Effective Interventions to Reduce Infection in ...

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Gretchen. Berggren,. M.D.,. Assistant. Professor,. Depart- ment of Population .... McCord,. M.D.,. Department of. International. Health,. School. ofHygiene and.

Effective Infection

Interventions in Malnourished

to Reduce Populations


Gerald Michael

T. Keusch, M.D. Katz, M.D.

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Proceedings of a Symposium held on June 12-16, 1977 Port-au-Prince, Haiti


Effective Interventions to Reduce Infections in Malnourished Populations

CONTENTS Part Session





II L. J. Mata

The potential for children: a position

2208 2219 2237

Ecological control of the bacterial diarrheas: a scientific strategy. G. T Keusch Viral diarrhea. Etiology and control. A. Z. Kapikian, R. H. Yolken, R. G. Wyatt, A. R. Kalica, R. M. Chanock, and H. W. Kim Vaccines and vaccination programs-special emphasis in malnutrition. W P. Faulk


and G. Edsall R#{233}sum#{233} of the


5. Health




antidiarrheal and nutrient-sparing paper. I. H. Rosenburg and N.





of oral


Chairman: therapy

effects of oral W. Solomons


2258 2269

R. B. Sack, N. F. Pierce, and N. Hirschhorn Preparing for the next round: convalescent care after The child and the chain, or 3 + 3 = 9. Twenty-five

in the

two superficially dissimilar projects and development of the appropriate technology world. M. King

Session 2279 2284 2292 2301 23 14 2324

R#{233}sum#{233} of the 6.



Models Control Strategies

on “Health


for educational of diarrheal


to control




interventions disease morbidity



G. T Keusch

F. T. Koster






of acute

this health


has for the systematic care in the developing

F. T Koster G. T Keusch

in malnourished and mortality:

in malnourished


acute infection. J. E. Rohde unexpected similarities between

implications for personal



populations. some strategic populations-holistic

M. Tonon issues. L. C. Chen approach


narrowly targeted interventions. M. C. Latham Medical technology in developing countries: useful, useless, or harmful? C. McCord Some economic aspects of planning health interventions among malnourished populations. B. M. Popkin The perilous journey of nutrition evaluation. J. E. Austin


Epidemiological insights retired. J. E. Gordon


R#{233}sum#{233} of the


on malnutrition: on “Interventions:




others for success”.

restructured, G. T Keusch

a few

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and Contributors

James E. Austin, Ph.D., Associate Professor of Business Administration and Lecturer in Nutrition Policy, Graduate School of Public Health, Harvard University, Boston, Massachusetts. Samir vision, World

S. Basta, Ph.D., Agriculture and Bank, Washington,

Nutrition Expert, Rural Development D.C.

Gretchen Berggren, M.D., ment of Population Sciences, Health, Boston, Massachusetts. Warren ment Public

Assistant Harvard

Berggren, M.D., Associate of Tropical Public Health, Health, Boston, Massachusetts.

Nutrition Department,

Professor, School

Professor, Harvard


Bertha Garcia, Instituto de Investigaciones (INISA), Universidad de Costa Rica, Ciudad taria “Rodrigo Facio”, San Jose, Costa Rica. Nancie Affairs, land.

Gonzalez, University

Ph.D., Vice of Maryland,

Linda Haverberg, Ph.D., Agency for International State, Washington, D.C.

Departof Public

DepartSchool of

Chancellor College

Nutrition Development,

John Briscoe, Ph.D., Sanitary Engineer, Division, Cholera Research Laboratory, desh.

Michael Katz, M.D., Chairman, rics, College of Physicians and versity, New York, New York.

Nutrition Advisor Port-au-Prince,

to Pan Haiti.


A. Cash, International

Lincoln Institute (currently Dacca,

C. Chen, M.D., of Development on study leave Bangladesh).

Zafrullah oshasthaya Cecile Health Lagos,


Chowdhury, Kendra,

Edelinan, Institute Institutes

Projects Bangladesh.

M.D., Dr.P.H., Planning, The

M.D., Chief, of Allergy of Health,

Geoffrey Edsall, M.D., ology, London School cine, London, England.

Faulk, M.D., Department Microbiology, Charleston,


AInfried Health, Hopkins

Bangladesh Bangladesh Foundation,


Program Ford

Gerald T. Keusch, M.D., cine, The City University York.


