancy. • Micronutrient fortification is not usually included locally, although it is an important central program, but local monitoring is a coming opportunity, especially of iodized salt testing kits. • Supplementary feeding, using external supplies may sometimes be appropriate in emergencies and in conditions of extreme poverty (for example, the Bangladesh Integrated Nutrition Program, or BINP), providing 200 to 500 kilocalories per person per day, but otherwise it is to be avoided as costly, with high opportunity cost, and not very effective; moreover, it can distort programs, which come to be seen largely as a source of free food. • Supplementary feeding, using local supplies can be useful for complementary feeding (weaning) if carefully organized (which requires some resources). Village community production and processing are useful, if feasible (for example, in Zimbabwe), and the system can move to coupon method (for example, in Thailand).

• Oral rehydration includes highly effective local preparations for dehydration in acute diarrhea, as well as (or better than) oral rehydration salts. These preparations require counseling of mothers and take a lot of parents’ time. Persistent diarrhea requires other intervention, especially nutritional. Care of children during sickness—especially continued breastfeeding and other foods—needs to be stressed (applies also to other illnesses). • Immunization includes informing, referring, and facilitating. • Deworming requires distribution and dosage supervision of mebendazole every few months, a highly effective nutrition intervention. Distribution methods are an issue. The relative suitability of community- and facility-based operations for the different components again depends on local conditions, and these operations should be complementary. Community activities are essential for infant and child feeding, other caring practices, environmental sanitation, and the like. Facilities have a key role in immunization, prenatal care, and—of course—referral for treatment. Growth monitoring, micronutrient interventions, oral rehydration, and similar activities may be focused in either. Because it has more regular contact with clients, a community-based program may be more effective in actually reaching mothers and children with the component interventions than one that is facility based. Box 56.1 compares two programs in Honduras that offered the same content but differed in where the programs were based. Community Health and Nutrition Programs | 1059


Box 56.1

Differential Effectiveness of Community- and Facility-Based Programs Effectiveness is more likely to be possible through community-based programs because contact with caregivers is typically more frequent and consistent. For example, 83 percent of children enrolled in a communitybased growth monitoring and promotion program in Honduras (Atención Integral a la Niñez Comunitaria, or AIN-C) were weighed two or more times in a given three-month period, whereas only 70 percent of children were weighed with the same frequency in a facility-based program. Workers visited 30 percent of mothers participating in the community program in their homes at least once for follow-up when their children were sick, were not growing, or had missed a weighing session. Controlling for a range of maternal and socioeconomic factors, researchers found that children 6 to 24 months of

age participating in the community-based program were 1.6 times more likely to be appropriately fed than were children not enrolled in growth monitoring and promotion. Children participating in the community program also were more likely to have received vitamin A and iron supplements than children participating in the facilitybased program. Results show that consistent participation in the community-based program was associated with better weight for age. When a range of maternal and socioeconomic factors were taken into account, children participating fully in the community program were 435 grams heavier than children who were enrolled but participated infrequently. In the facility-based program, there was little difference in weight for children based on levels of participation.

Source: Plowman and others 2002.

PROGRAMMATIC FACTORS Programmatic factors are considered first in terms of the characteristics of the activities—their population coverage and targeting, how much resources are applied per head (intensity), and the technologies used. Then the needs for initiating and sustaining these activities are discussed—the training needs, supervision methods, and (importantly) incentives and remuneration for field workers. Coverage, Targeting, Resource Intensity, and Technology Even effective programs improve the health and nutrition only of those they reach, so achieving as complete coverage as possible of those at risk is a major determinant of the effect. Although variations in the content of programs are seen in different circumstances, most activities are common to most programs. Variations in effect stem from factors such as coverage and adequacy of resources. How have CHNPs fared in reaching large sections of the population with adequate resources—and, indeed, what is the gap that would need to be filled? The achievements of the 14 programs drawn on here as case studies are summarized in table 56.3. The programs expanded to include most of the communities within the areas targeted. The common evolution was to target select areas and specific biological groups within those areas—generally women and children—but not to give priority to any great extent to poorer or less healthy communities. Screening is sometimes done of individuals for admittance into

the programs (a form of targeting), based on nutritional status, as in growth monitoring and promotion, as well as on a onetime basis (for example, thin children in Zimbabwe). Recent thinking suggests that because mortality risk, growth failure, and morbidity are concentrated in children less than two or three years of age, in contrast to an earlier focus on children under five, these younger children should increasingly be a focus of CHNPs. A common policy observed in practice, therefore, is to aim for complete coverage within the areas participating, adding new sites until the entire region is covered. Relatively untargeted expansion to universal coverage may have been at the expense of establishing adequate resources and quality in the areas initially covered. In at least one case (Thailand), having achieved broad coverage and reduced malnutrition, the program became more targeted to areas in which progress was lagging. The coverage figures in table 56.3, although approximate, demonstrate considerable success in initiating and implementing CHNPs on a large scale—usually enough to have a substantial effect if the other factors needed for success were met. How complete a coverage of the population should one recommend? This factor relates to targeting, to the additional resource requirements to reach the nonparticipants, and to their level of risk. Usually risk is spread throughout the population, although the extent varies considerably—at least a doubling of indicators of risk is usually seen between betterand worse-off areas or groups (for example, see Mason and others 2001, figures 1.4–1.7, 1.10–1.13). The remoter areas—or


Table 56.3 Characteristics of Selected Programs Country

Coverage, targeting

Resources, intensity

Population served 250,000 in 6 districts, 610 villages, 46,000 children, of which 33,700 participated (73 percent). Targeting: children 5 years and women; no socioeconomic selection of communities. Progressed from 168 to 610 villages 1984–88.

US$8 to US$17/child/year (approximately US$30/child/year from total costs: approximately US$6 million)

9 of 20 regions (population total approximately 12 million; 2 million children). Aimed for complete coverage.

US$2 to US$3/child/year

Population served: 56,000–96,000 with supplementary feeding; up to 60 percent of all children in community-based growth monitoring.

External: US$3 million over 10 years

Africa Tanzania: Iringa F: ()

Tanzania: Child Survival and Development Program F: 0 Zimbabwe: Supplementary Feeding Programme F:

2 village health workers/village 1,220 total; approximately 1:40 children [Volunteers]

[Volunteers]

For example, 1990, US$0.5 million, approximately US$0.50/child/year (Approximately 1:10–200, based on numbers per project) [Extension agents]

Asia Bangladesh: BINP F:

BINP: in 6 thanas, or subdistricts (7 percent of population), children 2 years, 8 million pregnant and lactating women.

US$14 million/year; approximately US$18/child/year 1 community worker per 1,000 population Approximately 1:200 children [Project supported]

Bangladesh: BRAC

Health coverage 25 percent. Nutrition with BINP, now expanding.

1 community health volunteer per 300 households; 1 community nutrition promoter per 200 households; community nutrition centers, 1:120 mothers and children; supervision of community nutrition promoters by community nutrition organizer, 1:10

India: ICDS

Children 0–6 years and pregnant and lactating women, in 3,900 of 5,300 blocks, or subdistricts; approximately 74 percent of population. Coverage expanded without targeting except by area.

Nonfood costs: approximately US$2/child/year.

F: /

India: TINP F:

Indonesia F: ()

1 community worker (anganwadi worker, or ANW) per 200 children; 1 supervisor per 20 ANWs [ANW paid, at low rate]

Children 6–36 months, pregnant and lactating women. Children with growth failure selected. 40 percent of blocks in Tamil Nadu; 20 percent of children in 1990.

US$9/child/year, plus approximately US$3 on food.

By 1990, 60,000 villages (of 65,000: 92 percent) had posyandus (village health/nutrition center). Women and young children.

US$2–11/child/year, depending on supplemental food; Rohde (1993) gives US$1 recurrent.

1 community nutrition worker per 300 children; 1 supervisor per 10 community nutrition workers [Project supported]

Village workers (approximately 3 million total), 1 per 60 people, approximately 1 per 10 children; supervision 1 per 200. [Volunteer]

Philippines: national F: 0

Several programs, all targeted (for example, to poorer areas), none with national coverage.

US$0.40/child/year in targeted areas. Village workers (barangay nutrition scholars) approximately 1:300 [Low allowance given]

Thailand: Primary Health Care Poverty Alleviation Program Basic Minimum Needs F: ()

Expanded over about 5 years to cover 95 percent of villages. 600,000 village health communicators (1 percent of population) trained; 60,000 village health volunteers.

Ministry of Public Health; approximately US$11/head/year (1990) 1 village health communicator or volunteer per approximately 20 children; 1 supervision extension worker per 24 village health communicators and volunteers [Volunteer]

(Continues on the following page.) Community Health and Nutrition Programs | 1061 ©2006 The International Bank for Reconstruction and Development / The World Bank 203

Table 56.3 Continued Country

Coverage, targeting

Resources, intensity

Expanded rural health program coverage 19–67 percent (1974–89).

Rural health program: US$1.70/child/year

Americas Costa Rica F: to 0

Food and Nutrition Program: US$12.50/child/year 2 health workers (full time) per 5,000 population; approximately 1:350 children [Health worker]

Honduras F: 0

Jamaica F: 0 Nicaragua F: 0

With community health volunteers, AIN-C covers 50 percent of health areas (expanded 1991 on), 90 percent of children 2 years in these; growth monitoring and home followup, plus referral and treatment.

Cost estimated as US$6/child/year

Community health aides (CHAs), waged, cover most of country from health centers, with home visiting.

CHAs (full time) 1:500 households; approximately US$7/household/year

Community health workers (brigadistas) with “multiplier” approach, training others; 1980 approximately 1 percent trained; many more for malaria control.

Volunteers, approximately 1:20 households

Volunteer teams 3:25 children, about 3.5 hours/volunteer/week

[Health worker]

Source: See sources for table 56.2. F role of supplementary feeding in the program; F: mainly a feeding program, or primary role; F: significant but not main role, often to selected children; F: () existed but relatively minor; F: 0 none. Note: The status of community workers is given in brackets in the last column.

groups that are hard to include for other reasons—may be more expensive to reach. Clearly the calculations depend on conditions and have to be made on a case-by-case basis. The principle is obvious: only those areas and people included in CHNPs are going to benefit; so wherever need exists, programs are indicated. The implementation strategy, in theory, may need to begin with the most urgent needs, although in practice, programs may expand from the easier, more accessible areas; this practice seems reasonable, provided that the expansion really occurs and leads to equitable use of resources. The program content is a mix of the components described earlier, varying with local priorities. The most crucial difference is whether extensive supplementary feeding is included. In middle-income countries, supplementary feeding was less prominent, often considered unnecessary, and because expensive, perhaps counterproductive (for example, in Costa Rica; Mata 1991). At the other extreme, such as for the Integrated Child Development Services (ICDS) in India, food distribution became the raison d’être of the program but, alone, was again probably not worthwhile. For some of the intermediate cases, supplementary food played a supporting role, with varying results. Except in the very poorest societies, supplementary feeding seems unlikely to be cost-effective. The resources used for the programs found in table 56.3 can be expressed per participant (referred to as intensity), as total expenditures, and in terms of personnel; the latter figures may be more generalizable. (The outcomes associated with these resources are shown in table 56.5.) Data such as these have been

the basis for estimating that US$5 to US$10 per child per year may be needed for effective programs. The dollar figures vary from less than US$1 to more than US$20. Probably the low end of this range (say, less than US$1 per child per year) does explain low or doubtful effect. Both low coverage and low intensity may explain the unchanged underweight prevalences in the Philippines until 2000. Fund levels in Indonesia are unsure; Rohde (1993) gave a figure of less than US$1, but others gave higher estimates. Most would reckon the intensity in India too low (Measham and Chatterjee 1999) at about US$2 per child per year. Looked at otherwise, the intensity planned for external funding (even if part of such funding is international costs) is in the US$10 to US$20 range (Bangladesh, India—Tamil Nadu, and Tanzania) and is the same as the estimate for Thailand. A level of US$10 to US$20 per participant per year is probably advisable for planning and sustaining effective programs. The intensity measures of workers per mother-child and the supervision ratios are relevant in assessing needs. The suggested norms, originating from the Thai experience are 1:10–20 for both. Since then, it has emerged that the full-time equivalence of community workers must be taken into account; the Thai workers are local volunteers, probably devoting 10 to 20 percent of their time. In Honduras, Fiedler (2003) in a careful cost study estimated that each volunteer spent 3.5 hours per week (less than 10 percent of full-time equivalent, or FTE), with a ratio of 1 volunteer to 8 children. The ratio of community health and nutrition workers (CHNWs) to children may, therefore, be as low as 1:200 for FTEs and as high as 1:8 or 1:10


for part-time volunteers. In Jamaica, where the community health aides work full time, the ratio is 1:500 households; in the BRAC program in Bangladesh, it is 1:300, about half-time work (afternoons) (Chowdhury 2003). (An indication of the status of community workers is shown in brackets in the last column of table 56.3.) In any event, these ratios provide some basis for gauging the adequacy of personnel, and it seems that an effective ratio may be about 1:500 for community workers employed full time and 1:10 or 1:20 for local volunteers working part time. In reality, the ratios of community workers to children are probably—not surprisingly—on the low side. Thailand, which trained 600,000 village workers (1 percent of the population), operated at about 1:20 for part-time volunteers, with similar supervision ratios. The Indonesian program was similar (or better) but had much less supervision. In contrast, the low resourcing of the ICDS in India shows up in a ratio of 1:200 (for part-time anganwadi workers, or ANWs), and in the Philippines, the ratio has until recently been 1:300 (for essentially voluntary workers). Increased application of technology can contribute to the organization and running of community-based programs. Technology can be applied easily to methods of assessment and monitoring of children’s progress; improved weighing scales (or in some circumstances, where rapid assessment in remote areas is important, using arm circumference) can simplify anthropometry. Modern computer technology for recordkeeping could be much more widely used, freeing staff time for home visits (for example, in Jamaica); e-mail, which is being rapidly adopted, has great potential for transferring information, troubleshooting, and consultation. Cell phone use is beginning to transform communications even in the poorest countries, where it is leapfrogging landline installation and use; as coverage expands, it will facilitate referral, for example, for emergency obstetric care, the need for which may first be identified by community workers. Coupled with improved transportation and procedures to allow the use of such transportation in cases of urgent need, modern communications can link communities to centers with advanced knowledge for information exchange and, by facilitating transportation when time is crucial, for referral. Modern communications may also provide more efficient ways of providing training, retraining, and supervision. Application of current research and resulting technologies can improve many of the other interventions discussed earlier. In the micronutrient field, periodic supplementation (with vitamin A in high doses) can be extended through community programs, and fortified foods and micronutrient “sprinkles” can be promoted (see chapter 28). The prospect of enabling communities to test their salt for iodine content with simple and cheap test kits is intriguing and has often been recommended but has not yet been widely applied. Improved immunization technology should continue to protect health, for

which CHNPs’ main role is to provide information and to ensure that children are taken for immunization (either to regular clinics or for National Immmunization Days and the like). Periodic deworming can be conducted by community programs (and hookworm vaccines currently under development may soon contribute). Supporting the use of insecticide-treated bednets could be fostered through CHNPs. By far the most potentially important application of technology, certainly in Sub-Saharan Africa, will be the unprecedented effort to provide millions of people with antiretroviral therapy and associated care and support, as discussed later.

Training, Supervision, Incentives, and Remuneration Community-based health and nutrition programs typically involve community workers, who may be entirely part-time volunteers (for example, in Honduras and Thailand) or may receive some remuneration financially or in kind (for example, in India). Community workers may be part of the health system, earning a wage and based in a local clinic (for example, in Jamaica) or in the community itself (for example, in Costa Rica); or they may be selected by and report to the community (for example, in Tanzania and Thailand). Table 56.3 indicates the status of community workers in the programs examined here. The training, supervision, and incentives for community workers are critical aspects of successful programs. Inadequate training and supervisory support of community workers are common weaknesses. Considerable attention was given to training for the Iringa project (Tanzania), with village health workers trained for up to six months. In the Tamil Nadu Integrated Nutrition Program in India, community workers received three months of training and participated in annual refresher trainings. ICDS (India) initially trained the ANWs for three months, with two annual refresher courses, but this process declined. In Thailand, volunteers had two to five days of initial training, with annual refresher courses; Indonesian practice was similar. In Jamaica, where the community workers are employees of the health system, two months of initial training is provided to recruits with significant prior educational requirements. In Bangladesh, the BRAC community health volunteers have four weeks of training. The quality of the training has varied, poor training having been blamed for inadequate implementation in cases such as ICDS in India (Measham and Chatterjee 1999). Sanders (1985, 176–93) describes experiences in the 1980s of village health workers (and barefoot doctors) and their relation to the community. Supervision of community workers is generally done by employees who are commonly in the sector. Training of supervisors (who often take on the role in addition to many other tasks) for these purposes is highly variable and not always adequate. Providing resources for visits to provide supervision to community workers is a further constraint. Supervision Community Health and Nutrition Programs | 1063


ratios in effective programs are about 1:20 (table 56.3, last column, when reported). Supervision and training of community workers are closely linked; indeed, supervision (which must be supportive rather than disciplinary) should include a substantial element of on-the-job training. Remuneration and incentives for sustaining motivation are key issues in replicating the successful features of these programs, and the options vary with the culture. In Thailand, it is argued that village volunteers consider the prestige associated with the role of health worker preferable to getting a low wage. In many cases, some right of access to health care is part of the incentive. For the ICDS in India, in contrast, the ANW receives a small financial remuneration, but the government (as elsewhere) will not grant formal employment status (and attempts to form unions have been strongly discouraged). Direct comparisons of the options of paid remuneration and voluntary work are rare. One opportunity to study options for remuneration is in the Philippines, where under a World Bank Early Child Development project, the child development worker receives a wage, which could be compared to near-volunteers at the barangay (village) level. When CHNWs are primarily voluntary, they are selected by the community and report to community committees in some form. CHNWs on government payrolls may come from the communities and thus may be known to and identify with the communities, but they may report to supervisors higher up in the system. Both models can work, depending on the culture. What probably works least well is when the community worker is paid little and receives inadequate support and recognition from the community or even comes from elsewhere. Furthermore, as development progresses, reliance on volunteerism may become less useful. For planning CHNPs in terms of community workers, the total numbers and resource implications can be estimated as follows. A full-time equivalent CHNW might visit 5 to 10 households per day, averaging a visit to each household roughly every two months; a ratio of 1 CHNW to 200 households, therefore, seems to be in the range within which an effect in terms of improving child health and nutrition is expected. Calculations from salaries of community health aides (CHAs) in Jamaica work out to US$7 per household per year, within the usual range for expected effect. An important factor in regard to financial resources, however, concerns the substantial cadre of personnel who have training and job descriptions for community work, are based in health centers, and for administrative and financial reasons seldom leave the health facility. Moreover, funds may not be released to allow travel to nearby villages. An example is from Jamaica, where, because of clinic workloads, CHAs spend time helping in clinics rather than on home visits; in fact, technology could free staff time for community work by automating tasks, such as record keeping, that detain the CHAs. More effective deployment of existing personnel may

frequently be an option. Hiring additional personnel as community health workers would consume a significant proportion of typical health budgets (at 1:200 households for FTEs, this would amount to US$1 to US$2 per person per year, or about 20 percent of public health budgets in low-income countries). A mix of redeployment of existing staff and new hiring from budget reallocations should, nonetheless, be cost-effective.

Organization Effective, respected, and socially inclusive organization at the community level seems to have been a key feature of the success in launching, expanding, and sustaining CHNPs. Most of the successful CHNPs drew and built on established community procedures; where they did not, effect and sustainability were in doubt. In Thailand, the health services and the religious organization at village level were important. The health services themselves play a key role in Costa Rica, Honduras, and Jamaica. In Indonesia, it was the community organizations (and women’s groups) together with (initially) the familyplanning services. In Iringa, Tanzania, it was the local political party structure, with substantial input from UNICEF. In Zimbabwe, immediately after independence, it was the village organizations that had fought the war, later helped by a consortium of national and international nongovernmental organizations (NGOs). The major part of the still-expanding program in Bangladesh is run by BRAC, an NGO, and has built on its links to the community for development, food security, and educational activities, as well as for health. In contrast, CHNPs that either failed to launch a wide program (for example, in the Philippines) or had limited effect (in India, ICDS) probably lacked some of these features. Inclusiveness is probably hard to achieve if not inherent. Support from the central government is also crucial: CHNPs need this support for training,supervision,wages,supplies,facilities, and the like. Where such support becomes a regular government budget item, activities tend to become embedded and are sustained, in contrast to where the support is from donors. A further issue concerns maintaining the community program’s preventive orientation. In Indonesia, for example, according to Rohde (1993), the health services co-opted (and medicalized) the posyandu (weighing post, or community health and nutrition center) system by adding a diagnostic and treatment module (in fact, a table in the meeting place). This module attracted most of the attention, to the disadvantage of the preventive aspects of the program. Thus, if the extension of IMCI into the community means treatment (by trained but not medically qualified people) in the community rather than referral to facilities, treatment could become the main or even sole focus, shifting attention from prevention. Some parallels exist to the experience of ICDS in India, where, as noted earlier, food became the raison d’être.


CONTEXTUAL FACTORS Community-based programs can work usefully, bringing steady progress; whether they do depends on myriad factors relating to the context. Three different concerns are (a) factors affecting widespread initiation of CHNPs of potentially adequate coverage, intensity, and content; (b) factors that lead to sustainability; and (c) factors that allow activities to be effective in improving health and nutrition—at best, when they, themselves, also contribute to a rapid transitional improvement, as in Thailand, Costa Rica, and Jamaica. Contextual factors may bring about improvements in health and nutrition without any additional direct action—through improving living conditions, education, and so forth. Often, the changes caused by such nonprogrammatic factors are diffi-

cult to distinguish from program effects (current examples are in Bangladesh and Vietnam, both showing rapid improvement in nutrition). Moreover, the same factors (again, such as education) may both produce endogenous change and increase the effect of program activities. Five contextual factors have been suggested as priorities (in Asia; Mason and others 2001): • • • • •

women’s status and education lack of social exclusion community organization literacy political commitment.

Table 56.4 shows estimates of the positions of countries with case study programs in regard to these factors. The levels of

Table 56.4 Context in Which Selected CHNPs Start and Run

Country

Approximate period

Women’s status and educationa

Lack of social exclusion

Community organization

Literacy

Level of health and administrative infrastructure

Political commitment

Total minus political commitment

Total

Tanzania Iringa starts

1984–90

2

4

4

3

2

5

15

20

Iringa declines

1990–

2

4

2

3

2

2

13

15

Supplementary Feeding Programme starts

1981–90

2

4

5

2

2

5

15

20

Supplementary Feeding Programme declines

1990–

2

2

2

2

2

2

10

12

1997–

1

3

2

2

3

3

11

14

ICDS

1975–

1

1

2

2

2

3

8

11

TINP

1980–9

2

2

3

3

3

4

13

17

Zimbabwe

Bangladesh BINP India

Indonesia UPGK starts

1975–

2

4

3

2

2

4

13

17

UPGK declines

1990–

2

4

2

2

3

2

13

15

Philippines b

1974–2000

4

4

3

4

3

1

18

19

Thailand

1982–

4

3

4

4

3

4

18

22

RHP

1973–

4

4

4

3

4

4

19

23

Jamaica

1985–

4

4

3

4

4

4

19

23

Nicaragua

1979–90

3

2

3

3

3

4

14

18

Costa Rica

Source: Authors. a. Women’s status and education can be quantified by indicators such as adult literacy rates, females as percentage of males, and secondary school enrollment for girls. b. Since 2000, the Philippines has begun a significantly improving trend, one factor being increased implementation of programs (CHNPs, as well as others, such as salt iodization); this increase is caused in part by increased political commitment, both as new legislation and resource allocations. Note: 0: worst; 5: best.

Community Health and Nutrition Programs | 1065 ©2006 The International Bank for Reconstruction and Development / The World Bank 207

health and administrative infrastructure have been added. The table also shows changes in these factors that may help explain why the CHNPs declined in three cases. Political commitment can lead to initiating community programs and mobilizing resources. It may also respond to emerging community mobilization, as seems to be the case when programs start after political upheavals, as in Zimbabwe and Nicaragua. Declining political commitment accounts for loss of interest by the government in CHNPs; economic decline undermining resource availability may cause a shift away from financial support of CHNPs (for example, in Tanzania). In table 56.4, estimates of levels of contextual factors are totaled both without and including political commitment (last two columns). The total without commitment may indicate how favorable the context is if commitment is then made. Costa Rica, Jamaica, and Thailand had a favorable context and, with commitment, succeeded. The Philippines had comparable favorable conditions—the position of women is generally good, there is limited social division (exclusion), and so on. However, the necessary commitment (of resources, in particular) was made only recently, with new legislation, adherence to regulations (for example, iodized salt went from 25 to 65 percent coverage), and increased resource allocation and assignment of community workers. This new commitment may well explain the recently resumed decrease in child malnutrition (figure 56.2). In other examples—such as Indonesia and Tanzania—the conditions were moderately favorable, and while political support and finance existed, progress was made. In Tanzania, financial crisis denied the programs sustained support; in Indonesia and Zimbabwe, bureaucratization and centralization of the political process, followed by political turmoil, contributed to a similar outcome (Sanders 1993). The situations in India and Bangladesh have not been very favorable. The position of women and social rifts, amounting to exclusion, have probably inhibited effective programs, even with political commitment. This context may now be changing in Bangladesh, as seen in the activities of BRAC. Finally, this analysis demonstrates the relation of decline in programs to falling political commitment in Tanzania, Zimbabwe, and Indonesia. If this analysis approximates the truth, the forward-looking policy implications may be important: • First, investing initially in a favorable context makes sense (as does possibly committing resources preferentially to interventions in the more favorable contexts). Supporting policies can address social constraints—such as improving education for women—and (relatedly) seek to improve human rights. In many cases, human rights may be of overriding importance for health: Farmer (2003) has made a compelling case for rethinking health and human rights as a

prerequisite for progress and as a responsibility for those working for health, especially of the poor and of the destitute sick. This investment may be long term and difficult— as in Kerala, India, for instance—but must be seen as integral to the struggle for health (Sanders 1985). Operationally, this commitment to human rights puts greater responsibility on advocates and investors in health to broaden the dialogue and scope for allocating resources and to avoid committing resources regardless of the prospect of success as influenced by the social and human rights context. In health and nutrition, as in other areas, adjustment of policies to support the success of interventions would be pragmatic as well as the right thing to do. • Second, even if the context is more favorable, genuine political commitment is still essential. Excessive donor input may inhibit this commitment. It is striking that Thailand had to reject donor influence and make its internal decisions before its programs became successful (Tontisirin and Winichagoon 1999), Costa Rica had to fight and overcome a medicalized approach (Muñoz and Scrimshaw 1995), and Indonesia’s posyandu system was undermined when treatment displaced prevention (Rohde 1993). • Third, it is clear that severe economic stress, political pressure, or both have caused unsustainability (Indonesia, Nicaragua, Tanzania, and TINP). • Fourth, if the context is unfavorable, it might be better to work on improving the context than to commit resources to programs that may not succeed—but, of course, success in improving context itself depends on circumstances, notably political commitment. Considerations like these should contribute to identifying supporting policies needed for programs to be effective and modifications to interventions in particular conditions. For example, it is often observed that a particular factor—say, access to health services—is more strongly related to improvement among the better off (for example, the educated) population. This interaction of program with context leads to identifying new needs—in this example, perhaps facilitating access for the illiterate. In the longer run, resources or legislation (for example, to combat social exclusion or discrimination against women) may be highlighted as prerequisites before a program can be expected to work. Often failure to take account of context when trying to transfer experiences from a pilot trial (“scaling up”) may explain why efficacious interventions prove ineffective in a larger population. This analysis of contextual circumstances indicates that targeting the poor may not always be cost-effective, and some interventions may not be feasible in certain contexts. An example is when the health infrastructure and services are almost nonexistent; under those conditions, it can be argued that


emergency treatment (especially for the diseases addressed by IMCI) should be established and reliable resources put in place first. A similar difficulty, often seen in food security, is that most interventions may not work for the poorest of the poor. For instance, supporting food (or cash crop) production in low-potential areas may not be realistic; nonagricultural employment may be better. Thus, community-based programs work in a specific time and place: programs may start, work for a time, and then evolve or fade away. Even if they fade away, some useful effect may be achieved: sustainability need not be forever. At the same time, short project cycles (three years for many donors) can act against sustained programs. Some compromise in donor policies to allow assurance of continuity for reasonable periods (such as 10 years) could do a lot to increase the effectiveness of donor support to CHNPs. The essence of time and place is not fully understood. Werner and Sanders (1997) give examples of favorable times, as when the old order is changing (for example, after internal conflict, as in Nicaragua and Zimbabwe) and when there is renewed vigor and some new organization is in place. Another generalization of a favorable context is when energy and interconnectedness exist in society. Thailand illustrates both: the Thais needed to change the approach, moving away from donor influence, in order to initiate the successful community programs that helped transform health and nutrition throughout the country, and that worked in part because of cohesive features of Thai society (Tontisirin and Winichagoon 1999). In these examples, programs that continued on a large scale—either until the problem was largely resolved, as in Costa Rica, Jamaica, and Thailand, or as it was expanding, as in BRAC in Bangladesh or AIN-C (Atención Integral a la Niñez Comunitaria) in Honduras—clearly had supportive context, but their specific common features (and hence how they could be replicated) are elusive. Perhaps one crucial condition for success is that circumstances are such that people and communities begin to have the sense that they can take responsibility for—and control of—their health and quality of life. Responsibility comes with the emancipation of societies from colonial or other repressive conditions and possibly when grassroots attention becomes widespread, as it did in Bangladesh through an NGO that identified with the people. Evidence is growing that, among the poor in the United States, this sense of control is directly related to better health and reduced exposure to HIV and AIDS; Sampson, Raudenbusch, and Earls (1997) call the concept collective efficacy. Cohen and others (2000) show that health conditions improve when communities themselves fix up their environment—the “broken windows” theory. Such ideas may equally apply to poor communities, especially urban ones, in developing countries too.

RESULTS Indicators of progress in implementation—process indicators— referring to coverage, intensity, and so on, are shown in table 56.3. As discussed earlier, most programs expanded population coverage without much targeting. But usually the level of resource application (intensity) was on the low side. More research is needed on the contribution of CHNPs to health process indicators, such as immunization coverage rates, as well as to nonhealth activities, for instance, in agriculture and community development. Impact evaluation, which refers to the net effects of interventions on changing health outcomes, is sorely lacking. The efficacy of most of the component parts of CHNPs, when resources are adequate and the problems are correctly identified, is established, but in routinely administered large-scale programs, the changes in outcome that can be ascribed to program actions are less known. Although controlled trials by definition are not applicable, plausible evidence can be obtained by careful attention to research design, measurement, and analysis (Habicht, Victora, and Vaughan 1999). Some form of “with and without” and “before and after” comparisons is needed; for instance, such methods as staggered implementation, natural experiments, and selection of comparison groups with some statistical control can yield valuable information now lacking and should be more widely attempted. In this context, it should be noted that because of the timing and level of effort necessary for the evaluation, the impact evaluation results (changes in outcome ascribed to the program) may be more important for policy decisions on future programs than for the program that has been evaluated. Moreover, not all programs require detailed evaluation. Thus, financial support for such policy-relevant evaluations may come from budgets other than that of the program to be evaluated. The evaluations should also be prospective as far as possible, so decisions on evaluation design and finance are needed earlier rather than later.

Impact For the examples used here, inferences were drawn from piecing together results either from ad hoc surveys or from program and administrative data; occasionally such inferences were made from the comparison of baseline estimates with midterm or final assessments, but the comparison groups, if any, were imperfectly matched. Thus, the conclusions on impact now put forward are tentative and based on judgments from available information. Some of these conclusions were drawn from trend assessments, details for which are in Mason (2000, annex 5). The most widely available indicators are mortality rates (infant, child, and to a lesser extent, maternal; reliable data on


age zero and cause-specific mortality rates are not usually available from most developing countries); prevalences of underweight in children from national surveys (often supported by demographic and health surveys or UNICEF Multi-Indicator Cluster Surveys); and indicators of health services (notably immunization coverage rates). Estimates of morbidity, even of the common diseases (such as diarrhea and ARI), are not available systematically enough to judge trends in relation to programs. Child underweight (or stunting) has a particular value, because it measures an attribute of all children (age and weight or height), rather than assessing a relatively rare event, as in mortality estimates. Moreover, experience is well established of how underweight prevalences behave as a robust indicator, having a useful degree of responsiveness but not being subject to wide fluctuations with transient events. Under controlled conditions, improving health and nutrition allows rapid catch-up in bodyweight and fast rates of reduction in underweight prevalence (for example, PinstrupAndersen and others 1993, 405). But in the real-world conditions of CHNPs, the expected rate is slower. As examples, Thailand maintained a reduction in underweight of about 2.9 ppts per year in the 1980s (see figure 56.1); the 22 projects reviewed as reported by Jonsson (1997) ranged between about 1 and 3 ppts per year. A reduction rate of 2 ppts per year, suggested earlier as an expectation from successful programs, would lead to very significant improvement if achieved at national levels: for South Asia, it would mean going from a prevalence of underweight of about 60 percent in 1980 to 20 percent in 2000; for Africa, from 30 percent in 1990 to 10 percent in 2000. Detecting this rate can be difficult with the noise of sampling and nonsampling errors and with the common seasonal changes, which can amount to 5 ppts fluctuations or more, certainly in Africa. The potential program-ascribed trend needs to be separated from the underlying secular trend for the country, roughly 0.5 ppts per year (from 1985 to 1995; ACC/SCN 1996). Clearly the longer the program and the observing periods, the easier it is to assess trends. Where the data are detailed enough, an initial rapid fall is seen in severe malnutrition—and probably in mortality,—followed by a slower fall in mild to moderate malnutrition. The reasons for the initial rapid fall are presumed to be immediate effects of improved health care, immunization, and the use of oral rehydration therapy. The outcomes estimated for the programs considered here concentrate on the sustained trend—after a year or two of implementation—as summarized in table 56.5. In Zimbabwe, from 1980 to 1988, the infant mortality rate (IMR) fell from 110 to 53 per 1,000 live births, and severe malnutrition fell from 17.7 to 1.3 percent. However, stunting fell only in 1982–88, from 35.6 to 29 percent (1.1 ppts per year). Tanzania shows a similar effect in Iringa, with severe and moderate malnutrition falling much faster for the first two years.

Interestingly, the Child Survival and Development Projects (supported by the World Bank, among others), which covered a much larger population (but with less intensity than in Iringa), appeared to show almost the same pattern as in Iringa: a rapid initial fall (as much as 8 ppts per year, for one to two years), continuing at 1 to 2 ppts per year. In Costa Rica, the child mortality rate plummeted in the late 1960s, well before stunting fell in the 1970s (Saenz 1995, 129; Vargas 1995, 111). A lag was seen in Thailand, where the child mortality rate started to fall rapidly in 1977, and both severe and moderate malnutrition appeared to start their fall in 1983–84. Both these improvements preceded the major growth in gross national product, which began in 1987 (Kachondam, Winichagoon, and Tontisirin 1992, tables 8 and 33). In analyzing Indian experience, where the IMR has fallen faster than child malnutrition, Measham and Chatterjee (1999) suggest that further improvements in child survival may be constrained by the high rates of child malnutrition. The sustained effects are generally of about an additional 1 ppt per year improvement (table 56.5). For Bangladesh (the BINP), Tanzania, and Thailand, it is possible to distinguish the sustained rate from the initial rapid fall. In Bangladesh, the BINP started during a period of rapid improvement overall, so extracting the underlying trend is especially important to give a plausible view of the “with-project” rate: about 1.6 ppts per year again seems a reasonable estimate. A similar extraction of likely with-project changes allowing for underlying trends was reported previously (Mason 2000, annex 5) for Tamil Nadu, Andhra Pradesh (ICDS), and Orissa, indicating plausible improvements for the first two states. In sum, these results support the contention that after an initial rapid fall, the sustained rates of improvement in child underweight prevalence settle down to about an additional reduction of 1 or 2 ppts per year. This conclusion is the same as previously reached (Gillespie and Mason 1991), now supported by some new results.

Cost-Effectiveness Therefore, if we use prevalences of underweight children as the basis for calculation, US$10 per child per year gives a reduction of 2 ppts per year. If we are to translate this cost into an implied effect on health and survival, underweight must be related to the measure of disease burden, DALYs lost. Then the resources needed per DALY saved—dollars per DALY—can be estimated. A 32.5 percent reduction in the loss of DALYs is associated with eliminating general plus micronutrient malnutrition as both direct effects and risk factors (see table 56.1, discussed earlier); as a first approximation, the average prevalence for developing countries of 30 percent underweight can be applied. We can calculate the associated DALYs gained from reducing malnutrition at this rate (and assume that loss of DALYs from all


Table 56.5 Outcomes and Resources in Selected Programs Country

Outcomes

Resources

Underweight: 50 to 35 percent (1984–88)

US$8 to US$17/person/year (US$34/child/year from total costs);

Immunization: 50 to 90 percent

2 village health workers/village 1,220 total;

Rates in underweight: initial 2 years, 8 ppts/year; first 4 years, 4.5 ppts/year; sustained (years 2–7), 0.8 ppts/year

Approximately 1:40 children

Tanzania: Child Survival and Development Program

Underweight reduction rates similar to Iringa

US$2 to US$3/child/year

Zimbabwe: Supplementary Feeding Programme

Stunting: 35.6 to 29 percent (1982–88)

External funds, approximately US$0.50/child/year

Africa Tanzania: Iringa

1.1 ppts/year IMR: 1980–88: 110 to 53

Asia Bangladesh: BINP

BINP, first 6 thanas, initial effect (1997): approximately 11 ppts/year; then (to February 1999) approximately 1.6 ppts/year additional

1 community worker per 1,000 population; Approximately 1:200 children; US$14 million/year, approximately US$18/child/year

Underlying (nonprogram) trend: national approximately 1.7 ppts/year, program area approximately 2.4 ppts/year Bangladesh: BRAC

No program-specific data, but child underweight and anemia in women have substantial falling trend in recent years.

Over all programs, US$196 million in 2003 (approximately US$8/household over all households); health program covered 31 million people, over 20 percent

India: ICDS

Overall underweight prevalence declining only slowly; some states reported faster, but link to ICDS not shown.

1 supervisor to 20 ANWs

India: TINP

1979–90: 1.4 ppts/year in TINP districts; 0.7 in non-TINP districts: increased improvement of approximately 0.7 ppts/year (Reddy and others 1992, 45). From other data, increased improvement of 1.0 ppts/year.

US$7–12/child/year

Indonesia

Probably about 1 ppt/year; underlying trend unknown

US$2 to US$11/child/year, depending on supplementary food. Rohde (1993) gives US$1 recurrent.

IMR: 1970, 1980, 1990: 118, 93, 61, respectively

Village workers (about 3 million total) 1:60 people; approximately 1:10 children; supervision 1:200

No change found in underweight.

Low coverage and intensity

Philippines: national

IMR: 1960, 1996: 77, 32, respectively Thailand

Approximately 2.9 ppts/year improvement in child underweight. Breaks down to 1982–84: 7.8 ppts/year; 1985–90, 1.9 ppts/year. IMR: 1970, 1980, 1990: 73, 55, 27, respectively

Ministry of Public Health, approximately US$11/head/year (1990) Village health communicator or volunteer approximately 1:20 children; supervision by extension workers: village health communicators and volunteers approximately 1:24

Americas Costa Rica

Stunting improved by approximately 1–1.5 ppts/year (estimated from Muñoz and Scrimshaw 1995, 111), 1979–89.

Rural health program: US$1.7/child/year Food and nutrition program: US$12.50/child/year 2 health workers (full time)/5,000 population, approximately 1:350 children

IMR: 1970, 1980, 1988; 62, 19, 16, respectively Jamaica

1.9 ppts/year 1985–89 IMR: 1960, 1996: 58, 10, respectively

Nicaragua

IMR fell from (at least) 92 to 80

Large numbers community health volunteers trained and supported

Source: See sources for table 56.2.


malnutrition comes down at this rate; CHNPs include some attention to micronutrients). This reduction is then cumulated through time (five years here) and assumes a linear relation between cost, underweight reduction, and disease burden avoided. The calculation also assumes a persistent effect of reducing malnutrition. Using these assumptions gives an estimate of US$200 to US$250 per DALY saved in sustained programs. This estimate does not include gains in DALYs from diseases that do not show up as underweight, which must be substantial. Moreover, if this calculation is applied just to the first rapid fall, typically (in the three cases examined) about 8 ppts per year, the ratio might fall by a factor of four, to US$50 to US$60 per DALY saved (but start-up costs are higher too). The sustained figure should be the more generalizable. Many further provisos exist. Much of the effect here is on a risk factor—malnutrition—reducing which, in turn, makes other interventions more effective; hence, the comparison of CHNPs with more direct interventions may not be valid. But conversely (or perversely) improving nutrition could actually reduce the cost-effectiveness of other interventions—such as measles immunization—by reducing the mortality risk of children who are not immunized.

FUTURE APPLICATIONS The experience so far in CHNPs can be applied more broadly, especially where community organizations can sustain support for CHNWs. CHNPs have worked best so far in Asia and Latin America. However, with the HIV/AIDS epidemic in SubSaharan Africa needing high-priority attention, application of CHNP experience to the HIV/AIDS crisis should be explored.

Extending CHNPs’ Coverage and Intensity In a project sponsored by the Asian Development Bank (ADB) and UNICEF that was aimed at identifying ways of investing in improved child nutrition, Mason and others (1999, 2001) have reviewed the extent of CHNPs in Asian countries. Resources were estimated in terms of annual expenditures per child and of ratios of population to community workers (“mobilizers”). The project addressed the needs of eight countries (Bangladesh, Cambodia, China, India, Pakistan, the Philippines, Sri Lanka, and Vietnam), and previous experience in Indonesia and Thailand provided additional guidance. The population coverage of CHNPs was estimated as about 5 to 20 percent, except for India with the ICDS, which reports about 70 percent coverage. The next indicators refer to estimates within programs. The calculated intensity was commonly 200 children to 1 community worker (for example, Bangladesh, India, Sri Lanka); ratios of up to 100:1 were reported in Pakistan

and Vietnam and up to 60:1 in the Philippines. Further research has stressed the variation in time commitment of CHNWs in different places—hence the need to convert to FTEs. The ratio used as the norm, derived from experience in Thailand and Indonesia, of about 1:20 is probably equivalent to 1:200 in FTEs. In India, opinion has been that about a doubling of the ANW numbers in the ratios is needed to get more effect (Measham and Chatterjee 1999). From this perspective, these estimates indicate that both coverage and intensity are low, although intensity may be half that needed, whereas coverage (except in India) is far too small. Supervision ratios are estimated as about 1:20 and higher. Expanding the numbers of CHNWs also means increasing the number of supervisors (usually from the health system), with associated costs. Calculations from scarce financial resource data show that most government programs cost about US$1 per participant child per year or less, whereas Bangladesh (BINP, with donor support and in line with other donor-supported programs) reached costs of US$15 to US$20 per child per year. By this calculation, too, the resources per head, as well as the coverage, were in most cases too low for widespread effect. The estimates of coverage and intensity can be combined to calculate the extent of current programs in relation to that needed for full coverage at adequate intensity. The results based on a 1:20 ratio of CHNW to children suggest that less than 1 percent of the need was currently available; at 1:200 (which would cost more, because the CHNW would work full time) perhaps 10 percent of the need would be covered. Either way, a massive expansion would be called for if CHNPs were to be used as a means for widely improving health (but still calling for only about 20 percent of the public budget for health). Expansion requires major resources, and not only financial ones. Thailand trained 1 percent of the population as community health workers (part time) and established an extensive supervision and support structure, including retraining. The estimates for the ADB-UNICEF project in financial terms were, for Bangladesh, Cambodia, Pakistan, Sri Lanka, and Vietnam, some US$190 million to US$280 million per year for improvement of underweight by an additional 1.5 ppts per year (Mason and others 2001, 64–68).

The Potential Role of CHNPs in Combating HIV and AIDS in Sub-Saharan Africa Controlling the epidemic of HIV and AIDS in Sub-Saharan Africa will take an unprecedented effort. As antiretroviral therapy becomes available there will be new opportunities to turn the tide. Supply of antiretroviral therapy drugs, although essential and the cutting edge of new programs, is only part of the need. Food and income support, care for children (orphans and others affected), counseling, support to promote and sustain behavior change, and rehabilitation of people and


communities are needed (see chapter 18). Many of these activities have precedents in the types of CHNPs run by community health workers that are discussed here. What lessons are transferable? One concern is that CHNPs have a greater history of success in developing countries outside Africa. Those within Africa seem to have been sustained for limited periods, often linked to donor interests. Reasons may have to do with lower levels of administrative infrastructure, different existing community organization, and varying political commitment (see table 56.4). These factors may now be weakened as the AIDS epidemic reduces the numbers of qualified people and undermines community organizations. It will be urgent to work on such contextual factors to create conditions in which community organizations can be refurbished and built on. Community organizations can work in Africa, as elsewhere, when they have a real function with activities perceived as useful to pursue and some resources (including mobilizing their own) to use. Some transferable lessons are that such local organizations are crucial; that in regard to supervision and access to certain resources, they need to work with the government structure—often through health system employees; and that they need sustained resource support, much of which must come from donors. Treatment and rehabilitation of people with AIDS will be home based in most cases and will depend substantially on community support. Nutrition is an important component; improved food intake is likely to enhance the effect of antiretroviral therapy, and when treatment progresses, nutrition will help get sick people back on their feet and returned to a productive life. A village health worker could play a key role in this process. In much of Africa, HIV and AIDS affect many communities, and in southern Africa, where HIV prevalences reach 30 to 40 percent, almost all communities have chronically sick adults. This fact means that most communities need programs: the problem is not highly concentrated. On the positive side, the more developed and accessible communities are those most affected by AIDS (Mason and others forthcoming; UNICEF 2004), where establishing programs may be easier. HIV and AIDS are affecting children both directly, as pediatric AIDS, and indirectly, through the impoverishment and destitution of affected households. This effect is seen in worsening child malnutrition. Here, too, support through CHNPs could play a useful role. The characteristics of CHNPs elsewhere—in terms of intensity, training, supervision, and so forth—may provide some guidance for establishing or extending them in Africa. Mechanisms for identifying, supporting, and training village or community health workers in this context can draw on experience with CHNPs; such issues as their identification in the community and links with community and facility programs will arise. A key issue will be the remuneration and incentives

for community workers, and this issue may need some research and testing of different approaches. The activities of community workers in dealing with treatment (and prevention) of HIV and AIDS have parallels to malnutrition and would probably include the following items: • social support and facilitating access to resources (possibly including food aid) • counseling • treatment and referral for opportunistic infections • promoting rehabilitation to productive life (which may benefit from improved nutrition) as antiretroviral therapy progresses. Schools too have an extremely important role in the fight against HIV and AIDS and should be linked to, or part of, CHNPs. Schools provide a refuge and a means of providing help for orphans and vulnerable children, and they also provide a crucial opportunity for preempting and combating high-risk behavior.

RESEARCH NEEDS The question of incentives, training, and support for community workers urgently needs research, both from current experience and with prospective designs. The issues include the following: • What is the CHNW’s status, relative to the community or to the government (or NGO) hierarchy? • How are CHNWs selected and to whom do they report (for example, community health committees, supervisors employed in the health or other system)? • What educational background and how much training and retraining—and by what methods—are needed for CHNWs? • What ratios of CHNWs to households are effective (or most cost-effective), both as part-time workers (volunteer or otherwise) and as full-time employees? • What supervision ratios work? • What remuneration and incentives are effective? • How can these efforts be financed? Enough programs have been in operation for long enough that researchers could base on them much of the needed research on processes of implementation, launching new trials only for processes for which sufficient information does not exist. In contrast, impact evaluation requires new and preferably prospective studies. A major gap in research is the application of communitybased programs to urban areas. Urban communities are Community Health and Nutrition Programs | 1071


conceived differently from the rural areas of most CHNPs, organizations run along different lines, and so forth. Yet population growth is in urban areas, and some problems, notably HIV and AIDS, are worse there. Finally, the cost-effectiveness analysis results given in an earlier section are based on rather few and approximate results. CHNPs may well provide a viable and cost-effective approach under many circumstances in poor countries, and it may be necessary to demonstrate this viability better and more quantitatively for support to CHNPs to compete with more traditional service delivery interventions. That, too, would constitute worthwhile research.

NOTES 1. Social exclusion refers to the exclusion of groups from the mainstream of public actions: lower castes in India, poorer groups in Pakistan, many indigenous ethnic groups throughout Asia and the Americas, and migrant workers in China and elsewhere; the result for public health is that excluded people do not participate in programs even if they are available. 2. Pinstrup-Andersen and others (1993) provide a more complete list.

REFERENCES ACC/SCN (United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition). 1989. Update on the World Nutrition Situation: Recent Trends in Nutrition in 33 Countries. Geneva: ACC/SCN. ———. 1992. Global and Regional Results. Vol. 1 of Second Report on the World Nutrition Situation. Geneva: ACC/SCN. ———. 1996. Update on the Nutrition Situation, 1996. Geneva: ACC/SCN. ———. 1998. Third Report on the World Nutrition Situation. Geneva: ACC/SCN. ———. 2004. Fifth Report on the World Nutrition Situation. Geneva: ACC/SCN. Administrative Staff College of India. 1997. “National Strategy to Reduce Child Malnutrition; Investment Plan; Final Report.” Asian Development Bank, Manila, December. Allen, L. H., and S. R. Gillespie. 2001. “What Works? A Review of the Efficacy and Effectiveness of Nutrition Interventions.” ACC/SCN Nutrition Policy Paper 19; Asian Development Bank (ADB) Nutrition and Development Series 5, United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition, Geneva; ADB, Manila. Berg, A. 1981. Malnourished People: A Policy View. Poverty and Basic Needs Series. Washington, DC: World Bank. ———. 1987. Malnutrition: What Can Be Done? Washington, DC: World Bank; Baltimore: Johns Hopkins University Press. BINP and UNICEF (Bangladesh Integrated Nutrition Program and United Nations Children’s Fund). 1999. “Preliminary Results.” UNICEF. BRAC (Bangladesh Rural Advancement Committee). 2004. “BRAC Health Programme,” http://www.brac.net/health_programme.pdf, and “BRAC at a Glance,” http://www.brac.net/aboutb.htm. Chowdhury, M. 2003. “Health Workforce for TB Control by DOTS: The BRAC Case.” Joint Learning Initiative Working Paper 5-2. http://www. globalhealthtrust.org/doc/JLI%20WG%20Paper%205-2.pdf.

