D Sethi, JG Wheeler, JM Cowden, LC Rodrigues, PN Sockett, JA Roberts, P Cumberland, DS Tompkins, PG Wall, MJ Hudson, PJ Roderick
A study of infectious intestinal disease in England: plan and methods of data collection
Key words: Summary: The Committee on the Microbiological Safety of Food, set up in 1989 by the Department of Health in response to national epidemics of foodborne infection, considered case control studies the available evidence and commissioned a study of infectious intestinal disease (IID) in cohort studies England. Seventy practices (with 489 500 patients overall) recruited from the Medical Research compliance Council’s General Practice Research Framework between August 1993 and January 1995 diarrhoea collected data for one year. The practice populations were representative of practices in England family practice by area and urban/rural location, but with fewer small and affluent practices. There were five gastrointestinal main components. i) A population cohort of 9776 (40% of those eligible) were enrolled to diseases estimate the incidence and aetiology of IID in the community, and a large proportion were incidence followed up. A median of 10% of patients on practice age-sex registers had moved away or intestinal diseases died. ii) A nested case control component based on cases ascertained in the cohort was used to methods identify risk factors for IID in the community. iii) In a case control component used to risk factors identify risk factors and to estimate the incidence and aetiology of IID presenting in 34 general practices 70% of the 4026 cases returned risk factor questionnaires, 75% submitted stools, and matched controls were found for 75% of cases. iv) An enumeration component was used to estimate the incidence of IID presenting to general practitioners (GPs) in 36 practices and the proportion of specimens sent routinely for microbiological examination. v) In a socioeconomic costs component used to estimate the burden of illness of IID in the community and presenting to GPs 63% of those who returned a risk factor questionnaire also returned a socioeconomic questionnaire and were representative by age, sex, and social class. Despite variable enrolment and compliance the study sample had sufficient power for the multivariable analysis. The characteristics associated with low enrolment and compliance must be considered in the interpretation of the main study results. Commun Dis Public Health 1999; 2: 101-7.
D Sethi, PJ Roderick MRC Epidemiology and Medical Care Unit JG Wheeler, LC Rodrigues, JA Roberts, P Cumberland London School of Hygiene and Tropical Medicine JM Cowden, PN Sockett, PG Wall PHLS Communicable Disease Surveillance Centre DS Tompkins Leeds Public Health Laboratory MJ Hudson Centre for Applied Microbiology and Research On behalf of the Infectious Intestinal Disease Study Executive: JS Brazier, MM Brett, D Brennan, W Browne, PE Cook, JM Cowden, P Cumberland, RP Eglin, N Fasey, S Gordon-Brown, P Hayes, MJ Hudson, V King, JM Kramer, J Martin, C Olohan-Bramley, RJ Owen, JA Roberts, PJ Roderick, LC Rodrigues, B Rowe, D Sethi, HR Smith, MT Skinner, R Skinner, PN Sockett, DS Tompkins, PG Wall, JG Wheeler, AL Wight. Address for correspondence: Dr Dinesh Sethi Department of Public Health and Policy London School of Hygiene and Tropical Medicine Keppel Street London WC1E 7HT tel: 0171 927 2122 fax: 0171 637 5391 email: [email protected]
COMMUNICABLE DISEASE AND PUBLIC HEALTH
Introduction Increases in notifications of food poisoning and reports of cases of campylobacter, salmonella, and listeria infection, and national epidemics of foodborne infections with organisms such as Salmonella enteritidis led the Secretary of State for Health and Minister of Agriculture, Fisheries and Food to set up the Committee on the Microbiological Safety of Food in 1989 (‘Richmond Committee’) 1-4. The committee reported that all indices of infectious intestinal disease (IID) had increased between 1980 and 1990 2 and recommended that a representative sample of all cases of IID in England should be studied to identify causal organisms, estimate the true incidence of disease and its relationship to reported cases, and determine the potential risk factors associated with the acquisition of IID and the costs incurred by individuals and by society. In response the Department of Health commissioned a study of IID in England whose methods are described in this paper. A pilot study carried out in 1991 and 1992 tested the feasibility of the design, established the basis for the sample size calculations, and compared options
VOL 2 NO 2 JUNE 1999
for selection and follow up of subjects in general practice5. The degree of underascertainment of cases presenting with IID in this setting has been discussed6. The main study began in August 1993 and data were collected until January 1996. The following organisations shared responsibility for the main study: the PHLS, including its Communicable Disease Surveillance Centre (CDSC), Leeds Public Health Laboratory (PHL), and PHLS reference laboratories for specific organisms, the Centre for Applied Microbiology and Research (CAMR), the Medical Research Council Epidemiology and Medical Care Unit (EMCU) and the General Practice Research Framework, and the London School of Hygiene and Tropical Medicine (LSHTM).