Advisor Foundation,

Professor of Hygiene

Emeritus of and Tropical

of Biology de Centro

Maurice Geneva, in

M.R.C. Path., Professor of Basic and Clinical Medical University South Carolina.


M.D., Haiti.


The American




and ViceImmunolof South

de Nutrition,


Sinai York,



School of McdiNew York, New

Kielmann, M.D., Department of International School of Hygiene and Public Health, The Johns University, Baltimore, Maryland.

H. King, Switzerland.



C. Latham, Nutrition, University,

Disease Division, City Hospitals, Bal-



de Investigaciones Costa Rica, Ciudad Jose, Costa Rica.

M.D., M.P.H., Professor Division of Nutritional Ithaca, New York.

Emily Leonard, Deputy Division, Bureau for Near Development, Department

Donald C. E. Ferguson, Ph.D., M.P.H., Chief, Health Delivery Systems, Office of Health, Development Support Bureau, Agency for International Development, Department of State, Washington, D.C. William Fougere, Port-au-Prince,

Mount of New

Richard A. Kronmal, Ph.D., Instituto en Salud (INISA), Universidad de Universitaria “Rodrigo Facio”, San Michael national Cornell


and Human America

Section, Institute of Institutes of

Department of PediatSurgeons, Columbia Uni-

Frederick T. Koster, M.D., Infectious Department of Medicine, Baltimore timore, Maryland.

Clinical Studies Branch, and Infectious Diseases, Bethesda, Maryland.

J. Faigenblum, Ph.D., Division Nutrition, Instituto de Nutricion Panama, Guatemala, CA. W. Page Chairman, ogy and Carolina,

Fellow, Harvard Cambridge,

Visiting Scholar, Studies, Dacca, from the Ford

M.D., Dacca,

De Sweemer, and Family Nigeria.

Robert National National

Institute Development,

Epidemiology National National

Kazuyoshi Kawata, Dr.P.H., Environmental Health gineering, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, Maryland.

Roy E. Brown, M.D., M.P.H., Associate Professor, Community Medicine, Mount Sinai School of Medicine, The City University of New York, New York, New York. Richard tute for chusetts.

Advisor, LA/DR. Department of

of InterSciences,

Chief, Health and Nutrition East, Agency for International of State, Washington, D.C.

Leonardo J. Mata, D.Sc., Instituto de Investigaciones en Salud (INISA), Universidad de Costa Rica, Ciudad Universitaria “Rodrigo Facio”, San Jose, Costa Rica. Colin Health, Hopkins

McCord, M.D., Department of International School ofHygiene and Public Health, The Johns University, Baltimore, Maryland.

Robert L. Parker, M.D., M.P.H., Assistant Professor, Department of International Health, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland. Nathaniel F. Pierce, M.D., The Departments of Mcdicine, The Johns Hopkins University School of Medicine and Baltimore City Hospitals, Baltimore, Maryland.







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Albert Z. Kapikian, M.D., Head, Laboratory of Infectious Diseases, Allergy and Infectious Diseases, Health, Bethesda, Maryland.

S. Donas Burach, Health Organization,

of Academic Park, Mary-

Irwin Hornstein, Ph.D., Deputy Director, Office of Nutrition, Development Support Bureau, Agency for International Development, Department of State, Washington, D.C.

Ary Bordes, M.D., Chef de la Division d’Hygiene Familiale, Departement de Ia Sante Publique et de la Population, Protection Materno-Infantile Planification Familiale, Port-au-Prince, Haiti. Epidemiology Dacca, Bangla-

en Salud Universi-

PARTICIPANTS Barry M. Popkin, ment of Nutrition, of North Carolina,

Ph.D., School Chapel


Assistant Professor, Departof Public Health, University Hill, North Carolina.

Allen P. Randlov, Health Operations Officer, Health and Nutrition Division, Bureau for Near East, Agency for International Development, Department of State, Washington, D.C. Jon Eliot Foundation, donesia.

Rohde, Gadjah

M.D., Field Staff, Mada University,

Irwin H. Rosenberg, University of Chicago cago. Illinois. R. Bradley Medicine, Medicine Maryland.