Cohen, D, S. Spear, R. Scribner, P. Kissinger, K. Mason, and J. Wildgen. 2000. “‘Broken Windows’ and the Risk of Gonorrhea.” American Journal of Public Health 90 (2): 230–36. Delgado, H. L., V. E. Valverde, R. Martorell, and R. E. Klein. 1982. “Relationship of Maternal and Infant Nutrition to Infant Growth.” Early Human Development 6 (3): 273–86. Engle, P. L., M. Bentley, and G. Pelto. 2000. “The Role of Care in Nutrition Programmes: Current Research and a Research Agenda.” Proceedings of the Nutrition Society 59 (1): 25–35. Ezzati, M., A. Lopez, A. Rodgers, S. vander Hoorn, C. J. L. Murray, and the Comparative Risk Collaborating Group. 2002. “Selected Major Risk Factors and Global and Regional Burden of Disease.” Lancet 360: 1347–60. Ezzati, M., S. Vander Hoorn, A. Rodgers, A. Lopez, C. D. Mathers, C. J. L. Murray, and the Comparative Risk Collaborating Group. 2003. “Estimates of Global and Regional Potential Health Gains from Reducing Multiple Major Risk Factors.” Lancet 362: 271–80. Farmer, P. 2003. Pathologies of Power: Health, Human Rights, and the New War on the Poor. Berkeley and Los Angeles: University of California Press. Fiedler, J. L. 2003. “A Cost Analysis of the Honduras Community-Based Integrated Child Care Program (Atención Integral a la NiñezComunitaria, AIN-C).” Health, Nutrition, and Population Discussion Paper, World Bank, Washington, DC. FNRI (Food and Nutrition Research Institute). 2004. “Results of FNRI National Nutrition Surveys, 2001 and 2003.” Department of Science and Technology, Food and Nutrition Research Institute, Government of the Philippines, Manila. Gillespie, S., and J. Mason. 1991. “Nutrition-Relevant Actions—Some Experiences from the Eighties and Lessons for the Nineties.” ACC/SCN State-of-the-Art Series Nutrition Policy Discussion Paper 10, United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition, Geneva. http://www.unsystem.org/scn/archives/npp10/ index.htm. Gillespie, S., J. Mason, and R. Martorell. 1996. “How Nutrition Improves.” ACC/SCN Nutrition Policy Discussion Paper 15, United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition, Geneva. http://www.unsystem.org/scn/archives/npp15/ index.htm. Gillespie, S., M. McLachlan, and R. Shrimpton. 2003. Combatting Malnutrition: Time to Act. Washington, DC: World Bank. Guillermo-Tuazon, A., and R. M. Briones. 1997. “Comprehensive Assessment of Nutrition Interventions.” Report prepared for Asian Development Bank–UNICEF Regional Technical Assistance project. University of Philippines at Los Baños, Regional Training Programme on Food and Nutrition. UNICEF, Manila. Photocopy. Gwatkin, D., J. Wilcox, and J. Wray. 1980. Can Health and Nutrition Interventions Make a Difference? Monograph 13, Overseas Development Council, Washington, DC. Habicht, J.-P., J. Mason, and H. Tabatabai. 1984. “Basic Concepts for the Design of Evaluation during Programme Implementation.” In Methods for the Evaluation of the Impact of Food and Nutrition Programmes, ed. D. Sahn, R. Lockwood, and N. Scrimshaw, 1–25. Tokyo: United Nations University. Habicht, J.-P., C. G. Victora, and J. P. Vaughan. 1999. “Evaluation Designs for Adequacy, Plausibility, and Probability of Public Health Programme Performance and Impact.” International Journal of Epidemiology 28 (1): 10–18. Heaver, R. A., and J. M. Hunt. 1995. Improving Early Child Development: An Integrated Program for the Philippines. Washington, DC: World Bank and Asian Development Bank. Heaver, R., and J. B. Mason. 2000. Making a National Impact on Malnutrition in the Philippines: You Can’t Get There from Here—A Case


Study of Government Policies and Programs, and the Role of UNICEF and the World Bank. New York: UNICEF. Horwitz, A. 1987. “Comparative Public Health: Costa Rica, Cuba, and Chile.” Food and Nutrition Bulletin 9 (3): 19–29. INFS (Institute of Nutrition and Food Science) and Department of Economics, University of Dhaka. 1998. “Strategies for Bangladesh.” Dhaka Urban Community Health Program. Asian Development Bank, Manila. Jennings, J., S. Gillespie, J. Mason, M. Lotfi, and T. Scialfa. 1991. “Managing Successful Nutrition Programmes.” ACC/SCN State-of-the-Art Series, Nutrition Policy Discussion Paper 8, United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition, Geneva. http://www.unsystem.org/scn/archives/npp08/index.htm. Jonsson, U. 1997. “Success Factors in Community-Based NutritionOriented Programmes and Projects.” In Malnutrition in South Asia: A Regional Profile, ed. S Gillespie, 161–89. ROSA Publication 5. Kathmandu: UNICEF, Regional Office for South Asia. Kachondam, Y., P. Winichagoon, and K. Tontisirin. 1992. “Nutrition and Health in Thailand: Trends and Actions.” ACC/SCN case study, Institute of Nutrition at Mahidol University, Bangkok, and United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition, Geneva. Kavishe, F. P., and S. S. Mushi. 1993. Nutrition-Relevant Actions in Tanzania. ACC/SCN case study. Tanzania Food and Nutrition Centre, Monograph Series 1. Geneva: United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition. http:// www.unsystem.org/scn/archives/tanzania/index.htm. Kelley, L. M., and R. E. Black. 2001. “Research to Support Household and Community IMCI. Report of a Meeting, 22–24 January 2001, Baltimore, Maryland, USA.” Journal of Health, Population, and Nutrition 19 (Suppl. 2): S111–54. Kielmann, A. A., C. E. Taylor, C. DeSweemer, I. S. Uberoi, H. S. Takulia, N. Masih, and S. Vohra. 1978. “The Narangwal Experiment: II. Morbidity and Mortality Effects.” Indian Journal of Medical Research 68 (Suppl.): 42–54. Mason, J. B. 2000. “How Nutrition Improves, and What That Implies for Policy Decisions.” Paper prepared for World Bank–UNICEF Nutrition Assessment, UNICEF, New York, and World Bank, Washington, DC. http://www.tulane.edu/~internut/publications/WB_Bckgrd_Pprs/ Narrative/NarrativethreeMason.doc. ———. 2003. “Philippines Case Study.” In Combating Malnutrition: Time to Act, ed. G. Gillespie, M. McLachlan, and R. Shrimpton, 85–101. Washington, DC: World Bank. Mason, J., A. Bailes, K. Mason, O. Yambi, U. Jonsson, C. Hudspeth, and others. Forthcoming. AIDS, Drought, and Child Malnutrition in Southern Africa. Public Health Nutrition.

ACC/SCN State-of-the-Art Series, Nutrition Policy Discussion Paper 8. Geneva: United Nations Administrative Committee on Coordination/Sub-Committee on Nutrition. Measham, A. R., and M. Chatterjee. 1999. Wasting Away: The Crisis of Malnutrition in India. Washington, DC: World Bank. Mills, A. 1994. “Decentralization and Accountability in the Health Sector from an International Perspective: What Are the Choices?” Public Administration and Development 14: 281–92. Muñoz, C., and N. S. Scrimshaw. 1995. The Nutrition and Health Transition of Democratic Costa Rica. Boston: International Nutrition Foundation for Developing Countries. Pelletier, D. L. 1991. “The Uses and Limitations of Information in the Iringa Nutrition Program, Tanzania.” Cornell Food and Nutrition Policy Program, Working Paper 5, Cornell University, Ithaca, NY. Pelletier, D. L., and E. A. Frongillo. 2003. “Changes in Child Survival Are Strongly Associated with Changes in Malnutrition in Developing Countries.” Journal of Nutrition 133 (1): 107–19. Pinstrup-Andersen, P., S. Burger, J.-P. Habicht, and K. Peterson. 1993. “Protein-Energy Malnutrition.” In Disease Control Priorities in Developing Countries, ed. D. T. Jamison, W. H. Mosley, A. R. Measham, and J. L. Bobadilla, 391–420. New York: Oxford University Press. Plowman, B., J. I. Picado, M. Griffiths, K. Van Roekel, and V. Vivas de Alvarado. 2002. BASICS II Evaluation of the AIN Program in Honduras. Arlington, VA: Basic Support for Institutionalizing Child Survival Project (BASICS II) for the U.S. Agency for International Development. Reddy, V., M. Shekar, P. Rao, and S. Gillespie, S. 1992. “Nutrition in India.” ACC/SCN case study. National Institute of Nutrition, Hyderabad, India. http://www.unsystem.org/scn/archives/india/index.htm. Rohde, J. 1993. “Indonesia’s Posyandus: Accomplishments and Future Challenges.” In Reaching Health for All, ed. J. Rohde, M. Chatterjee, and D. Morley, 135–57. Oxford, U.K.: Oxford University Press. Saenz, L. 1995. “Evolution of an Epidemiological Profile.” In The Nutrition and Health Transition of Democratic Costa Rica, ed. C. Muñoz and N. S. Scrimshaw, 119–43. Boston: International Nutrition Foundation for Developing Countries. Sampson, R. J., S. E. W. Raudenbusch, and F. Earls. 1997. “Neighborhoods and Violent Crime: A Multilevel Study of Collective Efficacy.” Science 277: 918–24. Sanders, D. 1985. With R. Carver. The Struggle for Health. London: Macmillan. ———. 1993. “The Potential and Limits of Health Sector Reform in Zimbabwe.” In Reaching Health for All, ed. J. Rohde, M. Chatterjee, and D. Morley, 239–66. Oxford, U.K.: Oxford University Press. ———. 1999. “Success Factors in Community-Based Nutrition Programmes.” Food and Nutrition Bulletin 20 (3): 307–14.

Mason, J. B., J. Hunt, D. Parker, and U. Jonsson. 1999. “Investing in Child Nutrition in Asia.” Asian Development Review 17 (1, 2): 1–32.

Sanders, D., and M. Chopra. 2004. “Child Health.” Paper prepared for Save the Children U.K., London.

———. 2001. “Improving Child Nutrition in Asia.” Food and Nutrition Bulletin 22 (3 Suppl.): 5–80.

Save the Children U.K. 2003. Thin on the Ground: Questioning the Evidence behind World Bank Funded Community Nutrition Projects in Bangladesh, Ethiopia, and Uganda. London: Save the Children U.K. http://www.savethechildren.org.uk/temp/scuk/cache/cmsattach/ 666_ThinOnTheGround.pdf.

Mason, J. B., P. Musgrove, and J.-P. Habicht. 2003. “At Least One-Third of Poor Countries’ Disease Burden Is Due to Malnutrition.” Disease Control Priorities Project Working Paper 1, Fogarty International Center/National Institutes of Health, Washington, DC. http://www. fic.nih.gov/dcpp/wps/wp1.pdf. Mason, J., J. Rivers, and C. Helwig, eds. 2005. “Recent Trends in Malnutrition in Developing Regions: Vitamin A Deficiency, Anemia, Iodine Deficiency, and Child Underweight.” Food and Nutrition Bulletin 26 (1) Special Issue: 1–110. Mata, L. 1991. “National Nutrition and Holistic Care Programme (NNHCP), Costa Rica.” In Managing Successful Nutrition Programmes, ed. J. Jennings, S. Gillespie, J. Mason, M. Lotfi, and T. Scialfa, 77–81.

Shekar, M. 1989. “The Tamil Nadu Integrated Nutrition Programme: A Review of the Project with Special Emphasis on the Monitoring and Information System.” Paper prepared for the Rockefeller Foundation and the Food and Nutrition Policy Programme, Cornell University, Ithaca, NY. Shrimpton, R. 1989. “Community Participation in Food and Nutrition Programmes: An Analysis of Recent Governmental Experiences.” Paper prepared for the Food and Nutrition Policy Programme, Cornell University, Ithaca, NY. Community Health and Nutrition Programs | 1073


Soekirman, I. Tarwotjo, I. Jus’at, G. Sumodiningrat, and F. Jalal. 1992. Economic Growth, Equity and Nutritional Improvement in Indonesia. ACC/SCN case study. http://www.unsystem.org/scn/archives/ indonesia/index.htm. Tagwireyi, J., and T. Greiner. 1994. Nutrition in Zimbabwe. Washington, DC: World Bank. Taylor, C. E., A. A. Kielmann, and R. L. Parker. 1978. “The Narangwal Nutrition Study: A Summary Review.” American Journal of Clinical Nutrition 31: 1040–52. Tontisirin, K., and P. Winichagoon. 1999. “Community-Based Programs: Success Factors for Public Nutrition Derived from Thailand’s Experience.” Food and Nutrition Bulletin 20 (3): 315–22. UNICEF (United Nations Children’s Fund). 1990. “Strategy for Improved Nutrition of Children and Women in Developing Countries.” Policy Review Paper E/ICEF/1990/1.6, UNICEF, New York.

Vargas, W. 1995. “Development and Characteristics of Health and Nutrition Services for Urban and Rural Communities of Costa Rica.” In The Nutrition and Health Transition of Democratic Costa Rica, ed. C. Muñoz and N. S. Scrimshaw, 68–117. Boston: International Nutrition Foundation for Developing Countries. Waterlow, J. C. 1992. Protein Energy Malnutrition. London: Edward Arnold. Werner, D., and D. Sanders. 1997. Questioning the Solution: The Politics of Primary Health Care and Child Survival. Palo Alto, CA: HealthWrights. Whitehead, R. G., M. G. Rowland, and T. J. Cole. 1976. “Infection, Nutrition, and Growth in a Rural African Environment.” Proceedings of the Nutrition Society 35 (3): 369–75.

———. 1998. State of the World’s Children: Progress against Worms for Pennies. New York: UNICEF.

Winichagoon, P., Y. Kachondam, G. Attig, and K. Tontisirin. 1992. Integrating Food and Nutrition into Development: Thailand’s Experiences and Future Visions. UNICEF/EAPRO and Institute of Nutrition at Mahidol University, Bangkok, Thailand.

———. 2004. Drought, AIDS, and Child Malnutrition in Southern Africa: Preliminary Analysis of Nutritional Data on the Humanitarian Crisis. Nairobi: UNICEF, Eastern and Southern Africa Regional Office.

WHO (World Health Organization). 1997. Improving Child Health. IMCI: The Integrated Approach. WHO/CHD/97.12 Rev 2. Geneva: WHO.


Chapter 59

Adolescent Health Programs Elizabeth Lule, James E. Rosen, Susheela Singh, James C. Knowles, and Jere R. Behrman

This chapter reviews the main direct causes of loss of productive life years among adolescents and the range of interventions to address these causes.It pays special attention to sexual and reproductive health because adolescence is when important transitions occur that can have a direct effect on young people’s health as well as potential long-term consequences. In addition, a number of interventions have focused on this aspect of young people’s behavior. The discussion centers on defined interventions that have some relatively rigorous evaluation component. There are some limitations to this chapter, however. First, it reviews existing research and does not carry out new research; however, it points to gaps in research and areas needing more work. Second, the chapter uses a focused definition of health that includes the most basic health outcomes (death,illness,timing of transitions, or specific risky or protective behaviors that research has attempted to measure). It does not attempt to cover aspects that would be included in a broad definition of health and wellbeing (for example, potential for growth, creativity, or participation) that are important but are poorly researched to date. Finally, although the broader environment in which adolescents live influences their behavior and responses to programs, this chapter does not attempt to review that important group of factors or the broader set of programs that have a more indirect effect on the health of young people (for example, school quality or public health promotion activities at the societal level).

NATURE AND CAUSES OF THE BURDEN OF DISEASE IN YOUNG PEOPLE At first glance, adolescence appears to be a relatively healthy— although not hazard-free—period of life, given the relatively low mortality rates of young people.1 Nevertheless, adolescents

and young adults engage in a range of behaviors that can affect the quality of their health and the probability of their survival in the short term as well as affect their lifetime health and survival. Health Challenges of Adolescents If we look only at disability-adjusted life years (DALYs) for the adolescent age group, adolescents appear to be relatively healthy. Nonetheless, more than 33 percent of the disease burden and almost 60 percent of premature deaths among adults can be associated with behaviors or conditions that began or occurred during adolescence—for example, tobacco and alcohol use, poor eating habits, sexual abuse, and risky sex (WHO 2002). Adolescence-related risk factors are a greater problem in wealthier countries, largely because of the relatively greater impact of smoking and diet-related risks in those countries, though the prevalence of these risks is expanding rapidly in many low- and middle-income countries (LMICs). Thus, although adolescents are apparently healthy, they are practicing unhealthy behaviors that will ultimately result in much death and disability. This is an immense public health issue. Therefore, focusing attention both on diseases experienced during adolescence and on risk factors with their roots in adolescence makes sense. Adolescent health efforts should emphasize prevention because so much of the disease burden is preventable and because prevention is a particularly cost-effective strategy in relation to adolescents, given the long duration over which benefits will be reaped and adolescents’ greater openness to change than adults. Burden of Disease in Adolescence The global burden-of-disease approach used to calculate DALYs is an imperfect representation of the prevalence, morbidity, and 1109


Table 59.1 Worldwide Distribution of DALYs for Major Categories of Diseases and Conditions by Age Group and Sex, 2002 (percent) Women Category

Age 5–14

Sexual and reproductive causes

4.6

HIV/AIDS Maternal conditions Other sexual and reproductive conditions Cardiovascular conditions Neuropsychiatric conditions

3.9 11.9 16.3 5.2

Age 15–29 9.5

3.7 0.0 0.2

8.6 0.0 0.9

3.7

9.9

3.7

2.2

2.9

2.0

3.3

33.8 5.4 0.6 0.7 1.0 0.1 0.1 7.6

25.0

Unintentional, road traffic accidents Unintentional, other Intentional, self-inflicted Intentional, not self-inflicted (war, violence)

14.9 10.1 4.1 4.4 4.4 1.1 0.6 9.1

14.0 5.7 16.8 1.0 1.5

31.1

Tuberculosis Total

33.4

15.5

Injuries

Age 5–14

11.9

Unipolar depressive disorders Bipolar disorders Schizophrenia Other mental health conditions Alcohol use disorders Drug use disorders Other

Other noncommunicable diseases

Age 15–29

3.8 0.4 0.4

Respiratory conditions

Other communicable diseases

Men

32.4 2.2 7.7 2.9 1.2

7.1 1.5

32.0 5.6 0.7 2.3 0.6 0.3 0.2 5.2

7.1 4.2 4.2 2.6 5.7 2.3 5.9 33.1

7.7 21.8 0.9 2.0 27.7

3.0

7.5 12.9 3.8 8.9 11.1

1.4

3.9

9.9

9.6

9.2

10.0

100.2

104.5

100.0

102.7

Source: WHO 2004a.

mortality of conditions that adolescents face. DALYs fail to capture fully the complexity of adolescent health concerns. Nonetheless, no better comprehensive and comparative measure currently exists; thus, the discussion in this section will rely primarily on available DALY data. The World Health Organization (WHO), in 1999, commissioned a special analysis of the burden of disease in adolescence, which examined the 10 to 14 and the 15 to 19 age groups. The study found that young people age 10 to 19, who constitute 19 percent of the world’s population, account for 15 percent of the disease and injury burden worldwide. It also found that more than 1 million people in that age group die each year (WHO 1999). The top three causes of DALYs were found to be unipolar major depression, transportation accidents, and falls. The profile of disease burden was significantly different for younger and older adolescents. In the 10 to 14 age group, injuries and communicable diseases were prominent causes of DALYs. For the 15 to 19 age group, the disease burden shifted to outcomes of sexual behaviors and mental health.

Using 2002 data, WHO has made more detailed calculations of DALYs by sex for the 5 to 14 and 15 to 29 age groups (table 59.1). These age ranges overlap adolescence and are, thus, broadly indicative of the 10 to 19 age group. Notably, table 59.1 shows large differences by sex in the pattern and level of DALYs. These differences are important, because they relate to the different needs of young women and young men for interventions and services. Particular interventions also potentially have different costs and benefits because of the different proportions of females and males. Worldwide, among young men age 15 to 29, injuries and neuropsychiatric illnesses account for a high proportion of DALYs (33 percent and 32 percent, respectively). By comparison, among young women age 15 to 29, injuries account for 14 percent of DALYs, and neuropsychiatric illnesses account for about the same percentage of DALYs as among young men. However, sexual and reproductive health conditions account for 33 percent of young women’s DALYs, much higher than the 10 percent for young men. For both young men and young women, all other communicable and noncommunicable

1110 | Disease Control Priorities in Developing Countries | Elizabeth Lule, James E. Rosen, Susheela Singh, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 218

diseases account for moderate proportions of DALYs (7 to 11 percent, depending on sex and disease group). The disease burden among 5- to 14-year-olds is markedly different from that for the 15- to 29-year-olds, and differences between males and females are quite small. Communicable diseases and respiratory illnesses account for much larger proportions of DALYs for this age group compared with the 15 to 29 age group, whereas neuropsychiatric and sexual and reproductive conditions account for much smaller proportions. HIV/AIDS accounts for less than 4 percent of DALYs for both males and females age 5 to 14.

Health Risk Behaviors among Adolescents and Young People Young people’s vulnerability to risky or unwanted sex and other unhealthy behaviors is tied to a host of individual, family, and community factors that influence their behavior and that are closely related to their economic and educational opportunities. Good health and other physical, moral, and intellectual development outcomes are often mutually reinforcing. For example, healthy children do better in school. Similarly, having more years of schooling provides essential information and skills that are linked to more protective and less risky behaviors. Injuries. Violence and war account for more than a quarter of injury-related deaths among young men age 15 to 29. Adolescent boys and men in their 20s are an important part of the military forces in all countries that have such forces. As such, they are at high risk, particularly in areas where armed conflict is occurring. The United Nations Children’s Fund estimates that approximately 300,000 soldiers under the age of 18 are involved in armed conflicts worldwide (National Research Council and Institute of Medicine 2005). Homicide is also an important cause of death for young men, in particular, and it is the leading cause of death for young men in some Latin American countries (WHO 2001b). In addition, road accidents account for significant proportions of injuries and deaths among young people. Self-inflicted injuries, including suicide, which are often related to mental illness, are also a major health problem for young people, accounting for 4 percent of DALYs in men age 15 to 29 and 3 percent of DALYs in women age 15 to 29. Mental Health. Depression, schizophrenia, and other mental illnesses are important causes of illness and death among young men and women and account for a significant proportion of DALYs for both men (18 percent) and women (23 percent) age 15 to 29; for 5- to 14-year-olds, it is about 9 percent for boys and 8 percent for girls. The relative importance of mental illnesses is much greater in the high-income countries.

Smoking, Alcohol, and Drug Use. Most adult smokers worldwide begin smoking in adolescence or earlier (World Bank 1999a). An estimated 15 percent of young men and 7 percent of women age 13 to 15 are currently smoking cigarettes, according to more than 100 surveys that have been conducted since 1999 by the Global Youth Tobacco Survey Program and carried out under the auspices of WHO and the U.S. Centers for Disease Control and Prevention (National Research Council and Institute of Medicine 2005). Every day, worldwide, almost 100,000 young people start smoking, more than two-thirds of them in LMICs (World Bank 1999a). Of the 300 million young people smoking today, half will eventually die from tobacco use (WHO 2001b). By 2030, tobacco is expected to be the single biggest cause of death worldwide, accounting for about 10 million deaths per year (World Bank 1999a). Although discouraging young people from starting to smoke and providing means for them to quit is extremely important, deaths caused by tobacco tend to occur many years later. Therefore, tobacco use as an underlying risk factor accounts for very few DALYs in the 5 to 29 age group (WHO 2002). Alcohol and drug use account for 8 percent of all DALYs for young men age 15 to 29 but for only 2 percent for young women. Evidence indicates that young people are starting to drink at earlier ages. Longitudinal studies have found that the earlier young people start drinking, the more likely they are to experience alcohol-related injuries and alcohol dependence later in life (WHO 2001a). Nutrition and Exercise. Nutritional deficiencies such as anemia are widespread in both young men and women. Worldwide, these conditions account for almost 5 percent of DALYs among girls age 5 to 14 and almost 4 percent among boys of the same age, with anemia being an important component for both girls and boys. Although nutritional deficiencies are relatively less important among 15- to 29-year-olds (just over 1.0 percent among young men and about 1.5 percent among women), anemia accounts for the bulk of these deficiencies. Chronic undernutrition that causes stunting among young people delays growth and physical maturation, increases risks to pregnant mothers and their newborns, and decreases the capacity to learn and to work (Behrman and others 2004; Hoddinott and Quisumbing 2003). Malnutrition can take other forms, some of which lead to being overweight or obese, thereby increasing the risks for diseases such as diabetes. Such forms of malnutrition are of increasing relevance in middleincome countries such as Brazil, China, the Arab Republic of Egypt, Mexico, and South Africa and at times coexist with undernutrition (see, for example, Doak and others 2000). Nutritional deficiencies increase the risks that girls and young women face during pregnancy and childbirth (Delisle, Chandra-Mouli, and de Benoist 2001), and evidence is emerging about the connection between poor maternal nutrition and Adolescent Health Programs | 1111


greater risk of transmission of HIV from mothers to their infants (Piwoz and Greble 2000). Diet and lifestyle-related chronic diseases—many with their roots in childhood and adolescence—are emerging as one of the most important health problems in LMICs. Cardiovascular diseases, which are responsible for 10 percent of DALYs lost in LMICs, typically occur in middle age or later; however, risk factors are determined to a great extent by behaviors learned during childhood and adolescence and continued into adulthood, such as dietary habits and smoking. Throughout the world, these risks are starting to appear earlier. Physical activity has decreased markedly in adolescence, particularly in girls, and obesity has increased substantially (MacKay and Mensah 2004). Sexual and Reproductive Behaviors. Worldwide, the majority of young people initiate sexual activity during adolescence. Significant proportions—in some regions and countries, the majority—marry and become parents (table 59.2). Globally, the age of onset of puberty has been decreasing progressively for both boys and girls (National Research Council and Institute of Medicine 2005). The age at first marriage has also increased in most parts of the world over recent decades, except in Latin America (Mensch, Singh, and Casterline 2003). The decline in the age at puberty, combined with the general trend toward later marriage, increases the period of time during which adolescents may be sexually active before marriage and may result in sexual initiation at an earlier age (National Research Council and Institute of Medicine 2005). Young women typically make the transition to marriage and parenthood at an earlier age than young men, and early marriage predisposes girls to HIV infection through unprotected sex, because the partner, by virtue of age, has an elevated risk of being HIV positive. In addition, marriage changes adolescent girls’ support systems, thereby limiting their access to knowledge about HIV/AIDS (Bruce and Clark 2003). All these key transitions to adulthood bring with them the potential for risks to health that may have both immediate and longer-term effects. Among young women age 15 to 29, illnesses related to pregnancy and childbearing account for 16 percent of their DALYs. Some have unwanted pregnancies, and in countries where abortion is legally restricted, unsafe abortion is an important source of mortality and morbidity for young women, with abortion complications accounting for almost 3 percent of DALYs worldwide among females age 15 to 29. (WHO 2004c). Even though adolescent childbearing has declined in recent years, the proportion of young women who become mothers during adolescence remains high in most LMICs, and very early childbearing remains an issue in some regions (table 59.2). Childbearing before age 16 also brings with it a high risk of health consequences, both for the mother and for the newborn (Save the Children U.S.A. 2004; WHO forthcoming-b).

In the most recent surveys carried out in LMICs, high proportions of adolescents report that they have heard of contraceptive methods; however, little is known about the quality and accuracy of young people’s knowledge of contraception. Moreover, substantial proportions of young women appear to have an unmet need for contraception; they are not using contraception even though they are sexually active and do not want to have a child (CDC and ORC Macro 2003; Westoff and Bankole 1995). In addition to having a risk of early and unwanted pregnancy, adolescents are also at risk of acquiring sexually transmitted infections (STIs), including HIV. HIV/AIDS accounts for most of the sexual and reproductive health DALYs lost by young men age 15 to 29 (almost 9 percent). Among young women age 15 to 29, HIV/AIDS accounts for a higher proportion of DALYs than for young men (almost 12 percent) because of their higher levels of susceptibility. STIs and other sexual and reproductive health disorders together account for just over 5 percent of young women’s DALYs, much more than among young men. About half of all HIV infections occur in people under age 25, and for biological, social, and economic reasons, young women are disproportionately affected, especially in Sub-Saharan Africa, where young women have twice the prevalence rate of young men (UNAIDS 2003).

Poverty and Adolescent Health Poverty and inadequate health systems compound adolescents’ vulnerability to sickness and early death. At the same time, poor health exacerbates poverty by disrupting and cutting short school opportunities, by weakening or killing young people in the prime of their working lives, or by placing heavy financial and social burdens on families. Poor adolescents bear a disproportionate burden of the health problems in their age group. An analysis of data from demographic and health surveys (Macro International 1990–98, unpublished raw data) indicates a strong association between poverty and the health status of adolescents and between poverty and adolescents’ use of health services. For example, the poorest 20 percent of young women are between 1.7 and 4.0 times as likely to have an early birth as the richest 20 percent of young women. Similar disparities between rich and poor adolescents are seen for indicators such as early marriage, skilled attendance at birth, use of contraception, and knowledge of HIV/AIDS transmission, and these disparities tend to be greater for adolescents than for older women. For example, surveys in 45 countries show that the poorest 20 percent of women age 15 to 49 have a total fertility rate almost double that of the richest 20 percent, whereas among adolescents age 15 to 19, total fertility among the poorest 20 percent is more than triple that of the richest 20 percent (Macro International 1990–98, unpublished raw data).


Table 59.2 Indicators of Sexual and Reproductive Behaviors among Adolescents and Youth by Gender and Age Group, Late 1990s to Early 2000s a. Sexual Activity Percentage of females age 20–24 who became sexually active before age 18

20

Percentage of males age 20–24 who became sexually active before age

Region

15

15

18

20

East and Southern Africa

17

57

77

West and Central Africa

21

59

77

14

45

65

12

40

Caribbean and Central America

13

44

62

31

61

70

84

South America

9

41

61

31

73

87

Former Soviet Asia

1

20

53

—

—

—

Middle East

—

—

—

—

—

—

South and Southeast Asia

—

—

—

—

—

—

b. Marriage Percentage of females age 20–24 who married before age

Percentage of males age 20–24 who married before age

Region

18

20

18


37


45


20

Percentage of men age 20–24 ever married

55

14

28

60

12

27

35

53

22

38

South America

23

38

14

29

Former Soviet Asia

16

50

—

24

Middle East

23

40

—

17


42

60

—

41

c. Childbearing Percentage of females age 20–24 whohad a child before age Region

Percentage of males who ever fathered a child at age

16

18

15–19

20–24


9

27

2

24


13

31

2

13


7

22

2

27

South America

4

16

3

23

Former Soviet Asia

0

4

—

—

Middle East

3

11

—

—


9

24

—

—

d. Contraceptive Use

Region

Percentage of sexually active females age 15–19 using contraception

Percentage of sexually active females age 20–24 using contraception

All

All

Unmarried

Unmarried


21

28

30

42


20

26

23

35


24

—

36

—

South America

28

38

33

59

Former Soviet Asia

25

—

43

—

Middle East

—

—

—

—


—

—

—

—

Source: National Research Council 2005. — not available.

Adolescent Health Programs | 1113 ©2006 The International Bank for Reconstruction and Development / The World Bank 221

INTERVENTIONS Improving the health of young people is complex and difficult, arguably more so than for other age groups. Compared with children, adolescents are less protected by their families and communities and less amenable to simple solutions to their health problems, many of which are behavior based. Compared with adults, adolescents know less about how to stay healthy and have fewer resources to prevent or treat health problems. By contrast, their behaviors are less firmly entrenched, and they are often involved in institutional activities, such as schools, training programs, and the military, where programs with high coverage can be sustained. The influences on young people’s behaviors are becoming better understood (Blum and Mmari 2004; Pitts and others 2004), but even given what is known about such influences, the challenge of designing interventions to reinforce protective factors and mitigate risk factors remains. Many of the factors associated with less risky health behaviors, such as family connectedness and academic performance, go far beyond the purview of health program managers. Programs will have to seek multisectoral solutions that link health sector interventions with other types of interventions delivered through other sectors, either at the program level or at the policy level. The difficulty in attributing improvements in health outcomes among adolescents to interventions delivered in multiple settings or sectors reflects the challenges involved. Programs aimed at young people are relatively new and untested. Nevertheless, accumulated experience, backed by an increasing body of research, has created international consensus around a multi-intervention approach centered on the following (WHO 1999): • Young people need information and skills to make the right decisions about behaviors that affect their health, such as whether and when to have sex and whether to use tobacco. • Young people need access to a broad range of health services that give them the means to act on their knowledge, including access to condoms. • Young people need a social, legal, and regulatory environment that supports healthy behaviors and protects them from harm. Interventions to improve adolescent health have typically reflected this consensus and are echoed in goals that have been adopted internationally. This section summarizes what is known about the effectiveness of such interventions. Note that the health community’s consideration of adolescent health has only occasionally advocated attention to those health conditions that are of relatively greater importance to the adolescent age group, at least as measured by indicators such as DALYS. Much of the focus has been on sexual and reproductive health and on risky behaviors

such as tobacco and drug abuse. The lack of age-specific data and traditional reliance on mortality and morbidity statistics contribute to the unbalanced attention. Another factor may be that such behaviors tend to have longer-term health consequences that are not reflected in standard DALY calculations. An additional reason for the imbalance in adolescent data may be the significant social impacts of sexual and reproductive behavior (for example, the contribution of high fertility to rapid population growth); the social and economic implications of large proportions of HIV-infected adolescents in many countries; the mortality implications of initiating tobacco use during adolescence; and the antisocial behavior associated with substance abuse. Public health systems’ efforts to address health problems associated with road safety, malaria, and mental health have devoted inadequate attention to developing and implementing programs that target adolescents.

Evidence on Sexual and Reproductive Health Interventions Two recent reviews summarize research on the effectiveness of adolescent sexual and reproductive health interventions. Table 59.3 presents the results of the FOCUS on Young Adults (2001) review. The FOCUS report looks at interventions in LMICs and is based on relatively rigorous evaluations of 40 programs. The general findings from the FOCUS review, supplemented by more recent research findings, are as follows: • Almost all programs are effective in promoting positive knowledge and attitudes. Almost all the rigorously evaluated programs that FOCUS reviewed improved knowledge of reproductive health and selected attitudes. • Most programs effectively influence behaviors. A majority of programs significantly changed at least one important adolescent behavior pertaining to reproductive health. Often, however, programs tried and failed to improve many important behaviors. Where research has found programs to be effective in changing behaviors, such changes have typically not been large. • All six categories of interventions studied proved effective at influencing reproductive behavior in at least one study. However, maintaining that certain models are more effective than others is impossible because the period of observation and the behaviors that were influenced varied by study. Moreover, further replications in multiple settings are necessary to provide a basis for identifying the key features or elements of successful interventions. • The evidence base is limited in a number of ways. Few studies look at the effects on ultimate health outcomes, such as pregnancy rates or rates of HIV infection. Furthermore, many promising approaches have not been rigorously evaluated. Only a few studies assessed effects on the use of health services, and none examined the effect of creating a


Table 59.3 Effectiveness of Adolescent Sexual and Reproductive Health Programs, LMICs Number of programs showing significant impact/Total number of programs studied Impact on key behaviors Number of studiesa

Improved knowledge and attitudes

Delayed sex

Reduced number of partners

Increased contraceptive use

Increased service use

Improved at least one behavior

All programs

40

33/36

6/17

6/10

18/23

4/9

23/30

School

21

17/19

4/11

3/6

6/10

1/3

9/14

6

5/6

1/4

2/3

5/5

1/2

5/5

Type of program

Mass media Community

4

4/4

1/1

—

4/4

—

4/4

Youth development

(1)

1/1

—

—

1/1

1/1

1/1

Peer education

(3)

3/3

1/1

—

3/3

—

3/3

4

4/4

—

—

2/2

—

2/2

Workplace Health facility

4

2/2

—

—

0/1

2/3

2/4

Youth-friendly services

(3)

1/1

—

—

—

2/3

2/3

Youth center

(1)

1/1

—

—

0/1

—

0/1

Multicomponent

1

1/1

0/1

1/1

1/1

0/1

1/1

Sources: Multicomponent program: AMREF, LSHTM, and NIMR 2003; all other programs: FOCUS on Young Adults 2001. — not available. a. Numbers of studies in parentheses are subsets.

supportive environment on behaviors. Furthermore, much of the available evidence from strong studies is for smallscale programs that are carried out over short periods of time, and little evidence is available on long-term effects on behaviors (Speizer, Magnani, and Colvin 2003). A recent study in Tanzania provides the first rigorous evidence that the benefits of adolescent sexual and reproductive health programs in low-income countries can last for at least three years (AMREF, LSHTM, and NIMR 2003). Kirby’s (2001) review covers roughly 70 rigorously evaluated programs in Canada and the United States. The review divides programs into three categories: (a) programs that focus on sexual antecedents, such as sexuality and HIV education and clinical programs; (b) programs that focus on nonsexual antecedents; and (c) programs that incorporate both youth development and reproductive health components. Kirby finds that programs in all three categories proved effective in reducing sexual risk taking, pregnancy, and childbearing among teens. In relation to youth development programs, Kirby finds that a type of intervention known as service learning, in which students work on community projects, had the strongest evidence of effectiveness. By contrast, other types of youth development programs were not effective in improving reproductive health outcomes. Programs that incorporate both youth development and reproductive health components were effective over long periods.

In synthesizing U.S. and international data, Kirby (2003) finds that programs are effective with different groups of adolescents in different countries. Also, programs seem to be particularly effective for adolescents who are at especially high risk of negative sexual and reproductive behaviors. In addition, programs do not hasten or increase sexual activity—a common criticism of opponents of adolescent programs. Of all the programs that have been rigorously evaluated, none has reported a decrease in the age of sexual debut or an increase in sexual activity among young people. A recent effort to review the evidence on interventions for preventing HIV among young people has made tentative conclusions about the effectiveness of and subsequent support for wide-scale implementation (WHO 2004b). On the basis of these international reviews, relatively strong evidence of effectiveness on a range of outcomes has emerged for the following interventions: • Life-skills and health and sexuality education in schools. Welldesigned, well-implemented sexuality and reproductive health education can provide young people with a solid foundation of knowledge and skills to enable them to engage in safe and responsible sexual behavior. • Peer education. Peer education programs are especially appropriate for young people who are not in school and for hard-to-reach, at-risk subsets of the youth population, including sex workers and street children. Adolescent Health Programs | 1115


• Mass media and community mobilization. Mass media and community mobilization efforts that engage influential adults, such as parents, teachers, community and religious leaders, and music and sports stars, can help normalize positive adolescent behaviors and gender roles as well as direct young people to appropriate health services. • Youth development programs. Youth development programs typically address a range of key adolescent needs, including life skills, education, jobs, and psychosocial needs. U.S. programs with a voluntary community service component have successfully improved key reproductive health behaviors, but no evidence is available for developing countries. • Clinical health services. Although some young people seek care through the formal health system, many others are deterred by the often judgmental attitudes of health workers, particularly when seeking care and advice on matters related to sexuality. • Social marketing. This approach involves the use of public health messages to promote healthy behaviors and the use of condoms and other health products and services. Effective programs bring products and services to places in the community that young people frequent, such as shops, kiosks, and pharmacies. • Workplace and private sector programs. Programs that reach young people do so at their places of work and through private channels, such as pharmacies and for-profit medical services, where many young people prefer to seek care. Many successful U.S. youth development programs have a work component.

Evidence of Other Adolescent Health Interventions Data on the effectiveness of other adolescent health interventions are more scattered, partly because some issues have not been recognized as adolescent-specific problems that require youth-focused interventions. Nutrition. Because anemia is a critical health problem in many countries, many efforts have focused on improving the iron intake of adult women. Interventions aimed at adolescent girls have found that daily iron supplementation effectively lowers anemia and iron deficiency (Elder 2002; MotherCare 2000). Obesity is rapidly becoming a serious health problem among adolescents in many middle-income countries and is often also associated with loss of self-esteem among adolescents. A few studies show that preventing obesity is more successful among adolescents than among adults (Delisle, Chandra-Mouli, and de Benoist 2001). Mass Deworming. In the Busia district of western Kenya, an ongoing World Bank study is evaluating the effect on learning outcomes of providing deworming treatment to all students in

a school. After two years, observed effects of deworming treatment included fewer absences and lower dropout rates, but no effect on test scores (World Bank 2002a). The treatment also resulted in health and school participation benefits among untreated children in the same schools, as well as in neighboring schools, suggesting that the deworming had positive externalities. Tobacco. Price increases are the most effective tool for reducing or deterring the use of tobacco products by young people. Studies in the United States have shown that price increases have a greater effect on tobacco use by young people than on use by older age groups (University of Illinois at Chicago Health Research and Policy Centers 2001). Other interventions have also reduced tobacco use among young people, such as comprehensive bans on all advertising, including bans on the promotion of tobacco products and trademarks (World Bank 2002c). Programs that give young people the skills to resist peer pressure and other social pressures to smoke have demonstrated consistent and significant reductions or delays in adolescent smoking. School-based programs are also more effective when combined with communitywide supportive efforts. Information campaigns that help young people see how the tobacco industry tries to manipulate their behavior through advertising have been highly effective in changing behavior and attitudes toward smoking among young people in the United States (American Legacy Foundation 2002).

Promising but Unproven Interventions Many promising adolescent-focused interventions have not yet been rigorously evaluated. These interventions include programs aimed at providing young, newlywed couples with reproductive health information and services (Alauddin and MacLaren 1999); programs that combine livelihoods skills with reproductive health information and services (Rosen 2001b); voluntary counseling programs on and testing for HIV (YouthNet 2002); actions aimed at changing social norms such as gender roles (Horizons 2004); and interventions that address the political and social context (WHO forthcoming-a). A few studies of multipronged approaches are just becoming available and have shown mixed results. Findings from a four-country study found little or no effect of such an approach on key reproductive health behaviors among adolescents (Frontiers, Horizons, and YouthNet 2004). By contrast, a study in Tanzania found that a multicomponent approach had a significant effect on key reproductive health behaviors but no effect on health outcomes (AMREF, LSHTM, and NIMR 2003). Other possibly promising efforts include suicide prevention programs, tuberculosis education linked with health education (interpersonally or through the mass media), and malaria treatment programs that focus on young people. Adequate


evaluation is available on the efficacy of programs promoting the use of seat belts and crash helmets through enforcement of related laws and the support of intensive publicity and information campaigns, as well as on the efficacy of programs preventing alcohol use among adolescents. The evaluations are sufficient for building confidence for investment, and they serve as a basis for intervention design (National Research Council and Institute of Medicine 2004; WHO 2004d).

COSTS AND COST-EFFECTIVENESS OF INTERVENTIONS Good cost studies of adolescent health programs in LMICs are rare. The reported cost of such programs varies greatly depending on the country, type of intervention, target group, and so on. For example, such programs cost between US$0.03 per adolescent reached in a family life education radio program in Kenya and US$71.00 per year per adolescent reached in a school-based HIV prevention program in Zimbabwe. Of the 32 programs studied, 12 have a unit cost of less than US$10 per year, and others have a unit cost of US$10 to US$25 (table 59.4). Cost estimates are available only for certain types of interventions, with most of the estimates being for reproductive health and HIV education programs. A few studies have tried to measure cost per DALY of adolescent sexual and reproductive health interventions; however, the estimates vary widely. For example, in India, a youth-focused HIV prevention program costs US$66.20 per DALY gained; in Honduras, the cost of a voluntary counseling and testing program aimed at youth is US$5,873 per DALY gained. The estimates shown in table 59.4 should be interpreted with great caution. Comparing costs across types of programs and countries is difficult, but so is choosing comparable effectiveness measures.3,4

ECONOMIC ANALYSIS Economic analysis of adolescent health programs can provide important information on their value relative to other interventions.

Economic Benefits of Interventions The macro approach to measuring the economic benefits of interventions is to define the benefits of investing in youth in terms of the investments’ effect on economic growth, which typically is measured in terms of growth in gross national product per capita. Some research suggests that investments in young people—whether in access to reproductive health care, in education, or in other key facets of their lives—have

synergistic effects that promote overall economic development (Birdsall, Kelley, and Sinding 2001). For example, shifts to smaller family size and slower rates of population growth in East Asia appear to have played a key role in the creation of an educated workforce, the accumulation of household and government savings, the rise in wages, and the spectacular growth of investment in manufacturing technology. The shift to smaller families that is taking place in many countries will open another window of opportunity as workers have proportionately fewer old and young dependents to support. If societies invest in health, education, and job creation, the resulting economic gains will improve their overall quality of life. Education, particularly for girls, is strongly related to reproductive behavior. In most countries, girls who are educated are more likely to delay marriage and childbearing, whereas girls with less education are more likely to become mothers as adolescents. Unfortunately, the causal relationships involved are not clear. Are girls more likely to get married when they leave school, or do some girls prefer to terminate their schooling and marry early? The difference is critical. In the first case, the appropriate policy response would focus on improving schooling opportunities for girls. In the second case, research would need to be done first to determine the underlying reasons for girls’—and their parents’—preferences for early marriage instead of additional schooling. The next step would be to assess whether these reasons appear to reflect the girls’ (and society’s) best interests and, if not, to find interventions to address the root causes of this preference. The micro approach to measuring the economic benefits of interventions is to build on microeconomic estimates of direct productivity effects that can be measured in monetary terms. For other effects that cannot readily be translated into monetary terms, analysts can use the cost of the most cost-effective alternative to achieve the same effects. Knowles and Behrman (2003a) use this approach to estimate the benefits of various youth-focused investments, including in health. They summarize the three types of effects: (a) those that can be directly valued in monetary terms, (b) those that may require indirect valuation, and (c) those that are particularly difficulty to monetize. Table 59.5 presents examples of these effects.

Cost-Benefit Analysis Cost-benefit analysis is well suited to the economic analysis of projects aimed at youth, in part because many investments in young people yield multiple benefits, such as additional schooling and improved health. Finding any effectiveness measure that adequately reflects the wide range of benefits obtained from some types of investments in youth is difficult, but costbenefit analysis has the advantage of allowing comparisons across a range of interventions that may vary considerably in terms of type and effects. Adolescent Health Programs | 1117


Table 59.4 Cost and Cost-Effectiveness of Adolescent Health Programs Region and country

Number served per year

Program type (name)

Unit cost (US$)

Unit

Cost per DALY gained (US$)

Source

Sexual and reproductive health interventions Latin America Brazil

School-based HIV/AIDS prevention program

—

0.70

Per condom

—

Antunes and others 1997

Honduras

School-based reproductive health program to prevent HIV/AIDS

—

10.44

Per targeted adolescent

1,323

World Bank 2002b

Honduras

Social marketing of condoms to adolescents

904,612

10.20

Per targeted adolescent

3,292

World Bank 2002b

Honduras

Symptomatic treatment of STIs

—

48.97

Per adolescent treated

Honduras

Voluntary counseling and testing for youth

1,000

18.29

Per adolescent undergoing voluntary counseling and testing

Honduras

Workplace information, education, and communication

1,000

20.88

Per worker

Mexico

Community peer educators

4,000

63.64

Per active user of contraception per year

—

Townsend and others 1987

Mexico

Youth center

4,000

203.47

Per active user of contraception per year

—

Townsend and others 1987

Peru

School-based sexuality and HIV/AIDS prevention education

604

3.00

Per student reached

—

Caceres and others 1994

28,306

World Bank 2002b, as cited in Knowles and Behrman 2003b

5,873

World Bank 2002b, as cited in Knowles and Behrman 2003b

2,623.77

World Bank 2002b

Europe and Central Asia Hungary


41,250

1.40

Per student per year

—

Soderlund and others 1993

Newly independent states


—

1.33

Per student reached

—

Forrai, personal communication, 1992

Information, education, and communication programs targeted to youth

—

1,324

Per HIV infection averted

66.20

World Bank 1999b

Asia India

Sub-Saharan Africa Africa


—

75–200 (primary school); 121–241 (secondary school)

Average unit cost of teacher training and simple materials

—

UNECA 2000

Africa


—

1.40–7.90

Per student reached

—

Watts and others 2000

Africa

Peer education

—

8.00–10.81

Per out of school adolescent reached

—

Kumaranayake and Watts 2001

Cameroon


10,000

6.72

Per student reached

—

Kumaranayake and del Amo 1997

Kenya

Radio program delivering family life education (Youth Initiatives Project)

3,354,000

0.03

Per adolescent reached

—

Knowles and Behrman 2003b


Table 59.4 Continued Region and country

Program type (name)

Number served per year

Unit cost (US$)

Unit

Cost per DALY gained (US$)

Source

Mozambique

Community based “stepping stones” approach (Action Aid)

500,000

0.30

Per person per year

—

World Bank 2003

Mozambique

Voluntary counseling and testing, peer education

11,726

18.40

Per person per year

—

World Bank 2003

Senegal

Mulitpronged school, clinic, and community interventions

—

68,215– 111,714

Total intervention cost over a two-year period

—

RamaRao and Diop 2003

South Africa

Television show, mass media campaign (Soul Buddyz)

6 million

0.38

Per person per year

—

World Bank 2003

South Africa

Mass media campaign (LoveLife)

Tanzania

Primary school peer education (MEMA kwa Vijana)

Tanzania

Secondary school peer education (School Health Education Program)

Uganda

Outreach program for street children (GOAL: Baaba Project)

Uganda

Newsletters, radio show (Straight Talk)

Zambia

Life skills for teachers and pupils (AIDS Action Program for Schools)

—

Zambia

School clubs, health clinics, peer education (Kafue Adolescent Reproductive Health Program)

Zimbabwe Zimbabwe

—

20 million

Annual budget

—

World Bank 2003

2,850

1.37

Per person per year

—

World Bank 2003; Ross, personal communication. 2003

16,250 (over three years)

24.12

Per person per year

—

World Bank 2003

5,000

18.50

Per person per year

—

World Bank 2003

Amount spent in 2001

—

World Bank 2003

0.16

Additional cost of one child-year of AIDS education

—

Knowles and Behrman 2003b

53,000 (over five years)

2.26

Per person per year

—

World Bank 2003

Secondary school clubs, income generation, peer education (Africare)

35,200 (over two years)

8.89

Per person per year

—

World Bank 2003

Secondary school clubs, counseling, peer education (Midlands AIDS Service Organisation)

2,000

71.00

Per person per year

—

World Bank 2003

Nationwide 630,000 program reaching all schools

Other health interventions LMICs

Tax on tobacco products

—

—

—

LMICs

Iron supplementation for 13- to 15-year-olds

—

0.18

Per child per year

5–17 —

World Bank 1999a Knowles and Berhman 2003a

Source: Authors. — not available.

One of the few cost-benefit analyses specific to adolescent health is Knowles and Behrman’s (2003a) study that examines three interventions: a program to provide iron supplementation for secondary schoolchildren, a school-based program of health education to prevent HIV/AIDS, and a tobacco tax. The study estimates benefits and costs over a youth’s life cycle, discounted back to the age of 18. The study uses direct estimates of benefits that could be readily estimated in monetary terms (such as gains in labor productivity) and indirect estimates of other benefits, such as reduced fertility and improved health, that could not be easily monetized. The latter were estimated as

the least cost of investments currently made to obtain the same benefit; for example, the cost per birth averted in a family planning program was used to value reduced fertility. Table 59.6 summarizes the findings of these cost-benefit studies, together with estimates of the benefit-cost ratios for selected other youth-targeted interventions. The examples of cost-benefit studies cited here and other calculations of benefit-cost ratios show that health interventions aimed at adolescents can be good public investments; however, the results must be interpreted with some caution. For example, the relatively low benefit-cost ratio of an HIV Adolescent Health Programs | 1119


Table 59.5 Types of Effects of Adolescent Health Interventions Categorized According to Ease of Monetization Type of effect

Examples

Directly monetizable effects of investments in youth

Enhanced labor productivity Reduced underutilization of labor Increased or decreased work effort Expanded access to risk-pooling services Reduced age at which children achieve a given level of schooling Reduced cost of medical care

Indirectly monetizable broad effects of investments in youth

Increased education Averted teen pregnancy Averted HIV infection Averted tuberculosis infections Improved health Improved nutritional status Delayed marriage Averted abortion Reduced tobacco use

Effects that are particularly difficult to monetize

Increased social capital Averted infertility Averted social exclusion Improved self-esteem Enhanced national security (an effect of military training)

Source: Adapted from Knowles and Behrman 2003a.