FIGURE 1 Study design Population cohort component 70 practices
Enumeration component 36 practices
Nested case control component 70 practices
GP case control component 34 practices
Socioeconomic costs component 70 practices
Setting: stratification and selection of practices The General Practice Research Framework is a network of over 800 practices committed to research, that care for about 10% of the registered national population. Based on sample size calculations (described below), a total of 70 volunteer practices were selected from the framework. The country was divided into three areas of similar population sizes for comparison: i) North (former health regions of Northern, Yorkshire, North Western, and Mersey), ii) Midlands and South West (East Anglia, West Midlands, Trent, South Western, and Wessex), and iii) South East (Thames Regions). The number of practices selected in each area was in proportion to the area’s total population according to the 1981 Census. Practices were selected to represent each area’s socioeconomic and urban or rural characteristics. Tertiles of the population distribution of ward-based Jarman deprivation scores 7 were used to stratify by socioeconomic characteristics and Office of Population Censuses and Surveys area aggregates used to classify locations as urban or rural. Design of the main study and study components The study included five main components (figure 1): • a population cohort component to estimate the incidence and aetiology of IID in the community • a nested case control component based on cases ascertained in the cohort to identify risk factors for IID in the community • a GP case control component to identify risk factors and to estimate the incidence and aetiology of IID presenting to GPs • an enumeration component to estimate the incidence of IID presenting to GPs and the proportion of specimens sent routinely for microbiological examination • a socioeconomic costs component to estimate the burden of illness of IID occurring in the community and presenting to GPs. Practice recruitment was staggered between August 1993 and January 1995. Each practice collected data for one year from recruitment. Each practice dedicated a part
VOL 2 NO 2 JUNE 1999
time research nurse to the study. All 70 practices took part in the cohort component and were randomised within each stratum to take part in either the GP case control or the enumeration component (see below). Population cohort with nested case control component Two consecutive cohorts were each followed up for six months. For each cohort, 200 people selected by stratified random sampling by age and sex from the age-sex registers of 70 practices were invited to take part. The notes of people who the nurse could not contact were searched at three months to determine whether they had moved away or died. Participants attended a briefing interview, completed a baseline questionnaire, and were given a stool collection kit. They posted diary cards each week to the nurse, to declare that they had no symptoms of IID that week. Those who developed symptoms (incident cases) were asked to contact the nurse, fill in a risk factor questionnaire, and submit a stool specimen. A control matched for age and sex was selected systematically from the cohort for the nested case control component and asked to submit a stool specimen and fill in a risk factor questionnaire 5. Two consecutive cohorts of six months rather than one of 12 months were used to increase the level of participation5. Age and sex strata with poor responses in the first cohort were oversampled in the second. General practice case control component Cases who presented in the surgery or on home visits were ascertained in 34 practices over one year. Those who fulfilled the case definition (box) were contacted by the nurse and asked to fill in a risk factor questionnaire and submit a stool specimen. Out-ofhours deputising agencies were contacted for details of consultations for IID. For each case up to five sex and age matched controls selected systematically from the register were invited in sequence to attend until one accepted. If the first potential control refused then a second was invited, and so on. Controls were asked to fill in a risk factor questionnaire and submit a stool specimen.