Department of Medicine, School of Medicine, Chi-

Sack, M.D., Sc.D., The Johns Hopkins and Baltimore City

Shiffman, Department School Chapel

The Departments University School Hospitals, Baltimore,

M.D., Chief, Program Function, Division Instituto de Nutricion Guatemala, CA.

of of

of Nutriof Biology de Centro

M.D., Professor of Environmental of Environmental Science and Enof Public Health, University of North Hill, North Carolina.

Noel W. Solomons, M.D., Assistant Professor, Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts. Carl E. Taylor, M.D., Dr.P.H., Chairman, Department of International Health, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland. Marilyn Education ucation,

Faigenbloom Division, University

Tonon, Assistant Professor, Health School of Physical and Health Edof Washington, Seattle, Washington.


James F. Thomson, Chief Office of Health, Development for International Development, Washington, D.C.


Environmental Support Bureau, Department

Health, Agency of State,

Juan J. Urrutia, M.D., Chief, gram, Institute of Nutrition Panama, Guatemala, CA.

Nutrition-Infection of Central America

Willy Haiti,

Verrier, M.D., Port-au-Prince,

of Health,


V. Wheatley, International Cooperation SpeASIA/TR, Agency for International DevelopDepartment of State, Washington, D.C.

cialist ment, Cicely (Lend),

D. Williams, 57, Poplar

Minister Haiti.

B.A., Walk,

D.M., London


D. Wray, M.D., M.P.H., Health, Harvard University,



Robert Board,

B. Bennett, Washington,

Staff D.C.

Myrtle Nutrition

L. Brown, Board,


F.R.C.P., D.T.M. SE 24, England.

Harvard Boston,



& H

School of Public Massachusetts.


Ph.D., Executive Washington, D.C.







Consultant Paul E. Johnson, Washington, D.C.

Ph.D., 4516 (Deceased).





Recorder Richard Church,

Peloquin, Virginia.





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Roberto E. Schneider, tion and Gastrointestinal and Human Nutrition, America y Panama, Maurice Health, gineering, Carolina,

M.D., Pritzker

The Rockefeller Yogyakarta, In-


The potential for antidiarrheal and nutrient-sparing effects of oral antibiotic use in children: a position paper1’ 2 Irwin

H. Rosenberg,

M. D. and


W. Solomons,


cent efforts have emphasized once again the impact of infectious disease on nutritional status and have called particular attention to the potential importance of enteric disease and malabsorption in the development of malnutrition in developing nations (6, 7). Taken together, infectious disease and enteric disease may be the most important environmental factors that affect the requirement for, and the utilization of, nutrients in countries where malnutrition is common. If true, it follows that interaction in the cycle of enteritis, malabsorption, and malnutrition may be important and that public health efforts to break that cycle should be applied. Evidence that improved nutrition would result from efforts toward the prevention of enteric infection and enteric disease may be summarized as follows: 1) The profound effects of infection on nutritional status induced by excessive metabolic losses and decreased food intake are well documented (6). 2) An additional effect of infection on nutrition must now be considered in view of evidence that when infection, whether systemic or enteric, produces diarrhea, malabsorption of nutrients occurs (7). This malabsorption in association with acute infection is best documented and most devastating in small children (8). 3) To these effects of clinically apparent infectious disease on the hosts’ nutrition must now be added the potential effects of chronic, subclinical, enteric disease (9, 10). A morpho-

In the developing world, there appears to be a synergistic relationship among enteritis, malabsorption, and malnutrition (1, 2). It has been estimated that 25 to of the children born in the developing countries die before the age of years, and that many of these deaths are associated with diarrheal disease (3). Almost all the victims have suffered from malnutrition ranging from mild to full-blown protein-calorie malnutrition. The many interactions of infection and malnutrition have been amply discussed (3). Crowding, poor sanitation, poorly accessible supplies of clean water, and the resultant widespread fecal contamination remain the norm in many parts of the less developed world (4, Regrettably, programs of improved sanitation, diet supplementation, hygiene, and immunization have thus far been too limited in application to have had a major impact on this massive problem. Current efforts, national or international, have not been sufficient in size or scope to alleviate worldwide malnutrition even if widespread starvation has been averted. Re-

‘From the Department of Medicine, University of Chicago, Chicago, Illinois and Division of Human Nutrition and Biology, INCAP, Guatemala City, Guatemala, CA. 2Address reprint requests to: Irwin H. Rosenberg, M.D., Section of Gastroenterology, University of Chicago, Chicago, Illinois.














in U.S.A.