Table 59.6 Estimated Benefit-Cost Ratios, Selected Investments in Youth

Investment

Estimated benefit-cost ratio (assuming 3 percent annual discount rate)

Scholarship program (Colombia)

4.4

Plausible range of estimated benefit-cost ratio 2.8–25.6

Adult basic education and literacy program (Colombia)

27.6

School-based reproductive health program to prevent HIV/AIDS (Honduras)

0.5

Iron supplementation administered to secondary schoolchildren (hypothetical low-income country)

45.2

25.8–45.2

Tobacco tax (hypothetical middle-income country)

20.2

7.0–38.6

Source: Adapted from Knowles and Behrman 2003a.

prevention program in Honduras was for a program in a country where HIV incidence among young people is relatively low (0.1 percent). Where the incidence is much higher, as in many of the hardest hit countries in Africa (1 percent or more), this ratio would be proportionately higher. In addition, in the Honduran study, the benefits included were limited to the prevention of HIV/AIDS and did not include other possible benefits, such as increased education, reduced STIs other than HIV, and reduced teen pregnancies and abortions. The Honduran study also assumed that the effects of the intervention would not continue beyond one year; however, if they were to continue at the same level to age 29 (assuming that any decrease in the effect of the intervention over time would be offset by increases in the incidence of HIV infection with age), the benefit-cost ratio would increase from 0.5 to 4.6. More than anything else, Knowles and Behrman’s estimates demonstrate the sensitivity of the benefit-cost ratios of investments in youth to wide variations in key assumptions, which may be equally plausible because of the limited information available on the costs and effects of many investments in youth. Beyond the question of how sensitive such estimates are to the underlying assumptions and the context, the basic question is what guidance they provide for public policy. High benefit-cost ratios certainly point to areas that merit further consideration for possible policy interventions, but they do not indicate whether using public resources for interventions has an efficiency rationale, because they generally do not identify differences between private and social benefit-cost ratios.If the purely private benefitcost ratios for an investment are high, then presumably incentives to use private resources for this investment are high, but an efficiency rationale for using public resources does not exist unless the social benefit-cost ratio exceeds the private one because of factors such as spillovers or market imperfections. High benefit-cost ratios that do not distinguish between social and private returns, therefore, call for further investigation. Interventions may warrant the use of public resources on efficiency grounds, but they also must answer that important question of whether the benefits are social or private.

8.1–1,764.0 0.1–4.6

PROGRAM IMPLEMENTATION AND LESSONS OF EXPERIENCE Relatively few adolescent-focused programs have been tried on a large scale. Sexual and reproductive health interventions and suicide prevention are some of the few that have gone to scale, and even in those areas, large-scale interventions are relatively infrequent. The vast majority of interventions have been in relatively small programs, often through nongovernmental organizations. Perhaps the main lesson learned from the experience to date is an obvious one: programs to reach young people are not


simply programs for adults applied to a younger population; they require different thinking and a different approach. Determining Key Principles of Health Programming for Adolescents Experience to date suggests that effective, youth-focused efforts share a set of common general principles. These principles include the following: • Recognize the diversity of the youth age group. A sexually inexperienced 11-year-old has vastly different needs than a married 20-year-old. Programs should apply different strategies to reach youth, who vary by age, sex, employment, schooling, and marital status. • Involve young people. Policies and programs are more effective when young people are involved in all aspects of their design, implementation, and evaluation. Involvement must go beyond tokenism and be genuine, meaningful, and sustained. • Make health services appealing to youth. A key to rapidly expanding young people’s access to health services is to make them more youth friendly by using specially trained health workers and by bolstering the privacy, confidentiality, and accessibility of care. • Address gender inequality. Gender inequalities expose young girls to coerced sex, HIV infection, unwanted pregnancy, and poor nutrition. Efforts should focus on changing the factors that perpetuate gender inequalities. • Address the needs of boys. Adolescence presents a unique opportunity to help boys form positive notions of gender relations and to raise their awareness of health issues. At the same time, boys seem to be disproportionately exposed to a number of adolescent health risks, including accidents and injuries, suicide, tobacco use, substance abuse, and violence. Program design should take into account the specific needs of boys and young men as well as of girls and young women. • Design comprehensive programs. Comprehensive programs that provide information and services while addressing the social and political context are more effective than narrowly focused interventions. • Consider all important benefits. Many adolescent health interventions focus on only one benefit. For example, a school-based sex education program may focus exclusively on HIV prevention and may neglect other possible benefits from the intervention, such as increased education, averted teen pregnancy and abortions, and other averted STIs. • Address the many nonhealth factors that influence adolescent health. Linking school and livelihood opportunities to adolescent health programs, at either the policy or program level, is key to helping young people avoid risky behaviors. • Address underlying risk and protective factors. Factors such as feelings of self-efficacy, attitudes and behaviors of friends, connectedness with parents and other influential adults, and

involvement in the community can either increase (risk factor) or decrease (protective factor) the chances that a young person will engage in unhealthy behaviors. Making a Difference on a Large Scale Adolescent health programs are complex and may not be easy to scale up because of technical, management, and political challenges. The following are examples of adolescent health programs that are national in scope. Unfortunately, little is known about the costs and effectiveness of such large-scale efforts. National Suicide Prevention Program in New Zealand. Among industrial nations, New Zealand has one of the highest suicide rates for both males and females age 15 to 24 (New Zealand Ministry of Health 2002). In 1998, on the basis of international good practice, the government developed the National Youth Suicide Prevention Strategy. This strategy, which includes a component for the general population and one that focuses on the indigenous Maori community, provides a framework for understanding suicide prevention and signals the steps that government agencies, communities, and service providers must take to reduce suicide. Even though the national strategy has not been in place long enough to adequately gauge its effects, in 1999, the first year following the adoption of the strategy, youth suicide rates fell to their lowest levels since 1991. Sexuality Education in Mongolia. Mongolia has implemented a locally developed and tested sexuality education curriculum in 60 percent of schools nationwide. Current challenges include increasing the number of hours allocated to sexuality education; developing more and better written resources for adolescents, including textbooks; developing materials that will help parents communicate better with their children on sexuality; expanding access to clinical services for adolescents through the public health system; reaching out-of-school youths and the broader community with sexuality education; and monitoring and evaluating the program regularly to assess its weaknesses and strengths and how it could be improved (Gerdts 2002). Addressing the Health Needs of Poor Youth The following strategies, based on what is known about services for poor people more generally and about the specific needs of young people, show promise for meeting the needs of poor youth: • Targeting out-of-school youth. Out-of-school youth of a given age are likely to be more marginalized than those who are in school, and they are often those most in need of critical services, such as pregnancy prevention and prevention of HIV/AIDS and other STIs. A number of countries, including Paraguay, South Africa, and Zimbabwe, have launched effective programs targeting out-of-school youth Adolescent Health Programs | 1121


that combine the use of mass media, peer education, and community-based efforts. For instance, the Arte y Parte project targeted out-of-school youth in three cities in Paraguay using a booklet about adolescent sexuality, street drama, radio programming, newspaper columns, and distribution of promotional items (Magnani and others 2000). • Focusing efforts on vulnerable youth. Young people who have been orphaned or left vulnerable by AIDS typically rely first on their extended families and communities for support. Efforts to help vulnerable youth should strengthen those safety nets. One example is the COPE program in Malawi, where a nongovernmental organization–sponsored effort works through existing government structures to help orphans and other vulnerable children (Phiri, Foster, and Nzima 2001). • Tailoring subsidized programs to poor youth. Social marketing of reproductive health products and services—such as contraceptives and condoms for pregnancy and disease prevention or promotion of iron supplementation—often targets young consumers, but such efforts should ensure that they reach the desired clients—namely, those who are poor and less likely to be able to afford market prices. The Social Marketing for Adolescent Sexual Health Project in four African countries combined the use of mass media with peer education to encourage young people to practice safer sex, including condom use (Agha 2000). Improving Health Systems to Meet Adolescents’ Health Needs The shortcomings of health systems in LMICs are well known, and adolescents in particular would benefit from the following health system improvements: • Strengthening human resource capacities. The poor quality of the interaction with health workers is one of the main barriers to adolescents’ use of health care in public sector facilities. Through training, supervision, and other means, health systems should encourage health workers to adopt a more youth-friendly outlook. In addition, health systems should integrate such training into the curricula of medical, nursing, and nurse auxiliary schools. • Involving the private sector. Many young people already seek care from private doctors, nurses, and nurse-midwives or from local pharmacies or other drug distribution outlets. Along with encouraging private for-profit health providers to serve youth, government policies should encourage efforts to tap into the private sector as a source of health care for adolescents by means of interventions such as social marketing, contracted services, youth-focused social franchising, and programs that serve young people at their place of work. (Carranza 2003; LaVake and Rosen 2003; Rosen 2001a; Senderowitz and Stevens 2001).

• Strengthening the stewardship oversight function of governments. Governments have a key role to play in developing supportive policies, both within the health sector and across sectors; in contributing to cross-sectoral policies such as national youth policies; and in providing input into policy making in other sectors, especially education and labor. Ideally, governments should have an overarching adolescent health policy with specific reference to adolescent health in policy documents for specific programs or diseases, such as for AIDS, tuberculosis, malaria, sexual and reproductive health, and population (WHO forthcoming-a; POLICY Project and YouthNet forthcoming).

RESEARCH AND DEVELOPMENT AGENDA The striking lack of good research and evaluation of adolescent health interventions limits countries’ ability to address serious health problems. At this juncture, research in the following broad areas is critical: • Refining estimates of DALYs for adolescents. Available DALY information is inadequate to fully explore the burden of disease for adolescent age groups. Future DALY estimates should be made for five-year age groups in the 10 to 24 age range. • Documenting the effectiveness of current approaches. This area includes better process evaluation to understand the functioning of successful programs. Such evaluation necessitates more rigorous research designs so that the effectiveness of programs can be better documented, both in terms of health outcomes and in terms of DALYs saved. Another area in which more research could help is better documentation of the nonhealth effects of adolescent health interventions. Greater investment is also needed to evaluate the effects of health promotion strategies on reducing smoking, including the smoke-free spaces prevalent in the Americas and life-skills education. • Testing new interventions. This area includes more research on multicomponent programs and on new types of interventions. In relation to sexual and reproductive health, new interventions include approaches such as providing antiretroviral therapy to HIV-infected youth and voluntary counseling and testing for HIV, encouraging adolescents to have fewer sexual partners, reducing the trafficking of young people, preventing and addressing the health consequences of early marriage, and reaching young married women with information and services. Research must better inform interventions so that they reach groups at particularly high risk of poor health outcomes, such as child prostitutes, child workers, refugees, AIDS orphans, and street children. More research is also needed on a broad range of other adolescent


health interventions, especially for those health problems that are among the biggest killers and disablers of young people: HIV/AIDS and mental illnesses for both males and females, maternal conditions for females, and road accidents for males. In addition, research is needed on programs that attempt to influence gender roles and social norms and investments designed to avert drug and alcohol abuse and to improve mental health. • Enhancing understanding of the risk and protective factors influencing young people’s behavior. Even though our understanding of the major influences on youth behaviors has come far, more refinement of such understanding is needed, along with a better understanding of how to incorporate such knowledge into the design of programs and policies. • Improving cost and cost-benefit analysis. Good cost estimates are rare, and more needs to be done to more fully estimate the costs of the range of adolescent health interventions. This effort means collecting more data on program costs and more accurate data that include programs’ nonmonetary costs. Few full cost-benefit analyses of youth programs exist, and more need to be done to improve evaluations of the economic value of investments targeted at young people.

CONCLUSIONS The health community has only recently recognized the importance of adolescent health problems. To address the unique health problems associated with the adolescent years, policy makers and the health community must expand the knowledge base on effectiveness, costs, and economic benefits and pay more attention to areas such as road safety, nutrition, mental health, and malaria. Well-documented implementation experiences from mostly small programs have produced a sound body of knowledge about how programs function. These experiences can provide the foundation for scaled-up efforts and can help the health community improve health systems in ways that will benefit adolescent health efforts.

2. Regional data cited from this report here and elsewhere in the chapter are based on nationally representative surveys carried out between the mid 1990s and 2001. 3. Knowles and Behrman (2003b) find that many cost estimates incorrectly treat income transfers as costs and frequently fail to include estimates of administrative and distortionary costs (for example, the distortionary cost of financing programs through taxes). 4. In cost-effectiveness analysis, as in cost-benefit analysis, estimates are needed not only of what has actually happened, but also of what would have happened in the absence of the program or intervention (that is, an estimate of the counterfactual). There are no exceptions to this rule.

REFERENCES Agha, S. 2000. “An Evaluation of Adolescent Sexual Health Programs in Cameroon, Botswana, South Africa, and Guinea.” Population Services International Research Division Working Paper 29, Population Services International, Washington, DC. Alauddin, M., and L. MacLaren. 1999. InFOCUS: Reaching Newlywed and Married Adolescents. Washington, DC: FOCUS on Young Adults. American Legacy Foundation. 2002. “New American Legacy Foundation Study Shows Truth® Campaign Helping to Drive Down Youth Smoking Rates.” American Legacy Foundation, Washington, DC. http://www.americanlegacy.org. AMREF (African Medical and Research Foundation), LSHTM (London School of Hygiene and Tropical Medicine), and NIMR (National Institute for Medical Research). 2003. “MEMA kwa Vijana: Randomised Controlled Trial of an Adolescent Sexual Health Programme in Rural Mwanza, Tanzania.” Technical briefing document, LSHTM, London, August 11. Antunes, M., R. Stall, V. Paiva, C. A. Peres, J. Paul, M. Hudes, and others. 1997. “Evaluating an AIDS Sexual Risk Reduction Program for Young Adults in Public Night Schools in São Paulo, Brazil.” AIDS 11: S121–27. Behrman, J. R., J. Hoddinott, J. A. Maluccio, A. Quisumbing, R. Martorell, and A. D. Stein. 2004. “The Impact of Experimental Nutritional Interventions on Education into Adulthood in Rural Guatemala: Preliminary Longitudinal Analysis.” Paper presented to the 2004 Population Association of America Annual Meeting, Boston, April 1–3. Birdsall, N., A. C. Kelley, and S. W. Sinding, eds. 2001. Population Matters: Demographic Change, Economic Growth, and Poverty in the Developing World. New York: Oxford University Press. Blum, R., and K. Mmari. 2004. Risk and Protective Factors Affecting Adolescent Reproductive Health in Developing Countries. An Analysis of the World’s Literature 1990–2004. Summary. Geneva: World Health Organization. Bruce, J., and S. Clark. 2003. “Including Married Adolescents in Adolescent Reproductive Health and HIV/AIDS Policy.” Paper prepared for technical consultation on married adolescents, World Health Organization, Geneva.

ACKNOWLEDGMENTS The authors acknowledge the generous help of the following people: Peju Olukoya for sharing materials and studies and for providing early feedback; Kimberly Switlick for preparing graphics and providing editorial assistance; and peer reviewers, including Maria Teresa Cinqueira, Jane Ferguson, Elena Nightingale, and Audrey Smith Rogers.

NOTES 1. The United Nations defines youth as those age 15 to 24. The World Health Organization defines adolescence as age 10 through 19 and uses the term young people to refer to those age 10 to 24.

Caceres, C. F., A. M. Rosasco, J. S. Mandel, and N. Hearst. 1994. “Evaluating a School-Based Intervention for STD/AIDS Prevention in Peru.” Journal of Adolescent Health 15 (7): 582–91. Carranza, J. M. 2003. “What Do Salvadoran Teens Think? Determining the Feasibility of Youth-Friendly Pharmacies: A Focus Group Report.” U.S. Agency for International Development and Commercial Market Strategies Project, Washington, DC. http://www.cmsproject.com/ resources/PDF/CMS_ElSalvador_Youth.pdf. CDC (U.S. Centers for Disease Control and Prevention) and ORC Macro. 2003. Reproductive, Maternal, and Child Health in Eastern Europe and Eurasia: A Comparative Report. Atlanta: U.S. Department of Health and Human Services. Delisle, H., V. Chandra-Mouli, and B. de Benoist. 2001. “Should Adolescents Be Specifically Targeted for Nutrition in Developing Adolescent Health Programs | 1123


Countries? To Address Which Problems, and How?” http://www. who.int/child-adolescent-health/New_Publications/NUTRITION/ Adolescent_nutrition_paper.pdf. Doak, C., L. Adair, C. Monteiro, and B. M. Popkin. 2000. “Overweight and Underweight Co-exists in Brazil, China, and Russia.” Journal of Nutrition 130: 2965–80. Elder, L. 2002. “Adolescent Nutrition: Issues and Interventions.” Background paper prepared for the World Bank Learning Exchange on Exploring Strategies for Reaching and Working with Adolescents, Washington, DC, June 5. FOCUS on Young Adults. 2001. Advancing Young Adult Reproductive Health: Actions for the Next Decade. Washington, DC: FOCUS on Young Adults. Frontiers, Horizons, and YouthNet. 2004. “New Findings from Intervention Research: Youth Reproductive Health and HIV Prevention.” Meeting report, Washington, DC, September 9, 2003. Gerdts, C. 2002. “Universal Sexuality Education in Mongolia: Educating Today to Protect Tomorrow.” Quality 12, Population Council, New York. http://www.popcouncil.org/publications/qcq/QCQ12.pdf. Hoddinott, J., and A. Quisumbing. 2003. “Investing in Children and Youth for Poverty Reduction.” Unpublished paper, International Food Policy Research Institute, Washington, DC. Horizons. 2004. “Promoting Healthy Relationships and HIV/STI Prevention for Young Men: Positive Findings from an Intervention Study in Brazil.” Population Council’s Research Update series, Population Council and Horizons Communications Unit, Washington, DC. http://www.popcouncil.org/pdfs/horizons/ brgndrnrmsru.pdf. Kirby, D. 2001. Emerging Answers: Research Findings on Programs to Reduce Teen Pregnancy. Washington, DC: National Campaign to Prevent Teen Pregnancy. ———. 2003. “Changing Youth Behaviors: Findings from U.S. and Developing Country Research and Their Implications for A, B, and C.” Paper presented at the meeting on HIV Prevention for Young People in Developing Countries, Washington, DC, July 24. http://www. fhi.org/en/Youth/YouthNet/NewsEvents/HIVprevenmeeting.htm. Knowles, J. C., and J. R. Behrman. 2003a. “Assessing the Economic Benefits of Investing in Youth in Developing Countries.” Health, Nutrition, and Population Discussion Paper, World Bank, Washington, DC. ———. 2003b. “The Economic Returns to Investing in Youth in Developing Countries: A Review of the Literature.” Unpublished paper. World Bank, Washington, DC. Kumaranayake, L., and J. del Amo. 1997. Resource Allocation for HIV Prevention: Cost, Epidemiological, and Behavioural Analysis— HIV/AIDS Education in Schools. London: London School of Hygiene and Tropical Medicine. Kumaranayake, L., and C. Watts. 2001. Scaling-Up Priority HIV/AIDS Interventions: A Problem of Constrained Optimisation. London: London School of Hygiene and Tropical Medicine, Department of Public Health and Policy Publication. LaVake, S., and J. Rosen. 2003. Private Sector Country Assessment Manual, 2003: A Handbook for Assessing the Potential for Youth Reproductive Health and HIV/AIDS Interventions in the Private Sector. Arlington, VA: YouthNet. MacKay, J., and G. A. Mensah. 2004. The Atlas of Heart Disease and Stroke. Geneva: World Health Organization. Magnani, R., A. Robinson, E. Seiber, and G. Avila. 2000. Evaluation of “Arte y Parte”: An Adolescent Reproductive Health Communications Project Implemented in Asunción, San Lorenzo, and Fernando de la Mora, Paraguay. Washington, DC: FOCUS on Young Adults. Mensch, B. S., S. Singh, and J. Casterline. 2003. “Trends in the Timing of First Marriage among Men and Women in the Developing World.”

Paper presented at the Annual Meeting of the Population Association of America, Minneapolis, May 1–3. MotherCare. 2000. “Anemia and Iron Deficiency in Adolescent Students in Lima, Peru: Causes, Consequences, and Prevention.” Reproductive Health Focus 14. http://www.jsi.com/intl/mothercare/rhfocus.htm. National Research Council and Institute of Medicine. 2004. Reducing Underage Drinking: A Collective Responsibility. Washington, DC: National Academies Press. ———. 2005. Growing up Global: The Changing Transitions to Adulthood in Developing Countries. Washington, DC: National Academies Press. Phiri, S., G. Foster, and M. Nzima. 2001. Expanding and Strengthening Community Action: A Study of Ways to Scale Up Community Mobilization Interventions to Mitigate the Effect of HIV/AIDS on Children and Families. Washington, DC: Displaced Children and Orphans Fund. http://www.usaid.gov/pop_health/dcofwvf/reports/ orphanreps/dcaction.html. Pitts, M., G. Dowsett, M. Couch, D. Keys, and S. Dutertre. 2004. “Looking for More: A Review of Social and Contextual Factors Affecting Young People’s Sexual Health.” Document prepared for the World Health Organization, Department of Child and Adolescent Health and Development. La Trobe University, Melbourne, Australia. Piwoz, E., and E. Greble. 2000. HIV/AIDS and Nutrition: A Review of the Literature and Recommendations for Nutritional Care and Support in Sub-Saharan Africa. Washington, DC: USAID Support for Analysis and Research in Africa (SARA) Project and the Academy for Educational Development. POLICY Project and YouthNet. Forthcoming. Guide to Key Elements of Youth Reproductive Health Policy. Washington, DC: POLICY Project; Arlington, VA: YouthNet. Rosen, J. 2001a. “A Dialogue on Social Marketing and Other Commercial Approaches to Improving Adolescent Reproductive Health.” Meeting report. FOCUS on Young Adults, Washington, DC, February 15. ———. 2001b. In FOCUS: Youth Livelihoods and HIV/AIDS. Washington, DC: FOCUS on Young Adults. RamaRao, S., and N. J. Diop. 2003. “Serving the Reproductive Health Needs of Adolescents in Senegal: Analysis of Costs.” Frontiers Project Report. Population Council, Washington, DC. Save the Children U.S.A. 2004. Children Having Children: State of the World’s Mothers 2004. Westport, CT: Save the Children U.S.A. Senderowitz, J., and C. Stevens. 2001. Leveraging the For-Profit Sector in Support of Adolescent and Young Adult Reproductive Health Programming. Washington, DC: Futures Institute for Sustainable Development. Soderlund, N., J. Lavis, J. Broomberg, and A. Mills. 1993. “The Costs of HIV Prevention Strategies in Developing Countries.” Bulletin of the World Health Organization 71 (5): 595–604. Speizer, I. S., R. J. Magnani, and C. Colvin. 2003. “The Effectiveness of Adolescent Reproductive Health Interventions in Developing Countries: A Review of the Evidence.” Journal of Adolescent Health 33 (5): 324–48. Townsend, J. W., E. Dias de May, Y. Sepulveda Santos de Garza, and S. Rosenhouse. 1987. “Sex Education and Family Planning Services for Young Adults: Urban Strategies in Mexico.” Studies in Family Planning 18 (2): 103–8. UNAIDS (Joint United Nations Programme on HIV/AIDS). 2003. AIDS Epidemic Update: December 2003. Geneva: UNAIDS. UNECA (United Nations Economic Commission for Africa). 2000. Costs of Scaling HIV Programme Activities to a National Level in Sub-Saharan Africa: Methods and Estimates. http://www.uneca.org/adf2000/ costsofaids.htm. University of Illinois at Chicago Health Research and Policy Centers. 2001. Cigarette Taxes and Kids. Policy Briefs, vol. 1, April. Chicago: Health Research and Policy Centers, University of Illinois at Chicago.


Watts, C., P. Vickerman, L. Kumaranayake, C. Cheta, C. C. Nama, G. Kwenthieu, and J. Del Amo. 2000. “Impact and Cost-Effectiveness Modelling of In-School Youth Programmes in Sub-Saharan Africa.” Paper presented at the 13th International AIDS Conference, Durban, South Africa, July 9–14. Westoff, C. F., and A. Bankole. 1995. Unmet Need: 1990–1994. Comparative Studies 16, Demographic and Health Surveys. Calverton, MD: Macro International. WHO (World Health Organization). 1999. Programming for Adolescent Health and Development: Report of a WHO/UNFPA/UNICEF Study Group on Programming for Adolescent Health. Technical Report 886. Geneva: WHO. ———. 2001a. Global Status Report: Alcohol and Young People. WHO/MSD/MSB/01.1. Geneva: WHO. ———. 2001b. The Second Decade: Improving Adolescent Health and Development. Geneva: WHO. ———. 2002. World Health Report. Geneva: WHO. ———. 2004a. “Estimates of DALYs by Sex, Cause, and WHO Mortality Subregion, Estimates for 2002, 2003.” WHO, Geneva. http://www3. who.int/whosis/menu.cfm?path=evidence,burden,burden_ estimates_2002,burden_estimates_2002_subregion&language= english. ———. 2004b. “Steady, Ready GO!” Information brief on the Talloire consultation to review the evidence for policies and programmes to achieve the global goals on young people and HIV/AIDS. WHO, Geneva.

———. 2004d. World Report on Road Traffic Injury Prevention: Summary. Geneva: WHO. ———. Forthcoming-a. Making Policy Happen: Lessons from Countries on Developing National Adolescent Health and Development Policy. Geneva: WHO, Department of Child and Adolescent Health and Development. ———. Forthcoming-b. Pregnant Adolescents: Delivering on Global Promises of Hope. Geneva: WHO. World Bank. 1999a. Curbing the Epidemic: Governments and the Economics of Tobacco Control. Washington, DC: World Bank. ———. 1999b. Project Appraisal Document on a Proposed Credit in the Amount of SDR 140.82 Million to India for a Second National HIV/AIDS Control Project. Report 18918-IN, Washington, DC: World Bank. ———. 2002a. “The Impact of Deworming Treatment on Primary School Performance in Busia, Kenya.” Abstract of Current Research. http:// www.worldbank.org/research. ———. 2002b. Optimizing the Allocation of Resources among HIV Prevention Interventions in Honduras. Washington, DC: World Bank. ———. 2002c. Tobacco at a Glance. Washington, DC: World Bank. ———. 2003. Education and HIV/AIDS: A Sourcebook of HIV/AIDS Prevention Programs. Washington, DC: World Bank. YouthNet. 2002. “VCT and Young People.” YouthLens. http://www.fhi.org/ en/youth/youthnet/publications/youthlens+english.htm.

———. 2004c. Unsafe Abortion: Global and Regional Estimates of Incidence of Unsafe Abortion and Associated Mortality in 2000. 4th ed. Geneva: WHO.

Adolescent Health Programs | 1125 ©2006 The International Bank for Reconstruction and Development / The World Bank 233


Chapter 62

Control and Eradication Mark Miller, Scott Barrett, and D. A. Henderson The Controversy: Control or Eradication? We cannot refrain altogether from examining the roots of this controversy if only because the extreme views for and against eradication have exerted and are still exerting a . . . highly detrimental influence on public health practice. —P. Yekutiel, Eradication of Infectious Diseases: A Critical Study

Eradication of an infectious disease is an extraordinary goal. Its possibility became apparent as soon as Edward Jenner demonstrated an ability to provide immunity to smallpox. Writing in 1801, Jenner observed that, through broad application of vaccination, “it now becomes too manifest to admit of controversy that the annihilation of the Small Pox, the most dreadful scourge of the human species, must be the result of this practice” (Jenner 1801). Louis Pasteur claimed that it was “within the power of man to eradicate infection from the earth” (Dubos and Dubos 1953). And yet, by and large, public health has proceeded with more modest goals of local and regional disease control. Notable successes have occurred. Indeed, some diseases now thought of as “tropical” were previously endemic in temperate climates. Systematic application of hygiene, sanitation, environmental modification, vector control, and vaccines have led, in many countries, to the interruption of transmission of microbes causing such diseases as cholera, malaria, and yellow fever. Intensive efforts to eliminate breeding sites of the yellow fever mosquito vector, Aedes aegypti, interrupted transmission of this disease in Havana in 1901 and throughout Cuba soon thereafter. Subsequently, yellow fever and malaria were able to be controlled in Panama, thus permitting construction of the Panama Canal. In 1915, the Rockefeller Foundation launched an effort to eradicate the disease worldwide. Transmission appeared to have ceased in the Americas by 1928, but then cases reappeared, and by 1932, it became clear that a nonhuman

endemic focus was serving to reinfect areas otherwise free of yellow fever. In the 1930s, F. L. Soper set out to eradicate the Aedes aegypti vector from the Americas. By 1961, Soper reported that he had largely succeeded except for the United States, where the program received little support. By the 1980s, Aedes aegypti had become reestablished in Central and South America. In 1953, Brock Chisholm, the first director-general of the World Health Organization (WHO), tried to persuade the World Health Assembly (WHA) to undertake smallpox eradication, but a number of countries objected on the grounds that eradication was not technically feasible. Instead, in 1955, under the leadership of his successor, Marcolino Candau, WHO began a global effort to eradicate malaria primarily by means of household spraying of DDT. The relatively sophisticated science of malaria control was abandoned in favor of this simplistic technology (Jeffrey 1976). Despite an expenditure of more than US$2 billion, the effort failed. Even while the malaria eradication effort was under way, the Soviet Union, in 1958, proposed to the WHA that smallpox be eradicated. A resolution to this effect was offered in 1959 and passed unanimously. However, the resolution provided little international funding or support. Over the next seven years, disease transmission was interrupted in some 30 countries in Africa, Asia, and South America, but endemic smallpox persisted in the Indian subcontinent, Indonesia, most of SubSaharan Africa, and Brazil. WHO launched an intensified effort in 1967 to eradicate the disease within a decade. This new


resolution included an annual budget of US$2.4 million, to be paid according to the WHO scale of assessments. The resolution passed by the narrowest of margins, but a reinvigorated effort was soon under way and paved the way for a historic public health achievement (Henderson 1988). Following an extraordinary worldwide effort, the last case of smallpox was isolated in October 1977, and the disease was certified as being eradicated in 1979, 170 years after Edward Jenner first dreamed of that possibility. Understanding how and why smallpox eradication succeeded is essential to the study of control and eradication. The smallpox success was inspirational, even though the leaders of WHO’s smallpox eradication effort cautioned that, among all the diseases that might be considered candidates for eradication, smallpox was unique (Fenner and others 1988) and that they foresaw no other disease as a candidate for eradication (Henderson 1982). At a meeting convened by the Fogarty International Center of the National Institutes of Health in 1980, scientists, public health officials, and policy makers discussed the merits of eradicating other diseases, with schistosomiasis, dracunculiasis, poliomyelitis, and measles identified as possible candidates (Henderson 1998a). However, no consensus was reached at that time on moving forward with any of those diseases. Poliomyelitis became the next principal target when mass vaccination campaigns, proposed by Albert Sabin (1991), proved remarkably successfully in Cuba and Brazil. In 1985, an American Health Organization coordinated campaign was launched to interrupt poliovirus transmission in the Americas by 1991, and this effort succeeded. Some believed that global eradication might be possible, although others were concerned that the far less developed infrastructure of health, transportation, and communications services in many parts of Asia and Africa would make it an unachievable task. In 1988, the WHA adopted a resolution to eradicate polio, but at that time, a longer-term strategy for ending polio vaccination was neither formulated nor agreed on by the public health and scientific community. The WHA has adopted only one other resolution to eradicate a disease—guinea worm, or dracunculiasis. The eradication of this disease can be achieved by applying simple technologies for providing water that is free of the vector copepod and parasite and for treatment of patients with the disease. This eradication program has made steady progress but has been hampered in part by civil and political unrest and lack of program priority because of low mortality and low incidence in some remaining endemic areas. However, given the environmental restriction of the parasite to rural tropical areas and its relatively low transmissibility, eventual global eradication seems within reach. One other case—that of measles—is worth noting. A number of public health authorities have raised the possibility of

eradicating that disease. In the Americas, spurred on by the success of regional cessation of transmission of wild poliovirus, eventual consensus was reached to intensify measles control efforts, primarily through surveillance and periodic pulse application of measles vaccine in national campaigns. As a consequence, transmission of measles virus was temporarily interrupted in the Americas on several occasions but reestablished again by importations (CDC 1998a). Although the U.S. Centers for Disease Control and Prevention (CDC) and WHO have advocated extending measles “elimination” through vaccination campaigns and second-dose opportunities to other regions (Biellik and others 2002; CDC 1998a, 1998b, 1999a, 1999b, 2003d, 2004b, 2004d, 2004f), the intensive control efforts required to break transmission of this highly infectious agent make global eradication unlikely at this time.

DEFINITIONS Yekutiel (1980, 5–8) provides an excellent treatise on the concept of eradication, which includes a summary of the multiple definitions that have been formulated (Andrews and Langmuir 1963; Cockburn 1961, 1963; Payne 1963a, 1963b; Spînu and Biberi-Moroianu 1969). A conference devoted to eradication held in Dahlem, Germany, in 1997 (Dowdle and Hopkins 1998) set out to provide precise definitions for control, elimination, eradication, and extinction in a biological, economic, and political context (Dowdle 1998, 1999; Ottesen and others 1998); however, a number of eminent public health officials (Cochi and others 1998; de Quadros 2001; Goodman and others 1998b; Henderson 1998b; Salisbury 1998) challenged these definitions at two subsequent meetings at the CDC (Goodman and others 1998a, 1998b) and the U.S. Institute of Medicine (Knobler, Lederberg, and Pray 2001). Unfortunately, broadly accepted, standard definitions for key concepts pertaining to disease control and eradication do not exist in the literature. Making matters more confusing, certain of the concepts have been given names that are part of our everyday language and so are easily misinterpreted by nonspecialists as meaning something different from the meanings understood by those who are preoccupied with eradication programs. Most unfortunate is the all too casual use of the words elimination and eradication to promote programs that cannot reasonably be expected to achieve the promise implicit in these words. Moreover, the two words themselves are commonly used interchangeably. Control Two concepts are central to this chapter: control and eradication. By control, we mean a public policy intervention that restricts the circulation of an infectious agent beyond the level that would result from spontaneous, individual behaviors to protect against infection (Barrett 2004).

1164 | Disease Control Priorities in Developing Countries | Mark Miller, Scott Barrett, and D. A. Henderson ©2006 The International Bank for Reconstruction and Development / The World Bank 236

Although control is a range rather then a level, a particular level of control may be an aim of policy. Because every choice entails consequences, choice of the “optimal” level of control requires economic analysis. Optimal here is defined in relation to the model that gives rise to the result. Control is local and so needs to be looked at from the local perspective. Because one country’s (or region’s) control may affect other countries (regions), a global perspective exists as well. The level of control that is optimal for one country (region) may not be optimal from the perspective of the world as a whole. Thus, a need exists to distinguish between, say, a locally optimal level of control and one that is globally optimal. Finally, control requires ongoing intervention. Sustaining a given level of control requires an annual expenditure. Eradication Eradication differs from control in that it is global. The term denotes the certified total absence of human cases, the absence of a reservoir for the organism in nature, and absolute containment of any infectious source. Eradication permits control interventions to stop or at least to be curtailed significantly. Finally, eradication is binary. Control levels can vary, but a disease is either certified as eradicated or not. Every disease can be controlled, even if only by using simple measures, such as quarantine. The ultimate achievement of control is eradication. But not every disease that can be controlled can be eradicated. Very few diseases, in fact, are potential candidates for eradication. The criteria for the feasibility for eradication as a preference over control are discussed in the section titled “Economic Considerations.” Elimination Control and eradication are the essential concepts, but two other terms bear mention. The first is elimination. Some who are concerned with eradication programs have explicitly defined this term to denote the cessation of transmission of an organism throughout a country or region. In contrast, eradication is defined as a global achievement. Like control, elimination is location-specific and would require ongoing interventions to be sustained in order to prevent reemergence of the disease from microbe importations. Two problems exist with the term elimination. First, it has been used to describe different phenomena, not just that described in the definition given above. For example, some public health officials have promoted programs aimed at “eliminating a disease as a public health threat,” which is interpreted to mean reducing incidence to an “acceptable” level but not necessarily to zero. This usage is very different from the one outlined above and is almost certain to be misunderstood. Second, the definition of the word elimination in common use, as applied to disease control, is indistinguishable from eradica-

tion. The 1993 edition of the New Shorter Oxford English Dictionary, for example, defines eliminate as to “remove, get rid of, do away with, cause to exist no longer.” This same dictionary defines eradicate as “pull up or out by the roots, uproot, remove or destroy completely, extirpate, get rid of.” This ambiguity invites misunderstanding among those not intimately involved in an eradication effort. For purposes of clarity, we seldom use the term elimination in this chapter and then only to signify control measures sufficient to interrupt microbe transmission in a specified area. Extinction Finally, the literature sometimes refers to extinction as a possible policy goal. In the context of infectious disease control, the concept is problematic for two reasons. First, proving that an organism has become extinct is impossible. To do so would require demonstrating not only that the organism no longer exists in nature but also that it no longer exists in any controlled environment—a practical impossibility. Second, de novo synthesis of viral agents from published genomes (Cello, Paul, and Wimmer 2002) now put the concept in peril, although much research remains to be done in this area. Extinction, in the context of infectious diseases, may no longer be irreversible. Clearly, policy making will be improved by stating the goal of any particular intervention in precise language.

FRAMEWORKS FOR ERADICATION Numerous issues need to be considered in planning expanded control measures that lead, possibly, to regional cessation of transmission or global eradication of disease. These complex issues will be further examined in the chapter. Scientific Considerations Scientific considerations include the nature of potential reservoirs for disease-causing microbes or their vectors, technologies available for interrupting disease transmission, changes in host capabilities to deter infections and disease, and satisfactory containment of organisms in laboratories. Geographic and Environmental Controls. The limit of endemicity for microbes and their associated diseases is determined in part by their ability to exist in nature outside the human host. Both geographic and temporal variations determine the ecological niche of microbes, resulting in variable annual incidence rates throughout the world. This niche limitation is further extended to intermediary vectors and hosts in complex biological systems. Natural environmental barriers also may isolate the habitats of helminths. Infectious agents that are not limited to an environmentally restricted intermediary Control and Eradication | 1165


host or those that have longer latent periods, thereby allowing translocation, may have a global pattern of distribution. Examples include the highly transmissible viral agents such as measles, rubella, influenza, and varicella. Although these agents are not geographically constrained, their transmission patterns are directly and indirectly influenced by seasonal environmental factors and population-based immunity. Potential Reservoirs. A microbe and associated disease can not be eradicated if the microbe is capable of persisting and multiplying in a reservoir. Microbes that thrive in nonhuman species may reemerge if control efforts cease, thus leaving human populations susceptible. Similarly, if the infectiousness of a human is long lived or could lead to potential recrudescence, surveillance efforts would have to continue as long as the last individual remained potentially capable of transmitting infection, as would be the case with tuberculosis or hepatitis B infection. Transmissibility. The inherent rate of a microbe’s ability to cause secondary infections is defined by an organism’s reproductive rate in a fully susceptible (R0) and partially susceptible (R) population. The reproductive rate of organisms that infect individuals only once because of durable immunity is inversely proportional to the average age of infection in an endemic area. Agents that cause childhood infections, such as viral respiratory agents, are far more transmissible than helminths and subsequently require more intensive control efforts to interrupt transmission. Natural Resistance to Reinfection. Many natural infections induce long-lived immunity to reinfection. Although the most commonly used vaccines have been available for fewer than 50 years—less than the lifetime of an individual—they, too, are assumed to offer long-lasting immunity. Because eradication depends on reducing susceptible populations in potentially endemic areas, long-lived protection through immunization or natural disease is important to successful programs. Laboratory Containment. Laboratory specimens containing the organism targeted for eradication could serve as reservoirs. Considerable effort may be necessary to ensure their maximum security. That these microbes may be inconspicuous in specimens collected for other purposes poses special challenges. This situation is especially true for the poliomyelitis virus, which may be found in many stool specimens collected for studies completely unrelated to current poliomyelitis eradication efforts. Operational Considerations Optimization of control requires a fundamental appreciation of the biological systems that govern the ecology of microbes

and their intermediary and human hosts. The reproductive rate, R, is influenced by many local factors, including population density (of vectors, intermediary hosts, and humans) and other environmentally determined conditions, all highly variable throughout the world. For a disease to be controlled to stop transmission, the intervention-altered reproductive rate must be maintained below 1.0. At the same time, all reservoirs of the responsible microbe must be controlled. Three main components of possible eradication programs are • surveillance, including environmental sampling where appropriate and clinical testing • interventions, including vaccination and chemotherapy or chemoprophylaxis or both • environmental controls and certification of eradication. Each of these components must be undertaken at local, community, national, regional, and global levels. Eradication differs from control in that it is expected to be permanent. Success depends on having adequate surveillance to identify potentially infectious persons and on stopping transmission before infection of a new cohort of susceptible persons arises as a result of births, migration, or the waning effectiveness of prophylactic measures. Disease Surveillance. Effective surveillance requires a sensitive system to detect the presence of microbes within the environment, intermediary hosts, and clinical cases. Surveillance and response systems need to be more efficient than the rate of transmission of the targeted agent. As eradication progresses, the sensitivity of detection systems must be steadily enhanced to detect all existing foci. Nonclinical or latent infections pose formidable barriers to eradication efforts. Operationally, the need for nearperfect sensitivity comes at the expense of lower specificity. Thousands of skin lesions from suspected smallpox patients were tested in reference laboratories during confirmation of smallpox eradication, and tens of thousands of stool specimens are being examined for poliovirus. Highly sensitive systems used to detect measles cases in the Americas began to identify a greater proportion of rubella and parvovirus infections because of the nonspecific surveillance of rash illness. Such findings are important because the identification of other diseases that mimic the targeted disease can lead to a misdirection of resources. However, the ability to detect such similar clinical cases can serve as a proxy measure for the adequacy of surveillance. For example, identification of a minimum incidence of cases of acute flaccid paralysis that is not related to polio has served as an indicator of adequate efforts of case finding for polio. Interventions. Interventions to block transmission of the targeted infectious agent should be easy to deploy and adaptable


to diverse conditions, given the global goal of eradication. Cost considerations and local acceptance of the required sacrifices (both short and long term) are crucial for success. Interventions may be designed for environmental control of microbes, isolation (quarantine) of clinically infectious individuals to limit their contacts with susceptible persons, treatment of clinical cases to limit the duration of infectiousness, or reduction in the infected pool of individuals through immunoor chemoprophylaxis. Certification. The last tool for eradication is a certification process whereby independent, respected parties certify the absence of disease transmission or the existence of any specific microbe in an uncontrolled reservoir, including laboratories (Breman and Arita 1980). Although certification can be implemented on a regional basis, it must ultimately be done globally. Certification is one of the greatest challenges in any eradication effort, given the exceedingly great difficulty of verifying a negative finding in a reasonably short period of time. When certification is completed, curtailment of control measures should be possible. Strengthening control efforts sufficiently to achieve eradication is a difficult and expensive task. It requires that scaling up of such efforts occur over a wide area—at the community, national, regional, and global levels. Its efficacy depends heavily on the adequacy of local financial and human resources, as well as on a broad range of logistical factors.

Economic Considerations Control and eradication programs have many economic dimensions: private versus social net benefits, short-term versus long-term net benefits, and local versus international net benefits. Such interventions also have implications for existing public health programs. Private versus Social Net Benefits. Individuals have private incentives to protect themselves from disease—by means of vaccination, for example. But when individuals protect themselves—when they elect to be vaccinated—they offer a measure of protection to others by helping limit the spread of infection. In brief, the social benefit of vaccination is greater than the private benefit alone. As more people become vaccinated, the marginal private and social benefit of vaccination— that is, the benefit of vaccinating an additional susceptible person—declines. The marginal private benefit is likely to fall because, as more people are vaccinated, the probability of a susceptible person becoming infected falls. The marginal social benefit is likely to fall for the same reason and for one other: as more people become protected, the total number of susceptible persons falls. The marginal social benefit of vaccination falls sharply at the critical level of immunization—the level at which

herd immunity is conferred on all susceptible persons. When a population is immunized to this level, a disease ceases to be endemic, and imported infections cannot spark an epidemic. This level is determined by the epidemiology of a disease, but whether it pays to vaccinate to this level depends on the economics, and the economics depend in turn on the social costs and not only the social benefits of vaccination. These costs consist of the direct costs of producing, distributing, and administering a vaccine. The economics depend also on the costs borne by the individuals who are vaccinated, such as those incurred by individuals who experience vaccine complications. The proportionate costs of reaching people who live in remote areas and those who are at special risk, such as migrants and the homeless, increase as the fraction of the population vaccinated increases. The economics of varying levels of disease control depend on the relationship between the marginal social benefits and the marginal social costs of vaccination. As vaccination levels increase, the marginal social benefits of vaccination fall, whereas the marginal social costs rise. Social welfare is maximized where these two relations intersect, which might be called the “optimal” level of vaccination—a level that may or may not achieve cessation of transmission or eradication. Short-Term versus Long-Term Net Benefits. Control programs require ongoing intervention. Sustaining a given level of protection requires that, over time, a certain proportion of new susceptible persons be vaccinated. Eradication differs from control in being permanent. The economics of eradication must therefore take account of long-term benefits as well as short-term costs. The long-term benefits of eradication consist of avoided future infections and vaccination costs—a dividend. To calculate this benefit, one projects future infection and vaccination levels in the absence of eradication, attaches values to these, and discounts them. If this sum exceeds the costs of eradication, then eradication enhances social well-being, and it therefore should be undertaken. In deciding on the benefits of eradication, the cost of future infections and vaccination should ideally be compared with the best alternative to eradication: the level of optimal control (Barrett and Hoel 2003). The costs of eradication must also take into account ongoing surveillance requirements, laboratory containment, and perhaps the maintenance of stockpiles of vaccine in the chance event of disease reemergence. From an economic perspective, attractive candidates for eradication are those diseases that some countries have themselves targeted for interruption of transmission nationally or regionally. Local versus International Net Benefits. Control differs from eradication in another important way. Control refers to Control and Eradication | 1167


location-specific interventions. Eradication, by contrast, is global. In economic terms, eradication is a global public good. No country can be excluded from the benefit of eradication, and no country’s consumption of that benefit diminishes the amounts available to other countries. Control, by contrast, supplies only a local public good. Eradication requires a global effort. A disease can be eradicated only if microbe transmission ceases everywhere. This spatial dimension to eradication is of fundamental importance because no world government can implement an eradication policy; the WHA can declare its support for eradication, but WHO does not have the power to enforce the execution of a national program in support of that goal. The outcome experienced by any country depends not only on whether the country itself eliminates the disease within its borders but also on whether all other countries do so. Indeed, eradication is a weakest-link public good. Whether eradication is achieved depends on the level of control adopted by the country that undertakes the least control. In practical terms, any country in which disease is endemic can prevent eradication from being achieved. In 2004, the global polio eradication initiative, after investing more than US$3 billion and involving some 20 million volunteers over a period of 16 years, was placed at risk of failure by the actions of one local administration. In the Kano state of Nigeria, local leaders claimed that the polio vaccine was tainted with the AIDS virus and sterility drugs and declined to participate in a national immunization day program. The European Union then declined to pay for the national program in Nigeria, believing the money would be wasted (Roberts 2004). One consequence was the subsequent spread of polio to nine formerly polio-free countries. Concerted efforts by WHO later persuaded local leaders in Nigeria to rejoin global efforts, but special vaccination programs had to be launched over a population area of more than 300 million persons. This situation dramatically illustrated the vulnerabilities inherent in a weakest-link public good. What are the incentives for states to participate in an eradication effort? To begin, assume that countries are symmetric, meaning that all countries have the same benefits and costs of control. Assume as well that eradication is feasible. Four possible situations then exist (Barrett 2003): • First, the global net benefit of eradication may be negative— the cumulative programmatic costs outweigh the net present value of the cumulative benefits. In this case, elimination would also yield a negative net benefit to every country, and so no country would eliminate the disease. • Second, the global net benefit of eradication may be so large that each country would choose to eliminate the disease even if others did not. In this case, all countries would eliminate the disease, and the disease would therefore be

eradicated. In these two cases, no need exists for an international policy. • Third, each country may have an incentive to eliminate a disease only if all other countries have eliminated it. In this case, achieving global eradication requires coordination. Here a role exists for international policy, but all that is required is for each country to be assured that all others will eliminate the disease. • Finally, and noting that the “last” country to eliminate a disease would get just a fraction of the global dividend from eradication, under some circumstances no incentive may exists for this country to eliminate the disease—even if all other countries have done so and even if the entire world would be better off if it did. This case is the most worrisome, because implementation of the efficient outcome would likely require enforcement. All this hypothesizing assumes that countries are symmetric, and of course they are not. Some countries gain less from control and would gain less from eradication than others. Some are unable to implement an elimination program, even if they would very much like it to succeed. In these situations, achieving an eradication goal will require international financing and technical assistance, with the countries that benefit most from eradication compensating the other countries for the costs of eradicating the disease. National and international reproach are often expressed if a country lags in its eradication efforts. International financing has been a key element in all eradication programs. We have thus far looked at eradication from the perspective of only the self-interests of states. But eradication also has implications for development. In particular, eradication has two advantages over control programs. The first is that the rich countries may gain directly if the goal is achieved, giving them a vested interest in ensuring that the goal is achieved. The second is that eradication is permanent, making an investment in eradication financially sustainable. This second advantage is important because financial sustainability has proved to be a key problem for disease control programs in developing countries (Kremer and Miguel 2004). Vertical versus Horizontal Programs. Control and eradication programs cannot be viewed in isolation. All programs have implications for the delivery of comprehensive primary care services. An important question is whether targeted, or socalled vertical, programs draw critical resources away from other health care programs or whether they serve instead to augment competence and capacity. The evidence is mixed. Evidence suggests that disease-specific systems can serve to expand polyvalent services (Aylward and others 1998). Smallpox eradication, for example, gave many national governments the confidence to introduce the Expanded Program on


Immunization, with the ability to deliver vaccines and micronutrients in routine schedules and through national campaigns. However, other evidence suggests that some vaccination programs have adversely affected primary health services (Steinglass 2001; Taylor, Cutts, and Taylor 1997) and may have even increased costs. Implementation of international initiatives can also expose conflicts of priorities. The polio eradication initiative, for example, has successfully vaccinated children in the poorest of countries against this disease, but in some of these countries it has failed to timely include the coadministration of measles and other common childhood vaccines, which would have had a much greater effect on child mortality.

DISEASE-SPECIFIC CASE STUDIES In this section, we apply the reasoning developed previously to provide an empirical analysis of the three most recent eradication programs—smallpox and the two ongoing programs, poliomyelitis and dracunculiasis.