COMMUNICABLE DISEASE AND PUBLIC HEALTH
Case definition People of all ages with loose stools or significant vomiting (more than once in 24 hours, incapacitating, or accompanied by cramps or fever) lasting less than two weeks, in the absence of a known non-infectious cause and preceded by a symptom free period of three weeks. Exclusions: people with non-infectious causes of diarrhoea - such as Crohns disease, ulcerative colitis, cystic fibrosis, and coeliac disease - and non-infectious causes of vomiting such as surgical obstruction, alcohol intoxication, morning sickness, infant regurgitation. Control definition People free of loose stools or significant vomiting for three weeks before the matched case became ill. Controls were matched to cases by age (within age group for children aged 0 to 5 months, within age group for children aged 6 to 11 months, within one year for children aged 1 to 4 years, but not below 11 months, within two years for those aged 5 to 19 years, but not below 4 years, and within five years for adults, but not below 18 years). Controls for cases over 5 years of age were also matched for sex.
General practice enumeration component All cases presenting over one year in 36 practices were eligible for inclusion. GPs were asked to follow their normal clinical practice in requesting laboratory investigations. The research nurse recorded personal and clinical details, whether a stool specimen was taken, and, if so, the results. Deputising agencies were contacted for details of out-of-hours consultations. Socioeconomic costs component Three weeks after inclusion in the cohort, case control, and enumeration components all cases received a socioeconomic questionnaire. Cases who did not return the questionnaire were sent a repeat questionnaire. Stool testing Stool collection kits provided in the case control and cohort components comprised a plastic ‘universal’ specimen pot, a sealable bag, a small plastic spoon, a cardboard box, and an adhesive postage-paid label addressed to Leeds PHL. Microbiological methods and their prioritisation are described in the study protocol8 and the accompanying paper (page 108)8a. Specimens of at least 10 g were needed for complete testing and archiving. Leeds PHL performed initial tests and coordinated further tests at reference laboratories. Clinically significant findings were reported to the local nurse and consultant in communicable disease control. Questionnaires The risk factor questionnaire sent to cases and controls in the GP case control and nested case control components asked for sociodemographic characteristics, clinical details, and known and suspected risk factors for IID, both short and long term (for example, consumption of foods, contact with pets, travel, contact with cases of gastroenteritis, medicines taken, type of accommodation, food handling, social factors)5. The baseline cohort questionnaire sought sociodemographic, accommodation, and food handling details. Non-respondents were sent a questionnaire that asked about family size, social class, and reasons for refusal to take part. The socioeconomic questionnaire asked about household
COMMUNICABLE DISEASE AND PUBLIC HEALTH
composition, income, the impact of the illness in terms of consequent use of resources by individuals, their families, the NHS, and absence from work, and willingness to pay to avoid illness. Questionnaires were modified for child cases and controls.