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In view of the interactions of diarrhea, malabsorption, and malnutrition, particularly in infants living under poor sanitary conditions, one approach for control that has been proposed and debated is the prophylactic administration of antibiotics to children (1, 2). Any decision to recommend such use of antibiotics must be based on a weighing of the seriousness of the public health problem and the likelihood of success of the intervention against the possible alternative approaches, and deleterious and adverse side effects. The present paper examines the relevant previous experience with the chronic administration of antibiotics in animals and man.

Al. D.









countries can be measured not only by the reduction in morbidity and mortality from enteric infection but also by improvement in the utilization of foods and in the nutritional status of the people. This should be particularly apparent in those populations on a margina! nutritional intake. Antibiotics exert specific or nonspecific action against bacterial causes of enteritis and diarrhea. They are known to be effective in the treatment of some forms of malabsorption and intestinal bacterial overgrowth syndromes 17). In addition, low doses of antibiotics have had remarkable success in improving nutrition and growth and prevention of infection in animal and poultry husbandry (21). (15,

Antibiotics The


in animal


Low-level antibiotic feeding is an accepted component of modern animal husbandry (21). Feed antibiotics give a measure of insurance against morbidity and mortality and provide increased weight gains with increased feed efficiency; a recent evaluation has shown that their use is economically advantageous (22). Carcass quality is unchanged and a marketable product is obtained in a shorter period of time (23). Low-level feeding of antibiotics such as bacitracin, penicillin, and the tetracydines is most effective early in life. Its effects are greatest under conditions in which growth is otherwise poor, morbidity and/or mortality is high, birth weight is low, diet quality is poor, the environment is dirty, and stresses (i.e., unfavorable temperature) are present (24). When any of these adverse conditions are present, feed antibiotics result in a much greater than the 10% average increased meat production (2!). Conversely, under ideal husbandry conditions, antibiotics may provide little or no advantage. Antibiotic feeding improves utilization of nutrients present in suboptimum quantity and utilization of low quality proteins (24). In rats, growth promoting effect of antibiotics was inversely related to protein adequacy of diet and was unexplained by changes in appetite or food intake (25).

Animal feed antibiotics promote faster growth and greater feed efficiency by several

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logical abnormality of the intestine may be observed by biopsy in more than 80% of asymptomatic adults in countries where ma!nutrition is highly prevalent (1 !, 12). Defective intestinal absorption of xylose has been reported by clinical tests in 30 to of these individuals. Recent studies in Bangladesh indicate that subclinical malabsorption, as judged by this criterion, is apparent by the end of the first year of life ( 13). Although the quantitative impact of this malabsorption on nutritional status is not yet known, preliminary studies indicate a relationship among diarrhea! disease, subclinical intestinal malabsorption, and delayed growth in children in Bangladesh (13). 4) Several lines ofevidence point to chronic or recurrent intestinal infection or altered microbial ecology as contributing factor in the etiology of this widespread intestinal abiormality. A) Abnormal bacterial colonization of the small intestine has been demonstrated in patients with this nonspecific intestinal abnormality in tropical countries (14). B) Similar bacterial overgrowth of the gut occurs in children with severe protein-energy malnutrition (15, 16). The bacterial count is greatly diminished after appropriate dietary therapy (15). C) Bacterial overgrowth in the small intestine is commonly associated with malabsorption in the clinical setting (17). There is clear evidence that the morphological abnormality in the intestine is acquired and not genetic. The abnormality is not present in newborns and, as noted above, may appear early in life (18, 19). Preliminary data from Bangladesh suggest an association between the frequency of diarrheal disease early in life, and the development of subclinical malabsorption (13). Visitors, such as Peace Corps volunteers, to countries where these intestinal changes are common acquire morphological and functional changes similar to those in natives (20); these changes revert to normal when visitors return from the tropics. In view of this evidence of the impact of enteric infections on intestinal function, there is sufficient reason to contend that the success of programs directed at the prevention of acute and chronic enteric disease in tropical