Smallpox As noted before, smallpox eradication was achieved in October 1977, 11 years after the intensified program began. Following implementation of a rigorous certification procedure, the WHA declared smallpox eradicated in 1980. Fenner and others (1988) have estimated the annual benefits of smallpox eradication to developing and industrial countries (see table 62.1). These aggregate estimates, obtained by

Table 62.1 Benefits and Costs of Smallpox Eradication (Millions of U.S. dollars) Annual amount Beneficiary India

722

United States

150

All developing countries

1,070

All industrial countries

350

Total annual benefit

1,420

Expenditure Total international, on eradication

98

Total national, by endemic countries

200

Combined total, on eradication

298

Benefit-cost ratio International expenditure

483:1

Combined total expenditure

159:1

Source: Adapted from Fenner and others 1988.

prorating estimates of the benefits of eradication for India and the United States to all developing and industrial countries, respectively, suggest that developing countries benefited more from smallpox eradication than industrial countries. Qualitatively, a consistent picture emerges: smallpox eradication was not only an extraordinary investment for the world; it was also an investment that benefited every country, rich and poor alike. When the eradication effort began, smallpox was no longer endemic in most industrial countries. Nonetheless, these countries needed to maintain populationwide immunity under the threat of possible imported cases from endemic countries. They would gain from eradication not only through the cessation of vaccination and its associated costs but also by being able to decrease the number of quarantine inspectors at ports of entry and by averting costs of care related to the adverse events from this live vaccine. The still-endemic countries would also save vaccination costs, although most were vaccinating only a comparatively small proportion of their populations. The greater benefit to them was the avoided cost of disease, including the extraordinary death toll. A number of developing countries had accorded smallpox prevention a high priority, as was evidenced by the number that succeeded in interrupting transmission without international assistance. This list includes China, which was not a member of WHO at the time the eradication effort commenced. Indeed, and as shown in table 62.1, the still-endemic countries contributed an estimated two-thirds of the US$298 million cost of eradication. International sources funded the balance. If the latter cost is interpreted as the incremental cost of achieving eradication, the benefit-cost ratio of global smallpox eradication was over 450:1, a singularly high figure. Even including the expenditure by endemic countries, the benefit of eradication exceeded the cost by an unusually large amount. Brilliant (1985) calculated the annual costs of the smallpox eradication campaign for India to be about US$17 million per year, including indirect costs (lost productivity caused by adverse reactions to vaccination) and opportunity costs (health workers being diverted from other programs). These costs were only a fraction of the annual benefits of eradication to India, which, by Brilliant’s calculations, were US$150 million. The benefit estimates by Fenner and others (1988) are much larger, and those of Ramaiah (1976) are smaller, but all three studies draw the same (qualitative) conclusion: smallpox eradication was a good investment for India. Basu, Jezˇek, and Ward (1979, 312) present estimates identical to those in Ramaiah (1976), but without giving attribution. Originally, India had decided to undertake a smallpox program just one month after the WHA voted to eradicate the disease globally in 1959. The attempt failed, however, largely for administrative reasons (Basu, Jezˇek, and Ward 1979; Brilliant Control and Eradication | 1169


1985; Fenner and others 1988). Essentially, India had an economic incentive to control smallpox on its own (Brilliant 1985, 33) but lacked organizational capacity and an effective strategy for achieving this goal. Note, however, that India had other health priorities, including family planning. According to Brilliant (1985, 33), “for India’s health planners, occupied then by emergencies and competing political demands on scarce resources, the long-term benefits from disease eradication were not a great motivation. Health planners are sensitive to immediate political realities, and the benefits of smallpox eradication would be realized only at some future time when the $3 million annual expenditures for smallpox could be applied to other health problems. In the meantime, however, the cost of putting so many scarce resources into one program rather than into many health needs was high.” Table 62.2 provides estimates of the benefits of smallpox eradication to the United States. The total benefit of eradication to the United States is about the same order of magnitude as India’s, but the breakdown is different. Whereas India benefited mainly from avoided infections, the United States benefited mainly from avoided vaccinations. By the time the eradication program was launched, the United States had already interrupted smallpox transmission, but vaccination was costly, both in economic and human health terms (a small number of people died every year from infections arising from the live vaccine). Defending the nation from imported infections imposed additional costs. In health terms, smallpox eradication saved millions of lives; in economic terms, it yielded a benefit many times greater than the cost. Identifying another investment that has yielded comparable returns and has benefited every country is difficult. One reason that the economics of smallpox eradication were so favorable is that all countries had strong incentives to join in

Table 62.2 Benefits of Smallpox Eradication to the United States, 1968 (Millions of U.S. dollars) Amount Direct costs for medical services Vaccination

92.8

Treatment of complications

0.7

Indirect costs, loss of productivity Work losses attributable to vaccination and reactions

41.7

Permanent disability attributable to complications

0.4

Premature death

0.1

Cost of international traffic surveillance and delays in clearance of vessels Total

14.5 150.2

Source: Sencer and Axnick 1973; see also Fenner and others 1988, table 31.2.

the eradication of the disease. A huge organizational effort, but only a relatively small incremental cost, was needed to achieve eradication. The specter of global terrorism has recently caused some countries to prepare themselves for a possible smallpox attack by stockpiling vaccine. Although such actions reduce the benefits of eradication, the economics remain favorable. Smallpox, however, was a special case. Many attributes of the disease and the vaccine favored eradication. The vaccine was heat stable and required only a single dose to protect a person for a period of at least 5 to 10 years. Vaccination was easily performed and protected immediately on application. Every individual who became infected exhibited a typical, easily recognized rash, thus permitting accurate surveillance without recourse to laboratory diagnosis. The disease spread slowly so that transmission could readily be stopped by isolating the patient and vaccinating contacts within the area.

Poliomyelitis The polio eradication program, launched by the WHA in 1988, has made substantial progress (CDC 2003a, 2003b, 2003c, 2004a, 2004c, 2004e, 2004g, 2005). The incidence of paralytic poliomyelitis in children fell by more than 99 percent, from an estimated 1,000 cases per day worldwide in 1988 to fewer than 4 cases per day in 2003. The number of poliomyelitis-endemic countries also fell, from 125 in 1988 to just 6 by 2003 (Afghanistan, the Arab Republic of Egypt, India, Niger, Nigeria, and Pakistan). This laudable reduction was the result of repetitive vaccination campaigns with easily administered oral polio vaccine to whole regions, to nations, and to large subpopulations. During 2004, however, polio immunization activities in northern Nigeria were halted for an extended period for fear of tainted vaccines, and this permitted the development of epidemics extending throughout the country. The disease spread as well to 10 other African countries and to Saudi Arabia, Yemen, and Indonesia. Transmission has again been reestablished in several African countries (Burkina Faso, Central African Republic, Chad, Côte d’Ivoire, and Sudan). Heroic efforts are being made to control these outbreaks by large-scale immunization, but in countries such as these, where health services are stressed and the health, communication, and transportation infrastructures are weak, disease transmission is difficult to interrupt. Meanwhile, other countries throughout the world that appear to be polio free are continuing their vaccination programs but finding it increasingly difficult to maintain a momentum of interest, effort, and financing. The difficulties of maintaining credible surveillance systems throughout the developing countries were vividly demonstrated by the discovery of polio in Sudan in May 2004, more than three years after the last case had been reported (CDC 2005). In the interim, specimens from 75 to 90 percent of such


cases were processed in the laboratory, and measures of surveillance for acute flaccid paralysis cases were reported to have been entirely satisfactory. At first, the Sudanese cases were considered to have resulted from importations from Nigeria, and, indeed, some cases were. However, from more detailed laboratory studies, it was determined that type 1 wild virus had been circulating undetected for more than three years and type 3 virus for nearly five years. Clearly, stopping the continuing transmission of wild poliovirus is itself a formidable challenge, the success of which is by no means certain. A problematic discovery since the global eradication program began was the finding that individuals with particular immunologic disorders shed polio vaccine virus for many months to years, thus serving as a reservoir for this virus. The virus, in turn, can revert to a neurovirulent form, which is capable of causing outbreaks of disease (Bellmunt and others 1999). Such individuals may be wholly without symptoms and impossible to identify except through fecal cultures. Moreover, no treatment is known to stop them from shedding virus. They pose an all but insurmountable challenge to the current poliomyelitis eradication effort. The program is further hampered by the tool that has provided so much success—oral poliovirus vaccine (OPV). In resource-poor environments, poliomyelitis is best controlled with the inexpensive, live, and easily administered oral vaccine. The live vaccine is excreted and can infect other susceptible contacts. The ability of OPV to immunize others indirectly makes it an ideal vaccine for achieving high levels of population-based immunity, especially in lower socioeconomic populations that are the most difficult to reach. However, the excreted virus occasionally reverts to a pathologic state, causing not only cases but outbreaks of vaccine-associated paralytic polio, which may not emerge until months or even years after the vaccine has been administered (Kew and others 2004). Unfortunately, the alternative inactivated polio vaccine (IPV) is not immediately an option in many nations, not least because global manufacturing capacity could not begin to meet demand. Other problems include the current cost differential between OPV and IPV, the increased difficulty of administering the vaccine by syringe and needle, and the need to achieve higher coverage rates with IPV because it does not spread from person to person as does OPV. Tragically, if OPV use were discontinued, in the absence of alternative immunity, polioviruses would likely circulate silently (Eichner and Dietz 1996) and reemerge. Preliminary results from a model presented by WHO indicate a greater than 60 percent chance of an outbreak within two years of the possible global cessation of OPV (WHO 2004) because of continuous circulation of undetected live vaccine viruses that can revert. Outbreaks have already been observed in several regions where decreasing use of live vaccine has left pockets of susceptible persons who eventually have been exposed to vaccine-

derived pathogenic viruses (Kew and others 2002). Such an outbreak could occur with disastrous speed because the polio virus is far more contagious than that of smallpox. In developing countries, virtually all cases of polio occurred among those under five years of age, older persons having been protected by the natural immunity of earlier infection. Within five years after vaccination ceased, therefore, the population immunity level in the developing countries would be no better than it was before vaccination was introduced. With this is mind, it seems questionable as to whether all health ministers could be persuaded to call for a country-wide cessation of poliomyelitis vaccination itself, given the uncertainties of virus detection in so many remote and inaccessible areas of the world. By definition, eradication implies certifying cessation of virus transmission and the absence of reservoirs so that control interventions can cease. As noted earlier in this chapter, it is only for this reason that eradication yields a dividend. Although the interruption of wild poliomyelitis virus transmission is theoretically feasible, the obstacles to achieving and maintaining this goal are formidable. At this time, it is difficult to foresee a future that does not envisage a continuing vaccination program, perhaps with IPV use in countries that can afford the substantial additional costs entailed and with OPV use in all other countries. The polio eradication initiative, like that for smallpox, has had to rely primarily on voluntary donations provided both to WHO and bilaterally. Playing an especially important role have been the Rotary International Foundation and the Bill & Melinda Gates Foundation. From 1988 to 2004, more than US$3 billion was spent on the effort (WHO 2003). What are the economics of polio eradication? Bart, Foulds, and Patriarca (1996) developed the first global cost-benefit analysis of polio eradication, beginning with the costs incurred since 1986, the year that the Pan American Health Organization launched a regional eradication effort, and extending to 2040. They assumed that eradication would be achieved in 2005, using OPV, and that vaccination would cease after eradication had been certified. Benefits (like costs, discounted at 6 percent) reflect the avoided costs of acute care and avoided vaccination costs after certification. Their analysis showed that the initiative would break even by 2007 and yield a net benefit to the world of more than US$13 billion by 2040—an encouraging result, but it was based on the assumption that all vaccination would stop abruptly in 2005. Khan and Ehreth (2003) developed a similar analysis but provided regional detail. They estimated the costs and medical costs avoided of polio immunization and eradication over the period 1970 to 2050, assuming that vaccination could cease after 2010. As table 62.3 shows, Khan and Ehreth estimated that polio immunization and eradication would entail a negative net cost overall, with Europe and the Americas saving the most and with other regions incurring a positive net cost. Compared Control and Eradication | 1171


Table 62.3 Net Costs of Polio Immunization and Eradication (Millions of U.S. dollars) WHO region Africa Americas Eastern Mediterranean

Medical care cost savings

Immunization costs

Net costs

Cost/DALY saved

1,100

3,942

2,842

442

76,900

25,460

51,440

4,983

1,930

3,512

1,582

426

38,250

17,249

21,001

2,780

Southeast Asia

1,270

6,519

5,249

1,041

Western Pacific

8,670

10,327

1,657

356

128,120

67,009

61,111

1,457

Europe

World

Source: Khan and Ehreth 2003. Note: Cost savings, immunization costs, and net costs are present values for 2000 in millions of U.S. dollars, calculated for the period 1970–2050 and discounted at 5 percent. These estimates assume that immunization by OPV can cease after 2010.

with other health interventions, this cost to developing countries may still be comparatively cost-effective. However, Khan and Ehreth comment that the cost per disability-adjusted life year (DALY) saved is high for developing countries (see table 62.3). As they explain (Khan and Ehreth 2003, 705), “This implies that without the financial support from developed countries of the world many developing countries would not have opted for polio interventions for implementation. From the developed countries’ point of view, providing support for the polio program is not simply helping the poor and the disadvantaged, it actually represents a good economic investment.” Unfortunately, both of these cost-benefit studies have substantial limitations. First, both show that eradication is economically attractive if one incorporates all costs and benefits from the inception of this program. Because eradication has not yet been achieved, this approach mixes retrospective evaluation and prospective analysis (historical expenditures and benefits are sunk and so are irrelevant to the current situation). Second, benefits and costs are calculated in both studies relative to a world without immunization. A better approach would be to calculate the net benefits of eradication compared with the alternative of an optimal control program. The choice is not between doing nothing and eradication. It is between an optimal level of control and eradication. Finally, both studies assume that vaccination can cease in 2005 or 2010. As explained previously, this possibility is highly unlikely. A more recent analysis by Sangrujee, Cáceres, and Cochi (2004) calculates the costs for 15 years following the goal of certification of eradication in 2005 for three different scenarios: continued use of OPV, OPV cessation with optional use of the killed or inactivated polio vaccine, and OPV cessation with universal IPV. Table 62.4 shows their results.

Table 62.4 Postpolio Eradication Costs (Millions of U.S. dollars) Continue OPV Low-income countries Middle-income countries

487

4,418

12,196

12,196

12,196

6,409

6,409

6,409

19,969

19,092

23,023

1,120

1,320

1,120

21,089

20,412

24,143

Global response capacity Total

Universal IPV

1,364

High-income countries Subtotal

Stop OPV

Source: Sangrujee, Cáceres, and Cochi 2004. Note: Costs are expressed in present value terms, calculated over the period 2005 to 2020, and discounted at 3 percent.

The respective cost to middle- and high-income countries is the same for all three scenarios, reflecting the assumption that the high-income countries will switch to IPV by 2005 and middle-income countries will do so between 2006 and 2008. The scenarios differ only for the low-income countries. In the first scenario, these countries are expected to continue routine immunization using OPV; in the second, immunization ceases in 2011, followed by a system of surveillance and response. In the third scenario, the low-income countries join the others in switching to IPV between 2008 and 2010. Of these three scenarios, the second comes closest to the 2005 post-eradication strategy now advocated by the polio eradication program leadership. Unfortunately, this analysis is also deficient. First, interruption of transmission will not occur before 2006, and certification will take an additional three years. Hence, analysis of post-eradication costs should begin in 2009 at the earliest, with the costs of continuing immunization needing to be borne up until that time. Second, the analysis assumes a capacity to supply IPV that exceeds current estimates. It is not obvious that this scenario is feasible or, if it were, if the costs of scaling up production are adequately reflected in the calculations. Third, and most importantly, table 62.4 indicates that only low-income countries would benefit from polio eradication over this 15-year time scale—and yet the table does not include any estimate of the risk these countries would bear of a possible outbreak. Although this analysis suggests that the discontinued use of OPV promises the greatest return to eradication, this assumes that circulating vaccine-derived polioviruses could be contained if and when they emerged. However, preparing for this possibility would require a far more effective global surveillance system than now exists, maintenance of a laboratory infrastructure, and stockpiles of OPV. In addition, controlling outbreaks with OPV without the risk of viruses reverting to virulence will be exceedingly difficult in the setting of an accelerating proportion of immunologic-naive individuals. The use of OPV in this scenario could very well cause poliomyelitis to


again become endemic. In any case, the estimated cost of any of the strategies exceeds $20 billion. The economics of polio eradication are thus not as favorable as concluded by either Bart, Foulds, and Patriarca (1996) or Khan and Ehreth (2003). Both studies assume that vaccination can cease without IPV being used as a substitute anywhere, both exclude the costs of maintaining a response capacity, and neither accounts for the real threat of reemergence. Sangrujee, Cáceres, and Cochi (2004) take account of two of these considerations, but their analysis calculates only the costs for 15 years, ignoring both the risk of reemergence and the benefits of eradication. Hence, each study provides only a partial glimpse of the economics of polio eradication and does not adequately address the fundamental difficulty (inability) of stopping vaccination and maintaining eradication. In conclusion, although the economics of polio eradication may have been thought to be favorable by some (Aylward and others 2003), they are far less favorable than were the economics of smallpox eradication, even assuming that polio vaccination could cease.

This last omission is especially relevant to the study’s analysis of the eradication program in Sudan. The study projected that, by 1998, infections would cease everywhere except Sudan. (Plainly, this prediction was wrong, although Sudan is the largest problem for the program, mainly because of the ongoing civil war, which has limited accessibility to endemic areas; see Hopkins and others 2002.) It then calculates the net present value of eliminating the disease there. The results are not promising. They show that eradication is attractive only if the disease can be eliminated in Sudan within five years. However, this analysis ignores the dividend that eradication would earn Sudan. It also disregards the most important feature of eradication—that if the disease were certified to have been eliminated from its last stronghold, it would yield a benefit to all potentially vulnerable countries. Thus, the economics of eliminating dracunculiasis from Sudan, if that is where the disease makes its last stand, will be much more attractive than suggested by this analysis.

Dracunculiasis

Of the several attempts to eradicate diseases, all but one has failed. Even the exception, smallpox, barely succeeded despite the many factors favorable to eradication. Whether any eradication effort will ultimately succeed or fail cannot be known with certainty at the time it is launched. Eradication entails risk. Money spent on eradication may not ultimately pay a dividend. Health risks may also exist. If eradication fails and vaccination levels drop after the eradication goal is abandoned, susceptible persons who were previously shielded from infection may become infected at a later age, when the disease can cause greater harm. The risk also exists that, even if eradication succeeds, the disease may be reintroduced by accidental or deliberate release. The reasons for potential failure of an eradication effort are many. A nonhuman host may not be discovered until the number of infected humans drops to a very low level (as happened with yellow fever). The tools of eradication may be vulnerable to resistance (insecticides and drugs in the case of malaria). Political problems and civil strife may prevent an eradication program from being executed in critical areas where the disease makes its last stand (a problem today for guinea worm). Termination of vaccination may leave populations vulnerable to microbe reintroduction from an unforeseen reservoir or vaccine strain reversion (a risk now facing the poliomyelitis initiative). Another potential reason for failure is the inability to raise the financial resources needed to complete programs that extend beyond expected targets. All eradication programs have experienced serious financial stringencies during the course of their execution. Most eradication programs to date have been launched as visionary, far-reaching efforts but with vastly incomplete

Dracunculiasis, or guinea worm disease, is a nematode infection, which is controlled not by vaccination but by education of the affected population, provision of nematode-free water through wells or filtration, and treatment of cases. It is not a global disease but found only in the rural areas of a few very poor tropical countries. This last difference is especially important from an economics perspective. It means that international financing of a guinea worm eradication program needs to rely more heavily on development assistance rather than on the self-interest of donor countries. Thus far, the eradication program has been successful in reducing the number of cases of guinea worm 99 percent from the 1986 level (Carter Center 2004). The geographic range of the disease has also been reduced from 20 to just 12 countries. Although this achievement is important, eradication remains elusive many years beyond 1995, the year that the WHA set for eradication in 1991 (Cairncross, Muller, and Zagaria 2002, 232). Only one cost-benefit study of the guinea worm eradication program has been published (Kim, Tandon, and Ruiz-Tiben 1997), and it is unfortunately flawed in a number of respects. First, as indicated previously, eradication costs should be compared with those associated with an alternative optimal control program. Second, the cost-benefit analysis applies to the period 1987 to 1998 and thus is backward looking. The analysis can reveal whether the money spent previously yielded a benefit in excess of the cost (it did), but it cannot reveal whether eradication was worth pursuing at the time that this study was undertaken. Finally, it takes no account of the investment decision of eradication—the main reason for pursuing the eradication goal in the first place.

CONCLUSIONS

Control and Eradication | 1173 ©2006 The International Bank for Reconstruction and Development / The World Bank 245

information. Basic epidemiological information and knowledge of the effectiveness and operational constraints of interventions and costs in different settings are often inadequate, and the required monitoring, evaluation, training, and research components of the program may be absent. If a program’s administrators lack a careful, probing analysis of the epidemiology of the various candidate diseases or of the technologies available, and if their comprehension of the potential costs and who would bear them is limited, a program is likely to founder, causing a dispirited staff, confused beneficiaries, and donor fatigue and ambivalence. It is crucial that the eradication methodologies and assumptions in those regions of the world that would be most likely to pose the most significant problems be tested and addressed before launching an eradication program and that evaluation and research continue during the program. Proposals for disease eradication have seldom been brought to the WHA with specific plans, costs, and uncertainties fully laid out. Nor have the expected sources of fiscal support and needed country support been addressed with specific commitments requested of the members. The WHA has only a limited deliberative capacity, and too much cannot be expected of its members in session. However, designated special committees of the WHA can and should be appointed, consisting of both visionary eradicationists and field-experienced public health and social science personnel. The WHA should take up the question of eradication only after the subject has been thoroughly vetted and sufficiently large-scale pilot programs in the most problematic areas have clarified that an adequate understanding of the epidemiology exists and that the appropriate technologies are available. In the past, members have not voted for a specific program for which all the uncertainties have been laid out and the benefits and costs associated with different outcomes have also been calculated. Nor, with one exception, have they voted for a resolution imposing responsibilities, including financing obligations, on individual states. The next time a proposal to eradicate a disease is presented to the WHA, it should be comprehensive. It should demonstrate why the effort is worth taking, even if the final outcome is uncertain; it should bind states, morally if not legally, to fulfill the pledges needed to see the program through to its completion; and it should prepare contingencies should the eradication effort fail.

REFERENCES Anderson, R. M., and R. May. 1991. Infectious Diseases of Humans: Dynamics and Control. Oxford, U.K.: Oxford University Press. Andrews, J. M., and A. D. Langmuir. 1963. “The Philosophy of Disease Eradication.” American Journal of Public Health 53: 1–6. Aylward, R. B., A. Acharya, S. England, M. Agocs, and J. Linkins. 2003. “Polio Eradication.” In Global Public Goods for Health: Health Economic and Public Health Perspectives, eds. R. Smith, R. Beaglehole, D. Woodward, and N. Drager, 33–53. Oxford, U.K.: Oxford University Press. Aylward, R. B., J. M. Olive, H. F. Hull, C. A. De Quadros, and B. Melgaard. 1998. “Ensuring Common Principles Lead to Mutual Benefits: Disease Eradication Initiatives and General Health Services.” In The Eradication of Infectious Diseases, eds. W. R. Dowdle and D. R. Hopkins. New York: John Wiley and Sons. Barrett, S. 2003. “Global Disease Eradication.” Journal of the European Economic Association 1: 591–600. ———. 2004. “Eradication vs. Control: The Economics of Global Infectious Disease Policy.” Bulletin of the World Health Organization 82 (9): 683–88. Barrett, S., and M. Hoel. 2003. “Optimal Disease Eradication.” Disease Control Priorities Project Working Paper 22. Bart, K. J., J. Foulds, and P. Patriarca. 1996. “Global Eradication of Poliomyelitis: Benefit-Cost Analysis.” Bulletin of the World Health Organization 74 (1): 35–45. Basu, R. N., Z. Jezˇek, and N. A. Ward. 1979. The Eradication of Smallpox from India. New Delhi: World Health Organization. Bellmunt, A., G. May, R. Zell, P. Pring-Akerblom, W. Verhagen, and A. Heim. 1999. “Evolution of Poliovirus Type I during 5.5 Years of Prolonged Enteral Replication in an Immunodeficient Patient.” Virology 265: 178–84. Biellik, R., S. Madema, A. Taole, A. Kutsulukuta, E. Allies, R. Eggers, and others. 2002. “First 5 Years of Measles Elimination in Southern Africa: 1996–2000.” Lancet 359 (9317): 1564–68. Breman, J. G., and I. Arita. 1980. “The Confirmation and Maintenance of Smallpox Eradication.” New England Journal of Medicine 303 (22): 1263–73. Brilliant, L. B. 1985. The Management of Smallpox Eradication in India. Ann Arbor: University of Michigan Press. Cairncross, S., R. Muller, and N. Zagaria. 2002. “Dracunculiasis (Guinea Worm Disease) and the Eradication Initiative.” Clinical Microbiology Reviews 15 (2): 223–46. Carter Center. 2004. “Guinea Worm Eradication: Review, June 1, 2003.” Carter Center, Atlanta. http://www.cartercenter.org/printdoc.asp? docID=1785andsubmenu=news. CDC (U.S. Centers for Disease Control and Prevention). 1998a. “Progress toward Elimination of Measles from the Americas.” Morbidity and Mortality Weekly Report 47 (10): 189–93. ———. 1998b. “Progress toward Global Measles Control and Regional Elimination, 1990–1997.” Morbidity and Mortality Weekly Report 47 (48): 104.

ACKNOWLEDGMENTS We would like to acknowledge Walter Dowdle and Maria Teresa Valenzuela for their critical review of our manuscript; Joel Breman and Philip Musgrove for providing editorial guidance; John Sentz for his numerous hours devoted to research and editorial assistance; and Cherice Holloway for her preparation of various versions of this manuscript.

———. 1999a. “Global Measles Control and Regional Elimination, 1998–1999.” Morbidity and Mortality Weekly Report 48 (49): 1124. ———. 1999b. “Progress toward Measles Elimination—Southern Africa, 1996–1998.” Morbidity and Mortality Weekly Report 48 (27): 585. ———. 2003a. “Global Progress toward Certifying Polio Eradication and Laboratory Containment of Wild Polioviruses—August 2002–August 2003.” Morbidity and Mortality Weekly Report 52 (47):1158.


———. 2003b. “Progress toward Poliomyelitis Eradication—Angola and the Democratic Republic of Congo, January 2002–June 2003.” Morbidity and Mortality Weekly Report 52 (34): 816. ———. 2003c. “Progress toward Poliomyelitis Eradication—Southern Africa, 2001—March 2003.” Morbidity and Mortality Weekly Report 52 (22): 521. ———. 2003d. “Update: Global Measles Control and Mortality Reduction—Worldwide, 1991–2001.” Morbidity and Mortality Weekly Report 52 (20): 471. ———. 2004a. “Brief Report: Global Polio Eradication Initiative Strategic Plan, 2004.” Morbidity and Mortality Weekly Report 53 (05): 107. ———. 2004b. “Measles Mortality Reduction—West Africa, 1996–2002.” Morbidity and Mortality Weekly Report 53 (02): 28. ———. 2004c. “Progress toward Global Eradication of Poliomyelitis, January 2003–April 2004.” Morbidity and Mortality Weekly Report 53 (24): 532.

Fenner, F., A. J. Hall, and W. R. Dowdle. 1998. “What Is Eradication?” In The Eradication of Infectious Diseases, eds. W. R. Dowdle and D. R. Hopkins, 3–17. New York: John Wiley and Sons. Fenner, F., D. A. Henderson, I. Arita, Z. Jezˇek, and I. D. Ladnyi. 1988. Smallpox and Its Eradication. Geneva: World Health Organization. Goodman, R. A., K. L. Foster, F. L. Trowbridge, and J. P. Figueroa, eds. 1998a. “Comments and Discussion Following Work Group Reports.” In “Global Disease Elimination and Eradication as Public Health Strategies,” Bulletin of the World Health Organization 76 (Suppl. 2): 104–8. ———. 1998b. “Global Disease Elimination and Eradication as Public Health Strategies: Proceedings of a Conference. Atlanta, Georgia, February 23–25, 1998.” Bulletin of the World Health Organization 76 (Suppl.) 2: 5–162. Henderson, D. A. 1982. “The Deliberate Extinction of a Species.” Proceedings of the American Philosophical Society 126: 461–71.

———. 2004d. “Progress toward Measles Elimination—Region of the Americas, 2002–2003.” Morbidity and Mortality Weekly Report 53 (14): 304.

———. 1988. “Development of the Global Smallpox Eradication Programme, 1958–1966.” In Smallpox and Its Eradication, eds. F. Fenner, D. A. Henderson, I. Arita, Z. Jezˇek, and I. D. Ladnyi, 365–419. Geneva: World Health Organization.

———. 2004e. “Progress toward Poliomyelitis Eradication—Nigeria, January 2003–March 2004.” Morbidity and Mortality Weekly Report 53 (16): 343.

———. 1998a. “Eradication: Lessons from the Past.” Bulletin of the World Health Organization 76 (Suppl. 2): 17–21.

———. 2004f. “Progress toward Sustainable Measles Mortality Reduction—South-East Asia Region, 1999–2002.” Morbidity and Mortality Weekly Report 53 (25): 559. ———. 2004g. “Wild Poliovirus Importations—West and Central Africa, January 2003–March 2004.” Morbidity and Mortality Weekly Report 53 (20): 433. ———. 2005. “Progress toward Poliomyelitis Eradication—Poliomyelitis Outbreak in Sudan, 2004.” Morbidity and Mortality Weekly Report 54 (4): 97–99.

———. 1998b. “The Siren Song of Eradication.” Journal of the Royal College of Physicians of London 32 (6): 580–84. Hopkins, D. R., E. Ruiz-Tiben, N. Diallo, P. C. Withers Jr., and J. H. Maguire. 2002. “Dracunculiasis Eradication: And Now, Sudan.” American Journal of Tropical Medicine and Hygiene 67 (4): 415–22. Jeffrey, G. M. 1976. “Malaria Control in the Twentieth Century.” American Journal of Tropical Medicine and Hygiene 25: 361–71. Jenner, E. 1801. The Origin of Vaccine Inoculation. London: Shury. Quoted in Fenner, Hall, and Dowdle 1998.

Cello, J., A. V. Paul, and E. Wimmer. 2002. “Chemical Synthesis of Poliovirus cDNA: Generation of Infectious Virus in the Absence of Natural Template.” Science 297 (5583): 1016–18.

Kew, O. M., V. Morris-Glasgow, M. Landaverde, C. Burns, J. Shaw, Z. Garib, and others. 2002. “Outbreak of Poliomyelitis in Hispaniola Associated with Circulating Type 1 Vaccine-Derived Poliovirus.” Science 296 (5566): 356–59.

Cochi, S., C. de Quadros, W. Dowdle, R. Goodman, P. Ndumbe, D. Salisbury, and others. 1998. “Post-Conference Small Group Report.” In Global Disease Elimination and Eradication as Public Health Strategies, eds. R. A. Goodman, K. L. Foster, F. L. Trowbridge, and J. P. Figueroa. Bulletin of the World Health Organization 76 (Suppl. 2): 113.

Kew, O. M., P. F. Wright, V. I. Agol, F. Delpeyroux, H. Shimizu, N. Nathanson, and M. A. Pallansch. 2004. “Circulating Vaccine-Derived Polioviruses: Current State of Knowledge.” Bulletin of the World Health Organization 82 (1): 16–23.

Cockburn, A. 1961. “Eradication of Infectious Diseases.” Science 133: 1050–58.

Khan, M., and J. Ehreth. 2003. “Costs and Benefits of Polio Eradication: A Long-Run Global Perspective.” Vaccine 21: 702–5.

———. 1963. The Evolution and Eradication of Infectious Diseases. Baltimore: Johns Hopkins University Press.

Kim, A., A. Tandon, and E. Ruiz-Tiben. 1997. “Cost-Benefit Analysis of the Global Dracunculiasis Eradication Campaign.” Policy Research Working Paper 1835, World Bank, Washington, DC.

de Quadros, C. 2001. “Introduction.” In Considerations for Viral Disease Eradication Lessons Learned and Future Strategies, eds. S. Knobler, J. Lederberg, and L. A. Pray, 22–32. Washington, DC: National Academy Press.

Knobler, S., J. Lederberg, and L. A. Pray, eds. 2001. Considerations for Viral Disease Eradication Lessons Learned and Future Strategies. Washington, DC: National Academy Press.

Dowdle, W. R. 1998. “The Principles of Disease Elimination and Eradication.” Bulletin of the World Health Organization 76 (Suppl. 2): 22–25. ———. 1999. “The Principles of Disease Elimination and Eradication.” Morbidity and Mortality Weekly Report 48 (Suppl.): 23–27. Dowdle, W. R., and D. R. Hopkins, eds. 1998. The Eradication of Infectious Diseases. New York: John Wiley and Sons. Dubos, R., and J. Dubos. 1953. The White Plague: Tuberculosis, Man and Society. London: Gollancz. Quoted in Fenner, Hall, and Dowdle 1998. Eichner, M., and K. Dietz. 1996. “Eradication of Poliomyelitis: When Can One Be Sure That Polio Virus Transmission Has Been Terminated? American Journal of Epidemiology 143 (8): 816–22.

Kremer, M., and E. Miguel. 2004. “The Illusion of Sustainability.” NBER Working Paper W10324, National Bureau of Economic Research, Cambridge, MA. New Shorter Oxford English Dictionary. 1993. Ottesen, E. A., W. R. Dowdle, F. Fenner, K. O. Habermehl, T. J. John, M. A. Koch, and others. 1998. “Group Report: How Is Eradication to Be Defined and What Are the Biological Criteria?” In The Eradication of Infectious Diseases, eds. W. R. Dowdle and D. R. Hopkins. New York: John Wiley and Sons. Payne, A. M.-M. 1963a. “Basic Concepts of Eradication.” American Review of Respiratory Disease 88: 449–55. ———. 1963b. “Disease Eradication as an Economic Factor.” American Journal of Public Health 53: 369–75.

Control and Eradication | 1175 ©2006 The International Bank for Reconstruction and Development / The World Bank 247

Ramaiah, T. J. 1976. “Cost-Benefit Analysis of the Intensified Campaign against Smallpox in India.” National Institute of Health Administration and Education Bulletin 9 (3): 169–203. Roberts, L. 2004. “Polio Endgame. Polio: The Final Assault?” Science 303 (5666): 1960–68. Sabin, A. B. 1991. “Measles, Killer of Millions in Developing Countries: Strategy for Rapid Elimination and Continuing Control.” European Journal of Epidemiology 7 (1): 1–22. Salisbury, D. 1998. “Report of the Work Group on Disease Elimination/Eradication and Sustainable Health Development.” In Global Disease Elimination and Eradication as Public Health Strategies, eds. R. A. Goodman, K. L. Foster, F. L. Trowbridge, and J. P. Figueroa. Bulletin of the World Health Organization 76 (Suppl. 2): 72–79. Sangrujee, N., V. M. Cáceres, and S. L. Cochi. 2004. “Cost Analysis of Post-Polio Certification Immunization Policies.” Bulletin of the World Health Organization 82 (1): 9–15. Sencer, D. J., and N. W. Axnick. 1973. “Cost Benefit Analysis.” In International Symposium on Vaccination against Communicable Diseases, Monaco 1973, 22: 37–46. Symposia Series in Immunobiological Standardization. Basel, Switzerland: Karger.

Spînu, I., and S. Biberi-Moroianu. 1969. “Theoretical and Practical Problems Concerning the Eradication of Communicable Diseases.” Archives roumaines de pathologie experimentales et de microbiologie 28: 725–42. Steinglass, P. 2001. Thematic Evaluations in 2001 Eradication of Poliomyelitis. Report by the director general, Programme Development Committee of the Executive Board Eight Meeting, December 13, 2001. Document EBPDC8/3. Geneva: World Health Organization. Taylor, C. E., F. Cutts, and M. E. Taylor. 1997. “Ethical Dilemmas in Current Planning for Polio Eradication.” American Journal of Public Health 87 (6): 922–25. WHO (World Health Organization). 2003. Global Polio Eradication Initiative: Estimated External Financial Resource Requirements 2004–2008. Geneva: WHO. ———. 2004. Report of the Strategic Advisory Group of Experts (SAGE). Geneva: WHO. http://www.who.int/vaccines-documents/DocsPDF05/ Sage_Report_2004.pdf. Yekutiel, P. 1980. Eradication of Infectious Diseases: A Critical Study. New York: Karger.


Chapter 63

Integrated Management of the Sick Child Cesar G. Victora, Taghreed Adam, Jennifer Bryce, and David B. Evans

NATURE, CAUSES, AND BURDEN OF CHILD MORTALITY Every year, over 10 million children under five years of age die. Most of those deaths are due to a small number of causes. In the mid 1990s, it was estimated that 70 percent of all global child deaths were due to five conditions: diarrhea, pneumonia, malaria, measles, and malnutrition (Gove 1997; Tulloch 1999). The World Health Organization (WHO) has since conducted a comprehensive review of under-five deaths using additional data and improved methods (Bryce and others 2005), and now estimates that six causes accounted for 73 percent of these deaths in 2000–2003: pneumonia (19 percent), diarrhea (18 percent), malaria (8 percent), neonatal pneumonia or sepsis (10 percent), preterm delivery (10 percent), and asphyxia at birth (8 percent). Undernutrition is an underlying cause in at least half of all under-five deaths. Few conditions, therefore, account for a large proportion of all deaths. These deaths are not randomly distributed.They tend to occur in the poorest countries of the world, mostly in Sub-Saharan Africa and South Asia (Black, Morris, and Bryce 2003), and within any country they affect mostly the poorest families (Victora and others 2003). Fortunately, cost-effective interventions are available to prevent most of these deaths. Chapters 19, 21, 24–28, and 56 in this volume, as well as the next section in this chapter, describe these interventions in greater detail.Achieving universal coverage with these interventions would likely prevent 60 percent of those deaths (Jones and others 2003). Yet coverage levels for nearly all of these interventions remain below 50 percent (Bryce and others 2003), and children from the poorest families are least likely to be reached (Victora and others 2003).

In addition, comorbidity is common. Among children who die, a large proportion present with two or more diagnoses (Black, Morris, and Bryce 2003). Comorbidity is also highly prevalent at the community level and among children seeking health care. Nutritional factors—including underweight, micronutrient deficiencies, and inadequate infant feeding practices (see chapter 28)—play a major role in morbidity and mortality, and yet these are often overlooked by practitioners. Also, there are many missed opportunities for preventive interventions during outpatient visits—for example, immunizations and promotion of insecticide-treated mosquito nets.

POLICY SHIFT TO INTEGRATED MANAGEMENT Until the mid 1990s, actions aimed at improving child health were organized as vertical programs, each addressing a specific disease or providing a given intervention or set of interventions (Claeson and Waldman 2000). Typical examples of these programs are the Expanded Program on Immunizations (EPI), Control of Diarrhoeal Diseases (CDD), acute respiratory infection (ARI) programs, malaria control programs, and nutrition programs that include growth monitoring, breastfeeding promotion and support, and micronutrient supplementation. The need for an integrated approach to improve child health became evident in the mid 1990s for a number of reasons. From the perspective of epidemiology, a small number of diseases accounted for a high proportion of deaths, and those diseases were often present in the same children and had overlapping clinical signs. Integrated management was expected to increase the probability that children would receive treatment


for all major diseases and to decrease the possibility that children would receive correct treatment for one disease and die from another unrecognized illness. The important role played by nutrition across these major diseases also suggested that an integrated approach to case management was needed to ensure that health workers addressed children’s nutritional needs throughout the clinical encounter. A second set of reasons for the policy shift to an integrated approach was based on the need to promote managerial efficiency. The vertical approach required countries to appoint managers at national, provincial, and district levels to run each program. It also led to separate training activities; for example, health workers might be required to leave their posts on a number of occasions to be trained for the programs. Similar examples of duplication of effort were often found in supervision and provision of essential drugs. There was a strong logical basis for believing that integrating the management structure of child health programs would lead to improved efficiency. A third group of reasons for the shift to integrated case management related to the need to improve the quality of case management provided by health workers. Vertical programs trained health workers to manage one disease at a time, and decisions about how best to assess and treat those diseases, as well as how to promote nutrition and educate caretakers, were often left to individual health workers. An integrated set of guidelines for managing sick children ensured that health workers, including those with low levels of training, applied the best available knowledge of case management systematically and in correct sequence. The realization that a few diseases were responsible for most child deaths, that comorbidity was highly prevalent, that effective interventions were available, and that there were many missed opportunities for prevention led to the recognition that an integrated approach was needed. Thus, WHO and United Nations Children’s Fund (UNICEF) launched the Integrated Management of Childhood Illness (IMCI) strategy in the mid 1990s (Tulloch 1999). Tanzania and Uganda began implementing IMCI in 1996. By 2003, more than 100 countries had adopted the strategy (http://www.who.int/childadolescent-health).

on a set of adapted algorithms (Gove 1997) that guide health workers through a process of assessing signs and symptoms, classifying the illness according to treatment needs, and providing appropriate treatment and education to the child’s caregiver. Figure 63.1 shows a general outline of the approach for children age two months to five years (WHO and UNICEF 2001). Sick children attending a first-level health facility are initially checked for danger signs and for the main symptoms of the key IMCI diseases: diarrhea, malaria, pneumonia, measles, and other severe infections. Next, all children are assessed for malnutrition and anemia, and vaccination status is verified. Children under two years of age, as well as older children presenting low weight for age, receive nutrition counseling. Other health problems related by caretakers are then assessed, and children are classified according to a color code: pink (immediate referral), yellow (management in the outpatient facility), or green (home management). Separate case-management algorithms are available for children under two months of age. IMCI health worker training emphasizes the integration of curative care with preventive measures, including nutrition and vaccinations. A special training module addresses how to communicate effectively with mothers. The training course was originally designed to last 11 days, including a large amount of hands-on experience.

Improving Health Systems The second component of IMCI is aimed at providing support for child health service delivery, including drug availability, effective supervision, referral services, and health information systems. Tools were developed for implementing specific system-strengthening interventions, including a planning guide for national and district managers, an integrated health facility assessment tool, and a tool for improving referral level care. In particular, several countries—beginning in Latin America through the Pan American Health Organization (PAHO) and more recently in Africa with WHO’s Regional Office for Africa—made substantial efforts to improve the management and availability of the specific drugs required for IMCI (A. Bartlett, personal communication).

Improving Family and Community Practices

INTERVENTIONS A key aspect of IMCI was the integration of effective interventions to improve child health and nutrition into a coordinated strategy. IMCI has three components, each of which was meant to be adapted at the country level according to local epidemiology, health system characteristics, and culture. Improving Health Worker Performance The first component of IMCI includes health worker training and the reinforcement of correct performance. Training is based

The third component, known as community IMCI, focuses on 12 key family practices relevant to child health and development (see http://www.who.int/child-adolescenthealth/PREVENTION/12_key.htm). Community IMCI supports the development and implementation of communityand household-based messages and interventions to increase the proportions of children exposed to these practices. These behaviors address breastfeeding, complementary feeding, micronutrients, personal hygiene, immunizations, insecticidetreated nets, mental and social development, continued feeding

1178 | Disease Control Priorities in Developing Countries | Cesar G. Victora, Taghreed Adam, Jennifer Bryce, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 250

The Integrated Case Management Process Outpatient health facility

Check for danger signs • Convulsions • Lethargy or unconsciousness • Inability to drink or breastfeed

Assess main symptoms • Cough or difficulty breathing • Diarrhea • Fever • Ear problems

Assess nutrition and immunization status and potential feeding problems

Check for other problems

Classify conditions and identify treatment actions according to color-coded treatment charts

Pink Urgent referral

Outpatient health facility • Give prereferral treatments • Advise parents • Refer child

Yellow Treatment at outpatient health facility

Outpatient health facility • Treat local infection • Give oral drugs • Advise and teach caretaker • Follow up

Green Home management Home Caretaker is counseled on how to • Give oral drugs • Treat local infections at home • Continue feeding • Determine when to return immediately • Follow up

Pink Urgent referral

Referral facility • Provide emergency triage and treatment • Diagnose • Treat • Monitor and follow up

Source: WHO and UNICEF 2001.

Figure 63.1 Schematic Outline of IMCI Case Management for Children Age Two Months to Five Years

Integrated Management of the Sick Child | 1179 ©2006 The International Bank for Reconstruction and Development / The World Bank 251

and increased fluids during illness, home treatment of infections, care-seeking practices, compliance with health worker recommendations, and prenatal care. This chapter addresses issues related to the integrated delivery of these interventions, most of which are covered in greater detail in other chapters in this book. These include case management of ARI (chapter 25), diarrhea (chapter 19), malaria (chapter 21), and malnutrition (chapter 28); community interventions to improve nutrition, including breastfeeding promotion and complementary feeding (chapter 56); insecticideimpregnated bednets (chapter 21); anthelmintic treatment (chapter 24); vaccinations (chapter 20); and micronutrient supplementation (chapter 28).

INTERVENTION COST AND COST-EFFECTIVENESS One of the rationales for developing the IMCI strategy was the belief that treating the sick child in an integrated manner, by building on interventions that had already been shown to be cost-effective, would result in gains in efficiency. Two types of questions can be asked from an economic perspective. First, is treating children on the basis of the IMCI strategy cost-effective? Second, do the additional health benefits gained by switching from routine practice to IMCI justify the additional costs (if any)? Only one publication has reported the cost-effectiveness of the IMCI strategy as a whole. Using a modeling exercise, the World Development Report 1993 identified IMCI as being able to avert 14 percent of the global burden of disease in children under age five in resource-poor countries at a cost of only US$1.60 per capita per year, with a cost-effectiveness of US$30 to US$100 per disability-adjusted life year (DALY) averted. No details of the methods used to derive those estimates are available (World Bank 1993). It is not clear if the costs are the additional costs of moving from current practice to IMCI or the costs of undertaking care for children under age five using IMCI, nor is it clear if the effectiveness is the additional effectiveness of changing current practice or the total effect of the package. Detailed studies of the cost-effectiveness of some of the components of IMCI are available. For example, oral rehydration therapy for diarrhea, case management for pneumonia, and childhood vaccinations have been shown to be very cost-effective when evaluated as separate interventions (see chapters 19, 25, and 26). It is likely that the combination of different sets of childhood interventions, as proposed by IMCI, would also be cost-effective, although this depends on the relationship between costs and effects when the interventions are undertaken at the same time in the same population. No published studies of the extent and nature of efficiency gains through integration were found. WHO has recently explored some of these gains for slightly different combina-

tions of childhood interventions in different parts of the world (see http://www.who.int/evidence/cea). This research resulted in estimates of the cost-effectiveness of single or combined interventions compared with doing nothing or with incremental intervention or current practice. Because large-scale trials on the effects of joint interventions have not yet been undertaken, the joint effects were modeled using the effectiveness of the individual interventions taken from systematic reviews. The interventions included vitamin A and zinc fortification and supplementation, oral rehydration therapy, case management for pneumonia, and supplementary feeding and growth monitoring. Costs and effects were estimated at various levels of population coverage and in various combinations. The results showed that a childhood package consisting of vitamin A and zinc supplementation, oral rehydration therapy, and case management of pneumonia was cost-effective compared with doing nothing in most settings but that including supplementary feeding and growth monitoring was not costeffective. Implementation of this combination at 50 percent coverage was estimated to cost, in 2000 prices, approximately US$4.10 per child (US$0.60 per capita) in poor African countries such as Tanzania. The cost-effectiveness was US$38 per DALY averted. Costs increase faster than the increase in coverage. In Tanzania, it was estimated to cost an additional US$12.10 per child under age five (US$1.80 per capita) to reach 95 percent coverage, with a resulting incremental costeffectiveness ratio of US$60 per DALY averted. This study is important because it is one of the few that has specifically explored the cost-effectiveness of undertaking combined interventions in the same population, and the effect of increasing coverage on costs. These absolutely critical questions for policy makers considering different intervention strategies are also critical to IMCI. However, the WHO study did not analyze the same interventions included in the IMCI package, nor did it evaluate the effect of moving from current practice to IMCI-based care. Some information on the effect of moving from current practice is available from two studies in Kenya and Nigeria. Those studies compared the cost to the provider of traditional prescribing patterns with the costs of pharmaceuticals that would have resulted if the IMCI guidelines had been followed strictly. In Nigeria, the traditional prescribing method was five times more expensive: US$1.44 per child visit for pharmaceuticals compared with US$0.29, using 1996 estimates (Wammanda, Ejembi, and Iorliam 2003). In Kenya, also in 1996, the traditional method was almost three times costlier per child visit if the low-cost combination of drugs was assumed (US$0.44) and similar if the high-cost combination was assumed (US$0.16) (Boulanger, Lee, and Odhacha 1999). In Bangladesh, it was estimated that strict adherence to the IMCI protocol could result in US$7 million in savings at the national level simply from more rational use of drugs—almost 3 percent


of the total health budget of the government of Bangladesh (Khan, Ahmed, and Saha 2000; Khan, Saha, and Ahmed 2002). These estimates were based on models and assumptions, sometimes using evidence from separate systematic reviews addressing the costs and effects of an intervention. It would be valuable if information on relative cost-effectiveness of different combinations of interventions at variable levels of coverage could be derived from field studies rather than developed solely by modeling. Such an approach would allow the use of comparable methods and counterfactuals across the evaluation sites to make the results more useful and generalizable to other settings. In addition to answering questions related to the costeffectiveness of IMCI, it would clarify gains that can be obtained from delivering interventions at the same time as part of an integrated package rather than delivering them in a vertical manner. This is one of the reasons the Multi-Country Evaluation of IMCI Effectiveness, Cost, and Impact (MCE) was launched (Bryce and others 2004). Five countries are currently participating in in-depth studies—Bangladesh (in 20 catchment areas), Brazil (in 46 municipalities), Peru (in all 24 departments in the country), Tanzania (in 4 districts), and Uganda (in 10 districts). Seven other countries—Bolivia, Cambodia, Kazakhstan, the Kyrgyz Republic, Morocco, Niger, and Zambia—were assessed for the evaluation but could not be included, mostly because of insufficient implementation of IMCI. The overall objective of the MCE is to evaluate the actual changes associated with IMCI as it is implemented in different settings. All studies measured an identical set of indicators and, with minor exceptions, used identical data collection tools (Bryce and others 2004). The remainder of this section presents the main findings from two MCE countries, Tanzania and Brazil, for which evaluation results are currently available.

training for health workers had been achieved, but there had been no increase in the provision of under-five interventions at the community level, as opposed to the facility level. Cost data were collected for the start-up period of implementing IMCI (from 1996 to 1997)—defined as the time from the national decision to implement IMCI to the time when IMCI started to be provided in health facilities—and for the maintenance of child health services in both types of districts. Costs were estimated from the societal perspective and were collected from the national, district, hospital, health facility, and household levels. Costs at all these levels were summed to obtain the total cost to the district of providing care for children under age five. So that comparison could be made across districts, cost estimates were standardized to a hypothetical district with a population of 50,000 children under age five. This figure corresponds to a total population of around 300,000, which is roughly the average district population for Tanzania. Estimates of the additional cost to the district of implementing IMCI were based on the difference in cost of under-five care between the IMCI districts and the comparison districts, which, at the time of the study, had not yet implemented IMCI (Adam and others 2004b). For 1999, the cost per child of caring for children under age five in IMCI districts was US$11.19, 44 percent lower than in the comparison districts (US$16.09) (Adam and others 2004b). The lower cost per child in IMCI districts was due to lower hospitalization and administrative costs at the district level. There was no statistically significant difference in costs incurred to treat children at primary care facilities and at the household level (figure 63.2). 1999 US$ 8

MCE in Tanzania

7

The MCE in Tanzania uses an observational design to compare two districts where IMCI has been implemented since late 1997 (IMCI districts) with two districts where implementation began in 2002 (comparison districts). The four districts had reasonably well-functioning health services, comparable levels of per capita health expenditure, high utilization rates of government health facilities, and high coverage of selected interventions (for example, EPI). Large numbers of governmental and nongovernmental health actors were also active in the districts, many of which were involved in health worker training and community activities, although their coverage was patchy. The two IMCI districts had engaged in activities designed to strengthen district management skills; the districts also had authority for priority setting and control over their health budgets. These activities of national health sector reform had not started in the comparison districts at the time of the study. In the comparison districts, a high level of coverage of IMCI

6

IMCI (US$11.19) Comparison (US$16.09)

5 4 3 2 1 0 National

District

Hospital

Primary facility

Household

Level Source: Adam and others 2004b. Note: Standard district with 50,000 children under age five.

Figure 63.2 Cost Components of Under-Five Care per Child in a Standard District Integrated Management of the Sick Child | 1181


Hospital costs were 2.5 times higher in the comparison districts, not because of differences in the cost per under-five admission, but because more children under age five were hospitalized in those districts relative to IMCI districts (6 percent in IMCI districts compared with 15 percent in comparison districts; t–test: p 0.001). There are two possible explanations: (a) improved quality of care and drug availability for children under age five at IMCI primary facilities reduced the need for referral and subsequent admission to hospitals, or (b) factors other than IMCI, such as differences in quality or geographical access to the hospitals in the different settings, meant that children in non-IMCI districts were more likely to seek care at hospitals. Given that IMCI training had only started one year before data collection of hospital admissions, the second possibility may have played a bigger role in this finding. Even if one takes the most conservative assumption—that all the difference was due to other factors—and excludes the hospital component from the analysis, the total cost per under-five child in IMCI districts was still lower than in comparison districts (6 percent). The other important difference in costs between both types of districts was found in costs incurred at the district level, which were 50 percent higher in the comparison districts. These costs were mainly linked to more frequent trips for drug distribution and general purpose supervision in comparison districts than in IMCI districts. Similar costs of training were observed in both types of districts during the study period. This finding was unexpected given the emphasis of IMCI on training, but a wide variety of training courses were performed in comparison districts for preventive, curative, and administrative issues during the study period. These courses included training for immunization, for use of insecticide-treated bednets, and for use of district Health Management Information System forms. At the facility level, univariate comparison between IMCI and comparison district health facilities showed a 16 percent difference in the average cost per under-five visit (including vaccination visits) at government health centers and dispensaries (US$1.40 and US$1.60 in IMCI and comparison districts, respectively; t-test: p 0.5). The average number of visits per child per year was 30 percent higher in the IMCI districts (3.28) compared with comparison districts (2.49). Taken together, the lower cost per visit but higher number of visits per child per year in IMCI facilities resulted in similar overall costs per child under age five for treatment in the two types of districts. Multivariate regression analysis, however, led to a different conclusion. Taking into account differences in other determinants across facilities, in particular the number of visits per facility, the cost per visit was at least 30 percent lower in IMCI facilities (t-test: p 0.001). Sensitivity analysis showed the importance of hospitalization costs in interpreting total district costs—the difference between IMCI and comparison districts was not sensitive to

variation in the other parameters, only to the assumption about rates of hospitalization. Therefore, if one assumes that hospital admission rates were not related to IMCI, there is no difference in the cost of under-five care in the two types of districts. Otherwise, the costs in IMCI districts are lower than in the comparison districts. In the IMCI districts, IMCI was implemented concurrently with measures designed to strengthen district management, such as evidence-based planning and expenditure mapping at district level (http://web.idrc.ca/en/ev-3170-201-1-DO_ TOPIC.html). In fact, it has been argued that the decision to implement IMCI in the study districts was a result of the introduction of the evidence-based planning. It is not possible to separate the effects of IMCI from district-strengthening measures. The findings of the MCE study in Tanzania, therefore, can be interpreted as the costs of IMCI in the presence of a strong health system with adequate managerial capacity. The US$11.20 cost per child of treating children under age five using IMCI in Tanzania translates into a per capita cost of US$1.70, compared with US$2.30 for routine care. This finding is similar to previous per capita estimates of the cost of IMCI in resource-poor countries (World Bank 1993). In addition, the Tanzania evaluation had similar findings with respect to savings from drug costs to those expected based on previous studies (Khan, Saha, and Ahmed 2002; Wammanda, Ejembi, and Iorliam 2003; World Bank 1993). The effects of IMCI can be assessed in terms of changes in intermediate outcomes, such as improved quality of care at health facilities, or in terms of final outcomes, such as changes in under-five mortality or DALYs averted. In the Tanzania evaluation, a health facility survey was carried out in 2000 to compare the quality of case management and health systems support in IMCI and comparison districts. The results indicate that children in IMCI facilities received better care than children in comparison districts. Their health problems were more thoroughly assessed, they were more likely to be diagnosed and treated correctly as determined through a gold-standard reexamination, and the caretakers of the children were more likely to receive appropriate counseling and reported higher levels of knowledge about how to care for their sick children (Tanzania IMCI Multi-Country Evaluation Health Facility Survey Study Group 2004). Estimating the effectiveness of IMCI training in improving health workers’ performance required measuring the proportion of children correctly managed in IMCI and comparison facilities. Correct management is defined as the correct drug being provided in the correct formulation (amount, times per day, number of days) and the health worker explaining correctly to the caretaker how the drug should be administered at home. Not prescribing an antibiotic or antidiarrheal drug for a child who did not need one was also considered to be correct performance. In Tanzania, 65 percent of children under age five


Box 63.1

Impact of IMCI on Mortality and Nutrition in Tanzania Tanzania is the only MCE site where the evaluation has been completed. Its design included a comparison of mortality in four districts—two with and two without IMCI— over the two-year period starting in mid 2000. Demographic surveillance systems were used to compare under-five mortality rates in areas of the IMCI and control districts. Adjustments for age (zero to one and one to four years) and rainfall were made using Poisson regression models. During the IMCI phase-in period (July 1999 to June 2000), under-five mortality levels were almost identical in IMCI and comparison districts, at about 27 deaths

per 1,000 child-years or approximately 120 deaths per 1,000 children between birth and the age of less than five years. The quality of health care provided in the IMCI districts was substantially higher than in the control districts (see box 63.2). Over the following two years, mortality levels became 13 percent lower in IMCI districts than in the comparison areas, corresponding to a rate difference of 3.8 fewer deaths per 1,000 children per year. Stunting rates also became significantly lower in the IMCI districts. Contextual factors, such as mosquito net use, all favored the comparison districts.

Source: Armstrong Schellenberg and others 2004.

presenting to the surveyed IMCI facilities were correctly managed, compared with 16 percent in the comparison facilities. When the information on costs and effectiveness are taken together, the cost per child correctly managed is six times less in IMCI districts (US$4.02) than in the comparison districts (US$25.70) (Bryce and others forthcoming). Some of the differences in costs might be due to factors other than IMCI, so these ratios have to be interpreted with care. What is clear, however, is that treating children using IMCI in Tanzania was no more costly—and probably less costly—than treating children using routine care. At the same time, it resulted in higher quality of care. To the extent that this higher quality of care leads to better health outcomes, IMCI is cost-effective—it costs less (or at least no more) and results in better outcomes (see box 63.1).

MCE in Brazil Brazil is another MCE site where IMCI is being implemented in the context of an ambitious family health program (FHP), which is supported by the Ministry of Health and the World Bank and based at first-level government facilities. IMCI implementation started in 1996 and is moving ahead in the whole country, particularly in the northeast regions. IMCI training is targeted at FHP team members. The MCE in Brazil was carried out in four states, all in northeast Brazil, the poorest area of the country. In total, 23 municipalities with both FHP and IMCI were compared with matched municipalities with FHP but without IMCI. Early results from one component of the evaluation—the time and motion study—provide useful insights. After controlling for possible confounding factors using regression analysis, the

evaluation found that IMCI-trained providers spent 1 minute and 26 seconds longer per consultation with under-five children than untrained providers did. The difference was much greater when patient load was low but decreased as the number of patients a provider saw per day increased. This finding suggests that the system’s ability to absorb IMCI depends on current capacity utilization. In terms of the assessment of quality of care in the surveyed facilities, IMCI-trained health workers were shown to provide significantly better care than those who had not been trained (Amaral and others 2004; Gouws and others 2004). (See “Lessons about Implementation Success and Failure” later in this chapter for additional results on quality of care.) These results are important for policy development relating to child health. Where current caseloads are relatively low, providers spend additional time to provide better child health services, using IMCI as the basis of part of their current activities. In this study, the mean number of consultations per provider per day was 34, and 95 percent of the providers had caseloads of fewer than 50 patients per day. If this finding is representative of the rest of Brazil, it would be possible to introduce IMCI relatively easily throughout the country without encountering capacity constraints in terms of provider time. In areas with high patient loads, however, it would be important to explore whether it is possible to maintain high quality of care under IMCI in those areas and what the alternatives should be (Adam and others, forthcoming).

Summary of MCE Results The available results from the MCE so far show that costs of child health care in Tanzania were comparable or lower in Integrated Management of the Sick Child | 1183


districts with IMCI than with routine case management. Quality of care was higher, and a 13 percent reduction in mortality was also found in the IMCI districts in the study period. This finding strongly suggests that IMCI is a cost-effective intervention compared with routine care, as it costs less and is more effective in saving children’s lives. In Brazil, the MCE study also showed improved quality of care for children under age five after health workers were trained in IMCI. The results also showed that staff time constraints were unlikely to limit the application of IMCI, because, in settings with low caseloads, health workers could be expected to use the available excess capacity to provide better care for children under age five. Assuming that primary health facilities will experience savings on drug costs similar to those observed in Tanzania and previous modeling studies, one could also argue that IMCI is a good value for money in the Brazilian setting.

Proportion of children (percent) 100 First source of care from an appropriate provider 90 Antibiotics for probable pneumonia Antimalarials for fever 80 70 60 50 40 30 20 10 0 Most poor

Very poor

Poor

Less poor

Least poor

Socioeconomic status Source: Victora and others 2003, based on data taken from Schellenberg and others 2003.

Equity Issues Some of the equity implications related to care seeking and treatment have also been evaluated in the four rural districts included in the IMCI evaluation in Tanzania (Schellenberg and others 2003; Victora and others 2003). The MCE analysis found no association between sex and any indicator of morbidity, care seeking, case management, or compliance with treatment or follow-up instructions, suggesting that mothers and health workers treat boys and girls similarly (Schellenberg and others 2003). This finding is in accordance with that of Gwatkin and others (2000). Similarly, there were no statistically significant associations between socioeconomic status and reported prevalence of fever, diarrhea, severe diarrhea, or pneumonia. However, hospital admissions were almost half as common in the lowest socioeconomic status quintile as in the highest (t-test: p 0.0093), suggesting that referral care is more readily accessible to the wealthy. Positive associations were observed between socioeconomic status and care seeking from an appropriate provider (a qualified health worker practicing allopathic medicine) for fever without cough or diarrhea, for care seeking for episodes perceived as severe, and for using an appropriate provider as the first source of care. This finding is illustrated in figure 63.3, which puts households into five wealth categories. The poorest group was at least 25 percent less likely to have sought care than the least poor. Among the children who sought care, antibiotic use for probable pneumonia was less than half as common among the poorest than among the least poor. Also, children in the lowest socioeconomic group were half as likely to have been given antimalarials as those in the highest category (t-test: p 0.0001). These findings suggest that, although the prevalence of disease (self-reported) does not differ by socioeconomic status, care seeking and the probability of receiving appropriate care

Figure 63.3 Proportions of Children, by Socioeconomic Quintiles, Who Were Brought to an Appropriate Provider and Who Received Correct Care, in Rural Tanzania

vary markedly, even within an apparently homogeneous rural population. This observation agrees with data on mortality and nutritional status inequalities for Tanzania (Schellenberg and others 2003). There is no evidence yet showing whether the introduction of IMCI has reduced or increased this type of inequality.

IMPLEMENTATION OF PROGRAMS: LESSONS OF EXPERIENCE The IMCI strategy was thoroughly evaluated from its onset. Only two years after the first health worker training course took place, the MCE was launched (Bryce and others 2004). MCE researchers visited 12 countries and carried out in-depth studies in five of those. The MCE and the more recent Analytic Review of IMCI (DFID and others 2003), which included visits to six countries, provide the background for this section.

Institutions and Programs IMCI introduction was highly successful. As of December 2002, WHO’s global monitoring team reported that IMCI had been introduced in 109 countries (see http://www.who.int/ child-adolescent-health/overview/child_health/map12_ 02.jpg). Twelve countries were included in the introduction phase, in which the strategy was officially endorsed, a national IMCI coordination group was appointed, and key ministry of health staff members were trained in the IMCI clinical


guidelines. Another 50 countries were in the early implementation phase, which included development of a national plan, selection of initial districts for implementation, adaptation of the IMCI clinical guidelines and materials, training of course facilitators, and planning at the district level. Finally, 47 countries were in the expansion phase, which included scaling up IMCI activities in districts already covered and expanding to cover additional districts (WHO and UNICEF 1999). The fact that a country has adopted the IMCI strategy, however, does not mean that a high population coverage has been reached. The best available estimates of IMCI coverage are provided by the percentage of health workers who underwent IMCI training and are managing sick children. For example, the Brazil MCE (Amaral and others 2004) has shown that IMCI is being implemented in all 27 states, but in some of those states only a few health professionals were trained. In the three states selected for the evaluation because of reportedly strong IMCI implementation, there was at least one IMCItrained health worker in 239 out of 443 municipalities (54.0 percent), but only 23 municipalities (5.2 percent) had at least 50 percent of health workers trained after three years. In Peru, also a leading country in IMCI training, approximately 10 percent of all doctors and nurses providing child care were trained after seven years of IMCI implementation (Huicho and others 2005). Therefore, levels of training coverage in most countries appear to be low.

Lessons about Implementation Success and Failure Both the MCE (Bryce and others 2004) and the Analytic Review of IMCI that were carried out in 2002–3 (DFID and others 2003) confirm that IMCI has been highly successful in motivating managers and health workers. The training pro-

gram is highly regarded, and trainees are pleased with its logical, consistent approach to child health problems. Innovative clinical skills, such as the use of palmar pallor to diagnose anemia and the use of breathing rate for pneumonia, are often praised. Nutritional counseling, an area in which most health workers receive little formal training in school, is also greatly appreciated. When asked about the limitations of IMCI, health workers often mention the increased time required for a consultation and the difficulty of following the IMCI guidelines when there is a high patient load. Several studies have shown that health workers trained in IMCI do perform better than those not trained. Health facility surveys carried out in Tanzania (Schellenberg and others 2003), Brazil (Amaral and others 2004), and Uganda show that IMCI training substantially improves health worker performance in assessing and managing sick children, and in counseling their caretakers. Box 63.2 summarizes MCE findings on antibiotic prescribing patterns, a critical area for managing sick children (Gouws and others 2004). Important constraints to IMCI implementation were also identified through visits to 17 countries by the MCE and Analytic Review teams. Using the framework developed by the Commission on Macroeconomics and Health (Hanson and others 2001), the teams described shortcomings in three areas: community and household issues, health service delivery issues, and issues related to health sector policy and strategic management. Community and Household Issues. Coverage levels for effective interventions to improve child survival are remarkably low in most developing countries. A review of the 42 countries that account for 90 percent of global child deaths showed that only two out of nine key interventions reached more than half of all children (Bryce and others 2003). This finding agrees with

Box 63.2

Improving the Use of Antimicrobials through IMCI Case-Management: Findings from the MCE Antimicrobial drugs, including antibiotics and antimalarials, are an essential child survival intervention. Prompt and correct provision of drugs to children under age five who need them can save lives. Ensuring that these drugs are not prescribed unnecessarily and that those who receive them complete the full course can slow the development of antimicrobial resistance. Analysis of data collected through observation-based surveys at randomly selected first-level health facilities in Brazil, Tanzania, and Uganda shows that children receiving care from health workers trained in

IMCI are significantly more likely than those receiving care from workers not yet trained in IMCI to receive correct prescriptions for antimicrobial drugs, to receive the first dose of the drug before leaving the health facility, to have their caregivers advised on how to administer the drug, and to have caregivers who are able to describe correctly how to give the drug at home as they leave the health facility. IMCI training is an effective intervention to improve the rational use of antimicrobial drugs for sick children visiting firstlevel health facilities in low- and middle-income countries.

Source: Gouws and others 2004.


those of the MCE, showing that the third component of IMCI—improving family and community practices—was poorly implemented. At the global level, UNICEF was primarily in charge of developing this component (see http://www. childinfo.org/eddb/imci/practices.htm), and at the country level, UNICEF often acted through nongovernmental organizations (NGOs). Coverage with these community-based programs tended to be patchy. In Peru (Huicho and others 2005) and Tanzania, the districts that were selected for implementation of the community component were not the same as those prioritized for health worker training, which were chosen by the ministry of health with WHO support. This precluded any possible synergy at the district level between improved quality of care in health facilities and community interventions, including those aimed at improving care seeking and compliance with health workers’ advice. All the countries that were visited, however, have a number of programs and projects that deliver child survival interventions at the community level. Many of these interventions are part of the key IMCI family practices, but they are being delivered in an uncoordinated manner by national, international, and nongovernmental organizations in limited geographical areas. The low population coverage of these projects makes it unlikely that they will ever result in a substantial effect on a larger scale. The notable exceptions are the EPI programs, which, despite some recent evidence of falling coverage (Bryce and others 2003), still reach the vast majority of children in developing countries. On the basis of the experience obtained in these countries, it appears that those key family practices that are most likely to be synergistic with facility-based IMCI—improved care seeking, home management of disease, and compliance with health worker advice—are among those least likely to be supported by existing programs. Existing programs seem to favor biological interventions such as vaccines, micronutrient supplementation, and insecticide-treated materials. The present criticism of community IMCI should not be extrapolated to community-level child health interventions in general, which can often be highly successful. These interventions are covered in chapter 56. Health Service Delivery Issues. Given the difficulties in implementing the community component, IMCI was largely restricted in nearly all countries to training health workers in the improved management of care for young children. Even there, some difficulties were apparent. In countries such as Peru, Brazil, and Uganda, after an initial sharp increase in the number of health workers who were trained, budgetary and other restrictions led to a decrease in the number of training courses being offered. In Peru, about 10 percent of all eligible health workers in the public sector were trained after seven years of implementation. At the

current rate of training, several decades will be needed before full coverage is reached (Huicho and others 2005). Similar results were observed in Uganda (J. Nsungwa-Sabiti, personal communication). Staff turnover is also a major problem. In Peru, between 1996 and 2001, 43 percent of IMCI-trained health workers had already been rotated since their training (Huicho and others 2005). In Tanzania, where staffing patterns appear to be quite stable in comparison with the situation in other countries, 23 percent of trained staff had moved within three years of initial training (C. Mbuyia, personal communication). Problems with turnover were also observed in Bolivia, Brazil, and Niger. These health workers did not necessarily leave government employment, but high rotation means that IMCI may not be continually delivered to the same target population over time. Another relevant issue mentioned in several countries was that of low staff motivation, which was often associated with low salary levels. In Uganda, the performance of health workers fell dramatically in 2001 after the government discontinued cost-sharing schemes that were used to supplement drug supplies and health worker salaries at the facility level (Burnham and others 2004). In Cambodia and Tanzania, salary levels are so low that health workers need other sources of income to maintain their families. Issues related to human resources are addressed in greater detail in chapter 71. Poor supervision was a major issue in all countries that were visited. IMCI recommends regular supervisory visits that should include systematic observation and feedback on case management. In Peru, the average number of supervisory visits was 0.19 per facility per year (Huicho and others 2005). In Bangladesh, a baseline (pre-IMCI) health facility survey conducted in 2000 found that none of the facilities in the study area had received a supervisory visit, including observation of case management, within the previous six months (S. E. Arifeen, personal communication). Common reasons given by health workers for erratic supervision activities are shortages of vehicles, fuel, and staff members. Problems with referral were also common. The Urgent Referral category in figure 63.1 requires immediate referral to a hospital. In several countries (Bangladesh, Cambodia, Niger, Uganda, and Tanzania), it was reported that children in this category are often not taken to a hospital because of distance or lack of funds for travel and hospitalization-related expenses. For example, in a Tanzania survey, only 5 of 13 children who had been referred were actually taken to a hospital (Schellenberg and others 2003). Also, in some countries hospital staff members who had not been trained in IMCI were reluctant to admit children with danger signs identified through the IMCI algorithm. This situation highlights the need for reinforcing training of referral-level health workers using IMCI guidelines.


Another important limitation, observed in Bangladesh, Cambodia, Niger, and Uganda, is the low use of public sector health care for a variety of reasons (accessibility, official or under-the-table user fees, perceived poor quality, lack of drugs, and so on). For example, using Ministry of Health documents in Niger, the authors estimated that the average annual number of attendances by children under age five was 0.5. In Bangladesh, only 8 percent of children who were ill were taken to a qualified provider (S. E. Arifeen, personal communication). In the presence of such low utilization rates, it is unlikely that health worker training can have an effect on mortality rates, unless simultaneous community activities improve care-seeking practices. Although equipment and vaccines that are needed for IMCI delivery were available in most countries visited, availability of drug supplies varied from country to country. Shortages were reported in Cambodia and Zambia, and other countries, such as Peru and Tanzania, reported that essential IMCI drugs were mostly available. Health Sector Policy and Strategic Management Issues. Several of the problems described in the preceding section are directly related to health sector issues. In addition, issues related to higher-level policy and management may also represent constraints to successful IMCI implementation. In some countries, IMCI was not fully institutionalized at national or subnational levels. For example, a national coordinator was not appointed or was appointed on a part-time basis. In Peru, IMCI was implemented side by side with CDD and ARI programs, which it was expected to replace, and in several districts the ARI coordinator’s tasks were expanded to also encompass IMCI. In several countries, IMCI activities did not have a separate budget line, or they were not included in district health plans, or neither. A report on the Analytic Review of IMCI (DFID and others 2003, 39) states, “IMCI was generally introduced as a strategy, not as a program. If this was not a barrier in the pilot phase, it seemed to generate problems for rapid scaling up. In five of the six Analytic Review countries, IMCI focal persons did not have the rank or the responsibility of previous disease specific program managers within their Ministry of Health, and IMCI did not have a budget line and a strong management structure.” The report also argued that decentralization, as part of health sector reform, reduced managerial capacity at the central level and had, at least in the short term, a negative effect on IMCI implementation. Conflict between IMCI guidelines and existing policies and regulations was present in some countries, particularly the former Soviet republics of Kazakhstan and the Kyrgyz Republic, where policies for hospital admission—requiring, for example, that all children with diarrhea be hospitalized—were in conflict with IMCI guidelines. Another regrettable example comes from Brazil, where both doctors and nurses were being trained in IMCI until medical associations threatened legal

action to prevent nurses from being trained in using antibiotics for life-threatening conditions. This obstruction succeeded despite an MCE health facility survey that showed that IMCItrained nurses performed as well as doctors in managing sick children (Amaral and others 2004). In Morocco, IMCI-trained nurses are also unable to prescribe antibiotics because of central regulations. A particular challenge came to light when the MCE team visited Cambodia and Niger and the Analytic Review team visited Mali. These countries have high levels of under-five mortality and thus the greatest need for IMCI. They also have weak health systems and low utilization rates and are therefore having difficulty implementing IMCI successfully. Just as for individuals, the inverse care law—which suggests that those who most need high quality care are the least likely to get it— seems to also apply to countries (Hart 1971). However, there is a possibility that IMCI (or other approaches to managing sick children) might help strengthen selected health system functions through specific approaches, as the Analytic Review team observed in regard to drug and commodity availability, service management, and health worker motivation through IMCI in the Arab Republic of Egypt (DFID and others 2003).

Implications for Health System Development The first component of IMCI, which involves training of health care workers, has been implemented in many developing countries and has resulted in important improvements in the quality of care delivered to children in first-level facilities in limited geographic areas. The potential population-level effect of IMCI case-management training has not been realized, however, for three reasons: • Sufficient resources were not available for full implementation. • Few health systems in low-income countries are capable of providing the policy, personnel, and managerial support needed to expand and sustain high levels of IMCI training coverage. • At the time of this writing, not one country had succeeded in mounting a behavior-change program capable of improving care seeking, home management of illness, and nutrition-related practices to coverage levels that will result in population-level changes in service utilization or health status. One implication for health system development is that support should be continued and expanded for integrated case management in first-level facilities as an essential component of an effective child survival strategy. A second implication, however, is that greatly expanded efforts must be directed Integrated Management of the Sick Child | 1187


simultaneously to the development of new and innovative approaches to strengthening health systems and to reaching families and communities with known and affordable child survival interventions. An important distinction can be made between interventions and delivery strategies (Bryce and others 2003). The same intervention (vitamin A capsules, perhaps) can be delivered through different strategies—for example, to children attending health facilities, on National Immunization Days, or directly at the household level through community networks. In spite of its community component—which in most countries has not been operational anyway—IMCI, as implemented to mid 2004, relies on health facilities as its key delivery strategy. The first component of the IMCI strategy—a focus on improving health worker skills—was innovative to the extent that it provided clear technical guidelines and yet required country-level adaptation. Similar levels of technical clarity and country-level flexibility did not exist for the second and third components of the IMCI strategy, which focused on improving health systems to support IMCI and improving family and community practices. Within these two components, the IMCI strategy has been criticized for attempting to become a uniform global strategy, with guidelines for implementation that do not allow room for country-level modifications, especially the incremental approaches to implementation needed by weak health systems (Bryce and others 2003). The first component of IMCI can serve as a model for the types of development work that must now move forward in the health systems and family practice areas; however, in these areas, key decisions about how best to deliver interventions will need to be made at the country level and below. One example of progress is that WHO and its partners have now developed a process for assessing country-level opportunities and requirements for achieving population-level behavior change in relation to key family practices and for developing feasible and collaborative work plans for effectively implementing child health activities at the community level (A. Bartlett, personal communication). As the MCE and Analytic Review have shown, IMCI requires a functional health system with managerial capacity; an ability to train health workers and to keep them on the job; an efficient means of supplying drugs, vaccines, and equipment; and the capacity to maintain regular supervisory activities. It also requires appropriate care-seeking practices, leading to a reasonable level of health services utilization by children under age five. In most countries, appropriate health services utilization is unlikely to be achieved without strong family and household-level interventions such as those promoted by community IMCI. These problems, however, are not specific to IMCI; they affect every other delivery strategy that relies heavily on health facilities, including the predecessors of IMCI, namely the CDD

and ARI programs. In fact, at least in theory, the efficiency gains represented by the integration promoted by IMCI should make it easier for developing countries to implement as the key child health strategy, so a return to vertical programs is not the answer. Given these difficulties, however, there may be a temptation to bypass health services altogether in the poorest countries by promoting the delivery of child health interventions directly to families and households. There are successful examples of such community delivery schemes—for example, projects dispensing antimalarials (Pagnoni and others 1997; Kidane and Morrow 2000) and antibiotics for pneumonia (Sazawal and Black 1992). This approach may, in fact, be the most viable short-term solution for countries with weak health services, but it should not be forgotten that most success stories represent small-scale pilot projects with strong managerial backup. In countries with weak systems, the managerial support for implementing and sustaining high-quality, community-based interventions is also likely to be lacking, so it may be naive to assume that such programs will have the effects that health services have failed to deliver. Also, just as first-level health facility care depends on referral services for backup, community delivery schemes will require operational first-level health facilities to handle complications and treatment failures. There is no substitute for strengthening health systems in the poorest countries. In the long run, strengthening these systems will be the key intervention for reducing child mortality as well as for promoting healthy growth and development. Delivery strategies that reach communities either directly or through other mechanisms are needed in the short term, but the long-term goal of improving health services is paramount.

THE RESEARCH AND DEVELOPMENT AGENDA This section starts by addressing health systems research issues related to scaling up child health interventions effectively. Key issues on the research agenda are how to make the best possible use of integrated case management in settings where health systems are weak and how to design alternative delivery strategies to improve child survival in such settings. Specific issues relate to how to counteract the main constraints to scaling up IMCI that were described earlier in “Implementation of Programs: Lessons of Experience.” For example, research is needed in the following areas: • how to increase utilization in the public sector (and the role of user fees in this respect) • how to develop viable public sector–private sector partnerships • how to reduce staff turnover


• how to improve supervision and make it sustainable • how to institutionalize IMCI case-management training and supervision at the district level. In addition, research is needed on how to strengthen health systems and improve family and community practices for child survival in ways that take into account and build on features of the country context. These features include the epidemiologic profile and the characteristics of the health system. Countrylevel assessments and planning and support for longer-term implementation are required to achieve high and equitable coverage and population effect in different epidemiologic, health system, and cultural settings (Bellagio Study Group on Child Survival 2003). Innovative research is needed involving country-level investigators and program staff members, with international partnerships if required, to develop and evaluate different combinations of health facility–based and householdbased delivery schemes. In particular, research should address how to go to scale with interventions that have been proven effective in pilot studies. From the costing perspective, research should address the issue of how to estimate the cost of scaling up using different scenarios of resource availability and constraints. Monitoring and evaluation are key components of the required research. Tools must be developed for use at the district and national levels, and capacity to use them must be strengthened.

CONCLUSIONS: PROMISES AND PITFALLS IMCI was introduced in the mid 1990s as an ambitious global strategy that held many promises. Cost-effective vertical interventions against the main causes of under-five mortality in the world were integrated into a single, facility-based health worker training program. The program was accompanied by efforts to improve health systems support for child health care and to promote key family practices at the community level. Integration was expected to further improve coverage levels and the cost-effectiveness of child survival interventions relative to their delivery through separate vertical programs. IMCI case-management training was repeatedly shown to improve the quality of care delivered in first-level health facilities, and the costing data reviewed above suggest that it can do so at similar or lower costs than those of existing health services. IMCI, therefore, is able to deliver better child health care at no increase in costs. Nevertheless, community IMCI interventions only reached meager population coverage in the countries studied, and even health worker training was never effectively scaled up in most countries as a result of health system constraints. The major effect on child survival that was initially expected as a result of

IMCI implementation has not yet materialized, and country reports of the barriers to achieving and maintaining high coverage levels suggest that effects will not be seen unless IMCI in first-level facilities is buttressed by equally strong or stronger efforts to develop health system capacity and reach families and communities. In fact, progress in child survival in the late 1990s and early 21st century has been slower than in earlier decades (Bellagio Study Group on Child Survival 2003), and current trends suggest that the Millennium Development Goals are unlikely to be achieved for most countries unless major new investments are made very soon. The Tanzania results suggest that, in a setting where IMCI was implemented in conjunction with health system strengthening and where utilization of health facilities is high, an effect on mortality and nutritional status is likely. However, experience from other countries showed that reaching high and sustained implementation was difficult. Although IMCI has only partially lived up to initial expectations, it has many positive aspects that must be fostered. A return to isolated vertical programs for child survival will not solve the difficulties faced by scaling up IMCI effectively, and integration should continue to be a key goal of child survival strategies in the future. In fact, much of the frustration associated with reported underperformance of IMCI arises from the fact that sufficient resources—financial, human, and organizational—were not planned for or available to support its full implementation, either at national or at international levels. The meager training coverage levels observed in most of the MCE countries are clear evidence of insufficient implementation, and it is thus not surprising that coverage and effect were also less than expected. Renewed and expanded efforts to reduce child mortality should build on the proven effectiveness of IMCI case management in first-level facilities, but they also should incorporate new knowledge. Country-specific planning is needed to reach families and communities and to build on the existing health system to achieve and sustain population-level coverage. Countries with weak health systems will require creative approaches to intervention delivery in the short term at the same time that health systems are strengthened as a long-term strategy. The poorest strata of the population are also the neediest in terms of health care and the hardest to reach. The challenge of improving equity is not unique to IMCI or to child survival; it affects virtually every intervention and delivery strategy. Unless equity considerations become a key part of policy making and of monitoring outcomes, interventions may widen instead of narrow inequity gaps (Victora and others 2003). A continuing challenge is how to raise and sustain the standing of child survival in the international agenda. The more than 10 million annual deaths of children under age five—more than 20 deaths per minute—represent twice the number of Integrated Management of the Sick Child | 1189


deaths attributable to AIDS, malaria, and tuberculosis combined (Black, Morris, and Bryce 2003). Putting child survival back on the public health and development agenda is an essential developmental step in the process of refining country-level and global child health strategies. Only through taking stock of the lessons learned in early IMCI implementation can a flexible, integrated program be developed that will improve child survival in particular and child health in general.

Bryce J., E. Gouws, T. Adam, R. Black, J. A. Schellenberg, C. Victora, and J-P. Habicht. Forthcoming. “Improving the Efficiency of Facility-Based Child Health Care: A Success Story from Tanzania.” Bryce, J., C. G.Victora, J-P. Habicht, J. P.Vaughan, and R. E. Black. 2004.“The Multi-Country Evaluation of the Integrated Management of Childhood Illness Strategy: Lessons for the Evaluation of Public Health Interventions.” American Journal of Public Health 94 (3): 406–15. Burnham, G. M., G. W. Pariyo, E. Galiwango, and F. Wabwire-Mangen. 2004. “Discontinuation of Cost-Sharing in Uganda.” Bulletin of the World Health Organization 82 (3): 187–95. Claeson, M., and R. J. Waldman. 2000. “The Evolution of Child Health Programmes in Developing Countries: From Targeting Diseases to Targeting People.” Bulletin of the World Health Organization 78 (10): 1234–45.

ACKNOWLEDGMENTS A substantial portion of this chapter is based on early results from the Multi-Country Evaluation of IMCI Effectiveness, Cost, and Impact. The MCE is funded by the Bill & Melinda Gates Foundation and is supported by technical assistance from the World Health Organization and a technical advisory group representing global expertise in cost-effectiveness analysis, measurement, research design, and child health.

DFID (U.K. Department for International Development), UNICEF (United Nations Children’s Fund), World Bank, USAID (U.S. Agency for International Development), and WHO (World Health Organization). 2003. The Analytic Review of Integrated Management of Childhood Illness Strategy (Final Report). Geneva: World Health Organization. http://www.who.int/child-adolescent-health/ New_Publications/IMCI/ISBN_92_4_159173_0.pdf.

REFERENCES

Gove, S. 1997. “Integrated Management of Childhood Illness by Outpatient Health Workers: Technical Basis and Overview.” Bulletin of the World Health Organization 75 (Suppl. 1): 7–24.

Adam, T., D. G. Amorim, S. Edwards, J. Amaral, and D. B. Evans. Forthcoming. “Capacity Constraints to the Adoption of New Interventions: Consultation Time and the Integrated Management of Childhood Illness in Brazil.” Adam, T., D. Bishai, M. Khan, and D. Evans. 2004a. Methods for the Costing Component of the Multi-Country Evaluation of IMCI. Geneva: World Health Organization. http://www.who.int/imci-mce. Adam, T., F. Manzi, C. Kakundwa, J. Schellenberg, L. Mgalula, D. de Savigny, and others. 2004b. Analysis Report on the Costs of IMCI in Tanzania. Geneva: World Health Organization. http://www.who.int/ imci-mce. Amaral, J., E. Gouws, J. Bryce, A. J. M. Leite, A. L. A. Cunha, and C. G. Victora. 2004. “Effect of Integrated Management of Childhood Illness (IMCI) on Health Worker Performance in Northeast Brazil.” Cadernos de Saude Publica 2004. 20 (suppl. 2): 209–12. Armstrong Schellenberg, J. R. M., T. Adam, H. Mshinda, H. Masanja, G. Kabadi, O. Mukasa, and others. 2004. “Effectiveness and Costs of Facility-Based Integrated Management of Childhood Illness (IMCI) in Tanzania.” Lancet 364 (9445):1583–94. Bellagio Study Group on Child Survival. 2003. “Knowledge into Action for Child Survival.” Lancet 362 (9380): 323–27. Black, R. E., S. S. Morris, and J. Bryce. 2003. “Where and Why Are 10 Million Children Dying Every Year?” Lancet 361 (9376): 2226–34. Boulanger, L. L., L. A. Lee, and A. Odhacha. 1999. “Treatment in Kenyan Rural Health Facilities: Projected Drug Costs Using the WHOUNICEF Integrated Management of Childhood Illness (IMCI) Guidelines.” Bulletin of the World Health Organization 77(10): 852–58. Bryce, J., S. Arifeen, G. Pariyo, C. F. Lanata, D. Gwatkin, J. P. Habicht, and the Multi-Country Evaluation of IMCI Study Group. 2003.“Reducing Child Mortality: Can Public Health Deliver?” Lancet 362 (9378): 159–64. Bryce, J. C., Boschi-Pinto, K. Shibuya, R. E. Black, and the WHO Child Health Epidemiology Reference Group. 2005. “WHO Estimates of the Causes of Death in Children.” Lancet 365 (9465): 1147–52.

Gouws, E., J. Bryce, J. P. Habicht, J. Amaral, G. Pariyo, J. A. Schellenberg, and O. Fontaine. 2004. “Improving Antimicrobial Use among Health Workers in First-Level Facilities: Results from the Multi-Country Evaluation of the Integrated Management of Childhood Illness Strategy.” Bulletin of the World Health Organization 82 (7): 509–15.

Gwatkin, D. R., S. Rustein, K. Johnson, R. P. Pande, and A. Wagstaff. 2000. “Socio-Economic Differences in Health, Nutrition, and Population in Tanzania.” World Bank, Washington, DC. http://www.worldbank.org/ poverty/health/data/tanzania/tanzania.pdf. Hanson, K., K. Ranson, V. Oliveira-Cruz, and A. Mills. 2001. “Constraints to Scaling up Health Interventions: A Conceptual Framework and Empirical Analysis.” Working Group 5 Paper 14, WHO Commission on Macroeconomics and Health, Geneva. http://www.cmhealth.org/ docs/wg5_paper14.pdf. Hart, J. T. 1971. “The Inverse Care Law.” Lancet 1 (7696): 405–12. Huicho, L., M. Dávila, M. Campos, C. Drasbeck, J. Bryce, and C. G. Victora. 2005. “Scaling up IMCI to the National Level: Achievements and Challenges in Peru.” Health Policy and Planning 20 (1): 14–24. Jones, G., R. Steketee, R. E. Black, Z. A. Bhutta, S. S. Morris, and the Bellagio Study Group on Child Survival. 2003. “How Many Child Deaths Can We Prevent This Year?” Lancet 62 (9377): 65–71. Khan, M. M., S. Ahmed, and K. K. Saha. 2000. “Implementing IMCI in a Developing Country: Estimating the Need for Additional Health Workers in Bangladesh.” Human Resources for Health Development Journal 4: 73–82. Khan, M. M., K. K. Saha, and S. Ahmed. 2002. “Adopting Integrated Management of Childhood Illness Module at Local Level in Bangladesh: Implications for Recurrent Costs.” Journal of Health and Population Nutrition 20 (1): 42–50. Kidane, G., and R. H. Morrow. 2000. “Teaching Mothers to Provide Home Treatment of Malaria in Tigray, Ethiopia: A Randomised Trial.” Lancet 356 (9229): 550–55. Mathers, C. D., C. J. L. Murray, and A. D. Lopez. 2006. “The Burden of Disease and Mortality by Condition: Data, Methods, and Results for the Year 2001.” In Global Burden of Disease and Risk Factors, eds. Alan D. Lopez, Colin D. Mathers, Majid Ezzati, Dean T. Jamison, and Christopher J. L. Murray. New York: Oxford University Press. Pagnoni, F., N. Convelbo, J. Tiendrebeogo, S. Cousens, and F. Esposito. 1997. “A Community-Based Programme to Provide Prompt and


Adequate Treatment of Presumptive Malaria in Children.” Transactions of the Royal Society of Tropical Medicine and Hygiene 91 (5): 512–17.

Mortality: More of the Same Is Not Enough.” Lancet 362 (9379): 233–41.

Sazawal, S., and R. E. Black. 1992. “Meta-Analysis of Intervention Trials on Case-Management of Pneumonia in Community Settings.” Lancet 340 (8818): 528–33.

Wammanda, R. D., C. L. Ejembi, and T. Iorliam. 2003. “Drug Treatment Costs: Projected Impact of Using the Integrated Management of Childhood Illnesses.” Tropical Doctor 33 (2): 86–88.

Schellenberg, J. A., C. G. Victora, A. Mushi, D. de Savigny, D. Schellenberg, H. Mshinda, and J. Bryce. 2003. “Inequities among the Very Poor: Health Care for Children in Rural Southern Tanzania.” Lancet 361 (9357): 561–66.

WHO (World Health Organization) and UNICEF (United Nations Children’s Fund). 1999. IMCI Planning Guide: Gaining Experience with the IMCI Strategy in a Country. WHO/CHS/CAH/99.1. Geneva: WHO. http://www.who.int/child-adolescent-health/New_Publications/ IMCI/WHO_CHS_CAH_99.1.pdf.

Tanzania IMCI Multi-Country Evaluation Health Facility Survey Study Group. 2004. “Health Care for Under-Fives in Rural Tanzania: Effect of Integrated Management of Childhood Illness on Observed Quality of Care.” Health Policy and Planning 19 (1): 1–10. Tulloch, J. 1999. “Integrated Approach to Child Health in Developing Countries.” Lancet 354 (Suppl. 2): SII16–20.

———. 2001. Model Chapter for Textbooks: Integrated Management of Childhood Illness. WHO/CAH/00.40. Geneva: WHO. World Bank. 1993. World Development Report 1993: Investing in Health. New York: Oxford University Press.

Victora, C. G., A. Wagstaff, J. A. Schellenberg, D. Gwatkin, M. Claeson, and J. P. Habicht. 2003. “Applying an Equity Lens to Child Health and



Chapter 70

Improving the Quality of Care in Developing Countries John W. Peabody, Mario M. Taguiwalo, David A. Robalino, and Julio Frenk

Although the quantity rather than quality of health services has been the focus historically in developing countries, ample evidence suggests that quality of care (or the lack of it) must be at the center of every discussion about better health. The following examples are illustrative: In one study evaluating pediatric care in Papua New Guinea, 69 percent of health center workers reported that they checked for only two of the four examination criteria for pneumonia cases. Only 24 percent of these workers were able to indicate correct treatment for malaria. When clinical encounters were observed at aid posts, providers met minimal examination criteria in only 1 percent of cases (Beracochea and others 1995). In a study in Pakistan, only 56 percent of providers met an acceptable diagnostic standard for viral diarrhea, and only 35 percent met the acceptable standard for treatment (Thaver and others 1998).

QUALITY DEFINITION AND POPULATION FRAMEWORK These deficiencies in quality of care represent neither the failure of professional compassion nor necessarily a lack of resources (Institute of Medicine 2001). Rather, they result from gaps in knowledge, inappropriate applications of available technology (Murray and Frenk 2000), or the inability of organizations to change (Berwick 1989). Local health care systems may have failed to align practitioner incentives and objectives, to measure clinical practice, or to link quality improvement to better health outcomes.

Increasing evidence, much of it developed since the mid 1990s, shows that quality can be improved rapidly. However, to improve clinical practice—and thus quality of care—quality must be defined and measured, and appropriate steps must be taken (Silimper and others 2002). This chapter highlights approaches to improving clinical practice and quality of care that take place over months instead of years. Indeed, better quality can improve health much more rapidly than can other drivers of health, such as economic growth, educational advancement, or new technology.

Definition and Framework Health systems provide health actions—activities to improve or maintain health. These actions take place in the context of and are influenced by political, cultural, social, and institutional factors (shown along the edges of figure 70.1). Demographic and socioeconomic makeup, including genetics and personal resources, affect the health status of individuals seeking care. Access to the health care system is required to obtain the care that maintains or improves health, but simple access is not enough; the system’s capacities must be applied skillfully. Thus, quality means optimizing material inputs and practitioner skill to produce health. As the Institute of Medicine defines it, quality is “the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge” (Institute of Medicine 2001, 244).


Institutional Factors

Political Factors

Health Policy Reforms

Demographic and Socioeconomic Factors

Health Care Access

Structure

Process

Health Outcomes

The Quality of Care

Cultural Factors

Social Factors

Source: Peabody and others 1999.

Figure 70.1 Quality-of-Care Framework

Elements of Quality. Quality comprises three elements: • Structure refers to stable, material characteristics (infrastructure, tools, technology) and the resources of the organizations that provide care and the financing of care (levels of funding, staffing, payment schemes, incentives). • Process is the interaction between caregivers and patients during which structural inputs from the health care system are transformed into health outcomes. • Outcomes can be measured in terms of health status, deaths, or disability-adjusted life years—a measure that encompasses the morbidity and mortality of patients or groups of patients. Outcomes also include patient satisfaction or patient responsiveness to the health care system (WHO 2000). Structural measures are the easiest to obtain and most commonly used in studies of quality in developing countries. Many evaluations have revealed shortages in medical staff, medications and other important supplies, and facilities, but material measures of structure, perhaps surprisingly, are not causally related to better health outcomes (Donabedian 1980). Although higher technology or a more pleasant environment may be conducive to better-quality care, the evidence indicates only a weak link between such structural elements and better health outcomes (Donabedian 1988). The notable exceptions are cases in which physical improvements either increase access to primary care in very poor settings or increase the volume of a clinical procedure, such as cataract surgery, that is specifically linked to

better health outcomes (Javitt, Venkataswamy, and Sommer 1983). At best, however, structure is a blunt approximation of process or outcomes; structural improvements by themselves rarely improve the health of a population. Process, by contrast, can be measured with every visit to a provider. Measuring process is difficult, however, particularly in developing countries. The private nature of the doctorpatient consultation, a lack of measurement criteria, and the absence of reliable measurement tools have limited the ability to assess process (Peabody, Tozija, and others 2004). However, new methods are being developed that can provide valid measurements of clinical practice (Thaver and others 1998). In addition, evidence-based clinical studies have steadily revealed which process measures lead to better health outcomes. This combination of ubiquity, measurability, and linkage to health outcomes makes the measurement of process the preferred way to assess quality. Although good outcomes are the objective of all health actions, outcomes alone are not an efficient way to measure quality for two reasons. The first is the quality conundrum. A patient may receive poor-quality care but may recover fully, or a patient may receive high-quality care for an illness such as cerebral malaria and still not recover. Second, adverse health outcomes are relatively rare and obviously do not occur with every encounter. The classic framework of structure-process-outcome is well established. However, in recent years the concept of quality has been expanded to include specific aims for improvement. For example, the Institute of Medicine’s (2001) landmark report,

1294 | Disease Control Priorities in Developing Countries | John W. Peabody, Mario M. Taguiwalo, David A. Robalino, and others ©2006 The International Bank for Reconstruction and Development / The World Bank 266

Box 70.1

The Institute of Medicine’s Six Elements of Quality 1. Patient safety. Are the risks of injury minimal for patients in the health system? 2. Effectiveness. Is the care provided scientifically sound and neither underused nor overused? 3. Patient centeredness. Is patient care being provided in a way that is respectful and responsive to a patient’s preferences, needs, and values? Are patient values guiding clinical decisions?

4. Timeliness. Are delays and waiting times minimized? 5. Efficiency. Is waste of equipment, supplies, ideas, and energy minimized? 6. Equity. Is care consistent across gender, ethnic, geographic, and socioeconomic lines?

Source: Institute of Medicine 2001.

Crossing the Quality Chasm, broadens the concept to include other, more contextual elements to illuminate how process changes can improve care. It focuses on six aims: patient safety, effectiveness, patient centeredness, timeliness, efficiency, and equity (see box 70.1). Quality Assessment Perspectives. We can look at the Institute of Medicine’s aims from two perspectives: patient perception, and technical or professional assessment. Patients’ perceptions of quality depend on their individual characteristics and affect their compliance, follow-up decisions, and long-term lifestyle changes (Zaslavsky and others 2000). Interpersonal relationships, cultural appropriateness, and gender sensitivity—long thought to be luxuries of wealthier countries—are also major determinants of patient access and utilization in developing countries. These findings have led to the inclusion of patient satisfaction and patient responsiveness as outcome measures. Technical assessment concerns whether providers meet normative standards for appropriateness of care or adherence to explicit evidence-based criteria. Although patient perception or satisfaction is important, researchers increasingly rely on objective, evidence-based quality criteria that can be more readily linked to better health outcomes at both the individual and the population levels. Population-Level Considerations. Quality is typically assessed through the interaction between individual doctors and patients. However, emerging evidence shows that the average quality of care given by groups of doctors and other providers is an important determinant of overall community health status. For example, in a cross-sectional analysis in the former Yugoslav Republic of Macedonia, researchers found not only that patients’ heath status was significantly higher in areas where quality was higher but also that the overall self-reported health status of those members of the general population who

had not recently received care was higher (Peabody, Tozija, and others 2004). Our quality-of-care framework supports these findings. When process is improved among groups of providers,the aggregate improvement in quality leads to better health outcomes for the entire patient population. In addition, resources can be allocated among clinical interventions based on actual effectiveness and the overall impact of care on the population. For example, cancer chemotherapy may be available and may prolong the lives of cancer patients.However,it may result in fewer lives saved than the expansion of coverage of directly observed treatment shortcourse coverage for tuberculosis patients.

QUALITY OF CARE IN DEVELOPING COUNTRIES The process of providing care in developing countries is often poor and varies widely. A large body of evidence from industrial countries consistently shows variations in process, and these findings have transformed how quality of care is perceived (McGlynn and others 2003). A 2002 study found that physicians complied with evidence-based guidelines for at least 80 percent of patients in only 8 of 306 U.S. hospital regions (Wennberg, Fisher, and Skinner 2002). It is important to note that these variations appear to be independent of access to care or cost of care: Neither greater supply nor higher spending resulted in better care or better survival. Studies from developing countries show similar results. For example, care in tertiary and teaching hospitals and care provided by specialists may be better than care for the same cases in primary care facilities and by generalists (Walker, Ashley, and Hayes 1988). One explanation for variation and low-quality care in the developing world is lack of resources. Limited data indicate, however, that high-quality care can be provided even in environments with severely constrained resources. A study in Jamaica, which used a cross-sectional analysis of government-run Improving the Quality of Care in Developing Countries | 1295


primary care clinics, showed that better process alone was linked to significantly greater birthweight (Peabody, Gertler, and Liebowitz 1998). A study in Indonesia attributed 60 percent of all perinatal deaths to poor process and only 37 percent to economic constraints (Supratikto and others 2002). Cross-system or cross-national comparisons provide the best examples of the great variation in clinical practice in developing countries. In one seven-country study, researchers directly observing clinical practice found that 75 percent of cases were not adequately diagnosed, treated, or monitored and that inappropriate treatment with antibiotics, fluids, feeding, or oxygen occurred in 61 percent of cases (Nolan and others 2001). Another study compared providers’ knowledge and practice in California and FYR Macedonia, using vignettes to adjust for case-mix severity. Although the quality of the overall or aggregate process was lower in FYR Macedonia, a poor country, the top 5 percent of Macedonian doctors performed as well as or better than the average Californian doctor (Peabody, Tozija, and others 2004). In a study commissioned for this chapter, an international team measured quality in five developing countries (China, El Salvador, India, Mexico, and the Philippines), using the same clinical vignettes at each site. The team evaluated the process for common diseases according to international, evidence-based criteria. Quality varied only slightly among countries. The within-country range of quality of doctors was 10 times as great as the between-country range. Such wide variation strongly suggests that efforts to improve health status must involve policies that change the quality of clinical care.