The potential of antibiotics

risk oflong-term to humans



Of greatest concern is the observation that protracted use of antibiotics results in emergence of antibiotic-resistant strains of microorganisms that pose a theoretical threat to man. This concern has been expressed by the action of the British Government to disallow use of those antibiotics in animal feeds that lead to reservoirs of resistant bacteria (29). The United States Government has proposed a similar action (30), e.g., the Food and Drug


Administration Task Force concluded that while there was not enough evidence to indicate an iniminent and immediate health hazard, there was sufficient data to assure there is a potential, if not possible health hazard associated with feeding antibiotics to animals. The position was supported by documentation of the emergence of antibioticresistant bacteria in animals that pose a potential risk to humans. The Food and Drug Administration report takes note of the rarity of documented episodes of human infection by resistant organisms attributable to animal reservoirs in the 20 years of experience to date but reiterates the importance of the potential risk to human health. There are other potential risks of long-term antibiotic feeding. Many antibiotics have such undesirable side effects as toxic or allergic reactions. These are dose related in some instances, and dose independent (idiosyncratic) in others. In the instances in which resistant strains of microorganisms are selected, resistance due to plasmid-mediated mechanisms may spread to other microorganisms and may carry with it additional plasmid-borne factors (e.g., toxins). The extent to which this will happen and the risks of human disease cannot be predicted (30), but reports from India and Central America suggest that the increased use of antibiotics in therapy is increasing the populations of resistant enterobacteriacea significantly. Independent of drug resistance, alterations of the normal intestinal flora as the result of the antibiotic effect and the subsequent invasion by pathogens are possible. Finally, some long-term undesirable effects of the drugs may result from storage in fat and bones. Experience infants and

in prolonged children.

use of antibiotics


A considerable experience in man with the long-term use of antibiotics, largely of the tetracycline group, has been reported. This experience was reviewed in 1956 (3 1) and again in 1972 (32). Controlled design and statistical analysis has often been lacking. As noted in the summary of the results of these reviews in Table 1, the use of antibiotics has commonly been associated with improved weight gain and, occasionally, decreased moribidity and mortality (33-43). In general,

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different mechanisms. Antimicrobial effects of antibiotics include changes in microbic competition with the host for nutrients. The total numbers and kinds of intestinal microbes appear to change without consistent patterns after antibiotic feeding. In studies lasting more than 1 month, bacteria! changes revert to pretreatment patterns (24, 26). Other antimicrobial actions include changes in nutrients or toxins, or both, produced by microbes. Feeding antibiotics reduce microbic toxin production; specifically, ammonia (24), Clostridium toxins (24), and the Streptoccoccus factor(s) (27) causing malabsorption are decreased by antibiotic feeding. These changes are consistent with improved performance. Widespread endemic infections have been eliminated. Control of subclinical disease is exemplified by fewer liver abscesses in antibiotic-fed cattle than in the controls (21). Of special interest is the observation that microbic resistance, when it occurred, was found to revert quickly to the original susceptibility after withdrawal of the antibiotic. Low levels of dietary antibiotics stimulate growth by direct effects other than antimicrobial (24). This “direct” action was confirmed by growth increment and metabolic changes observed in germfree animals fed antibiotics, by growth stimulation of classic animals fed inactivated antibiotics and nonbacteriostatic compounds, and by the stimulation of microbes and higher plants in pure culture after the addition of dilute concentrations of bacteriostatic compounds. In one study, however, no improvement in growth and an adverse effect on intestinal mucosa was seen with antibiotic feeding to pigs with preexisting protein-calorie malnutrition (28).



(34) (35)

(36) (37) (38) Children (39) (40) (41) (42)





in which

chlortetracycline Reason

for drug





daily .







of tienu



50 mg/kg


Prematurity Prophylactic Malnutrition Malnutrition Prematurity

1952 1957 1957 1956 1963

50 5 50 25 25

Weeks 6-12 months 2-7 weeks 7 weeks 2 weeks

47 127 38 10

Rheumatic fever Poor diet Poor nutrition

1953 1955 1958

500 mg 20 mg 50 mg

Up to 20 mos 7 months 15-30 months

23 181 184

Legg-Calve-Perthes disease Growth failure


50 mg


50 mg

a Smallest children with antibiotic feeding. suspension of treatment.