POLICY INTERVENTIONS TO IMPROVE QUALITY The success of quality improvement policies can be measured by their ability to raise the average level of health and reduce variation in quality. Two types of policies are intended to improve quality and thus health outcomes: • those that influence provider behavior by altering the structural conditions of organization and finance or that involve the design and redesign of health care systems • those that directly target provider behavior at the individual or the group level. Within each category, the evidence is examined to see the effect of the policy on the health outcomes of populations. Interventions Affecting Provider Practice by Changing Structural Conditions Although structural components such as materials and staff are not strongly linked to outcomes, other components of structure—organization and finance—can influence process

by changing the socioeconomic, legal and administrative, cultural, and information context of the health care system. Legal Mandates, Accreditation, and Administrative Regulations. Legal mandates, accreditation, and administrative regulations affect quality by controlling entry into the practice of health care. These policies include the licensing of professionals and facilities, their accreditation or certification to perform certain procedures, and the formal delineation of functions that various types of health workers can legally perform. Although these policies assume that providers’ prior qualifications are good predictors of actual performance in health care delivery, there is little evidence that such policies have a positive effect on process or outcomes. They are more successful at barring unqualified persons from practicing than at ensuring quality among those who are allowed to practice. A review of health sector regulations in Tanzania and Zimbabwe, for example, revealed that the regulations primarily control entry into the market and ensure a minimum standard of quality (Kumaranayake and others 2000). Hospital accreditation, with its periodic reviews of health facility performance standards, can potentially provide ongoing regulatory pressure for improvement. To date, research has not demonstrated that hospital accreditation programs are linked to improvements in health outcomes. In a randomized controlled trial of a hospital accreditation program in the KwaZulu-Natal province of South Africa, researchers showed a conclusive link between the implementation of the program and improvements in the accreditation standard indicators. However, they were unable to link those indicators to improvements in health outcomes (Salmon and others 2003). Malpractice Litigation to Enforce Legal Mandates To be effective in promoting quality, malpractice litigation must rely on adequate legal and judicial systems, which are deficient in most developing countries. In India, one of the few developing countries with the appropriate legal structure in place, inclusion of the medical sector under the Consumer Protection Act of 1986 allows victims to receive redress for negligent medical practice. Although improvements have resulted, some argue that the system needs greater involvement of professional organizations to be effective (Bhat 1996). Professional Oversight Peer review is as old as professional societies. The power and the influence of such societies vary widely among countries (Heaton 2000). Large provider organizations, such as hospitals or public health institutions, often routinely collect information on provider practices and patient outcomes and use those data to guide, educate, supervise, discipline, or recognize providers. In the Philippines, public health managers used a checklist of 20 observable behaviors against which health workers in remote provinces were rated. The


performance of providers in facilities where workers were reviewed was significantly better than in comparable facilities that did not adopt the reviews (Loevinsohn, Guerrero, and Gregorio 1995). Others, however, assert that the “quality by inspection” environment engendered by oversight leads to an antagonistic relationship between workers and managers and precludes cooperative problem solving and continuous improvement (Berwick 1989). A qualitative study evaluating supervisor-provider interactions in health care facilities in Zimbabwe found that supervisors were adept at giving technical feedback but were not as proficient at making suggestions for improvement or at working with providers and patients to solve problems (Tavrow, Kim, and Malianga 2002). National and Local Clinical Guidelines In many industrial countries, evidence-based clinical guidelines are used to ensure high-quality care, better health outcomes, and cost-effective treatments. (Examples of institutions supporting this approach are the U.K. National Institute for Clinical Excellence, the U.S. Agency for Healthcare Research and Quality, and the Dutch College of General Practitioners.) Guidelines are typically developed for a clinical disease or symptom. They should be derived from evidence-based criteria resulting from welldesigned clinical investigations or expert opinion. Because they are derived from empirical studies, guidelines in developing countries can, in principle, be identical to those in industrial countries. When resource constraints limit transferability, diagnostic and treatment guidelines may have to be modified. Technologies such as x-ray studies have gained widest acceptance in preventive and primary care services, such as integrated management of childhood illness, where they serve both as clinical standards and as educational guides. Including physicians in the development and review of guidelines has proved particularly effective in the challenging process of implementing guidelines. Sharing Information on Quality Improvement Technology. Worldwide interest in quality has given rise to new professional bodies, scientific publications, and institutions dedicated to sharing ideas and innovations in quality improvement. Organizations such as the Robert Wood Johnson Foundation, the Nuffield Trust, and the Institute for Healthcare Improvement cultivate ideas for improvement, bring people and organizations together to learn from each other, and take action to achieve results. Although the sharing of information on quality health care practices has long been an established part of provider education and training networks, the sharing of information on successful systemwide policies for process improvements could potentially accelerate the scale-up of quality practice. One organization active in developing countries is the Council on Health Research for Development (COHRED),

which promotes, facilitates, and evaluates the Essential National Health Research strategy in such countries as Benin, the Arab Republic of Egypt, and Indonesia. COHRED aims to develop a system of effective health research to improve health services, including quality of care. The Quality Assurance project funded by the U.S. Agency for International Development has studied and shared information about quality in the developing world since 1990. Under the Quality Assurance project umbrella, researchers have studied and implemented quality measurement and improvement interventions and have used these case studies to develop a library of tools and articles to promote global quality improvement. Public-Private Provision of Care. In most health care systems, a professional regulatory framework governs the network of civil servants delivering health care. These civil servants operate alongside autonomous, self-governed, private providers— independent for-profit physicians and health clinics and nonprofit nongovernmental organizations (NGOs). Two conclusions arise from the often heated debate about the right balance between public and private services. First, private practitioners provide a significant amount of care in developing countries. Second, though there is no one prescription for striking the right public-private mix, in some cases the public regulatory framework has led to private provision of higher-quality care. The government of Senegal successfully contracted with community-based groups for preventive nutrition services. Eighteen months after nutrition services were implemented, severe malnutrition disappeared among children age 6 to 11 months (Marek and others 1999). The success of the program has led to its expansion nationwide. Targeted Education and Professional Retraining. Continuing medical education is a common approach to improving clinical practice, but it neither changes clinical practice nor advances health outcomes (Davis and others 1995). Newer techniques—targeted education, case-based learning, and interactive and multimodel teaching techniques—have had some success. In Guatemala, distance education targeting diarrhea and cholera case management increased accurate assessment and classification of diarrhea cases by 25 percent. Rehydration did not improve, however, and improvements in counseling were insignificant (Flores, Robles, and Burkhalter 2002). In Tanzania, training staff in the control of acute respiratory infections of young children yielded reductions in under-five mortality within two years (Mtango and Neuvians 1986). Organizational Change. In recent years, organizational change in the health care system has been shown to influence quality of care and to further the six aims of the Institute of Medicine by focusing on the continual design and redesign of Improving the Quality of Care in Developing Countries | 1297


systems. The emphasis is on developing organizational and individual capabilities where they most profoundly affect the process of care. Design and redesign interventions assume that simply adding a new resource or a new process in isolation will not improve care because better care is the product of many processes working together. Although change interventions have not been widely used in the developing world because they require large investments to plan and implement, four related models of organizational change have been successful in changing provider practice in developing nations: • Total Quality Management in health care Advances in business management practices to continually design and redesign systems for quality improvement have been effectively adapted for health systems. In Total Quality Management, also known as Continuous Quality Improvement, teams use mutually reinforcing techniques in a cycle of planning, implementing, evaluating, and revising to improve the quality of clinical and administrative processes. These techniques include process mapping, statistical quality control, and structured team activities. In rural Bihar, India, private practitioners who treat sick children were provided with standard case-management information, were given feedback on their performance, and were tracked and monitored over time. This strategy produced significant improvements in practitioners’ case-management skills (Chakraborty, D’Souza, and Northrup 2000). In Malaysia, anesthesia safety has been improved through the implementation of consensus-based protocols that emphasize (a) communication among the operating, recovery, and ward team members; (b) individual feedback; and (c) frequent monitoring to identify areas for improvement (Tan 1999). • Collaborative Improvement Model The early success of Total Quality Management techniques has given rise to a related model, the Collaborative Improvement Model. It addresses broad and complex systemic processes within health care systems and has facilitated the scale-up of quality improvements. This model, designed to continuously improve organizational and individual performance, comprises four elements: definition of an aim, measurement, innovation, and testing to see whether the innovation meets the original aim. This approach strikes a pragmatic balance between the need for action and the need to be scientifically grounded. It has been used with success in Peru and the Russian Federation. In Peru, the collaborative improvement model was used by multidisciplinary teams in 41 clinics to design changes aimed at achieving world-class tuberculosis care. The preliminary results have led to impressive changes in the process of care, but it is too early to determine whether they have been effective in improving quality (Berwick 2004). • Plan-Do-Study-Act cycle The Plan-Do-Study-Act (PDSA) cycle calls for action-oriented learning in quality improve-

ment. Team members using the PDSA model design a quality-improvement intervention (plan), implement it on a small scale (do), evaluate the results (study), and implement or alter the intervention accordingly (act). Often multiple PDSA cycles are necessary before the appropriate improvement method can be identified. All improvement techniques that involve the design and redesign of systems use some form of the PDSA cycle. Successful scale-up of a PDSA prototype is possible with careful leadership oversight. A team of investigators in Russia’s Tula province developed a series of successful interventions for adults who have poorly controlled hypertension. The interventions, which were started in 20 clinics, were expanded to 500 clinics within 18 months. The scale-up resulted in a sevenfold increase in patients receiving hypertension management at the primary care level and an 85 percent reduction in admissions for hypertension. In Tver province, the same group addressed problems related to prenatal care. They began with 5 hospitals and scaled up to cover all 42 hospitals and all maternity clinics in the province. The result was a 99 percent reduction in newborns with hypothermia and a reduction in pregnancy-induced hypertension from 44 percent to 6 percent (Berwick 2004). Although the experience of researchers implementing interventions that are based on system redesign in the developing world has been largely positive, it is not clear whether the resources and leadership exist to bring these interventions to scale through country or regional policies. Further evidence is needed concerning the real-world feasibility and cost-effectiveness of system redesign. • Internal enabling environment Creating the right environment for change involves leadership and leadership training, clinicians empowered to make quality improvement decisions, and resources for quality improvement planning activities (Silimper and others 2002). The internal enabling environment in Costa Rica promoted strong leadership that led to the adoption of structural adjustment loans in the early stages of health sector reforms. The loans were used to maintain such public health programs as mother and child nutrition, even though public spending dropped and prices increased dramatically (Peabody 1996). An enabling environment can also be created by teams of individuals, each representing different stakeholder groups (physicians, nurses, staff members, patients, and so forth) or simply by a strong leader with an interest in teamwork and the resources to support a discrete quality improvement function for team members.

Interventions Directly Affecting Provider Practice Practitioners are often forced to provide care in uncertain settings. Technical limitations may reduce the ability to diagnose


or predict outcomes, or they may have only probabilistic knowledge about the efficacy of their proposed treatment for a particular patient. The nature of clinical practice is often solitary, and physicians have few available ways to gauge their clinical acumen and skills. Performance-based feedback, however, can reward high-quality care and increase knowledge about appropriate actions. If the feedback mechanism is effective, it can also serve as the basis for establishing systemwide incentives for improving quality of care. Training with Peer Review Feedback. In Mexico City, physician retraining on treatment of diarrhea, combined with the concurrent creation of a peer-review structure, decreased the use of antibiotics and increased the use of oral rehydration therapy (ORT). These improvements continued to be seen in a follow-up evaluation 18 months later (Gutierrez and others 1994). The approach has been effectively expanded to prescribing practices for rhinopharyngitis among primary care physicians, using an interactive training workshop and a managerial peer-review committee (Perez-Cuevas and others 1996). Performance-Based Remuneration. A potentially powerful instrument for accelerating quality improvements involves making payments directly to providers who meet quality standards that are based on process indicators associated with favorable patient outcomes. Systems that tie performance to remuneration use relatively small incentives—equivalent to 3 to 10 percent of the provider’s total compensation. Performance-based remuneration has been successfully used in the United States to compensate both private and public providers (McBride, Neiman, and Johnson 2000). Examples of performance-based incentives come from developing countries too. The Nicaraguan Ministry of Health has implemented a pilot program in six hospitals that offers an incentive bonus (a maximum average of 17 percent of hospital revenue) for facilities that achieve performance targets that include quality measures (Jack 2003). In Haiti, a performancebased payment scheme was set up for NGOs that provided services to the population. The scheme resulted in all three participating NGOs reaching target immunization coverage rates (Eichler, Auxila, and Pollock 2001). Thus, payment for specified and observable performance (in terms of provider effort, client coverage, or health impact on the population) can be usefully applied to NGOs and private providers. The specific features of performance-based remuneration are crucial. A study evaluating the South African government’s experience in contracting with private organizations to operate district hospitals found no cost savings—in fact, the government was spending more than if it provided the services itself. The contracting may have failed because remuneration was not based on specific process or outcome measures. Instead, the

contractor’s obligation, the methods of monitoring performance, and the sanctions for nonperformance were only minimally specified (Broomberg, Masobe, and Mills 1997). High Volume of Care. Evidence exists that a high volume of care by individuals or institutions leads to better health outcomes (Habib and others 2004). Physician experience (learning) and practice (repetition) lead to fewer complications, less resource use, and better quality for a variety of procedures, such as cataract surgery and laparoscopy (Brian and Taylor 2001). More complex procedures, including endarterectomy, cancer surgery,and coronary bypass surgery,have shown similar effects. Volume effects leading to better health outcomes are not confined to surgical procedures (Zgibor and Orchard 2004). Facilities specializing in the care of chronic diseases such as diabetes, myocardial infarction, and heart failure are also associated with better outcomes. Debate exists over how much of the volume effect is due to specialist care. The benefits of highvolume care persist, however, even after controlling for referral and case-mix biases. When carefully trained nonphysicians are substituted for physicians, volume effects persist but can be accomplished at significantly lower costs. In one study, nurse practitioners and physician’s assistants were able to provide high-quality care for common outpatient conditions such as hypertension, diabetes, asthma, otitis media, pharyngitis, and back pain at substantially lower costs than that of physicians (Douglas and others 2004). Performance-Based Professional Recognition. Providers work in a community of peers in which professional status, prestige, and recognition are often as valuable as material rewards. Nonmonetary incentives, such as public recognition or disclosure, administrative privileges, and awards from professional organizations, can promote improvements in quality. Uganda, for example, implemented the Yellow Star Program as part of a broader health services improvement project. This program evaluated health facilities on a quarterly basis, using 35 indicators of technical and interpersonal quality, and awarded a large yellow star to facilities that scored 100 percent in two consecutive quarters. The star was then prominently displayed outside the facility. The Mexican Ministry of Health has implemented a strategy that combines the accreditation and the training strategies discussed earlier with nonmonetary incentives. The National Crusade for Quality in Health Care introduces quality-oriented incentives to health facilities and medical schools. It also includes public recognition in an effort to encourage learning and to change practice. The National Crusade has already generated measurable improvements in the responsiveness of state-level health systems (Secretaría de Salud de Mexico 2003). Both types of policies examined in this section are associated with better quality and better health outcomes—lower Improving the Quality of Care in Developing Countries | 1299


premature mortality and avoidable morbidity, increased patient satisfaction, and more health-seeking behaviors. When effective, these policies result in increased coverage rates, better prescribing patterns, and increased adherence to clinical guidelines. They can spell the difference between an individual’s survival or death, between an individual benefiting from the encounter with the health sector or being harmed by it, and between an individual and society rising from poverty or sinking deeper into it.

MEASURING QUALITY Improving quality requires that we measure it accurately. The successful outcomes discussed in the previous section rely on the links between policy and changes in clinical practice. Such links, however, can be created and demonstrated only when valid and reliable measures of process are easily understood, inexpensive to obtain, resistant to manipulation, and related to better health outcomes. Measuring Structure Material measures of structure abound. Numerous facilitybased surveys in developing countries have cataloged capital equipment and staffing levels, and financial reports track budgets and expenditures (but rarely production costs). Facility inventories of drugs and supplies are generally available; service utilization figures are routinely reported to national-level authorities. Such measurements, however, are often beside the point. Even when material structural deficiencies are corrected, they are not reliably linked to changes in health outcomes. Measuring the organization and financing of health care is more difficult. Although descriptions of the organization and financing of health systems exist, objective functional assessments of systems (such as patient flows, the patient referral system, or details of the relative pricing of services) are less often available.

or obtaining payments, for example) and thus lack crucial clinical details. One prospective study showed that charts identified only 70 percent of items performed during the clinical encounter (Luck and others 2000). In a related analysis, 6.4 percent of the items recorded in the chart were false and had never really occurred. Where resources and infrastructure are sufficient, the electronic medical record (EMR) is becoming a priority for health systems worldwide. EMR technology promotes uniformity, legibility, and communication, which can lead to guideline use and reduce prescription errors. It also holds the promise of managing populations rather than individuals by aggregating patients into groups. However, the EMR has not always lived up to its potential. In many countries, some impressive successes have occurred—as have spectacular failures, costing billions of dollars (McConnell 2004). The great heterogeneity in recordkeeping practices, problems with medical records (both paper and electronic), and costs of trained medical abstractors have led to a search for other reliable ways to measure quality. Direct Observation and Recording of Visits. Direct observation and recording of visits is a commonly used approach in developing countries (Nolan and others 2001). Ethically, the provider and the patient must be informed of the observation or recording, which introduces participation bias because provider behavior may change as a result of being evaluated. In addition, trained observers are costly, and variation between observers is difficult to remedy.

Technical advances have mitigated longstanding difficulties in measuring process. Five approaches and their strengths and weaknesses merit consideration: chart abstraction, direct observation and recording of visits, administrative data, standardized patients, and clinical vignettes.

Administrative Data. Administrative data, collected for purposes of managing the delivery of care, are available in all but the poorest settings. A data collection system, once established, is ubiquitous and can provide information on charges and many cost inputs. Administrative data, however, lack sufficient clinical detail to be useful in evaluating process. In a 2003 study, an incorrect diagnosis was recorded in the data 30 percent of the time (although the diagnosis was made correctly). Overall, these data reflected the actual clinical diagnosis only 57 percent of the time (Peabody, Luck, Jain, and others 2004). As information systems advance, accuracy problems may be mitigated, although the lack of adequate clinical detail will continue to limit the use of administrative data.

Chart Abstraction. Chart abstraction, or review of the medical record, has long been used to measure technical quality. Such familiar quality evaluations as clinical audits, physician report cards, and profiles are based on chart abstraction. The core strength of the medical record is that it is ubiquitous and can generally be obtained after each encounter. Chart reviews, however, suffer from problems of legibility when notes are handwritten. Often they are generated for reasons other than recording the actual events of the clinical visit (legal protection

Standardized Patients. Standardized patients can be a gold standard for process measurement (Luck and Peabody 2002). Trained to simulate illness, standardized patients present themselves unannounced into a clinical setting to providers who have previously given their consent to participate in the study. At the conclusion of the visit, the standardized patient reports on the technical and interpersonal elements of process. Standardized patients are reliable over a range of conditions and provide valid measurements that accurately capture

Measuring Process


variation in clinical practice among providers over time. However, they are expensive and useful only for adult conditions and only those conditions that can be simulated. Thus, they are not practical for routinely evaluating quality. Clinical Vignettes. Clinical vignettes were developed explicitly for measuring quality within a group of providers and evaluating quality at the population level. Vignettes are responsive to variation in quality, and providers readily accept them if they are given anonymously (Peabody, Luck, Glassman, and others 2004). More than 20 vignettes have been used in 13 countries around the world. They can be administered on paper, by computer, or over the Internet. Providers are typically presented with several cases. When process is being measured for many providers, each provider is presented with the same case or set of cases, thus eliminating the need for case-mix adjustment. The provider completing the vignette is asked to take a history, do an examination, order the necessary tests, make a diagnosis, and specify a treatment plan. The questions are open ended and include interactive responses that simulate the visit and evaluate the physician’s knowledge. In two separate, prospective validation studies among randomly selected providers, vignettes consistently demonstrated greater predictive validity of process than did the abstracted medical record. Vignettes have been validated against the gold standard of standardized patient visits, and they reflect actual clinical practice, not just physicians’ knowledge. Vignettes have several other advantages. Because exactly the same case can be given to many providers, vignettes are useful for comparison studies. They are also useful for pre- and postevaluations of policy interventions designed to improve quality. Finally, they are inexpensive to administer and straightforward to score, making them particularly useful in developing countries.

ECONOMIC BENEFITS AND COSTS OF QUALITY CARE Policy interventions can lead to higher-quality process of care and can rapidly improve a population’s health outcomes, but is quality improvement cost-effective? This section shows that it is. We compare the economic benefits of better quality of care at the individual and population levels with the costs of implementing quality improvement interventions. We then discuss why these interventions not only increase individual and social welfare but also are cost-effective in the long run.

Individual Economic Benefits Individuals benefit from better quality of care because they are physically, emotionally, and mentally healthier. These benefits can be quantified subjectively by self-report, objectively by

physiological assessments (such as blood pressure), and monetarily by measuring income. Other things being equal, a healthy individual generates more income than one who is often sick. This benefit goes beyond the period of illness. Research on early childhood development has shown that higher-quality prenatal and postnatal care not only decreases mortality but also improves subsequent school performance, which is critical to future labor productivity (Van der Gaag 2000). The monetary benefits of better individual health can be assessed by examining the individuals’ expected income in the context of a life cycle model. Expected income depends on the risk of death at various points in time and the corresponding opportunities for educational attainment. This scenario can be simulated by improving quality and then estimating how much the higher quality lowers mortality and increases education attainment, both of which increase an individual’s future income (see figure 70.2).

Social Macroeconomic Benefits Societies that have healthier populations also have higher levels of human capital and a greater capacity to generate wealth. Higher quality of care for the individual increases society’s human capital by reducing both the number of premature deaths (thus increasing the labor force) and the amount of temporary or permanent disability (thus improving worker productivity). Providers and insurers also benefit from lower costs by avoiding unnecessary or inappropriate care. Thus, society benefits from both better health and lower public expenditures for treatment, which can then be reallocated to other productive uses. Interventions that improve quality have an especially high social value when they have large positive externalities (for instance, when better process reduces the incidence of a communicable disease). Sometimes, however, society benefits but some stakeholders do not. For example, physicians who provide better preventive care may experience less demand for their curative services and associated resources. Several attempts have been made to estimate the correlation between health outcomes and long-term economic growth. The high prevalence of such diseases as malaria has been linked in some studies to a slowing of economic growth by one to two percentage points per year. These studies were severely limited by the number of countries and by the many unobserved factors excluded from the models (Sachs 2001). These limitations suggest another way to estimate the benefits of higher quality on health outcomes and long-term economic growth. Because diagnostic accuracy and treatment of malaria can be improved with better-quality care, improving quality should increase national income through reductions in mortality rates. Indeed, cross-country data suggest that a one-year increase in life expectancy is associated with an increase in the gross domestic product (GDP) growth rate of 1 to 4 percentage points (Bloom, Canning, and Sevilla 2001). Our own simulations show Improving the Quality of Care in Developing Countries | 1301


Increase in present value expected income (percent) 120 100 80 60 40

9 7

20

5 Effect of 0

nine policy intervention scenarios on quality

3

3

8

1

13

18

23

Unemployment rate (percent)

Source: Authors’ calculations. Note: These results model the effect on income of a policy intervention that leads to higher quality. The effect is determined as an increase in the present value of income for varying rates of unemployment. Higher quality is based on nine different scenarios of quality improvement. For each successive scenario, infant mortality rates are reduced by 1 percent and educational attainment is increased by 5 percent. The baseline possibilities are for the Islamic Republic of Iran.

Figure 70.2 Economic Benefits of a Quality Intervention That Reduces Child Mortality Rates and Leads to Higher Educational Attainment

Accumulated gains in GDP during a 50-year period relative to current GDP

0.20 0.18 0.16 0.14 0.12 0.10 0.08 0.06 0.04 0.02 0

5.0 4.0 3.0 2.0 0.01

0.015

0.02

0.025

1.0 0.03

0.035

Yearly decline in child mortality rates (percent)

0.04

Change in GDP growth rate from one year increase in life expectancy Source: Authors’ calculations.

Figure 70.3 Gains in GDP Resulting from Reductions in Child Mortality Rates

that quality improvements can result in as much as a 5 percent annual reduction in child mortality rates, which can generate, over 50 years, economic gains equivalent to 18 percent of current GDP (see figure 70.3). Similar results would be obtained if the effect of better quality on morbidity and disability were simulated.

Economic Costs Policies that improve the quality of care have both direct and indirect costs. Direct costs relate to the human and physical resources needed to implement the intervention. Indirect costs come from more subtle changes, including alterations in the quantity of health services provided, in provider demand for


various inputs (such as equipment and medication), in the market prices of heath care, in government health budgets, and ultimately in the macroeconomy. For interventions at the local level, such as training doctors in a particular region, it is usually sufficient to measure direct costs. Although the level of detail required can be overwhelming when the interventions are complex, the calculations are usually straightforward. The costs of local interventions depend on local prices of such inputs as labor, transportation, training kits, food, space rental, and accommodations. The cost of training providers in the appropriate treatment of childhood illnesses ranges from a low of US$1 to a high of US$430 (Santoso, Suryawati, and Prawaitasari 1996). The direct and indirect costs of interventions at the central or local government level are harder to quantify. Expanding training programs to all public providers, enforcing standards for private and public providers, changing payment systems, and developing policies to protect consumers against malpractice are macro-level interventions that have direct program-level costs. They affect the economy as a whole by changing the allocation of public resources and the relative prices of goods and services. Macroevaluations of health policy interventions are seldom conducted, even though systemwide interventions are likely to have the highest effect on quality and health-related benefits.

Cost-Effectiveness of Improved Process Two interventions that vividly illustrate the cost-effectiveness of improvements in clinical practice and outcomes have been chosen: detection and treatment of acute respiratory illnesses and appropriate drug use and treatment for diarrhea. Better Treatment of Pneumonia in Children. Part of the high mortality from childhood pneumonia in the developing world can be explained by poor-quality care, which is defined as the inability either to accurately diagnose or to treat the disease. Our prototype intervention has two cost components: the cost of implementing an educational activity for providers and the cost of treating nonsevere and severe childhood pneumonia. The former component is based on a study and uses conservative high-end cost estimations (Kelley and others 2001); the latter is the midpoint from another study (Stansfield and Shepard 1990). The number of lives saved depends on the effect of the intervention—that is, the change in the percentage of cases diagnosed and treated; the prevalence rate of both types of pneumonia; the population covered by each provider; the case-fatality ratio; and the effectiveness of the treatment. Both the case-fatality ratio and the effectiveness ratio were fixed at middle values suggested by earlier work (Stansfield and Shepard 1990). For the other parameters, a large range of variation was considered, producing 450 scenarios. Finally, six

impact levels were considered, which were based on two previous studies (Chakraborty, D’Souza, and Northrup 2000; Mtango and Neuvians 1986). The analysis showed that, under average conditions, improving quality of care for conditions of acute respiratory illness can be very cost-effective. When the baseline quality is low and the disease prevalence is high, an intervention that raises quality has a cost-effectiveness ratio of US$132 to US$800 per life saved; if the policy intervention is ineffective or the prevalence of pneumonia is low, the average cost of saving a life could be more than US$2,000. When 60 percent of cases are already appropriately diagnosed and treated, the costeffectiveness ratio rises to US$5,000 per life saved.1 Better Treatment of Diarrhea. Diarrhea remains one of the leading causes of childhood morbidity and mortality in the developing world. The diarrhea incidence rate among children in resource-constrained countries can reach six to seven episodes per year (Thapar and Sanderson 2004). ORT is the accepted standard of care for acute diarrhea. Unfortunately, a large proportion of cases are still treated with nonrehydration medication, including antibiotics and antidiarrheals. Improved diagnosis of dehydration and reduced use of unnecessary medications, however, lead to better outcomes. Various interventions can make sizable changes in the diagnostic and prescribing patterns of providers. Verbal case review, combined with a package of additional intervention referred to as INFECTOM (Information, Feedback, Contracting with Providers to Adhere to Practice Guidelines, and Ongoing Monitoring), increased the proportion of cases treated correctly from 16 percent to 48 percent (Bloom, Canning, and Sevilla 2001). One study reports that small group, face-to-face interventions reduced antimicrobial prescriptions by 16 percent and antidiarrheal prescriptions by 7 percent among a group of providers treating acute diarrhea in Indonesia (Santoso, Suryawati, and Prawaitasari 1996). The same study showed that formal seminars reduced antimicrobial use by 10 percent and antidiarrheal use by 7 percent. On the basis of these studies, an average cost per intervention was used, ranging from US$25 to US$125. The savings from switching to a less costly treatment (instead of antibiotics, for example) were subtracted from the direct costs that are related to implementing the training activity. Because other savings, such as those related to a lower use of inpatient services, were ignored, the estimates are conservative. Savings could be greater: Two years after an ORT unit was established at the Kamuza Central Hospital in Malawi, 50 percent fewer children with diarrhea were admitted to the pediatric ward, and those admitted required 56 percent less intravenous fluid for rehydration (Martines, Phillips, and Feachem 1990). Again, the number of lives saved depends on the disease prevalence; the effect of the policy on treatment quality; the Improving the Quality of Care in Developing Countries | 1303


population covered by each provider; the average case-fatality ratio, which was set at 6 per 1,000 on the basis of Snyder and Merson (1982); and the effectiveness of the treatment. For the latter parameter, reductions in mortality rates following ORT treatment of 40 to 60 percent and reductions in effectiveness ratios of 5 to 100 percent have been reported (Shepard, Brenzel, and Nemeth 1986). Accordingly, the effectiveness ratio was set at 80 percent. As before, alternative values for the other parameters were adopted, generating 450 scenarios. Educational interventions to improve the quality of care for treatment of diarrheal diseases are also highly cost-effective. In general, the cost of saving a life through educational interventions is less than US$500 and could be as low as US$14. Scenarios with high cost per life saved (more than US$6,000) are when prevalence rates are low or when implementation costs for quality-related interventions are high. Although the data available to estimate the costs and benefits of health outcomes and process are limited, these simulations, combined with published reports of successful policy interventions, clearly show the cost-effectiveness of interventions that improve health outcomes through better quality of care. However, reliable measures of quality are necessary to design and evaluate these interventions.

Such studies should be complemented by cost-benefit and cost-effectiveness analyses. Sometimes, in public health emergencies, for example, control groups may not be practical or ethical, in which case real-time operations research is an acceptable substitute. In the area of research topics, top priority should be given to quality monitoring and assurance strategies to gain an understanding of exactly what the health system is contributing to society and at what cost. Quantifying the associated costs of different variants of quality monitoring and assurance strategies should also be a high-priority item on the quality research agenda. The second priority should be to increase the evidence base regarding the effects on provider behavior of public policies concerning quality of care and whether they lead to better health outcomes. We need to learn more about the long-term effects of different contracting and remuneration policies on providers’ practices and the consequent results of such policies for health outcomes. Finally, we need to understand how contracting and remuneration policies affect problems unique to the developing world, such as the use of doctor substitutes and the migration of skilled providers to wealthier countries.

CONCLUSION RESEARCH AGENDA ON QUALITY Most of the issues discussed throughout this chapter represent important topics for research. Establishing a research agenda requires prioritizing both the type of research and the topics to be studied. Quality-of-care research must also strike a balance between relevance to decision making and excellence in scientific rigor (Frenk 1992). Observational studies are needed to document the extent and correlates of quality at various levels: individual providers, institutional providers, health care systems, and whole populations. Apart from offering much-needed basic descriptions (especially in developing countries), these studies can test specific indicators of the dimensions of quality and can compare the measurement approaches discussed earlier. Intervention studies introduce planned changes into health care settings and assess their consequences. It is fundamentally important that intervention studies compare one provider group or policy alternative with another. In addition, control groups must be used so that any observed change can be attributed to the intervention itself rather than to another source of variation. The external validity of studies is often undermined by the choice of highly specific sites, making it difficult to generalize the findings and to build a body of sound evidence. If randomized trials cannot be conducted, the preferred option is quasi-experimental studies with clear control groups and longitudinal designs (Peabody and others 1999).

Good quality means that providers are able to manage an individual’s or a population’s health care by timely, skillful application of medical technology in a culturally sensitive manner within the available resource constraints. Eliminating poor quality involves not only giving better care but also eliminating underprovision of essential clinical services (systemwide microscopy for diagnosing tuberculosis, for example); stopping overuse of some care (prenatal ultrasonography or unnecessary injections, for example); and ending misuse of unneeded services (such as unnecessary hysterectomies or antibiotics for viral infections). A sadly unique feature of quality is that poor quality can obviate all the implied benefits of good access and effective treatment. At its best, poor quality is wasteful—a tragedy in severely resource-constrained health care systems. At its worst, it causes actual harm. Despite the urgency of improving health in developing countries, quality of care has been largely ignored. Both providers and patients agree this must change, but how can this goal be reached? From the information marshaled for this chapter, we can draw five conclusions: • Better quality leads to better health outcomes in developing countries. • Process, the proximate determinant of health outcomes, can be measured in valid and reliable ways, such as clinical vignettes and electronic medical records.


• Measured in the above ways, the process of care in developing countries is poor. • The process of care can be improved in the short term. • Policies affecting structural conditions, including the actual process of care or the continual design and redesign of the health care system, have been shown to be effective in developing countries. We believe that two broad strategies would help to rapidly improve health care quality in developing countries: • encouraging explicit comparative research on outcomes and process • disseminating empirical findings on quality variation. Encouraging Explicit Comparative Research on Outcomes and Process Comparisons highlighting different outcomes can be compelling. For example, when 30-day mortality rates for coronary artery bypass surgery at various facilities were disclosed in the United States, care started to shift from many low-volume hospitals to high-volume hospitals (Chassin 2002). In developing countries, comparisons show that the insured are more likely to have cesarean sections than are the uninsured (Barros and others 1991). Although critics of comparative analysis are justified in saying that systems and populations vary, such criticism misses an important point: Differences in outcome highlight possibilities that help in the search for the underlying causes of poor quality. Although poor quality may have many causes, one of them is almost always poor clinical practice, which can be remedied. We also favor a league or summary table approach to making comparisons. In this approach, the providers being compared agree on criteria before prospective assessments are done. The data for the comparison should be of the highest quality; the league tables themselves should be easy to interpret; and the findings should be rapidly available (Devers, Pham, and Liu 2004). The league table itself should be set up at the regional, national, and international levels so that a variety of benchmarks are available. Implementing quality comparisons will greatly facilitate the process of policy evaluation and cost-benefit analysis and help indicate directions for future research. Access to accurate, consistent quality-of-care data will compel external funders, such as the World Bank, to build quality assurance into their lending and development programs. As major health programs such as the Global Fund to Fight AIDS, Tuberculosis, and Malaria are scaled up around the world, mechanisms to measure and improve care quality will grow more important. Disseminating Empirical Findings on Quality Variation Public dissemination of information on quality, particularly in low-literacy countries, does not seem to create the individual-

based choice market that many have envisaged. Instead, it motivates managers and providers to undertake changes that improve the delivery of care (Schneider and Lieberman 2001). Outside pressure—perceived or real—appears to extend the quality debate beyond traditional boundaries, allowing for innovative collaborations and “out of the box” thinking (Devers, Pham, and Liu 2004). Nongovernmental and private organizations involved in health care delivery should also be required to report basic quality measures, perhaps as a condition for funding, thus ensuring that similar pressure to improve quality is exerted outside the public sector. Public dissemination can create shock waves when poor quality is “discovered,” leading to popular demand to increase quality. For example, findings of widespread medical errors in the United States, estimated to have resulted in as many as 98,000 deaths per year, launched the medical safety revolution (Institue of Medicine 2001). Dissemination among physicians and surgeons by means of report cards and ratings has been effective at changing clinical practice. One advantage of dissemination among providers is that the results can be more refined and technical than ratings meant for wider audiences. Dissemination is the responsibility of public research and public initiative. Because dissemination is inherently controversial, it requires public financing—even more than other public goods (Jamison, Frenk, and Knaul 1998). Ultimately, improving quality is about value. In health care, price is not a reliable proxy for quality and cannot be used as a guide. Because patients and consumers cannot directly observe quality, their ability to demand high-quality services is limited, and they are often left to settle for a market that has suboptimal equilibrium and poor quality of care. In addition, providers often lack knowledge of optimal treatments and technologies and thus are not aware of how they can produce higher-quality care. Because the provider-patient interaction is so private and personal, quality of care is hard to observe and to measure. New measurement tools, however—such as clinical vignettes and the electronic medical record—are being developed and improved. As research links care with outcomes and cost inputs, we can expect to have more accurate and reliable data about clinical practice for use in making quality assessments. Investments in quality, however, must be judged critically as well. When we invest in quality, an investment can be beneficial but can come at a cost. So while quality goes up, value can go up or down—or costs can go up while quality actually goes down or stays the same, thus pushing the value of care down and undermining other efforts to improve quality. Finally, as we showed for acute respiratory illness and diarrhea, quality can go up and costs go down, thus increasing overall value. Examples of this optimal outcome must be actively sought out and reported, because the success of a given investment cannot be known in advance (Berwick 2004). Improving the Quality of Care in Developing Countries | 1305


Improving health status does not have to rely solely on macroeconomic growth or other long-term development indicators. Health outcomes can be rapidly improved in the short term by ensuring the appropriateness of the circumstances or setting under which the health care encounter occurs (structural improvement) or by increasing the likelihood that health care providers behave in ways most beneficial to patients under the prevailing circumstances (process improvement). However, this improvement will not occur spontaneously or routinely, despite the best intentions of beneficiaries, providers, and governments. Quality improvement tools and technologies and information on successful quality improvement policies must be consistently shared among developing countries to build local capacity. Funding and incentives must also be consistent with high quality. Finally, the political will to ensure that quality becomes a top priority on the health reform agenda must be sustained.

Davis, D. A., M. A. Thomson, A. D. Oxman, and R. B. Haynes. 1995. “Changing Physician Performance: A Systematic Review of the Effect of Continuing Medical Education Strategies.” Journal of the American Medical Association 274 (9): 700–5. Devers, K. J., H. H. Pham, and G. Liu. 2004. “What Is Driving Hospitals’ Patient-Safety Efforts?” Health Affairs 23 (2): 103–16. Donabedian, A. 1980. The Definition of Quality and Approaches to Its Assessment. Ann Arbor, MI: Health Administration Press. ———. 1988. “The Quality of Care: How Can It Be Assessed?” Journal of the American Medical Association 260 (12): 1743–48. Douglas W. R., D. H. Howard, E. R. Becker, E. K. Adams, and M. H. Roberts. 2004. “Use of Midlevel Practitioners to Achieve Labor Cost Savings in the Primary Care Practice of an MCO.” Health Care Economics 39 (3): 607–25. Eichler, R., P. Auxila, and J. Pollock. 2001. “Performance-Based Payment to Improve the Impact of Health Services: Evidence from Haiti.” World Bank Institute Online Journal. Flores, R., J. Robles, and B. R. Burkhalter. 2002. “Distance Education with Tutoring Improves Diarrhea Case Management in Guatemala.” International Journal of Quality in Health Care 14 (Suppl. 1): 47–56. Frenk, J. 1992. “Balancing Relevance and Excellence: Organizational Responses to Link Research with Decision Making.” Social Science and Medicine 35 (11): 1397–404.

NOTE 1. As a reference, if the average expected value of a life is close to US$30,000, even the highest cost-effectiveness ratio found in the analysis (US$12,000 per life saved), would imply a cost-benefit ratio below 50 percent, assuming an initial average wage of US$1,000 growing at 2 percent per year, a 5 percent discount rate, and unchanged mortality rates.

Gutierrez, G., H. Guiscafre, M. Bronfman, J. Walsh, H. Martinez, and O. Munoz. 1994. “Changing Physician Prescribing Patterns: Evaluation of an Educational Strategy for Acute Diarrhea in Mexico City.” Medical Care 32 (5): 436–46. Habib, M., K. Mandal, C. V. Bunce, and S. G. Fraser. 2004. “The Relation of Volume with Outcome in Pachoemulsification Surgery.” British Journal of Ophthalmology 88: 643–46.

REFERENCES

Heaton, C. 2000. “External Peer Review in Europe: An Overview from the ExPeRT Project. External Peer Review Techniques.” International Journal of Quality in Health Care 12 (3): 177–82.

Barros, F. C., J. P. Vaughan, C. G. Victora, and S. R. Huttly. 1991. “Epidemic of Caesarean Sections in Brazil.” Lancet 338 (8760): 167–69.

Institute of Medicine. 2001. Crossing the Quality Chasm. Washington, DC: National Academy Press.

Beracochea, E., R. Dickson, P. Freemand, and J. Thomason. 1995. “Case Management Quality Assessment in Rural Areas of Papua New Guinea.” Tropical Doctor 25 (2): 69–74.

Jack, W. 2003. “Contracting for Health Services: An Evaluation of Recent Reforms in Nicaragua.” Health Policy and Planning 18 (2): 195–204.

Berwick, D. 1989. “Continuous Improvement as an Ideal in Health Care.” New England Journal of Medicine 320 (1): 53–56. ———. 2004. “Lessons from Developing Nations on Improving Health Care.” British Medical Journal 328 (7448): 1124–29. Bhat, R. 1996. “Regulating the Private Health Care Sector: The Case of the Indian Consumer Protection Act.” Health Policy and Planning 11 (3): 265–79.

Jamison, D. T., J. Frenk, and F. Knaul. 1998. “International Collective Action in Health: Objectives, Functions, and Rationale.” Lancet 351 (9101): 514–17. Javitt, J., G. Venkataswamy, and A. Sommer. 1983. “The Economic and Social Aspects of Restoring Sight.” In 24th International Congress of Ophthalmology, ed. P. Henkind, New York: J. B. Lippincott.

Bloom, D. E., D. Canning, and J. Sevilla. 2001. “The Effect of Health on Economic Growth: Theory and Evidence.” NBER Working Paper 8587, National Bureau of Economic Research, Cambridge, MA.

Kelley, E., C. Geslin, S. Djibrina, and M. Boucar. 2001. “Improving Performance with Clinical Standards: The Impact of Feedback on Compliance with the Integrated Management of Childhood Illness Algorithm in Niger, West Africa.” International Journal of Health Planning Management 16 (3): 195–205.

Brian, G., and H. Taylor. 2001. “Restoring Sight to the Millions: The Aravind Way.” Bulletin of the World Health Organization 79 (3): 270–71.

Kumaranayake, L., P. Mujinja, C. Hongoro, and R. Mpembeni. 2000. “How Do Countries Regulate the Health Sector? Evidence from Tanzania and Zimbabwe.” Health Policy and Planning 15 (4): 357–67.

Broomberg, J., P. Masobe, and A. Mills. 1997. “To Purchase or to Provide? The Relative Efficiency of Contracting-Out versus Direct Public Provision of Hospital Services in South Africa.” In Private Health Providers in Developing Countries: Serving the Public Interest?, ed. S. Bennett, B. McPake, and A. Mills. London: Zed Press.

Loevinsohn, B. P., E. T. Guerrero, and S. P. Gregorio. 1995. “Improving Primary Health Care through Systematic Supervision: A Controlled Field Trial.” Health Policy and Planning 10 (2): 144–53.

Chakraborty, S., S. A. D’Souza, and R. S. Northrup. 2000. “Improving Private Practitioner Care of Sick Children: Testing New Approaches in Rural Bihar.” Health Policy and Planning 15 (4): 400–7. Chassin, M. R. 2002. “Achieving and Sustaining Improved Quality: Lessons from New York State and Cardiac Surgery.” Health Affairs 21 (4): 40.

Luck, J., and J. Peabody. 2002. “Using Standardised Patients to Measure Physicians’ Practice: Validation Study Using Audio Recordings.” British Medical Journal 325 (7366): 679. Luck, J., J. Peabody, T. R. Dresselhaus, M. Lee, and P. Glassman. 2000. “How Well Does Chart Abstraction Measure Quality? A Prospective Comparison of Standardized Patients with the Medical Record.” American Journal of Medicine 108 (8): 642–49.


Marek, T., I. Diallo, B. Ndiaye, and J. Rakotosalama. 1999. “Successful Contracting of Prevention Services: Fighting Malnutrition in Senegal and Madagascar.” Health Policy and Planning 14 (4): 382–89.

Santoso, B., S. Suryawati, and J. E. Prawaitasari. 1996. “Small Group Intervention vs. Formal Seminar for Improving Appropriate Drug Use.” Social Science and Medicine 42 (8): 1163–68.

Martines, J., M. Phillips, and R. G. Feacham. 1993. “Diarrheal Diseases.” In Disease Control Priorities in Developing Countries, ed. D. Jamison, W. H. Mosley, A. R. Measham, and J. L. Bobadilla, New York: Oxford University Press.

Schneider, E. C., and T. Lieberman. 2001. “Publicly Disclosed Information about the Quality of Health Care: Response of the U.S. Public.” Quality in Health Care 10 (2): 96–103.

McBride, A. B., S. Neiman, and J. Johnson. 2000. “Responsibility-Centered Management: A 10-Year Nursing Assessment.” Journal of Professional Nursing 16 (4): 201–9. McConnell, H. 2004. “International Efforts in Implementing National Health Information Infrastructure and Electronic Health Records.” World Hospitals and Health Services 40 (1): 33–37, 39–40, 50–52. McGlynn, E. A., S. M. Asch, J. Adams, J. Keesey, J. Hicks, A. DeCristofaro, and E. A. Kerr. 2003. “The Quality of Health Care Delivered to Adults in the United States.” New England Journal of Medicine 348 (26): 2635–45. Mtango, F. D., and D. Neuvians. 1986. “Acute Respiratory Infections in Children under Five Years: Control Project in Bagamoyo District, Tanzania.” Transactions of the Royal Society of Tropical Medicine and Hygiene 80 (6): 851–58. Murray, C. J., and J. Frenk. 2000. “A Framework for Assessing the Performance of Health Systems.” Bulletin of the World Health Organization 78 (6): 717–31. Nolan, T., P. Angos, A. J. Cunha, L. Muhe, S. Qazi, E. A. Simoes, and others. 2001. “Quality of Hospital Care for Seriously Ill Children in LessDeveloped Countries.” Lancet 357 (9250): 106–10. Peabody, J. 1996. “Economic Reform and Health Sector Policy: Lessons from Structural Adjustment Programs.” Social Science and Medicine 43 (5): 823–35. Peabody, J., P. Gertler, and A. Liebowitz. 1998. “The Policy Implications of Better Structure and Process on Birth Outcomes in Jamaica.” Health Policy 43 (1): 1–13. Peabody, J., J. Luck, P. Glassman, S. Jain, J. Hansen, M. Spell, and M. Lee. 2004. “Measuring the Quality of Physician Practice by Using Clinical Vignettes: A Prospective Validation Study.” Annals of Internal Medicine 141 (10): 771–80. Peabody, J., J. Luck, S. Jain, D. Bertenthal, and P. Glassman. 2004. “Assessing the Accuracy of Administrative Data in Health Information Systems.” Medical Care 42 (11): 1066–72. Peabody, J., M. Rahman, P. J. Gertler, J. Mann, D. O. Farley, and G. M. Carter. 1999. Policy and Health: Implications for Development in Asia. Cambridge, UK: Cambridge University Press. Peabody, J., F. Tozija, J. Muñoz, R. J. Mordyke, and J. Luck. 2004. “Using Vignettes to Compare the Quality of Care Variation in Economically Divergent Countries.” Health Services Research 39: 1937–56. Perez-Cuevas, R., H. Guiscafre, O. Munoz, H. Reyes, P. Tome, V. Libreros, and G. Gutierrez. 1996. “Improving Physician Prescribing Patterns to Treat Rhinopharyngitis: Intervention Strategies in Two Health Systems of Mexico.” Social Science and Medicine 42 (8): 1185–94. Sachs, J. D. 2001. Macroeconomics and Health: Investing in Health for Economic Development. Report of the Commission on Macroeconomics and Health. Geneva: World Health Organization. Salmon, J., J. Heavens, C. Lombard, and P. Tavrow. 2003. “The Impact of Accreditation on the Quality of Hospital Care: KwaZulu-Natal Province, Republic of South Africa.” Operations Research Results 2 (17). Published for the U.S. Agency for International Development (USAID) by the Quality Assurance Project, University Research Co., Bethesda, MD.

Secretaría de Salud de Mexico. 2003. Salud: México 2002. Mexico City: Secretaría de Salud. Shepard, D. S., L. E. Brenzel, and K. T. Nemeth. 1986. “Cost-Effectiveness of Oral Rehydration Therapy for Diarrhoeal Diseases.” PHN Technical Note 86-26, Population, Health, and Nutrition Development, World Bank, Washington, DC. Silimper, D. R., L. M. Franco, T. Veldhuyzen van Zanten, and C. MacAulay. 2002. “A Framework for Institutionalizing Quality Assurance.” International Journal for Quality in Health Care 14 (Suppl. 1): 67–73. Snyder, J. D., and M. H. Merson. 1982. “The Magnitude of the Global Problem of Acute Diarrhoeal Disease: A Review of Active Surveillance Data.” Bulletin of the World Health Organization 60 (4): 605–13. Stansfield, S. K., and D. S. Shepard. 1990. “Acute Respiratory Infection.” In Disease Control Priorities in Developing Countries, ed. D. Jamison, W. H. Mosley, A. R. Measham, and J. L. Bobadilla. New York: Oxford University Press. Supratikto, G., M. E. Wirth, E. Achadi, S. Cohen, and C. Ronsmans. 2002. “A District-Based Audit of the Causes and Circumstances of Maternal Deaths in South Kalimantan, Indonesia.” Bulletin of the World Health Organization 80 (3): 228–34. Tan, S. K. P. 1999. “Safety with Anaesthesia—The Paradigm of Continuous Improvement.” Medical Journal of Malaysia 54 (1): 1–3. Tavrow, P., Y.-M. Kim, and L. Malianga. 2002. “Measuring the Quality of Supervisor-Provider Interactions in Health Care Facilities in Zimbabwe.” International Journal of Quality in Health Care 14 (Suppl. 1): 57–66. Thapar, N., and I. Sanderson. 2004. “Diarrhoea in Children: an Interface between Developing and Developed Countries.” Lancet 363 (9409): 641–53. Thaver, I. H., T. Harpham, B. McPake, and T. Garner. 1998. “Private Practitioners in the Slums of Karachi: What Quality of Care Do They Offer?” Social Science and Medicine 46 (11): 1441–49. Van der Gaag, J. 2000. “From Child Development to Human Development.” In From Early Child Development to Human Development, ed. M. E. Young, Washington, DC: World Bank. Walker, G. J., D. E. Ashley, and R. J. Hayes. 1988. “The Quality of Care Is Related to Death Rates: Hospital Inpatient Management of Infants with Acute Gastroenteritis in Jamaica.” American Journal of Public Health 78 (2): 149–52. Wennberg, J. E., E. S. Fisher, and J. S. Skinner. 2002. “Geography and the Debate over Medicare Reform.” Health Affairs (Millwood) Suppl. Web Exclusives: W96–114. WHO (World Health Organization). 2000. World Health Report 2000 Health Systems: Improving Performance. Geneva: WHO. Zaslavsky, A. M., J. N. Hochheimer, E. C. Schneider, P. D. Cleary, J. J. Seidman, E. A. McGlynn, and others. 2000. “Impact of Sociodemographic Case Mix on the HEDIS Measures of Health Plan Quality.” Medical Care 38 (10): 981–92. Zgibor, J. C., and T. J. Orchard. 2004. “Specialist and Generalist Care for Type 1 Diabetes Mellitus—Differential Impact on Processes and Outcomes.” Disease Management and Health Outcomes 12 (4): 229–38.

Improving the Quality of Care in Developing Countries | 1307 ©2006 The International Bank for Reconstruction and Development / The World Bank 279


Part I

Global Burden of Disease and Risk Factors



Chapter 2

Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 Alan D. Lopez, Stephen Begg, and Ed Bos

Health status is both a determinant of population change, largely through population aging, and a consequence of population growth, with smaller family size associated with lower mortality, and of economic and social development. Studies of the interrelationship between demographic trends and health have typically focused on health as the independent or determining variable. Indeed, a population’s health status influences all components of population change. In addition to the obvious direct effect of individual health status on mortality and morbidity, it has a direct impact on fertility, largely through improved child survival, but also through the biological capability of a sick woman to bear children. Processes such as screening potential migrants for disease are also mechanisms whereby health status exerts a direct impact on population change, and thus on population size and composition. In contrast, demographic variables influence health through two interrelated phenomena. First, a population’s size, composition by age and sex, and geographical distribution have a direct influence on overall health status. Age has a particularly marked effect on the pattern and extent of illhealth in populations because of the strong relationship

between age and mortality and morbidity. Second, each of the dynamic processes influencing population size and growth, structure, and distribution, namely, fertility, mortality, and migration, will also affect health status. Thus, any discussion of disease control priorities and of the health system for delivering interventions requires an understanding of the demographic context and how it is changing. This chapter begins by providing an overview of global population trends in each major region of the world and the current size and composition of the population. Given this volume’s focus on the descriptive epidemiology of diseases, injuries, and risk factors, we then examine trends in mortality over the past decade in more detail as background against which the current assessment of the disease burden might be more usefully interpreted. This includes both an assessment of trends in age-specific mortality and summary measures of the age schedule of mortality, such as life expectancy and the probability of dying within certain age ranges, as well as a specific discussion of trends in the main causes of child mortality. The focus on child mortality is entirely appropriate because (a) the fact that at the end of 17


the 20th century, we remained woefully ignorant of its levels, let alone its causes, is highlighted; (b) the reduction of child mortality should remain a priority for global health development efforts, and the moral imperative to do so remains as relevant today as it was 30 years ago, when efforts to improve child survival became increasingly organized and focused; and (c) the resulting emphasis by the global public health community on reducing child mortality has yielded vastly more epidemiological information that can be used to assess trends in levels and causes. Nevertheless, we argue later in the chapter that large and unacceptable uncertainties about trends in cause-specific child mortality rates persist, with important implications for program planning and evaluation.

REGIONAL DEMOGRAPHIC CHARACTERISTICS The key characteristics of regional demography of concern for health services provision include the size, age structure, and sex structure of the population and its rate of growth and comparative measures of fertility and mortality.

Sources of Population Data and Methodology

The population and mortality estimates for various regions summarized here are based on different data sources and methods, and thus are not strictly comparable. This primarily concerns the impact of different estimates of deaths by age and sex on population size and structure. Because the effect of mortality on population size and structure is generally modest, such differences have little impact on the findings reported in this chapter. The population estimates are based on data the United Nations (UN) Population Division compiled and analyzed for its biennial assessment of global population trends and regional demographic patterns (United Nations 2003). The UN Population Division estimates population size and vital rates (births and deaths) from censuses, vital registration, and demographic and health surveys and evaluates the data for completeness, accuracy, and consistency. Where necessary, it adjusts the data to achieve internal consistency and cross-country comparability. The baseline from which the UN projections are made is mid-2003. Because the 2002 revision was produced without complete data for 2001 for all countries, the baseline estimates are also projections, and the population figures in this chapter are therefore a mixture of both observed and projected data.1

The UN Population Division assesses a number of demographic parameters to produce country projections. In addition to total population, the baseline assessment includes a breakdown of population by sex and age (in five-year aggregates). Fertility is specified as age-specific fertility rates for females and mortality rates are based on survival probabilities from life tables. Age-specific patterns of migration are also incorporated for countries in which migration flows are observed or are thought to occur. When these inputs are not available from any of the sources listed earlier, the UN uses demographic models, such as model life tables or indirect mortality estimation techniques, to generate the information. Additional modeling is applied to estimate mortality patterns in countries with significant HIV/AIDS prevalence levels. The UN Population Division provides a limited amount of information about the data in its reports, including the dates of censuses, the adjustment factors applied to total census populations, and the type and year of the latest surveys that contained mortality and fertility estimates. It does not provide information about the adjustments made to reported fertility rates, age and sex structures, or mortality rates. Basic information on population size and composition is available for most countries for 1990, and with the exception of Sub-Saharan Africa, for 2000 (or thereabouts) as well (table 2.1). Around both dates, censuses covered more than 90 percent of populations in all the regions except Sub-Saharan Africa. Thus, the basic population estimates developed by the UN Population Division and summarized in this chapter have a reasonable evidence base. The UN projections of population size and vital rates are based on assumptions about levels and trends in vital rates. Fertility is assumed to follow a path modeled on the experience of countries with declining fertility, except when a country’s recent fertility trend deviates considerably from

Table 2.1 Percentage of Regional Population Covered by Censuses, circa 1990 and 2000 Region

1990

2000

East Asia and Pacific

95.7

96.2

100.0

93.9

95.2

91.9

Europe and Central Asia Latin America and the Caribbean Middle East and North Africa

96.9

98.6

South Asia

87.0

98.1

Sub-Saharan Africa

81.6

53.4


90.2

99.0

Source: U.S. Census Bureau, Population Division, International Programs Center (July 7, 2004).

18 | Global Burden of Disease and Risk Factors | Alan D. Lopez, Stephen Begg, and Ed Bos ©2006 The International Bank for Reconstruction and Development / The World Bank 284

the model pattern, in which case the country-specific pattern is followed (United Nations 2003). Our 2001 estimates and future projections are generated on the basis of the cohort component methodology. This approach applies estimated trends in birth and death rates and migration by age and sex to a baseline age and sex structure. Population growth rates are determined by the levels of age-specific fertility and mortality rates and migration and the size of the initial age groups (base year population) against which these levels are applied. We constructed demographic estimates for the aggregate regional and income groupings used for the second edition of Disease Control Priorities in Developing Countries (Jamison and others 2006) from the UN Population Division countrylevel estimates by aggregating populations in specific age and sex groups and age-specific fertility rates. The aggregates are thus weighted by the different population sizes of individual countries. The mortality estimates presented in this chapter are developed from other sources using methods different than those the UN employed, as described later. As a result, the age and sex structures reported here, as well as any indicators derived from them (such as crude birth and death rates) are not strictly internally consistent. In particular, the mortality rates estimated for this chapter would, in some cases, have produced different age and sex population structures than those estimated by the UN, as well as different numbers of births and deaths. These differences are unlikely to be large, however, as the estimated age-specific mortality rates reported later in this chapter agree quite closely with those of the UN, except for Sub-Saharan Africa.

Population Size and Growth

Between 1990 and 2001, global population increased from about 5.3 billion to 6.1 billion people, an average rate of increase of 1.4 percent per year, equivalent to about 220,000 people per day (table 2.2). During the decade, the growth rate in developing regions ranged from 0.2 percent in Europe and Central Asia to 2.6 percent in Sub-Saharan Africa. Estimates at the global level conceal large differences in population growth among regions, which in turn consist of countries that may have quite different demographic trends. For example, Europe and Central Asia added just 1 million people per year between 1990 and 2001, whereas South Asia added 25 million people each year. The World Bank regions (see map 1 inside the front cover of this volume) vary substantially in terms of population

size, with East Asia and the Pacific accounting for about 30 percent of the global population and South Asia for roughly another 20 percent.Thus,about half the world’s population live in the low- and middle-income countries of these two regions. The smallest region in terms of population size is the Middle East and North Africa, with just 5 percent of the world’s population. Just over 10 percent of the world’s population live in Sub-Saharan Africa. Another 15 percent live in high-income countries, a proportion that is declining.

Distribution by Age, Sex, and Location

How populations are distributed by age matters a great deal for public health, because many aspects of risk behavior, as well as disease and injury outcomes, are strongly associated with age. While many other factors contribute to mortality and fertility levels, the age distribution of a population is an important factor in explaining differences in demographic and epidemiological indicators. Regions differ significantly in how their populations are distributed across age groups, with almost 45 percent of the population of Sub-Saharan Africa being younger than 15, compared with 20 percent of the population in high-income countries, where fertility has been low for decades. Nevertheless, the trends during 1990–2001 show a great deal of similarity: in all regions the proportion of the population in the youngest age groups was lower in 2001 than in 1990, with most of the increase occurring in the 15 through 69 age group. As a result, the median age of the population has increased in all regions. At the same time, the population aged 70 and older has been increasing in most regions as mortality has declined, and this age group now represents more than 10 percent of the population in the high-income countries. These changes in the relative age distribution of populations since 1990 reflect changes in the growth rates of different age groups (figure 2.1). In three of the six regions (East Asia and Pacific, Europe and Central Asia, and the Middle East and North Africa), as well as the world as a whole, the number of children under five was smaller in absolute terms in 2001 than in 1990. The highest growth rates during this period were in the 40- through 55-year-old age group and among those over 70. The irregularities in growth rates of different age groups reflect past trends in the initial size of each cohort and its subsequent mortality and migration experiences. This is particularly evident for Europe and Central Asia, where the impact of the regional conflicts in the early 1990s on demographic structure is particularly evident. Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 | 19


Table 2.2 Population Size and Composition, Fertility, and GNP, by World Bank Region, 1990 and 2001 Low- and middleincome countries Population Characteristic

Size Total population (thousands) Proportion of world population (%) Annual average growth rate, 1990–2001 (%) Composition (%) Age 0–14 15–59 60–69 70⫹ Urban Female Fertility Total fertility rate Total no. of births (thousands) Crude birth rate per 1,000 GNP (exchange rate dollars) GNP per capita




1990

2001

1990

2001

1990

2001

1990

2001

4,398,401 83.6

5,216,587 84.9

1,625,868 30.9

1,848,388 30.1

467,797 8.9

477,116 7.8

439,709 8.4

525,864 8.6

1.6

1.2

0.2

1.6

34.8 57.6 4.7 2.9 36.9 49.4

31.8 59.8 5.0 3.4 41.6 49.5

30.2 61.8 4.9 3.0 28.8 48.9

26.5 64.1 5.6 3.8 37.0 49.0

26.5 59.5 8.3 5.6 63.2 51.9

21.8 62.6 8.5 7.2 63.5 51.9

36.2 56.8 4.2 2.9 71.1 50.3

31.5 60.4 4.5 3.6 75.4 50.5

3.5 123,400 28.2

2.9 122,400 23.4

2.6 36,200 22.3

2.1 31,500 17.0

2.3 8,300 16.7

1.6 6,300 12.7

3.2 11,700 26.6

2.6 11,600 22.0

870

1,170

420

890

39,737

54,933

2,260

3,570

Source: UN Population Division 2002 revision estimates. Note: GNP ⫽ gross national product.

Along with the progressive aging of the population, the relentless trend toward increasing urbanization has continued, with consequences for health in terms of both health service provision, which, in principle, is better with urbanization, and risk of exposure to chronic disease, which is, on balance, worse (Ezzati and others 2005). Almost half the world’s population lived in urban areas in 2001, up 4 percentage points from 1990. The increase in urbanization was particularly marked in East Asia and the Pacific (increase from 29 to 37 percent of the population) and in SubSaharan Africa (from 28 to 34 percent). Overall, 42 percent of the population in low- and middle-income countries now live in urban areas. In general, more boys than girls are born, with sex ratios at birth of between 1.03 and 1.06 in most countries, though in some Asian countries, sex-selective abortions have skewed this ratio to more than 1.10. Differential mortality and, to a limited extent, migration, shape the sex ratio at other ages (figure 2.2). In South Asia, higher mortality for girls and for women during their childbearing years leads at first to an increasing and then to a constant sex ratio to about age 45, after which male mortality is higher. Excess mortality of adult males in Europe and Central Asia explains the particularly low sex ratio observed there (Lopez and others 2002). In all regions, the higher mortality of males

relative to females accounts for the sharp decline in the population sex ratio after age 50 or thereabouts. The overall effects of the age-specific mortality differences between the sexes are relatively minor in terms of total population sex ratios. All regions have roughly equal numbers of males and females in the population, with the proportion of males being slightly higher in Europe and Central Asia and in the high-income regions (51 to 52 percent) than in East Asia and the Pacific and South Asia (49 percent).

Fertility

Table 2.2 shows recent trends in fertility, as indicated by the total fertility rate for the period, that is, the average number of children a woman could expect to have if she were subject indefinitely to current age-specific fertility rates. Even though fertility levels vary a good deal among regions, all low- and middle-income regions witnessed large declines in fertility levels during the 1990s. Overall fertility levels in low- and middle-income countries fell by almost 20 percent over the decade, a remarkable decline, with levels falling by as much as 33 percent in the Middle East and North Africa, and even by 10 percent in Sub-Saharan Africa. However, fertility rates in Sub-Saharan Africa remain high, with the total fertility rate of 5.6 being about twice as high as that for any other region.


Table 2.2 Continued Middle East and North Africa

Sub-Saharan Africa

South Asia

High-income

World

1990

2001

1990

2001

1990

2001

1990

2001

1990

2001

243,973 4.6

309,762 5.0

1,117,887 21.2

1,387,873 22.6

503,166 9.6

667,583 10.9

862,342 16.4

928,110 15.1

5,260,742 100.0

6,144,696 100.0

2.2

2.0

2.6

0.7

1.4

43.1 51.5 3.5 1.9 53.5 49.0

36.4 57.7 3.6 2.4 57.5 49.3

37.8 55.7 4.2 2.3 25.0 48.4

35.3 57.6 4.4 2.7 27.4 48.5

45.7 49.7 3.0 1.6 27.9 50.4

44.3 51.0 3.0 1.7 34.0 50.4

20.0 62.5 9.0 8.5 74.4 51.0

18.5 62.2 9.1 10.2 77.1 50.8

32.4 58.4 5.4 3.8 43.0 49.6

29.8 60.2 5.6 4.5 46.9 49.7

5.0 9,300 34.8

3.6 9,400 27.3

4.3 36,500 32.7

3.4 37,300 26.7

6.3 21,400 44.6

5.6 26,300 40.8

1.7 11,300 13.4

1.7 10,800 11.9

3.2 134,700 25.7

2.7 133,200 21.6

1,770

3,570

380

450

470

550

19,760

26,760

4,060

5,180

Few low- and middle-income countries experienced increasing fertility during 1990–2001,2 though a few high-income countries have seen small upturns from previously low levels. Fertility is below replacement levels (about two children) in all but five high-income countries (Brunei Darussalam, Israel, Kuwait, Qatar, and the United Arab Emirates), as well as in most countries in Europe and Central Asia. When fertility drops to below replacement levels, population growth often continues for several decades,as the number of births exceeds the number of deaths because of the high proportion of women of childbearing age.

CHANGES IN MORTALITY, 1990–2001 Change in patterns of mortality is a major determinant of the demography of populations and underlies important population differentials. For example, the differences in mortality by sex across regions contribute to the variable pattern of population sex ratios described earlier. The theory of demographic transition suggests that the rapid declines in fertility observed during the 1990s in most regions would be preceded, and perhaps accompanied, by a similarly rapid decline in child mortality. To help interpret the broad regional demographic patterns described earlier, a review of trends in mortality and the causes underlying such trends is useful.

Estimating Mortality

Various methods are available to estimate age patterns and levels of mortality in populations. These fall into three broad categories depending on the available data: direct estimation from complete vital registration, estimates from vital registration corrected for undercounting, and estimates derived from models based on child mortality levels. Mathers and others (2005) review the availability and quality of mortality data and group the 192 member states of the World Health Organization into broad categories according to criteria pertaining to the coverage, completeness, and quality of cause of death data. Their findings indicate that only about 33 percent (64) of World Health Organization member states, mostly high-income countries, have complete mortality data and that another 26 percent (50 countries) have data that can be used for mortality estimation purposes. The approximately 40 percent of remaining countries either have no recent data or no data at all that can be used to estimate causes of death or the level of adult mortality directly. The situation is somewhat different for levels of child mortality, where decades of interest in monitoring child survival by the global public health community have yielded either direct or indirect estimates of child mortality for all but a handful of countries (Hill and others 1999; Lopez and others 2002). Based on a careful review of the time trend of Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 | 21







South Asia

Sub-Saharan Africa


World

80

Age

60 40 20 0

80

Age

60 40 20 0

80

Age

60 40 20 0 ⫺5

0 5 Average annual percentage change

⫺5 0 5 Average annual percentage change

⫺5

0 5 Average annual percentage change

Source: Calculated from United Nations 2003.

Figure 2.1 Changes in Population Age Distribution, 1990–2001

these estimates of child deaths, which come primarily from censuses and surveys, estimating child mortality levels in 1990 and 2001 is possible for virtually all countries with an acceptable level of uncertainty. Levels of child mortality are unavailable for only about 10 countries that together account for about 2 percent of child deaths (Lopez and others 2002). Formal curve-fitting procedures to estimate time trends in child mortality can be applied to all the data, but given the subjective assessments that are required to judge which data points are plausible and which are not, simple averaging of all plausible observations at any given point in time is likely to be sufficient, and this was the procedure used to estimate child mortality levels for this chapter. For those countries with complete vital registration data, age-specific and cause-specific death rates are easily derived directly from the registration data and from population censuses. For those countries where registration data are

incomplete, demographers have developed indirect demographic methods to correct for underreporting of deaths before estimating age-specific mortality (Bennett and Horiuchi 1984; Hill 1987). These countries include China and India, where application of such methods suggest that data from the disease surveillance points system in China and the sample registration system in India are 85 to 90 percent complete (Mari Bhat 2002; Rao and others 2005). For countries with no usable data on adult mortality levels, age-specific death rates were predicted from the modified logit life table system (Murray and others 2003). The median level of adult mortality was predicted based on a modeled relationship between adult and child mortality as determined from a historical data set of more than 1,800 life tables judged to be reasonably complete. Uncertainty about these predicted mean values of adult mortality is considerable given the few observations with comparatively







South Asia

Sub-Saharan Africa


World

80

Age

60 40 20 0

80

Age

60 40 20 0

80

Age

60 40 20 0 0.5

1.0 Ratio of males to females

1.5

0.5 1.0 Ratio of males to females

1.5

0.5

1.0 Ratio of males to females

1.5

Source: Calculated from United Nations 2003.

Figure 2.2 Population Sex Ratios at Different Ages, 2001

high levels of child and adult mortality. The estimated and predicted levels of child and adult mortality, respectively, were then applied to the modified life table system by selecting the best match from among 50,000 life tables to estimate a complete, smoothed set of age-specific death rates (Murray and others 2003). This method was applied for all but about 70 countries. Obvious uncertainties are associated with this procedure. Hence, the life tables for East Asia and the Pacific, the Middle East and North Africa, and Sub-Saharan Africa (where HIV/AIDS mortality was added to the predicted adult mortality rates) in particular need to be viewed with caution, because the rates for many countries in these regions have been modeled using these methods. Identical methods were applied to estimate national agespecific mortality rates for both 1990 and 2001; thus, the two sets of estimates are, in principle at least, comparable.

Annex 2A provides detailed estimates of summary measures of mortality by country for the two years based on these methods. The annex also shows the percentage decline in child mortality during the period. Whether these methods correctly describe levels and patterns of mortality is difficult to ascertain given the substantial uncertainties in the data, particularly for adult mortality. The only other systematic attempt to estimate national and global death rates in 1990 is that of the UN Population Division (United Nations 2003). Figure 2.3 presents estimated mortality parameters for 1990 by region. For a comparison of mortality estimates for 2001, see Lopez and others (2002). Despite the UN’s different model life table approach for estimating age-specific death rates based on child mortality, the two sets of estimates shown in figure 2.3 are remarkably congruent. Regional estimates of child mortality 5q0 (the Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 | 23


a. Males Probability of Mortality: Children under Five (per 1,000)

Life Expectancy at Birth (Years)

200

80

Sub-Saharan Africa

High-income countries Latin America and the Caribbean

UN

70


60

150 East Asia and Pacific

South Asia

South Asia East Asia and Pacific

100



50

50



Sub-Saharan Africa

40


0 40

50

60

70

80

0

50

100

800

500

Sub-Saharan Africa

Sub-Saharan Africa

750

400

UN

200

Probability of Mortality: 60- to 79-Year-Olds (per 1,000)

Probability of Mortality: 15- to 59-Year-Olds (per 1,000)

300

150


South Asia

700 Middle East and North Africa South Asia Europe and Central Asia

650


200





600 High-income countries


550

100 100

200

300

400

500

550

Authors’ estimates

600

650

700

750

800


Figure 2.3 UN’s versus Authors’ Life Table Parameters, 1990

mortality risk for children under five years of age) are virtually identical, with a possible exception being the UN’s slightly higher levels of child mortality for East Asia and the Pacific (which is dominated by China). This congruence is not unexpected given the intense collaborative efforts of the past five years or so by the World Health Organization, the United Nations Children’s Fund, the United Nations, and the World Bank to agree upon a common interpretation of the extensive data available on trends in child mortality in low- and middle-income countries. Somewhat surprisingly given the quite different methodological approaches, regional estimates of adult mortality 45q15 (the mortality risk for adults between the ages of 15 and 60) are remarkably similar, with our estimates tending to be

slightly higher in the Middle East and North Africa and South Asia for males and slightly lower in the same regions for females. That is, we have estimated larger sex mortality differentials among adults than the UN on the basis of observed patterns of mortality where data were available (as in the Arab Republic of Egypt and India), and where not, on the basis of observed differences in child mortality for boys and girls. Some investigators expect male excess mortality to increase with social development and economic growth (Bhatia 1983), but whether this is better reflected in our estimates or those of the UN is not clear. In any case, the differences are minor. Significantly more disagreement is apparent for Sub-Saharan Africa, with the UN estimates of adult mortality in 1990 being one-quarter to one-third higher than ours. This is obviously


b. Females Probability of Mortality: Children under Five (per 1,000)

Life Expectancy at Birth (Years) 80

200


Sub-Saharan Africa Europe and Central Asia

70

150 Latin America and the Caribbean


UN


South Asia

100



60

50

South Asia

50

Sub-Saharan Africa

0

50

60

70

80


0

Probability of Mortality: 15- to 59-Year-Olds (per 1,000) 400

Latin America and the Caribbean Europe and Central Asia

50

100

150

200

Probability of Mortality: 60- to 79-Year-Olds (per 1,000) 700

Sub-Saharan Africa

Sub-Saharan Africa

300

600


UN

South Asia Latin America and the Caribbean


200


100

South Asia


500

East Asia and Pacific Latin America and the Caribbean


400

High-income countries High-income countries

0

300 0

100

200

300

400


300

400

500

600

700


Sources: UN parameters are from United Nations 2005b; authors' estimates are from this chapter.

Figure 2.3 Continued

uncertain given the sparse data available on adult mortality in the region and the fact that the HIV epidemic in Sub-Saharan Africa was well established by then, and hence a higher estimate may be justified. Recent evidence, however, has suggested that basing mortality estimates on prenatal clinic data may well lead to an overestimation of death rates due to HIV. Differences in methodology and adjustment criteria appear to have the greatest effect at older ages, especially for males. The UN estimates indicate significantly higher mortality in high-income countries at ages 60 to 79 even though complete vital registration data are available for virtually all the countries except some of the small Gulf states. Differences in estimated mortality for the Sub-Saharan

Africa region are not unexpected given the differences reported for younger adults, and are less extreme than at ages 15 to 59, as one might expect given that HIV/AIDS mortality is not of major consequence for older ages. Otherwise, estimates for females at older ages agree quite closely, but the UN’s are significantly higher than ours for Latin America and the Caribbean and significantly lower for East Asia and the Pacific and South Asia. These differences arise because the model life table methods used by the UN tend to shift deaths from younger to older adult ages at lower levels of child mortality (Latin America and the Caribbean) and the converse at higher levels of child death rates (East Asia and the Pacific and South Asia). Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 | 25


Table 2.3 Selected Mortality Characteristics by Sex and World Bank Region, 1990 and 2001 Male

Sex and region

Expectation % of deaths Probability of dying per 1,000 Deaths Crude death of life at Year (millions) rate per 1,000 Under age 5 Over age 60 Ages 0–5a Ages 15–60 Ages 0–60 Ages 60–80 birth (years)

Low- and middleincome countries

1990 2001

22.5 25.5

10.1 9.7

27.9 21.2

39.5 42.2

98 86

269 269

351 341

712 667

59.9 61.2


1990 2001

6.6 6.9

8.0 7.4

16.3 10.2

50.6 56.2

54 41

215 189

265 228

699 623

64.9 67.8

Europe and Central Asia 1990 2001

2.5 3.0

11.1 13.0

7.9 3.2

55.9 59.6

45 32

286 328

323 353

696 711

63.6 63.0


1990 2001

1.7 1.8

7.8 7.0

19.5 12.4

44.7 49.1

56 38

245 218

294 252

640 572

64.5 67.6


1990 2001

1.0 1.1

8.2 6.8

34.9 21.6

34.2 45.2

83 56

247 216

318 267

688 674

62.0 65.2

South Asia

1990 2001

6.8 7.1

11.7 9.9

32.4 25.1

35.0 39.2

122 94

310 285

407 362

754 710

56.4 59.9

Sub-Saharan Africa

1990 2001

3.9 5.6

15.6 16.9

54.1 42.2

17.0 16.9

191 178

386 518

517 616

758 760

49.6 46.0


1990 2001

3.9 4.0

9.1 8.8

1.7 1.0

76.2 78.7

12 7

148 124

160 132

542 469

72.9 75.5

World

1990 2001

26.4 29.5

10.0 9.6

24.0 18.5

44.8 47.2

91 80

245 243

323 312

667 618

61.7 63.1

Sources: Estimates for 1990 are authors’ calculations, based on country-level life tables (see annex 2A). Estimates for 2001 are derived from Lopez and others 2002. a. Estimates of child mortality are rounded to the nearest whole number.

Overall, as figure 2.3 demonstrates, the age patterns are largely compensatory, with the result that estimates of life expectancy at birth for the two series are remarkably similar for both males and females, with the notable exception being Sub-Saharan Africa, where the higher adult mortality assumptions favored by the UN result in life expectancies at birth that are about 2.5 years lower than ours for males and 5.0 years lower for females.

Trends in Mortality Levels

The 1990s were characterized by significant economic gains in most regions, with growth in gross national product per capita ranging from 18 percent in South Asia and SubSaharan Africa to more than 100 percent in East Asia and the Pacific and the Middle East and North Africa (table 2.2). Overall, gross national product per capita grew by about 35 percent in low- and middle-income countries during the decade. One would expect this to have led to a significant improvement in life expectancy, and this indeed occurred in most regions with the notable exception of Europe and Central Asia and, in particular, Sub-Saharan Africa (table 2.3). In the former region, life expectancy was largely

unchanged over the decade, primarily because of the massive rise in adult mortality in countries such as the Russian Federation and its neighbors during the first part of the decade, which negated the declines in child mortality. Much of this extraordinary increase in adult mortality, which rose by about 50 percent between 1987 and 1994, has been attributed to alcohol abuse, particularly among men (Leon and others 1997; Shkolnikov, McKee, and Leon 2001). Economic development and better coverage of the population with essential child health services have ensured continued declines in levels of child mortality, as measured by the risk of death from birth to age five, in all regions. The notable exception is Sub-Saharan Africa, where child mortality among girls remained unchanged at around 165 per 1,000, with only a modest decline (5 percent) in the risk of death for boys. The absence of significant declines in child mortality in the 1990s in Sub-Saharan Africa is most likely largely due to the impact of HIV/AIDS. Overall, the risk of child death declined from 90 per 1,000 in 1990 to 80 per 1,000 in 2001, with the risk being remarkably similar for males and females (table 2.3); however, the differential in child mortality between the world’s richest and poorest populations is stark, with a newborn in Sub-Saharan Africa


Table 2.3 Continued Female Expectation % of deaths Probability of dying per 1,000 Deaths Crude death of life at (millions) rate per 1,000 Under age 5 Over age 60 Ages 0–5a Ages 15–60 Ages 0–60 Ages 60–80 birth (years) 19.4 22.8

8.9 8.8

29.7 22.5

44.6 48.3

95 86

182 191

270 271

585 554

64.2 64.9

5.5 6.1

7.0 6.8

17.8 11.4

56.2 64.6

53 44

152 127

204 171

577 519

68.8 71.3

2.4 2.7

9.9 10.8

6.4 2.9

77.5 81.5

37 26

125 133

162 159

503 511

72.3 72.8

1.3 1.4

5.7 5.4

20.1 12.5

53.9 61.3

45 32

138 124

182 155

493 434

71.3 73.9

0.8 0.8

6.9 5.5

37.7 23.5

36.1 49.7

76 51

174 144

245 193

593 562

66.1 69.5

6.1 6.5

11.2 9.6

37.0 28.3

33.7 40.2

131 101

243 226

357 317

680 645

57.9 61.5

3.3 5.2

12.9 15.5

54.8 40.9

19.6 18.3

168 166

265 437

403 545

664 680

55.1 48.9

3.6 3.9

8.2 8.2

1.3 0.8

87.3 88.3

9 6

74 65

83 73

346 297

79.7 81.6

23.0 26.7

8.8 8.7

25.2 19.3

51.3 54.1

88 80

161 168

244 244

516 487

66.6 67.3

facing 25 times the risk of death before the age of five than a newborn in a high-income country. Despite the much greater uncertainty in relation to levels of adult mortality compared with those for children, the estimates shown in table 2.3 nonetheless indicate substantially different trends in adult mortality across different regions between 1990 and 2001. For most regions, the risk of death between ages 15 and 60 fell by about 10 to 17 percent over the decade. This was not the case in Europe and Central Asia, where policy shifts, particularly in relation to alcohol, together with broader social change, have largely been responsible for the 15 percent rise in adult male mortality and the 6 percent increase in the risk of death for women. Note that these estimates mask the large cyclical fluctuations in adult mortality in Russia, in particular, that characterized the region’s mortality trends in the 1990s. Table 2.3 also reveals the large increase in adult mortality in Sub-Saharan Africa, which was due primarily to the unfolding of the HIV/AIDS epidemic in southern Africa. Notwithstanding the substantial uncertainty surrounding these estimates, the epidemic appears to have been of proportionately greater consequence for women, with the rise in their risk of death (67 percent) being twice that of males, among whom other causes of death such as violence were more common. If these estimates are correct, then

52.0 percent of African males reaching age 15 and 44.0 percent of females will die before their 60th birthdays, compared with, for instance, 6.5 percent of women in highincome countries, who despite their already low risk enjoyed a further 11 percent decline in mortality during the 1990s. These reversals in mortality decline have effectively negated gains elsewhere, with the result that the global risk of adult death has remained essentially unchanged for males, and may even have risen slightly for females. Taken together, the probability of death up to the age of five and between the ages of 15 and 60 are a better reflection of the risk of premature death than either alone, although both have particular public health implications. One might argue that health policy should be equally concerned with keeping adults alive into old age as it is with keeping children alive into adulthood. A convenient metric in this regard is the risk of death between birth and age 60 (table 2.3). In highincome countries, given 2001 mortality rates, only about 7 percent of females and 13 percent of males would be dead by age 60, compared with 55 percent of females and 62 percent of males in Sub-Saharan Africa. Significant improvements in this summary measure of premature death can be observed in all regions except Europe and Central Asia and Sub-Saharan Africa. Worldwide, the index appears to have improved slightly for males and not at all for females. Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 | 27


Other features of global mortality summarized in table 2.3 are worth highlighting. First is the impressive evidence of a continued decline in mortality among older age groups in high-income countries that began in the early 1970s. The risk of a 60-year-old dying before age 80 declined by about 15 percent for both men and women in highincome countries so that at 2001 rates, less than 30 percent of women who reach age 60 will be dead by age 80, as will less than 50 percent of men. Second, crude death rates in East Asia and the Pacific, Latin America and the Caribbean, and the Middle East and North Africa are lower than in high-income countries, reflecting the impact of the older age structure of rich countries, and are particularly low in Latin America and the Caribbean. Third, the proportion of deaths that occur below age five, while declining in all regions, varies enormously across them, from just over 1 percent in high-income countries to just over 40 percent in Sub-Saharan Africa. In some low- and middle-income regions, particularly East Asia and the Pacific, Europe and Central Asia, and Latin America and the Caribbean, the proportion is well below 20 percent. The net effect of these changes in age-specific mortality since 1990 has been to increase global life expectancy at birth by 0.7 years for females and by about twice this for males: a modest scorecard.

TRENDS IN CAUSES OF CHILD DEATH, 1990–2001 The estimation of cause of death patterns for world regions will, for the foreseeable future, be substantially uncertain given the paucity of data on medically certified deaths in many low- and middle-income countries (Mathers and others 2005; Sibai 2004). Verbal autopsies, that is, structured interviews with relatives of the deceased about symptoms experienced prior to death, will not yield the diagnostic accuracy achievable with medical certification based on good clinical case histories and medical records. This is not to deny that verbal autopsies can meet broad policy needs for information about causes of death, particularly with clinical input into the coding of interviewees’ responses, but their reliability for diagnosing leading causes of child death is questionable (Snow and others 1992). Thus, estimates of child mortality derived from proportionate mortality models that are based largely on verbal autopsies need to be viewed with caution (Lopez 2003; Morris, Black, and Tomaskovic 2003). Yet, despite these concerns about the quality of cause of death data, investigators can more confidently assess the

comparative magnitude of causes of death for children than for adults. The fact that the demographic “envelope” of child deaths is reasonably well understood in all regions limits excessive claims about deaths due to individual causes, a constraint that is not a feature of adult mortality given the relative ignorance of age-specific death rates in many countries. In addition, the need for data on cause-specific outcomes to assess and monitor the impact of various child survival programs in recent decades has led to a reasonably substantial epidemiological literature that might permit cause-specific estimation, but under an unacceptably large number of assumptions (Black, Morris, and Bryce 2003). A critical feature of any estimation exercise is a rigorous assessment of data sets for biases, study methods, and generalizability of results. Investigators have undertaken a number of efforts to estimate the causes of child mortality over the past decade or so (Bryce and others 2005; Lopez 1993; Morris, Black, and Tomaskovic 2004; Williams and others 2002), but undoubtedly the most comprehensive was the study by Murray and Lopez (1996) and its 2001 revision (chapter 3 in this volume). Both the latter Global Burden of Disease (GBD) studies apply methods to force epidemiological consistency according to the evidence available for each region, and inevitably the constraint of demography has meant that the GBD estimates of cause-specific mortality will differ from those developed largely independently of other causes. That is, the GBD estimates of specific causes of death are constrained to sum to the number of deaths derived from demographic analyses, whereas cause-specific estimates that are derived in the absence of such demographic constraints are unbounded and tend to be inclusive at the margin rather than exclusive. Differences in regional estimates between 1990 and 2001 arise in part because the countries included in the regions differed and, more important, because of better information for more recent periods. Yet, despite improved information, the true level of child death rates from major causes such as malaria and perinatal conditions (birth trauma, birth asphyxia, sepsis, and prematurity) remains largely unknown. Notwithstanding methodological differences and uncertainties, deriving implied estimates of trends in the leading causes of child mortality is possible by comparing results from the two GBD studies, and these are summarized in table 2.4. These estimates have been simply obtained as the difference between the regional estimates for 1990 and 2001, but the implied pattern of change is interesting nonetheless. The conversion of the 1990 regional GBD estimates (Murray and Lopez 1996) to the regions used for the 2001 assessment


Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 | 29


647 5.4 5

588 4.9 5

Malaria Deaths (thousands) % of childhood deaths Probability of dying before age 5 per 1,000 live births

2,362 19.7 19

Diarrheal diseases Deaths (thousands) % of childhood deaths Probability of dying before age 5 per 1,000 live births

Injuries Deaths (thousands) % of childhood deaths Probability of dying before age 5 per 1,000 live births

421 3.5 3

Congenital anomalies Deaths (thousands) % of childhood deaths Probability of dying before age 5 per 1,000 live births

62 0.5 0

2,521 21.0 20

Acute respiratory infections Deaths (thousands) % of childhood deaths Probability of dying before age 5 per 1,000 live births

HIV/AIDS Deaths (thousands) % of childhood deaths Probability of dying before age 5 per 1,000 live births

1990

Disease and indicator

1,086 10.3 9

302 2.9 2

340 3.2 3

1,599 15.2 13

421 4.0 3

1,943 18.4 16

2001


7 0.3 0

206 9.9 5

— 0.0 0

274 13.2 7

118 5.7 3

492 23.8 13

1990

27 1.9 1

82 5.8 2

5 0.4 0

201 14.3 6

115 8.2 4

197 14.0 6

2001


0 0.1 0

25 7.0 3

— 0.0 0

61 17.4 7

25 7.1 3

68 19.5 8

1990

0 0.0 0

11 6.6 2

0 0.2 0

12 6.9 2

24 13.5 4

36 20.6 6

2001


Table 2.4 Mortality in Children Under Five by Cause, 1990 and 2001

2 0.3 0

28 4.7 2

2 0.3 0

108 18.3 9

30 5.1 3

83 14.1 7

1990

1 0.3 0

19 4.6 2

6 1.4 1

46 11.4 4

41 10.1 4

44 10.9 4

2001

1 0.1 0

32 4.8 4

0 0.0 0

144 21.6 17

22 3.3 3

138 20.6 16

1990

17 3.9 2

24 5.6 3

1 0.1 0

66 15.3 8

41 9.5 5

76 17.7 9

2001

Latin America Middle East and and the Caribbean North Africa

9 0.2 0

188 4.2 5

— 0.0 0

991 22.4 28

186 4.2 5

1,027 23.2 29

1990

57 1.6 2

79 2.2 2

14 0.4 0

631 17.5 17

142 3.9 4

833 23.1 22

2001

South Asia

570 14.6 26

169 4.3 8

60 1.5 3

784 20.1 36

41 1.0 2

713 18.3 33

1990

984 21.8 38

87 1.9 3

313 7.0 12

643 14.3 25

58 1.3 2

757 16.8 29

2001

Sub-Saharan Africa

0 0.2 0

9 7.8 1

0 0.0 0

11 9.9 1

19 16.3 2

13 11.1 1

1990

588 4.8 4

656 5.4 5

62 0.5 0

2,374 19.6 17

440 3.6 3

2,533 20.9 19

1990

World

1,086 10.2 8

309 2.9 2

340 3.2 3

1,600 15.1 12

439 4.1 3

1,944 18.3 15

2001


0 0.1 0

7 9.8 1

0 0.1 0

0 0.6 0

18 24.6 2

2 2.3 0

2001


30 | Global Burden of Disease and Risk Factors | Alan D. Lopez, Stephen Begg, and Ed Bos


2,261 18.8 18

2,288 19.0 18

12,019 100.0 97

Perinatal conditions Deaths (thousands) % of childhood deaths Probability of dying before age 5 per 1,000 live births

Other causes Deaths (thousands) % of childhood deaths Probability of dying before age 5 per 1,000 live births

Total Deaths (thousands) % of childhood deaths Probability of dying before age 5 per 1,000 live births 10,532 100.0 86

1,792 17.0 15

2,492 23.7 20

556 5.3 5

2001

2,072 100.0 54

420 20.3 11

480 23.2 12

75 3.6 2

1990

1,407 100.0 43

228 16.2 7

506 36.0 15

45 3.2 1

2001


352 100.0 41

77 21.9 9

83 23.6 10

12 3.5 1

1990

174 100.0 29

28 16.3 5

57 32.9 10

5 2.9 1

2001


588 100.0 51

137 23.2 12

162 27.6 14

38 6.5 3

1990

407 100.0 35

85 21.0 7

164 40.3 14

— 0.0 0

2001

668 100.0 80

159 23.8 19

141 21.2 17

30 4.5 4

1990

429 100.0 53

90 20.9 11

106 24.7 13

10 2.3 1

2001

Latin America Middle East and and the Caribbean North Africa

4,434 100.0 127

888 20.0 25

906 20.4 26

239 5.4 7

1990

3,612 100.0 97

625 17.3 17

1,086 30.1 29

145 4.0 4

2001

South Asia

Sources: Estimates for 1990 are based on Murray and Lopez 1996, weighted to World Bank regions using population under five years old. Estimates for 2001 are from chapter 3 in this volume. Note: — ⫽ not available or not applicable. Estimates of child mortality are rounded to the nearest whole number.

869 7.2 7

1990


Measles Deaths (thousands) % of childhood deaths Probability of dying before age 5 per 1,000 live births

Disease and indicator

Table 2.4 Continued

3,904 100.0 180

607 15.5 28

487 12.5 22

474 12.2 22

1990

4,504 100.0 172

737 16.4 28

573 12.7 22

351 7.8 13

2001

Sub-Saharan Africa

115 100.0 10

22 19.1 2

38 33.0 3

3 2.5 0

1990

73 100.0 7

13 17.9 1

32 44.5 3

0 0.1 0

2001


12,134 100.0 89

2,309 19.0 17

2,298 18.9 17

872 7.2 6

1990

1,805 17.0 14

2,524 23.8 19

556 5.2 4

200

10,605 100.0 80

World

Acute Respiratory Infections

Congenital Anomalies

Diarrheal Diseases

HIV/AIDS

Injuries

Malaria

Measles

Perinatal Conditions

Other


Low- and Middle-income countries

Sub-Saharan Africa

World



Sub-Saharan Africa

World



Sub-Saharan Africa

World 0

20 Risk of death

40

0

20 Risk of death 1990

40

0

20 Risk of death

40

2001

Sources: Estimates for 1990 are from Murray and Lopez 1996; estimates for 2001 are from chapter 3 in this volume.

Figure 2.4 Change in Risk of Death for Children Under Five by Cause (probability of mortality per 1,000 live births), 1990–2001

was done simply by population weighting,a very approximate procedure. By contrast, the 2001 estimates were prepared as regional aggregates of country-specific estimates (see chapter 3,) and this has undoubtedly affected comparisons further. Global mortality from malaria increased by 0.5 million during the 1990s, with 80 percent of the deaths occurring in Sub-Saharan Africa. The proportion of all child deaths due to malaria doubled from 5 percent in 1990 to 10 percent in 2001 worldwide and increased from 15 percent in 1990 to

22 percent in 2001 in Sub-Saharan Africa. The only other causes that appear to have increased are HIV/AIDS in Africa, a reasonable conclusion given female prevalence levels, and the category of perinatal conditions, which are strongly dependent on the quality and availability of prenatal services. Causes that appear to have declined substantially include acute respiratory infections (2.5 million to 1.9 million deaths or 15 percent of all child deaths), diarrheal diseases (2.4 million to 1.6 million deaths or 13 percent of child deaths), measles (0.8 million to 0.5 million Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 | 31


deaths or 5 percent of child deaths), and injuries (0.6 million to 0.3 million deaths or 2 percent of child deaths). The implied pattern of change in the risk of child death varies across regions for all major conditions listed in table 2.4, particularly with regard to the magnitude of change. This can be seen more clearly from figure 2.4, which summarizes these trends for broad regional aggregates and for Sub-Saharan Africa. In general, the absolute change in risk of death has been greater in Sub-Saharan Africa than elsewhere, both for causes with increased risk (HIV/AIDS, malaria) and where risk has declined (diarrheal diseases, measles). While these changes may be in accord with what is known about regional health development and economic growth, they need to be confirmed. Some of the suggested changes warrant further investigation, for example, death rates from perinatal causes appear to have risen in both East Asia and the Pacific and South Asia and remained unchanged in Latin America and the Caribbean, which may or may not be in line with what is known about developments in prenatal care and safe motherhood initiatives. Similarly, measles appears to have disappeared as a cause of child death in Latin America and the Caribbean. The risk of child death from congenital anomalies appears to have risen in both Latin America and the Caribbean and the Middle East and North Africa, but why is unclear. Similarly, the large suggested declines in the risk of child deaths because of injury in South Asia and Sub-Saharan Africa appear unlikely and may largely reflect better data and methods for measuring injury deaths.

DISCUSSION Understanding the demographic context of health status assessments such as the GBD studies is essential if policy directions and program delivery are to be focused appropriately. Knowledge about the size and composition of populations and how they are changing is critical for health planning and priority setting. Demographers and demographic institutions such as the UN Population Division have applied the demographic ethos that available data permit making estimates and reasonable predictions of population change provided the data are interpreted and used appropriately. Such estimates and projections have been useful for social and economic development for countries, regions, and the world as a whole. They suggest that health and social policies

need to pay increasing attention to the key demographic trends observed in the 1990s, namely, rapidly falling fertility virtually everywhere, rapidly aging populations, and unprecedented reversals of the long-term path of mortality decline in Europe and Central Asia and Sub-Saharan Africa The causes of these so-called mortality shocks are reasonably well understood, but the lessons for health policy cannot be overemphasized. Globally, the mortality reversals caused by inadequate preventive programs, social disintegration, and failure to understand the gravity of rapidly expanding epidemics have meant that the 1990s were a lost decade for further improvements in adults’ survival prospects. Thus, despite the substantial and continued declines in mortality from major vascular diseases in high-income countries, worldwide the risk of death in adulthood did not change in the 1990s, although some gains in reducing mortality in the elderly were achieved, particularly in rich countries. The trend in child mortality during the 1990s was only marginally more satisfactory. While most regions achieved significant gains in child survival, progress was modest in Sub-Saharan Africa, and as a result, the global decline in child mortality slowed to an annual average of about 1 percent over the decade. Decades of intensive data collection on child mortality in many low- and middle-income countries by dedicated international survey programs and the efforts of agencies such as the United Nations Children’s Fund mean that trends in overall child mortality, and the numbers of child deaths they imply, can be established with reasonable certainty. The trends in the leading causes of child mortality are, however, much more difficult to establish (Rudan and others 2005). Much debate in the literature has centered on whether the risk of malaria infection in Sub-Saharan Africa increased in the 1990s, and thus whether the massive increase in malaria deaths suggested in table 2.4 is real (Korenromp and others 2003; Snow, Trape, and Marsh 2001; Trape 2001). Most malaria mortality in Sub-Saharan Africa is diagnosed via verbal autopsies, which, where studied, have been shown to be a poor diagnostic tool for malaria (Snow and others 1992). While some evidence from demographic surveillance sites using verbal autopsies indicates that malaria mortality rates have increased in eastern and southern Africa (summarized in Korenromp and others 2003) and that the spread of chloroquine resistance may have been the primary reason (Snow and others 1999; Trape 2001), whether this is sufficiently widespread to account for the implied rise of almost 50 percent in malaria mortality rates over the decade (figure 2.4) is unclear. Other factors, such as


a general deterioration in clinical care and a decline in the efficacy of chloroquine therapy, may also have contributed (Snow and others 2001), but how much of the rise is real and how much is due to different interpretations of available data in 1990 and 2001 remains unknown. Similarly, the substantial implied declines in the risk of child death from acute respiratory infections and diarrheal diseases need to be understood in the context of likely contributing factors. One of these is no doubt malnutrition, because it is a major risk factor for both conditions (Black, Morris, and Bryce 2003; Pelletier, Frongillo, and Habicht 1993; Rice and others 2000; Tupasi and others 1988). In the 1990s, malnutrition, as assessed by childhood stunting, declined in all regions except Sub-Saharan Africa (de Onis, Frongillo, and Blossner 2000), which is consistent with the modest declines in mortality from respiratory infections among children in the region. Increased use of oral rehydration therapy and improved access to safe water and sanitation in the 1990s would suggest some decline in mortality from diarrheal disease, but whether they were sufficient to account for the one-third decline in risk, including in Sub-Saharan Africa, is also unclear (Victora and others 2000). The large absolute decline in childhood diarrheal deaths from 2.4 million in 1990 to 1.6 million in 2001 is surprising, and suggests that the 2001 estimate may be an undercount. Some other studies (Morris, Black, and Tomaskovic 2003; UNICEF 2003) suggest a figure about 20 percent higher for 2001. Malnutrition is also a leading risk factor for measles mortality, and hence changes in the proportion and distribution of underweight children should be broadly consistent with mortality trends from the disease (Fishman and others 2004). Effective vaccination coverage is a primary determinant of mortality from measles, and further increases in vaccination coverage in the 1990s should have led to lower mortality. This is certainly apparent from the estimates reported here, but the extent of that decline is subject to some controversy, depending on the methods used to estimate current mortality. Using proportionate mortality models largely derived from verbal autopsy data, Morris, Black, and Tomaskovic (2003) estimate that measles deaths account for only about 2.2 percent of all child deaths in South Asia and Sub-Saharan Africa, significantly less than Stein and others’ (2003) estimates of 4 to 8 percent for the same period using data on vaccination coverage and assumptions about efficacy and case fatality rates. This implies a global estimate of measles deaths that is about half the 556,000 estimated for 2001 in chapter 3, and thus a

much faster rate of decline in the measles mortality rate during the 1990s than the one-third reduction suggested by the GBD estimates. The truth may well lie somewhere in between and requires urgent resolution if measles control efforts are to be appropriately guided. While the confirmation of mother to child transmission of HIV infection implies that mortality from the disease will increase with increasing prevalence among women, the extent of the impact on child mortality continues to be debated. The GBD estimates suggest that HIV/AIDS led to an increase in child mortality of, on average, 10 per 1,000 in Sub-Saharan Africa between 1990 and 2001. Recent research suggesting a potential overestimation of HIV/AIDS mortality may lead to lower estimates of child mortality from the disease, which may attenuate this trend estimate. What is clear is that HIV/AIDS has not been the only cause of recent reversals in the decline in child mortality in SubSaharan Africa (Walker, Schwartzlander, and Bryce 2002) and that its effect on child survival in the 1990s may not have been as great as initially thought (Adetunji 2000). Perinatal conditions that cover specific risks for the newborn, primarily birth asphyxia, birth trauma, prematurity, and sepsis, are undoubtedly a major cause of death among children, but until recently did not receive sufficient attention in the epidemiological literature, perhaps because interventions are largely related to the delivery of prenatal care and the intrapartum period. Virtually all children born alive who die from these causes do so in the first few days of life (Lawn, Cousens, and Zupan 2005). Hence some constraint on the probable demographic envelope of mortality from these causes can be derived by estimating the neonatal mortality rate in different regions as was done for the 1990 GBD study (Murray and Lopez 1996) and repeated for the 2001 estimates (chapter 3 in this volume). This has undoubtedly removed a major source of uncertainty about mortality from these conditions, but substantial uncertainty remains about their relative importance as a cause of neonatal death when considering other conditions such as tetanus (classified under infectious diseases in the 1990 and 2001 GBD studies), neonatal diarrhea, congenital anomalies, and injuries. As a result, the global estimate of deaths from perinatal causes is influenced by the availability and reliability of data on the causes of neonatal mortality, particularly in countries with the largest number of neonatal deaths: China, India, Nigeria, and Pakistan account for half of all neonatal deaths, and with the possible exception of China, none has reliable, nationally representative systems for cause of death reporting. Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 | 33


Given this context, judging whether mortality from perinatal causes indeed rose by 10 percent during the 1990s as suggested by figure 2.4 is difficult. If improvements in survival from these causes are largely related to better and more comprehensive service provision for pregnant women, which in turn is dependent on substantial infrastructure investments to improve health services, then modest declines in risk should be expected given economic growth in the 1990s. This was indeed the case in all regions except East Asia and the Pacific and South Asia, where the risk appears to have risen. Without compelling evidence that health service provision deteriorated in these regions during the 1990s, this increase in the risk of death from perinatal causes is probably a statistical artifact of data availability and different interpretation criteria used for 1990 and 2001. Privatization of the rural health care system in China during the 1990s may have led to a deterioration of prenatal care, but this remains to be established. Finally, note the 50 percent reduction in the risk of child death from injuries implied by the GBD studies, which is primarily due to large reductions suggested for East Asia and the Pacific, South Asia, and Sub-Saharan Africa. Some decline in injury mortality is to be expected with economic and social development and the introduction of injury control programs and legislation, but the massive declines estimated for these regions may well be attributable to methodological differences in estimation procedures between the two dates (see chapter 3 in this volume). The descriptive epidemiology of injuries remains a major neglected area of the information base for policy to improve child health. For example, Rudan and others’ (2005) review of information gaps in relation to assessing the burden of illness in children fails to even mention childhood injuries, even though burns, falls, and drownings are likely to be significant causes of child death (Etebu and Ekere 2004; Gali, Madziga, and Naaya 2004; Istre and others 2003; Mock and others 2004; Shen, Sanno-Duanda, and Bickler 2003). Thus, establishing the extent of changes in these risks, whose levels are based on essentially anecdotal evidence, remains difficult. Evidence of major declines in injury death rates therefore need to be viewed with great caution and may well be largely artifactual. The global public health community’s increasing interest in gaining a better understanding of the successes of, and challenges facing programs and policies to improve child survival has led to alternative assessments of the leading causes of child death. With the substantial data gaps and data quality issues pertaining to the estimation of child

mortality, varying estimates of the leading causes of child death because of different estimation principles and variable interpretation of the data are hardly surprising. Scientific debate is to be encouraged insofar as it will guide data collection strategies to reduce unacceptable uncertainty, but the existence of alternative estimates of child mortality for 2001 makes the interpretation of changes over the past decade even more complex. The World Health Organization’s Child Health Epidemiology Reference Group (CHERG), for example, working within the same total number of child deaths (10.5 million), has recently published quite different estimates of the causes of child mortality (Bryce and others 2005). According to CHERG’s estimates, in 2001 perinatal causes were responsible for 3.9 million child deaths, that is, 37 percent of all child deaths and 55 percent more than the GBD figure (see chapter 3). Conversely, CHERG estimated lower levels of malaria mortality in children (853,000 deaths compared with 1,110,000 in the GBD study) and much lower measles mortality (395,000 versus 562,000 deaths). CHERG’s implied rise in perinatal causes of child death is even more extreme than that suggested by the GBD study, whereas the rise in malaria deaths is less extreme. CHERG’s estimates also imply far greater success of vaccination programs to reduce measles mortality than does the GBD figure. Note also that CHERG, which does not include any experts in noncommunicable diseases, including congenital anomalies, estimated only about half the number of noncommunicable disease deaths among children than estimated in the GBD study. Public policy to accelerate the decline in child mortality would be well served through greater scientific collaboration to better understand the descriptive epidemiology of the leading causes of child death over the past decade or so and how this has changed. Notwithstanding the legitimate role of scientific discourse and the issue of comorbidity among the leading causes of child death, particularly diarrhea and pneumonia (Fenn, Morris, and Black 2005), the lack of clarity about the extent of the decline (or rise) in child deaths from specific causes or groups of causes, particularly those that have been the focus of massive programmatic efforts, hinders policy making. Having said this, it should also be borne in mind that for the GBD estimates at least, which have followed a consistent methodology and estimation framework, uncertainty in the rate of change of mortality for any given condition may well be less than period uncertainty around estimates for 1990 and 2001 because of the high likelihood of correlation of uncertainty of estimates for the two periods.