mg or 50 mg mg mg mg/kg




12 months

only. ti Only in one village was a significant increase in height Difference from controls, apparent after 18 months of study, In other villages, the positive effect of antibiotics were suggestive

the use of antibiotics was most successful when they were used in the management of children with malnutrition or for the prevention of respiratory disease in children with cystic fibrosis. Positive effects were most prominent in the youngest of the children studied. When antibiotics have been used “prophylactically” for children without disease, the results have been less dramatic and often the positive trends have not reached statistical significance. Because these studies involve over 900 infants and children treated as long as 3 years, and with the theoretical possibilities that prolonged antibiotic use could have serious detrimental side effects, we have examined these studies for evidence of deleterious effects. With the exception of staining of the teeth in patients with cystic fibrosis on long-term tetracycline therapy (38) and reversible suppression of bone growth in premature infants given chlortetracycine (44), there are few reports of toxic side effects with the use of antibiotics; none with low-dose antibiotic use in the series quoted. It should be noted that most of these studies did not seek evidence of side effects in a systematic way, and longterm evaluation after the studies is not reported. No serious superinfections by resistant bacteria or fungi are reported but neither are there reports ofcareful studies of bacterial

25 243



Weight gain Mortality I Weight gain Weight gain Weight gain Faster recovery Bone growth

Morbidity I Weight gain” No sustained effect” Improved growth and ossification Height and weight gain”

and weight gain associated were not maintained after but inconclusive.

alterations. The lack of toxic side effects in these studies is, therefore, only partially reassuring in view of the superficial nature of most of the study designs. Of special interest therefore is a recent double blind study to assess the impact of a nonabsorbed antibiotic, colistin, on diarrhea! morbidity in Apache children (45). In this study, diarrhea! incidence was decreased in the 7 to 13-month age group on antibiotics, but was slightly increased in the 1 to 6-month group. In the 13-week study, neither growth differences nor any evidence ofantibiotic side effects were observed. Antibiotic


The reported experience indicates that tetracycline is remarkably safe for chronic use. However, this is one antibiotic whose resistance is transferable to other organisms. The dangers from antibiotic use could be reduced by substances which fulfill the following criteria: 1) that plasmid transmission of resistance factor be non-existent, and that the antibiotic not be a first-line drug for use in intestinal infections. Bacitracin fulfills these requirements as it is a poorly absorbed, polypeptide antibiotic with a broad spectrum against Gram-positive organisms and against Escherichia coil which is not associated with the development ofdrug resistance. Zinc bac2)

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Infants (33)




itracin has been accepted as a feed antibiotic in the United Kingdom based on the criteria set forth in the Joint Committee on the Use of Antibiotics in Animal Husbandry and Veterinary Medicine (30). Conclusion

References 1. HIRSCHHORN, N. Can small daily doses of antibiotics prevent the cycle of diarrhea, malabsorption, and malnutrition in children? Am. J. Clin. Nutr. 24: 872, 1971. 2. ROSENBERG, I. H., W. R. BEISEL, J. E. GORDON, M. KATZ, G. T. KEUSCH, T. D. LUCKEY AND L. J. MATA. Infant and child enteritis-malabsorption-malnutrition: the potential of limited studies with low-dose antibiotic feeding. Am. J. Chin. Nutr. 27: 304, 1974. 3. SCRIMSHAW, N. S., C. E. TAYLOR AND J. E. GORDON. Interactions of Nutrition and Infection, Monograph Series no. 57. Geneva: World Health Organization, 1968. 4. GRACEY, M. Environmental pollution and diarrheal disease in Jakarta, Indonesia. J. Trop. Pediat. 22: 18, 1976. 5. CAPPARELLI, E., AND L. J. MATA. Microflora of maize prepared as tortillas. Appl. Microbiol. 29: 802, 1975. 6. BEISEL, W. R. Interrelated changes in host metabolism during generalized infectious illness. Am. J. Clin. Nutr. 25: 1254, 1972. 7. ROSENBERG, I. H., N. W. SoLoMoNs AND R. SCHNEIDER. Malabsorption associated with diarrhea and other infections. Am. J. Clin. Nutr. 30: 1248, 1977. 8. LUGO-DE-RIVERA, C., H. RODRIGUEZ AND R. TORRES-PINEDO.





of sugar


malabsorption Nutr.