CONCLUSIONS Priority setting in health, as in other sectors concerned with social development, will increasingly depend on the availability of reliable, timely, representative, and relevant information on the comparative importance of diseases, injuries, and risk factors for the health of populations and how these are changing. Population scientists, particularly epidemiologists, have provided important insights into the descriptive epidemiology of some segments of some populations and on the causes of disease and injuries in those populations. Administrative requirements have resulted in most countries undertaking routine data collection efforts, but these are highly variable in terms of both quality and of what is being measured. As a result, we have substantial partial data collections on many aspects of population health status, but no country has complete data on all aspects of health relevant for policy, and in many parts of the world, health status is largely unknown. Efforts to bring these fragmentary pieces of data together to develop comprehensive estimates of the disease and injury burden and its causes are likely to be extremely valuable for policy making, particularly if the analytical methods and frameworks employed are understandable, transparent, and rigorously argued. Demographers were the first to attempt global, regional, and national efforts to estimate population size, structure, and determinants of change in a coherent fashion, and despite scientific differences of opinion about some of the methods and assumptions, the results have been enormously influential for guiding social development policies and programs. The two GBD studies for 1990 (Murray and Lopez 1996) and 2001 (chapter 3 in this volume) attempted something similar for mortality and the burden of disease. Scholars and global health development agencies alike have repeatedly emphasized the interrelationship between demographic change and the health conditions of populations. This chapter has summarized the key quantitative findings about global demography and epidemiology that are relevant for disease control and public health development, leading to the following three broad conclusions: • Despite significant investments in disease control in lowand middle-income countries over the past 50 years and the considerable success in reducing mortality, commensurate investments have not been made in the health intelligence base needed to monitor and evaluate changes in population health. As a result, uncertainty about the

causes of child mortality in many countries and how these have changed over the last decade or so because of intervention programs is considerable. Moreover, data collection pertaining to health conditions among adults has been almost totally neglected, with the result that virtually nothing is known reliably about levels, let alone causes, of adult death in much of the developing world. HIV/AIDS has highlighted this neglect, but continued ignorance of the leading causes of adult mortality will continue to hinder policy action to reduce the large, avoidable causes of adult mortality that can be addressed through targeted prevention and treatment programs. • Demographic change is often poorly understood, and thus potentially underappreciated in relation to health and social development policies. The evidence summarized in this chapter suggests that population aging is likely to become rapidly more pronounced in low- and middle-income countries than is currently appreciated, in part because swift fertility declines are under way in much of the developing world. The little evidence that is available about mortality trends among adults in developing countries suggests different paths of mortality change among regions, but indicates that globally, little progress was achieved in the 1990s. At older ages, the impressive and widely unappreciated declines in mortality that began in the high-income countries in the 1970s continued through the 1990s and show little sign of deceleration. In large part, these declines reflect progress in the control of major vascular diseases and point to continued steady gains in life expectancy in high-income countries. • Despite at least two decades of intensive efforts by the global public health community to implement intervention programs and reorganize health services to reduce child mortality, knowledge about the major causes of death among children is insufficiently precise to resolve uncertainties about global progress with specific disease control strategies, and thus to be of maximum benefit for global policy action to reduce the more than 10 million child deaths that still occur each year. Results from the two GBD studies, while suggesting trends that are broadly consistent with public health knowledge, are equivocal about trends in specific conditions in some regions. Policy action to rapidly and substantially reduce this enormous burden of premature mortality will be better served if policy makers can be more appropriately informed about the causes of child death, including hitherto neglected areas such as perinatal conditions and injuries. Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 | 35




43.8 64.1 65.4 — — 42.7 — — 68.9 61.9 — 74.1 72.4 56.4 66.6 71.7 53.8 69.2 66.2 72.7 64.4 49.0 — 53.8 55.3 68.3 62.4 61.9 — 70.0 68.2 47.1 49.2 55.7 54.1

World Bank region

South Asia 13,799 Europe and Central Asia 3,289 Middle East and North Africa 25,017 East Asia and Pacific — High-income countries — Sub-Saharan Africa 9,340 Not included — Latin America and the Caribbean — Latin America and the Caribbean 32,527 Europe and Central Asia 3,545 High-income countries — High-income countries 16,888 High-income countries 7,729 Europe and Central Asia 7,192 High-income countries 255 High-income countries 490 South Asia 109,403 Latin America and the Caribbean 257 Europe and Central Asia 10,266 High-income countries 9,967 Latin America and the Caribbean 186 Sub-Saharan Africa 4,650 High-income countries — South Asia 1,696 Latin America and the Caribbean 6,669 Europe and Central Asia 4,308

Sub-Saharan Africa 1,354 Latin America and the Caribbean 148,809 Not included — High-income countries 257 Europe and Central Asia 8,718 Sub-Saharan Africa 8,921 Sub-Saharan Africa 5,609 East Asia and Pacific 9,744 Sub-Saharan Africa 11,661

Country/Territory

Afghanistan Albania Algeria American Samoa Andorra Angola Anguilla Antigua and Barbuda Argentina Armenia Aruba Australia Austria Azerbaijan Bahamas, The Bahrain Bangladesh Barbados Belarus Belgium Belize Benin Bermuda Bhutan Bolivia Bosnia and Herzegovina Botswana Brazil British Virgin Islands Brunei Darussalam Bulgaria Burkina Faso Burundi Cambodia Cameroon 69.0 69.0 — 77.7 74.9 52.9 55.4 62.4 60.2

47.8 71.2 67.8 — — 49.0 — — 75.8 69.0 — 80.4 79.0 63.6 74.2 73.6 58.1 76.4 75.8 79.5 69.5 55.5 — 59.5 61.1 75.3 64 68 — 18 20 224 198 126 142

267 52 70 — — 280 — — 32 68 — 10 10 119 35 25 145 21 17 11 50 201 — 145 129 26 52 51 — 11 15 196 169 103 123

253 38 68 — — 239 — — 26 52 — 8 9 93 23 26 143 14 12 8 48 168 — 129 114 18

Under age 5

271 276 — 182 216 398 384 334 346

421 253 188 — — 427 — — 196 276 — 124 153 327 224 124 348 193 282 139 250 385 — 349 336 204 158 158 — 85 97 267 252 207 222

295 140 153 — — 288 — — 103 158 — 66 74 199 115 104 236 96 107 75 154 251 — 227 216 105

Ages 15–59

Probability of dying per 1,000 Life expectancy at birth (years)

2001 Probability of dying per 1,000

Annual change in probability of dying under age 5, 1990–2001 (%)

1,750 174,029 20 342 8,033 12,259 6,412 13,478 15,429

22,083 3,122 30,746 59 68 12,768 11 72 37,529 3,088 92 19,352 8,106 8,226 307 693 140,880 268 9,986 10,273 245 6,387 80 2,125 8,481 4,067 41.5 65.5 68.0 74.7 68.6 40.6 39.0 52.3 48.0

41.4 67.0 67.4 59.9 76.6 37.5 68.0 68.9 70.9 67.0 66.9 77.6 76.1 62.5 68.8 72.4 62.3 70.5 63.0 74.9 67.2 50.4 68.0 60.0 61.6 69.1 42.2 72.1 72.8 77.4 75.2 42.7 42.7 57.5 50.0

43.3 73.4 71.0 36.4 83.7 42.3 72.8 73.7 78.5 72.9 72.8 83.0 82.2 68.2 75.2 74.3 62.2 77.7 74.5 81.4 72.2 52.8 72.8 62.1 64.4 76.3 99 44 34 15 18 232 192 147 160

257 28 55 86 5 277 34 22 20 38 36 7 6 77 14 14 76 18 14 6 45 165 34 95 80 21 97 36 27 13 15 217 180 123 155

255 23 44 79 4 246 27 18 17 34 28 5 5 68 11 10 78 17 11 5 34 157 27 94 75 16

762 247 215 115 221 596 680 392 498

510 171 172 295 113 605 216 197 177 208 230 94 121 247 249 112 251 187 361 128 191 415 216 275 261 193

718 135 116 87 97 520 565 290 434

419 97 129 229 45 475 116 128 91 99 116 54 61 129 152 82 258 103 129 67 124 351 116 228 211 91

4.0 ⫺4.0 — ⫺1.9 ⫺1.2 0.3 ⫺0.3 1.4 1.1

⫺0.3 ⫺5.6 ⫺2.3 — — ⫺0.1 — — ⫺4.2 ⫺5.3 — ⫺4.2 ⫺5.1 ⫺3.9 ⫺8.5 ⫺5.6 ⫺5.9 ⫺1.6 ⫺1.5 ⫺5.2 ⫺0.9 ⫺1.8 — ⫺3.8 ⫺4.4 ⫺2.0

5.7 ⫺3.3 — 1.6 ⫺0.1 0.9 0.5 1.6 2.1

0.1 ⫺4.4 ⫺3.9 — — 0.2 — — ⫺4.0 ⫺3.8 — ⫺4.1 ⫺5.6 ⫺2.8 ⫺6.4 ⫺8.6 ⫺5.5 1.7 ⫺1.0 ⫺4.5 ⫺3.2 ⫺0.6 — ⫺2.9 ⫺3.8 ⫺1.3

Under age 5 Ages 15–59 Population Population (thousands) Males Females Males Females Males Females (thousands) Males Females Males Females Males Females Males Females

Life expectancy at birth (years)

1990

Annex 2A Key Demographic Indicators, by Country/Territory, 1990 and 2001



Comoros Congo, Democratic Republic of Congo, Republic of Cook Islands Costa Rica Côte d’Ivoire Croatia Cuba Cyprus Czech Republic Denmark Djibouti Dominica Dominican Republic Ecuador Egypt, Arab Republic of El Salvador Equatorial Guinea Eritrea Estonia Ethiopia Faeroe Islands Falkland Islands Fiji Finland France French Guiana French Polynesia Gabon

China Colombia

Canada Cape Verde Cayman Islands Central African Republic Chad Channel Islands Chile 5,822 142 13,100

527 37,370 2,494 — 3,076 12,505 4,842 10,628 681 10,306 5,140 528 — 7,058 10,264 55,768 5,110 354 3,103 1,584 48,856 — — 724 4,986 56,735 — 195 953

Sub-Saharan Africa High-income countries Latin America and the Caribbean East Asia and Pacific Latin America and the Caribbean Sub-Saharan Africa Sub-Saharan Africa

Sub-Saharan Africa Not included Latin America and the Caribbean Sub-Saharan Africa Europe and Central Asia Latin America and the Caribbean High-income countries Europe and Central Asia High-income countries Middle East and North Africa Latin America and the Caribbean Latin America and the Caribbean Latin America and the Caribbean Middle East and North Africa

Latin America and the Caribbean Sub-Saharan Africa Sub-Saharan Africa Europe and Central Asia Sub-Saharan Africa High-income countries Not included East Asia and Pacific High-income countries High-income countries Not included High-income countries Sub-Saharan Africa

1,161,382 34,970

27,701 349 — 2,943

High-income countries Sub-Saharan Africa High-income countries Sub-Saharan Africa

62.2 47.3 52.9 64.8 47.5 — — 67.2 70.9 73.3 — — 58.0

55.9 — 73.0 51.7 68.6 72.8 71.7 68.0 72.1 46.4 — 61.2 62.5 57.8

55.0 47.4

66.9 65.8

47.5 — 69.8

74.0 61.6 — 49.0

68.7 53.5 58.6 74.9 53.6 — — 72.6 78.9 81.7 — — 64.1

63.2 — 77.7 58.0 76.3 76.7 77.3 75.5 77.9 49.8 — 68.5 69.2 62.4

61.9 53.6

69.6 72.4

53.7 — 76.6

80.7 69.4 — 56.5

66 222 156 18 219 — — 32 7 10 — — 103

123 — 19 169 14 15 12 14 10 188 — 74 63 109

132 221

38 40

218 — 21

9 71 — 200

54 190 138 14 189 — — 30 7 8 — — 89

96 — 15 144 10 11 12 10 8 161 — 55 50 99

107 189

46 31

187 — 17

7 49 — 159

273 397 356 298 395 — — 217 183 162 — — 313

331 — 129 365 223 155 161 220 152 487 — 283 270 307

339 397

190 234

395 — 191

132 279 — 385

160 263 232 107 263 — — 128 70 67 — — 196

202 — 79 237 89 111 88 95 99 417 — 162 156 215

210 263

145 130

262 — 97

71 155 — 246

6,313 468 3,847 1,353 67,266 46 3 822 5,188 59,564 169 237 1,283

3,542 18 4,013 16,098 4,445 11,238 789 10,257 5,338 681 78 8,485 12,616 69,124

726 49,785

1,292,586 42,826

8,103 145 15,419

31,025 445 38 3,770

66.2 51.8 42.9 65.1 46.2 75.5 68.0 64.4 74.5 75.7 68.1 59.8 57.2

52.2 68.9 74.4 43.5 70.9 75.2 75.0 72.1 74.7 49.5 71.1 64.8 67.5 65.0

60.9 41.1

69.5 67.5

45.7 75.5 73.1

77.0 66.4 68.0 42.6

72.6 54.7 57.3 76.7 49.5 81.6 72.7 70.2 81.5 83.7 72.8 36.6 61.3

54.5 74.1 79.3 48.1 78.5 80.0 78.8 79.0 79.6 51.9 75.7 71.4 73.1 68.7

64.5 46.1

72.6 76.3

49.2 81.6 79.9

82.5 72.7 72.8 44.1

37 160 118 12 186 6 34 30 5 6 33 88 101

109 23 12 192 9 9 8 5 6 157 13 38 36 42

84 222

32 27

203 6 17

6 44 34 187

34 147 103 8 169 5 27 27 3 5 27 81 80

101 19 10 143 8 7 8 4 5 144 14 32 32 42

75 198

42 19

181 5 14

5 32 27 173

409 112 75 498 73 90 53 74 77 400 121 151 135 158

210 449

104 102

401 60 68

59 121 116 556

⫺3.4 ⫺4.0 — 0.8 ⫺0.3 — ⫺2.0 ⫺0.7 ⫺4.4 ⫺3.3 0.4 0.5 — ⫺3.6 ⫺0.1 ⫺2.7 ⫺4.3 ⫺3.8 ⫺8.0 ⫺3.5 ⫺1.0 — ⫺5.0 ⫺4.2 ⫺7.8

⫺3.5 ⫺4.3 — ⫺0.6 ⫺0.7 — ⫺1.9 ⫺1.7 ⫺3.7 ⫺4.2 0.0 ⫺1.1 — ⫺3.6 1.2 ⫺4.3 ⫺4.4 ⫺3.8 ⫺8.7 ⫺4.5 ⫺1.7 — ⫺6.0 ⫺5.2 ⫺8.7

265 145 ⫺5.2 ⫺4.0 382 317 ⫺3.0 ⫺2.4 659 334 ⫺2.5 ⫺2.7 319 116 ⫺4.3 ⫺5.5 500 417 ⫺1.5 ⫺1.0 120 60 — — 216 117 — — 287 180 ⫺0.6 ⫺1.2 139 61 ⫺3.6 ⫺6.3 136 60 ⫺5.0 ⫺4.5 216 116 — — 295 230 — — 342 281 ⫺0.2 ⫺1.0 (Continues on the following page.)

460 176 128 567 180 139 105 168 124 455 204 256 219 240

273 583

166 235

485 120 137

98 209 216 607




68.7 73.8 80.7 58.0 64.9 66.5 68.3 77.6 — 78.4 80.4 75.5 82.4 71.0 69.9 64.2 —

61.9 65.1 75.5 57.3 58.3 62.5 63.5 71.9 — 75.0 73.7 69.0 76.1 66.5 63.2 57.6 —

Latin America and the Caribbean 4,868 Europe and Central Asia 10,365 High-income countries 255 South Asia 846,418 East Asia and Pacific 182,117 Middle East and 56,703 North Africa Middle East and North Africa 17,341 High-income countries 3,515 Europe and Central Asia — High-income countries 4,514 High-income countries 56,719 Latin America and the Caribbean 2,369 High-income countries 123,537 Middle East and North Africa 3,254 Europe and Central Asia 16,809 Sub-Saharan Africa 23,585 East Asia and Pacific —

58.1 74.9 78.5 61.0 — 79.5 — — — — 65.8 49.7 49.6 65.7 58.2 —

52.0 67.9 72.0 54.9 — 74.7 — — — — 59.5 45.2 43.3 57.9 52.7 —

Sub-Saharan Africa Europe and Central Asia High-income countries Sub-Saharan Africa Not included High-income countries High-income countries Latin America and the Caribbean Not included High-income countries Latin America and the Caribbean Sub-Saharan Africa Sub-Saharan Africa Latin America and the Caribbean Latin America and the Caribbean Not included

Gambia, The Georgia Germany Ghana Gibraltar Greece Greenland Grenada Guadeloupe Guam Guatemala Guinea Guinea-Bissau Guyana Haiti Holy See (Vatican City) Honduras Hungary Iceland India Indonesia Iran, Islamic Republic of Iraq Ireland Isle of Man Israel Italy Jamaica Japan Jordan Kazakhstan Kenya Kiribati

936 5,460 79,433 15,277 — 10,161 — — — 134 8,749 6,122 1,016 731 6,914 —

World Bank region

79 11 — 13 10 22 7 44 58 106 —

68 19 9 113 100 73

165 28 10 134 — 11 — — — — 89 248 273 104 157 —

71 9 — 11 8 17 6 42 46 87 —

54 15 5 126 82 71

143 20 8 115 — 10 — — — — 75 232 232 76 142 —

215 133 — 107 129 195 109 209 262 316 —

276 305 116 301 310 253

362 210 157 340 — 117 — — — — 299 411 424 314 357 —

138 81 — 71 60 103 53 137 151 194 —

160 133 77 246 189 173

235 109 77 217 — 56 — — — — 183 285 285 184 235 —

Ages 15–59

Probability of dying per 1,000 Under age 5

1990




23,860 3,865 74 6,174 57,521 2,603 127,271 5,183 15,533 31,065 85

6,619 9,968 285 1,033,395 214,356 67,245

1,351 5,224 82,349 20,028 27 10,947 56 81 432 158 11,728 8,242 1,407 762 8,111 1

58.7 74.1 75.5 77.1 76.6 71.0 78.2 68.5 58.4 50.4 61.8

64.4 68.0 78.1 60.0 64.4 65.8

55.3 68.3 75.4 56.3 75.5 75.5 75.5 65.8 68.0 59.9 62.9 50.5 45.4 61.3 48.8 75.5

62.8 79.5 81.6 81.2 82.6 74.4 85.8 73.1 68.9 52.6 66.5

70.4 76.7 81.7 61.8 67.4 71.1

58.8 74.3 81.6 58.8 81.6 80.9 81.6 68.7 72.8 36.5 68.7 53.5 48.4 66.7 50.8 81.6

122 8 6 7 6 16 5 29 40 117 82

45 11 4 89 50 45

134 26 6 107 6 7 6 25 34 86 58 166 219 62 140 6

112 6 5 6 5 14 4 27 30 112 69

42 9 3 98 40 38

119 20 4 100 5 6 5 21 27 80 51 155 201 51 130 5

258 117 120 100 99 164 97 193 420 496 288

263 264 88 291 246 225

330 216 121 355 120 118 120 263 216 295 285 408 464 302 497 120

180 68 60 54 50 123 47 122 192 434 194

148 113 56 222 213 140

264 89 62 303 60 49 60 224 116 229 167 333 384 206 444 60

4.2 ⫺3.6 — ⫺5.7 ⫺4.6 ⫺1.7 ⫺3.3 ⫺4.0 ⫺3.9 2.3 —

⫺2.1 ⫺4.6 ⫺5.5 ⫺2.3 ⫺6.4 ⫺5.8

⫺3.8 ⫺5.0 ⫺8.0 ⫺2.2 ⫺6.2 ⫺4.4 3.9 ⫺3.0 — ⫺5.0 ⫺5.5 ⫺3.0 ⫺3.9 ⫺3.9 ⫺3.4 0.9 —

⫺1.6 ⫺0.1 ⫺4.9 ⫺1.3 — ⫺5.7 — — — — ⫺3.5 ⫺3.6 ⫺1.3 ⫺3.5 ⫺0.8 —

⫺1.9 ⫺0.7 ⫺5.3 ⫺2.1 — ⫺3.8 — — — — ⫺3.8 ⫺3.7 ⫺2.0 ⫺4.6 ⫺1.0 —


Country/ Territory

Annex 2A Continued



Korea, Democratic People's Republic of Korea, Republic of Kuwait Kyrgyz Republic Lao People's Democratic Republic Latvia Lebanon Lesotho Liberia Libya Liechtenstein Lithuania Luxembourg Macedonia, FYR Madagascar Malawi Malaysia Maldives Mali Malta Marshall Islands Martinique Mauritania Mauritius Mexico Micronesia, Federated States of Moldova Monaco Mongolia Montserrat Morocco Mozambique Myanmar Namibia Nauru Nepal Netherlands Netherlands Antilles New Caledonia

19,956

42,869 2,143 4,395 4,132

2,713 2,712 1,570 2,135 4,306 — 3,739 378 1,909 11,956 9,456 17,845 216 9,046 360 — — 2,030 1,057 83,225 96

4,364 — 2,216 — 24,564 13,465 40,506 1,409 — 18,625 14,952 188 171


High-income countries High-income countries Europe and Central Asia East Asia and Pacific

Europe and Central Asia Middle East and North Africa Sub-Saharan Africa Sub-Saharan Africa Middle East and North Africa High-income countries Europe and Central Asia High-income countries Europe and Central Asia Sub-Saharan Africa Sub-Saharan Africa East Asia and Pacific South Asia Sub-Saharan Africa Middle East and North Africa East Asia and Pacific Not included Sub-Saharan Africa Sub-Saharan Africa Latin America and the Caribbean East Asia and Pacific

Europe and Central Asia High-income countries East Asia and Pacific Not included Middle East and North Africa Sub-Saharan Africa East Asia and Pacific Sub-Saharan Africa Not included South Asia High-income countries High-income countries High-income countries

66.9 — 57.0 — 63.1 44.7 53.8 59.0 — 54.4 73.8 — —

64.2 66.7 52.6 45.0 67.0 — 66.5 72.1 69.1 50.9 45.1 68.7 58.0 44.1 73.8 — — 49.3 65.5 64.4 —

69.5 72.7 59.0 51.4

63.6

73.3 — 62.6 — 67.4 50.3 61.2 65.3 — 57.7 80.2 — —

74.5 71.6 59.1 50.8 72.1 — 76.3 78.5 73.9 56.6 49.7 75.3 59.7 49.1 78.4 — — 55.5 73.3 70.5 —

78.2 75.6 66.1 57.1

68.5

33 — 112 — 90 255 146 93 — 139 10 — —

20 42 159 251 44 — 15 10 37 178 250 24 103 262 13 — — 197 27 50 —

20 20 93 173

55

27 — 101 — 80 225 114 78 — 147 8 — —

15 32 134 219 40 — 12 8 32 158 232 18 127 238 9 — — 169 20 42 —

9 16 73 153

55

221 — 322 — 206 415 349 304 — 344 116 — —

311 210 358 412 199 — 286 151 167 371 412 199 314 418 101 — — 383 263 250 —

189 118 304 368

259

123 — 206 — 141 281 215 186 — 238 67 — —

118 143 229 278 121 — 107 86 94 245 285 105 225 288 62 — — 251 121 146 —

81 81 181 242

162

4,276 34 2,528 4 29,585 18,204 48,205 1,930 12 24,060 15,982 217 220

2,351 3,537 1,794 3,099 5,340 33 3,484 441 2,035 16,439 11,627 23,492 300 12,256 391 52 388 2,724 1,198 100,456 107

47,142 2,353 4,995 5,403

22,409

63.8 77.3 59.8 68.9 68.6 41.7 56.2 49.7 59.3 59.6 75.8 68.1 59.8

64.8 67.4 34.6 40.5 70.2 75.5 66.5 75.6 69.0 54.2 40.0 69.6 66.3 43.7 75.9 60.7 68.0 49.7 68.1 71.8 64.6

71.5 75.6 60.1 53.8

64.4

71.4 84.3 66.0 73.6 72.6 44.4 61.8 52.2 66.2 59.6 80.9 72.8 36.5

75.8 71.9 40.1 43.9 75.4 81.6 77.7 81.8 75.0 58.2 40.9 74.8 65.4 45.5 79.8 64.3 72.8 54.4 75.4 77.1 67.8

79.1 76.5 68.4 55.9

67.1

32 5 80 32 45 211 118 92 19 87 7 33 87

15 36 159 244 20 6 11 5 19 147 199 10 42 235 8 47 34 187 21 31 65

8 14 65 149

56

24 4 70 26 43 201 95 88 14 93 6 27 80

12 29 153 223 19 5 10 5 16 127 192 9 49 226 6 37 27 156 14 25 53

7 10 57 133

54

301 113 320 205 161 596 332 572 456 300 97 216 295

323 205 871 569 174 120 297 120 195 335 648 193 211 489 89 347 215 394 222 175 214

173 84 346 340

236

⫺0.2

⫺2.8 ⫺3.8 ⫺2.3 ⫺1.3

⫺2.0 ⫺0.9 1.2 0.2 ⫺6.9 — ⫺1.9 ⫺4.6 ⫺6.4 ⫺2.0 ⫺1.7 ⫺6.7 ⫺8.7 ⫺0.5 ⫺2.7 — — ⫺0.7 ⫺3.5 ⫺4.9 —

⫺1.1 — ⫺3.3 — ⫺5.6 ⫺1.0 ⫺1.7 1.1 — ⫺4.2 ⫺3.1 — —

0.1

⫺8.5 ⫺3.5 ⫺3.2 ⫺1.4

⫺2.7 ⫺1.3 0.0 ⫺0.3 ⫺7.4 — ⫺2.5 ⫺5.9 ⫺6.3 ⫺1.7 ⫺2.1 ⫺7.5 ⫺8.1 ⫺1.0 ⫺4.5 — — ⫺0.5 ⫺2.4 ⫺4.3 —

⫺0.4 — ⫺3.1 — ⫺6.3 ⫺1.7 ⫺1.9 ⫺0.2 — ⫺4.3 ⫺3.7 — —


149 49 209 110 104 503 236 496 308 292 66 116 230

117 140 705 463 100 60 102 66 90 264 601 107 207 418 54 292 116 305 119 99 179

65 62 165 308

191



68.6 54.6 — 66.0 58.1 65.6 59.5 62.2 — 66.5 70.4 68.7 67.7 66.8 63.8 50.6 — 65.0 — — 66.3 52.6 66.8

High-income countries Middle East and North Africa

Middle East and North Africa 1,845 South Asia 110,901 East Asia and Pacific — Latin America and the Caribbean 2,411 East Asia and Pacific 4,114 Latin America and the Caribbean 4,219 Latin America and the Caribbean 21,753 East Asia and Pacific 61,104 Not included — Europe and Central Asia 38,111 High-income countries 9,899 Latin America and the Caribbean 3,528 High-income countries 467 Europe and Central Asia 23,207 Europe and Central Asia 148,292 Sub-Saharan Africa 6,775 Not included — East Asia and Pacific 160 High-income countries — Sub-Saharan Africa 116

Middle East and North Africa Sub-Saharan Africa Europe and Central Asia

16,554 7,345 10,156

73.4 —

4,241 2,154

High-income countries Latin America and the Caribbean Sub-Saharan Africa Sub-Saharan Africa Not included High-income countries

New Zealand Nicaragua Niger Nigeria Niue Northern Mariana Islands Norway West Bank and Gaza Oman Pakistan Palau Panama Papua New Guinea Paraguay Peru Philippines Pitcairn Poland Portugal Puerto Rico Qatar Romania Russian Federation Rwanda Réunion Samoa San Marino São Tomé and Principe Saudi Arabia Senegal Serbia and Montenegro

72.5 61.3 39.2 49.8 — —

3,360 3,824 7,650 86,018 — —

World Bank region

71.6 58.7 74.0

74.3 58.4 — 72.9 62.8 72.2 66.3 69.3 — 75.6 77.3 77.6 74.6 73.2 74.4 55.9 — 71.1 — —

79.9 —

78.5 68.0 42.9 54.7 — —

47 158 34

33 137 — 39 102 42 88 65 — 20 16 17 29 34 24 181 — 45 — —

10 —

13 73 329 191 — —

41 138 24

27 140 — 29 100 32 71 50 — 16 12 13 21 27 18 165 — 39 — —

7 —

9 58 311 177 — —

208 358 223

184 342 — 232 312 237 299 272 — 263 178 237 211 239 318 373 — 243 — —

128 —

143 282 449 379 — —

128 232 116

106 233 — 126 205 131 179 156 — 102 80 90 111 114 117 249 — 141 — —

65 —

93 166 320 256 — —

Ages 15–59


1990




22,829 9,621 10,545

2,688 146,277 20 3,007 5,460 5,604 26,362 77,151 0 38,651 10,033 3,838 591 22,437 144,877 8,066 734 175 27 153

4,494 3,310

3,815 5,204 11,134 117,823 2 73

68.4 54.2 69.7

70.8 61.1 66.3 73.1 58.3 68.7 67.1 64.9 59.9 70.2 73.2 70.5 75.2 67.9 58.6 41.6 49.4 66.7 77.2 61.1

76.1 68.4

76.5 67.7 42.6 48.1 67.9 65.3

73.8 57.1 74.8

76.1 61.5 71.4 78.4 61.4 74.2 71.6 71.4 36.4 78.5 80.5 78.4 74.3 74.9 72.1 46.3 52.0 69.6 84.0 63.1

81.7 72.0

81.6 72.3 42.6 49.8 73.1 36.4

31 140 17

17 105 24 26 99 37 41 41 86 9 7 13 15 24 22 189 176 28 6 85

5 27

8 39 251 184 34 86

26 131 13

16 115 22 22 92 27 37 35 80 8 6 11 13 20 17 173 168 22 3 86

4 29

6 34 257 181 26 80

192 350 187

168 228 241 143 310 170 206 260 295 209 155 217 93 235 453 608 422 235 85 262

103 200

101 213 496 448 193 295

113 285 98

95 203 194 85 250 123 145 136 230 84 66 93 82 107 163 483 352 203 32 220

61 140

65 146 442 387 132 229

⫺3.1 ⫺5.0 1.7 0.2 — — ⫺5.3 — ⫺4.8 ⫺1.7 — ⫺2.4 ⫺0.7 ⫺1.6 ⫺6.0 ⫺3.3 — ⫺6.2 ⫺6.7 ⫺1.2 ⫺4.3 ⫺3.0 ⫺0.6 0.5 — ⫺5.1 — — ⫺4.2 ⫺0.5 ⫺5.1

⫺4.8 ⫺5.7 ⫺2.5 ⫺0.3 — — ⫺6.1 — ⫺6.1 ⫺2.4 — ⫺3.6 ⫺0.2 ⫺1.0 ⫺6.9 ⫺4.2 — ⫺6.9 ⫺7.2 ⫺2.1 ⫺5.7 ⫺3.1 ⫺0.8 0.4 — ⫺4.4 — — ⫺3.9 ⫺1.1 ⫺6.2



Country/ Territory

Annex 2A Continued



Seychelles Sierra Leone Singapore Slovak Republic Slovenia Solomon Islands Somalia South Africa Spain Sri Lanka St. Helena St. Kitts and Nevis St. Lucia St. Pierre et Miquelon St. Vincent and the Grenadines Sudan Suriname Swaziland Sweden Switzerland Syrian Arab Republic Tajikistan Tanzania Thailand Timor-Leste Togo Tokelau Tonga Trinidad and Tobago Tunisia Turkey Turkmenistan Turks and Caicos Islands Tuvalu Uganda Ukraine United Arab Emirates United Kingdom United States U.S. Virgin Islands 5,303 26,068 54,389 740 3,455 — 99 1,215 8,207 57,593 3,668 — — 17,359 51,891 2,035 56,761 255,712 101

Not included Sub-Saharan Africa Europe and Central Asia High-income countries High-income countries High-income countries High-income countries

24,927 402 847 8,559 6,834 12,717

110

— 4,054 3,016 5,256 1,918 319 7,163 36,848 39,303 16,830 — — 131 —

Europe and Central Asia Sub-Saharan Africa East Asia and Pacific East Asia and Pacific Sub-Saharan Africa Not included East Asia and Pacific Latin America and the Caribbean Middle East and North Africa Europe and Central Asia Europe and Central Asia Not included

Sub-Saharan Africa Latin America and the Caribbean Sub-Saharan Africa High-income countries High-income countries Middle East and North Africa


Sub-Saharan Africa Sub-Saharan Africa High-income countries Europe and Central Asia High-income countries East Asia and Pacific Sub-Saharan Africa Sub-Saharan Africa High-income countries South Asia Not included Latin America and the Caribbean Latin America and the Caribbean Not included

— 51.4 65.6 68.5 72.9 71.9 —

60.1 51.6 64.6 — 52.1 — — 67.5 66.4 60.3 57.4 —

55.5 65.8 56.1 74.8 73.9 66.1

—

— 39.5 72.8 70.3 69.9 — 45.8 61.9 73.3 67.2 — — 66.9 —

— 57.6 74.9 75.7 78.6 79.0 —

66.8 56.8 72.4 — 58.5 — — 75.4 70.1 65.9 64.3 —

61.4 72.9 63.0 80.5 80.9 70.7

—

— 45.6 77.8 76.9 77.9 — 51.6 69.0 80.4 74.9 — — 72.3 —

— 172 19 25 11 13 —

83 170 48 — 165 — — 30 55 82 108 —

128 40 122 8 9 48

—

— 324 10 17 12 — 240 68 10 32 — — 22 —

— 148 14 17 8 10 —

67 156 31 — 139 — — 18 49 74 87 —

112 29 98 6 8 40

—

— 279 8 13 8 — 210 52 8 20 — — 17 —

— 367 287 201 129 172 —

293 366 248 — 362 — — 214 194 292 318 —

335 233 330 114 126 211

—

— 447 152 179 207 — 407 275 146 218 — — 246 —

— 239 112 102 78 91 —

175 244 130 — 233 — — 105 141 182 194 —

214 126 203 66 62 147

—

— 306 93 92 81 — 274 158 60 109 — — 158 —

10 24,225 49,290 2,879 58,881 288,025 110

6,144 35,565 61,555 711 4,686 2 102 1,294 9,624 69,303 4,720 19

32,151 429 1,058 8,860 7,173 16,968

118

80 4,573 4,105 5,394 1,988 450 9,088 44,416 40,875 18,752 5 42 147 6

60.3 47.2 61.8 71.3 75.2 74.5 68.0

60.7 45.4 66.1 55.2 50.1 59.9 69.2 67.3 69.3 67.8 58.7 68.0

55.4 64.2 38.5 77.8 77.4 68.6

68.0

66.7 31.2 76.8 69.5 72.5 63.5 43.7 50.4 76.1 66.1 49.5 68.4 69.5 74.7

61.4 50.0 73.1 75.1 80.0 79.7 72.8

66.0 47.5 72.6 60.9 53.5 36.4 71.7 72.8 73.8 72.1 66.8 72.8

59.6 70.6 42.1 82.5 83.2 73.4

72.2

77.7 35.8 81.7 78.0 80.2 67.3 46.1 54.5 83.2 74.2 52.0 72.1 74.9 80.0

73 150 23 10 7 9 34

69 164 33 139 150 86 23 24 32 44 65 34

112 34 145 4 6 28

24

15 330 4 10 6 86 217 80 6 21 176 21 14 9

57 138 17 10 6 7 27

58 145 27 106 128 80 15 18 25 42 49 27

106 28 137 3 5 21

20

10 301 3 8 4 75 223 75 5 17 168 24 14 7

279 449 137 123 70 83 116

182 510 156 237 388 230 175 153 116 113 192 116

269 166 673 54 53 128

180

113 567 54 79 72 149 407 448 48 125 352 150 138 81

— ⫺1.2 1.8 ⫺7.9 ⫺3.6 ⫺3.2 —

— ⫺0.6 1.9 ⫺5.0 ⫺3.0 ⫺2.9 —

⫺1.4 ⫺0.7 ⫺1.5 — ⫺0.7 — — ⫺0.1 ⫺6.3 ⫺5.2 ⫺5.3 —

⫺0.4 ⫺0.3 3.0 ⫺6.3 ⫺4.0 ⫺5.6

⫺1.2 ⫺1.4 1.6 ⫺5.9 ⫺3.7 ⫺4.8 ⫺1.7 ⫺0.3 ⫺3.4 — ⫺0.8 — — ⫺2.0 ⫺5.0 ⫺5.7 ⫺4.7 —

—

— 0.7 ⫺7.4 ⫺4.8 ⫺5.2 — 0.6 3.4 ⫺5.1 ⫺1.6 — — ⫺1.7 — —

— 0.2 ⫺8.3 ⫺4.4 ⫺6.6 — ⫺0.9 1.5 ⫺5.3 ⫺3.8 — — ⫺4.2 —


293 518 376 170 111 144 216

290 559 276 323 454 295 190 243 171 180 365 216

364 282 784 85 95 192

235

248 718 93 210 165 202 516 566 121 260 422 210 217 139




66,074 — — 11,944 8,200 10,467

Latin America and the Caribbean Europe and Central Asia East Asia and Pacific Latin America and the Caribbean

East Asia and Pacific Not included

Not included Middle East and North Africa Sub-Saharan Africa Sub-Saharan Africa

Uruguay Uzbekistan Vanuatu Venezuela, Républica Bolivariana de Vietnam Wallis and Futuna Islands Western Sahara Yemen, Republic of Zambia Zimbabwe — 54.5 48.7 59.7

63.1 —

69.0 62.3 61.9 69.1

— 57.1 54.9 66.0

69.8 —

76.5 69.0 66.1 74.4

— 147 204 87

59 —

27 65 68 35

— 137 175 73

47 —

23 52 72 29

— 327 387 297

264 —

196 272 276 181

— 271 255 181

152 —

98 158 180 107

Sources: Population data are from United Nations 2003. Mortality estimates for 1990 are authors’ calculations; estimates for 2001 are from chapter 3 in this volume. Note: — ⫽ not available or not applicable. Estimates of child mortality are rounded to the nearest whole number.

3,106 20,515 149 19,502

World Bank region

Ages 15–59


1990




293 18,651 10,570 12,756

79,197 15

3,366 25,313 202 24,752

63.2 58.2 39.3 38.5

67.1 59.9

71.1 65.2 66.2 70.9

49.7 61.7 40.5 38.8

72.0 36.4

79.5 70.7 68.9 77.0

72 111 192 114

42 86

18 39 43 24

67 98 177 105

33 80

13 28 42 20

233 292 692 805

200 295

181 246 219 185

159 232 646 775

132 230

89 150 177 98

— ⫺3.0 0.1 3.3

⫺3.1 —

⫺3.2 — — ⫺2.5 ⫺0.5 2.5

⫺5.2 ⫺5.7 ⫺5.0 ⫺3.5

⫺3.6 ⫺4.5 ⫺4.3 ⫺3.4


Country/ Territory

Annex 2A Continued

ACKNOWLEDGMENTS We are grateful to Colin Mathers for his input into the estimation of child mortality levels in 1990 reported in this chapter.

Hill, K., R. Pande, M. Mahy, and G. Jones. 1999. Trends in Child Mortality in the Developing World: 1960–1996. New York: United Nations Children’s Fund. Istre, G. R., M. A. McCoy, M. Stowe, K. Davies, D. Zane, R. J. Anderson, and R. Wieber. 2003. “Childhood Injuries Due to Falls from Apartment Balconies and Windows.” Injury Prevention 9 (4): 349–52. Jamison, D. T., G. Alleyne, J. G. Breman, M. Claeson, D. B. Evans, P. Jha, and others. 2006. Disease Control Priorities in Developing Countries, 2nd ed. New York: Oxford University Press.

NOTES 1. While it would have been much more informative to base this assessment of demographic change on the 2004 Revision of World Population Prospects (United Nations 2005a), the results were released too late to be incorporated into the estimates reported in this and subsequent chapters. The differences between the two revisions, at least for regional aggregates, are unlikely to be substantial.

Korenromp, E. L., B. G. Williams, E. Gouws, C. Dye, and R. W. Snow. 2003. “Measurement of Trends in Childhood Malaria Mortality in Africa: An Assessment of Progress toward Targets Based on Verbal Autopsy.” Lancet Journal of Infectious Diseases 3 (6): 349–58. Lawn, J. E., S. Cousens, and J. Zupan. 2005.“Four Million Neonatal Deaths: When? Where? Why?” Lancet 363 (9462): 9–18.

2. An exception is Timor-Leste, where fertility increased following independence in 2002 and is currently higher than in any other country.

Leon, D., A. Chenet, V. Shkolnikov, S. Zakharov, J. Shapiro, G. Rakhmanova, S. Vassin, and M. McKee. 1997. “Huge Variation in Russian Mortality Rates, 1984–1994: Artefact,Alcohol, or What?”Lancet 350 (9075): 383–8.

REFERENCES

Lopez, A. D. 1993. “Causes of Death in Industrial and Developing Countries: Estimates for 1985.” In Disease Control Priorities in Developing Countries, ed. D. Jamison, H. Mosely, A. Measham, and J. L. Bobodilla, 35–50. New York: Oxford University Press.

Adetunji, J. 2000. “Trends in under-5 Mortality Rates and the HIV/AIDS Epidemic.” Bulletin of the World Health Organization 78 (10): 1200–6. Bennett, N. G., and S. Horiuchi. 1984. “Mortality Estimation from Registered Deaths in Less Developed Countries.” Demography 21 (2): 217–33. Bhatia, S. 1983. “Traditional Practices Affecting Female Health and Survival: Evidence from Countries of South Asia.” In Sex Differentials in Mortality, ed. A. D. Lopez and L. T. Ruzicka, 165–77. Canberra: Australian National University Press.

Lopez, A. D. 2003. “Estimating the Causes of Child Deaths.” International Journal of Epidemiology 32 (6): 1052–3. Lopez, A. D, O. B. Ahmad, M. Guillot, M. Inoue, B. Fergusson, J. Salomon, C. J. L. Murray, and K. Hill. 2002. World Mortality in 2000: Life Tables for 191 Countries. Geneva: World Health Organization. Mari Bhat, P. N. 2002. “Completeness of India’s Sample Registration System: An Assessment Using the General Growth Balance Method.” Population Studies 56 (2): 119–34.

Black, R. E., S. S. Morris, and J. Bryce. 2003. “Where and Why Are 10 Million Children Dying Every Year?” Lancet 361 (9376): 2226–34.

Mathers, C. D., D. Mafat, M. Inoue, C. Rao, and A. D. Lopez. 2005. “Counting the Dead and What They Died from: An Assessment of the Global Status of Cause of Death Data.” Bulletin of the World Health Organization 83 (3): 171–7.

Bryce, J., C. Boschi-Pinto, K. Shibuya, R. E. Black, and the WHO Child Health Epidemiology Reference Group. 2005. “WHO Estimates of the Causes of Death in Children.” Lancet 365 (9465): 1147–52.

Mock, C., R. Quansah, R. Krishnan, C. Arreola-Risa, and F. Rivara. 2004. “Strengthening the Prevention and Care of Injuries Worldwide.” Lancet 363 (9427): 2172–9.

de Onis, M., E. A. Frongillo, and M. Blossner. 2000. “Is Malnutrition Declining? An Analysis of Changes in Levels of Child Malnutrition since 1980.” Bulletin of the World Health Organization 78 (10): 1222–33.

Morris, S. S., R. E. Black, and L. Tomaskovic. 2003. “Predicting the Distribution of Under-Five Deaths by Cause in Countries without Adequate Vital Registration Systems.” International Journal of Epidemiology 32 (6): 1041–51.

Etebu, E. N., and A. U. Ekere. 2004. “Paediatric Accidental Deaths in Port Harcourt, Nigeria: A 10-Year Retrospective Study.” Nigerian Journal of Medicine 13 (2): 140–3.

Murray, C. J. L., B. D. Ferguson, A. D. Lopez, M. Guillot, J. A. Salomon, and O. B.Ahmad. 2003.“Modified Logit Life Table System: Principles, Empirical Validation, and Application.” Population Studies 57 (2): 165–82.

Ezzati, M., S. Vander Hoorn, C. M. M. Lawes, R. Leach, W. P. T. James, A. D. Lopez, A. Rodgers, and C. J. L. Murray. 2005. “Rethinking the ‘Diseases of Affluence’ Paradigm: Global Patterns of Nutritional Risks in Relation to Economic Development.” PLoS Medicine 2: e133.

Murray, C. J. L., and A. D. Lopez, eds. 1996. The Global Burden of Disease, vol. 1. Cambridge, MA: Harvard University Press.

Fenn, B., S. S. Morris, and R. F. Black. 2005. “Comorbidity in Childhood in Northern Ghana: Magnitude, Associated Factors, and Impact on Mortality.” International Journal of Epidemiology 34 (2): 368–74. Fishman, S., L. E. Caulfield, M. de Onis M, M. Blossner, A. A. Hyder, L. Mullany, and R. E. Black. 2004. “Childhood and Maternal Underweight.” In Comparative Quantification of Health Risks: Global and Regional Burden of Disease Attributable to Selected Major Risk Factors, ed. M. Ezzati, A. D. Lopez, A. Rodgers, and C. J. L. Murray, 39–61. Geneva: World Health Organization. Gali, B. M., A. G. Madziga, and H. U. Naaya. 2004. “Epidemiology of Childhood Burns in Maiduguri, Northeastern Nigeria.” Nigerian Journal of Medicine 13 (2): 144–7. Hill, K. 1987. “Estimating Census and Death Registration Completeness.” Asian and Pacific Population Forum 1 (3): 8–24.

Pelletier, D. L., E. A. Frongillo, and J. P. Habicht. 1993. “Epidemiologic Evidence for a Potentiating Effect of Malnutrition on Child Mortality.” American Journal of Public Health 83 (8): 1130–3. Rao, C., A. D. Lopez, G. Yang, S. Begg, and J. Ma. 2005.“Evaluating National Cause of Death Statistics: Principles and Application to the Case of China.” Bulletin of the World Health Organization 83 (8): 618–25. Rice, A. L., L. Sacco, A. Hyder, and R. E. Black. 2000. “Malnutrition as an Underlying Cause of Childhood Deaths Associated with Infectious Diseases in Developing Countries.” Bulletin of the World Health Organization 78 (10): 1207–21. Rudan, I., J. Lawn, S. Cousens, A. K. Rowe, C. Boschi-Pinto, L. Tomaskovic, W. Mendoza, C. F. Lanata, A. Roca-Feltrer, I. Carneira, J. A. Schellenberg, O. Polasek, M. Weber, J. Bryce, S. S. Morris, R. E. Black, and H. Campbell. 2005. “Gaps in Policy-Relevant Information on Burden of Disease in Children: A Systematic Review.” Lancet 365 (9476): 2031–40. Demographic and Epidemiological Characteristics of Major Regions, 1990–2001 | 43


Shen, C., B. Sanno-Duanda, and S. W. Bickler. 2003. “Paediatric Trauma at a Government Referral Hospital in The Gambia.” West African Journal of Medicine 22 (4): 287–90. Shkolnikov, V., M. McKee, and D. A. Leon. 2001. “Changes in Life Expectancy in Russia in the Mid-1990s.” Lancet 357 (9260): 917–21. Sibai, A. M. 2004. “Mortality Certification and Cause of Death Reporting in Developing Countries.” Bulletin of the World Health Organization 82 (2): 83. Snow, R. W., M. T. Winstanley, V. M. Marsh, C. R. C. J. Newton, C. Waruiru, I. Mwangi, P. A. Winstanley, and K. Marsh. 1992. “Childhood Deaths in Africa: Uses and Limitations of Verbal Autopsies.” Lancet 340 (8815): 351–5. Snow, R. W., M. Craig, U. Deichmann, and K. W. Marsh. 1999. “Estimating Mortality, Morbidity, and Disability Due to Malaria among Africa’s Non-pregnant Population.” Bulletin of the World Health Organization 77 (8): 624–40. Snow, R. W., J.-F. Trape, and K. Marsh. 2001. “The Past, Present, and Future of Childhood Malaria Mortality in Africa.” Trends in Parasitology 17 (12): 593–7. Stein, C. E., M. Birmingham, M. Kurian, P. Duclos, and P. Strebel. 2003. “The Global Burden of Measles in the Year 2000: A Model That Uses Country-Specific Indicators.” Journal of Infectious Diseases 187 (Suppl1): S8–S14. Trape, J.-F. 2001. “The Public Health Impact of Chloroquine Resistance in Africa.” American Journal of Tropical Medicine and Hygiene 64 (1–2): 12–17.

Tupasi, T. E., M. A. Velmonte, M. E. G. Sanvitores, L. Abraham, L. E. De Leon, S. A. Tan, C. A. Miquel, and M. C. Saniel. 1988. “Determinants of Morbidity and Mortality Due to Acute Respiratory Infections: Implications for Intervention.” Journal of Infectious Diseases 157 (4): 615–23. UNICEF (United Nations Children’s Fund). 2003. State of the World’s Children 2003. New York: UNICEF. United Nations. 2003. World Population Prospects: The 2002 Assessment. ST/ESA/SER.A/222. New York: United Nations. . 2005a. World Population Prospects: The 2004 Assessment. New York: United Nations. . 2005b. World Population Prospects: The 2002 Revision and World Urbanization Prospects: The 2001 Revision. New York: United Nations, Department of Economic and Social Affairs, Population Division. http://esa.un.org/unpp. Victora, C. G., J. Bryce, O. Fontaine, and R. Monash. 2000. “Reducing Deaths from Diarrhea through Oral Rehydration Therapy.” Bulletin of the World Health Organization 78 (10): 1246–55. Walker, N., B. Schwartlander, and J. Bryce. 2002. “Meeting International Goals in Child Survival and HIV/AIDS.” Lancet 360 (9329): 284–9. Williams, B. G., E. Gouws, C. Boshi-Pinto, C. Bryce, and C. Dye. 2002. “Estimates of Worldwide Distribution of Child Deaths from Acute Respiratory Infections.” Lancet Journal of Infectious Diseases 2 (1): 25–32.