1248, 1972. 9. SCHENK, E. A., F. KLIPSTEIN AND J. T. TOMASINI. Morphological characteristics of jejunal biopsies from asymptomatic Haitians and Puerto Ricans. Am. J. Chin. Nutr. 25: 1080, 1972. 10. BAKER, S. J., AND V. I. MATHAN. Tropical enteropathy and tropical sprue. Am. J. Chin. Nutr. 25: 1047, 1972. 1 1. ROSENBERG, I. H., AND N. S. SCRIMSHAW. Workshop on malabsorption and nutrition. Am. J. Chin. Nutr. 25: 1046, 1226, 1972. 12. SPRINZ, H., R. SRIBHIBHADH, E. J. GANGAROSA, C. BENYAJATI, D. KUNDEL AND S. HALSTEAD. Biopsy of the small bowel of Thai people. Am. J. Chin. Pathol. 38: 43, 1962. 13. EINSTEIN, L. P., D. M. MACKAY AND I. H. RosENBERG. Pediatric xylose malabsorption in East Pakistan: correlation with age, growth retardation, and weanhing diarrhea. Am. J. Clin. Nutr. 25: 1230, 1972. 14. GORBACH, S. L. Microflora of the gastrointestinal tract in tropical enteritis: a current appraisal. Am. J. Clin. Nutr. 25: 1 127, 1972. 15. MATA, L. J., F. JIMENEZ, M. CORDON, R. ROSALES, E. PRERA, R. E. SCHNEIDER AND F. VITERI. Gastrointestinal flora of children with protein-calorie malnutrition. Am. J. Clin. Nutr. 25: 1118, 1972. 16. GRACEY, M., SUNHARJONO StmtoTo AND D. E. STONE. Microbial contamination of the gut: another feature of malnutrition. Am. J. Chin. Nutr. 26: 1170, 1973. 17. DONALDSON, R. M. Role of enteric microorganisms in malabsorption. Federation Proc. 26: 1426, 1967. 18. STANFIELD, J. P., M. S. R. Him AND R. TUNNICLIFFE. Intestinal biopsy in kwashiorkor. Lancet 2: 519, 1965. 19. SCHNEIDER, R. E., AND F. E. VITERI. Morphological aspects of the duodenojejunal mucosa in proteincalorie malnourished children and during recovery. Am. J. Chin. Nutr. 25: 1092, 1972. 20. LINDENBAUM, J., T. H. Kar AND H. SPRINZ. Malabsorption and jejunitis in American Peace Corps Volunteers in Pakistan. Ann. Internal Med. 65: 1201, 1966. 21. Use of Drugs in Animal Feeds. Proceedings of a symposium. Washington, D. C.: Natl. Acad. Sci., 1969, p. 3. 22. VAN HOUWELING, C. D. FDA Task Force Report-The use of antibiotics in animal feeds. Washington, D. C.: FDA, January, 1972. 23. Juic.aS, T. H. Antibiotics in Nutrition. New York: Medical Encyclopedia, 1955, p. 28. 24. LUCKEY, T. D. Antibiotics in nutrition. In: Antibiotics, Their Chemistry and Non-medical Uses, New York: Von Nostrand, 1959, p. 174. 25. CHAWLA, R. K., T. HERSH, D. W. LAMBE, JR., A. D. WADSWORTH AND D. RUDMAN. Effect of antibiotics on growth of the immature rat. J. Nutr. 106: 1737, 1976. 26. MCCOY, E. Changes in the host flora induced by chemotherapeutic agents. Annu. Rev. Microbiol. 8: 257, 1957. 27. EYSSEN, H., AND R. DESOMER. Effects of Streptococcus faecalis and a filterable agent on growth and nutrient absorption in gnotobiotic chicks. Poult. Sci.

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We have attempted to identify the magnitude of the problem faced as well as the seriousness of the dangers involved in the widespread consumption ofantibiotics by humans. In the face of the real risk to life that is faced by every infant born in areas of the world where poor hygiene, diarrheal disease, and childhood malnutrition are common, we present the position that additional pilot studies of antibiotic use are justified. Such studies could be directed at the entire high risk population between the ages of 6 months and 2 years or they could be targeted at those who demonstrate recurrent or persisting diarrhea or at those who begin to show growth failure. Although the experience with tetracycline in human studies has not produced evidence of unacceptable risk, the danger of emerging strains ofresistant bacteria would be obviated if bacitracin were used as the drug of choice.













44. 45.




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