Data management Staff of the EMCU and the LSHTM coordinated data collection and management. Data were coded, double entered using Epi-Info, validated, and monitored (manually or by computers) at every stage for irregularities9. Practice performance was monitored and progress reports were returned to nurses at six weeks and subsequently every three months. The reports compared the actual number of cases and controls monitored with the numbers predicted by the pilot study5. Regional training nurses made scheduled visits to each practice, investigating any underperformance. Overall study performance was monitored by the IID Executive Committee, which met every three months. Sample size calculations The sample size was selected in order to estimate the incidence of IID in England with a precision of 10% on each side (95% confidence interval), to estimate the incidence in each of the three geographical areas with a precision of 20%, and to ascertain the organisms present in at least 25% of cases8. This was based on the results of the pilot study, which estimated a community incidence of 13.8/100 person years, a presentation rate of 2.13/100 person years, a positive stool rate of 0.108/ 100 person years, and a compliance of about 75%5. The sample size estimates suggested that 70 practices in the cohort study with two six-month cohorts of 90 people each would yield 6300 person years of follow up, and that 35 practices in each of the case control and enumeration components followed up for one year would yield about 280 000 person years of follow up. Within this sample it was calculated that the numbers in the GP case control analysis would be large enough to detect an odds ratio of 2 at the 1% level for exposures with a prevalence of 10% in the population in both adults and children. For reasons of logistics and cost, the GP case control and enumeration components were run in the same practices as the cohort. Statistical analysis The practice and cohort populations were compared with those of England using the national registered population and the Office of National Statistics (ONS) 1994 population estimate respectively10,11. Multiple regression models were developed to predict the practice characteristics associated with list inflation (the retention on GP lists of patients who have moved away or died) and factors associated with low compliance, using Stata software12. Ethics Approval was obtained from the Royal College of General Practitioners, LSHTM, and PHLS and from
VOL 2 NO 2 JUNE 1999
TABLE 1 Study and regional (mid 1994) population distribution by area (North, Midlands and South West, and the South East), and by Jarman score tertiles Population (%) Study practices
North Midlands and South West South East
128 120 (29) 218 788 (44) 148 758 (30)
13 254 200 (27) 21 228 700 (44) 14 049 800 (29)
48 532 700
110 172 (22) 201 813 (41) 183 681 (38)
14 223 630 (30) 14 870 582 (32) 17 960 992 (38)
48 532 700
all 61 local research ethics committees. Written informed consent was obtained from cases and controls by each practice research nurse.
Representativeness GP practice population characteristics The study practice population of 495 660 accounted for 1% of the English population and was representative of the three geographical areas (table 1). The lower tertile (least deprived) of Jarman scores was slightly underrepresented in the study practice population (22%) when compared with England as a whole (30%). A lower proportion of the study population attended GP practices with four or fewer partners (43% ) than did the population of England (58%). The study practice population and the English population were similar as regards age and sex and urban/rural location (62% urban, 61% rural). Community cohort Forty-five per cent of the study population enrolled were male compared with 49% of the national population (table 2, ONS mid-1994 estimate). Enrolment was proportionately lowest in the 15 to 24 year age group when compared with the national population. Fifty-six per cent of the cohort were from TABLE 2 Age and sex distribution of community population taking part in cohort study, compared with population of England (mid 1994 estimate) Cohort population Age (yrs) 104/g and >106/g of faeces, respectively, were considered significant. Isolates were sent to PHLS reference laboratories for confirmation of identity and typing. Clostridium difficile cytotoxin (toxin B) was detected using Vero cells. C. perfringens enterotoxin was detected using an agglutination assay (PET-RPLA; Oxoid, Basingstoke, Hampshire) and positive results confirmed using an in-house enzyme immunoassay12 (EIA) at the Food Hygiene Laboratory of the PHLS Central Public Health Laboratory (CPHL). Conventional light microscopy of a wet film and formol-ether concentrate was used to detect ova, cysts, and parasites. An auramine-stained smear was examined using fluorescence microscopy for cysts of Cryptosporidium parvum and Cyclospora cayetanensis. Transmission electron microscopy (EM) was used to detect viruses, with EIAs for rotavirus group A (Rotascreen; Microgen, Camberley, Surrey) and adenovirus types 40/41 (Adenoclone type 40/41; Cambridge Biotech, Worcester, MA, USA). All astrovirus identifications were confirmed by culture and specific fluorescent antibody testing (Oxford PHL). Rotaviruses detected by EM but not by EIA were subsequently confirmed as rotavirus group C by the Enteric Virus Unit of CPHL using polyacrylamide gel electrophoresis. Written clinical reports were posted to participating surgeries and all clinically significant findings were reported by telephone. Data on microbiological findings were analysed at the London School of Hygiene and Tropical Medicine. Statistical methods The frequency with which organisms were identified in controls was standardised by age to reflect the age distribution of the general population rather than that of the cases. The direct standardisation method was applied, using the mid-1994 population age distribution of England.
Target organism sought
Results All 6743 stools received were cultured for all bacterial target organisms and 90% of them were of sufficient volume for investigation to stage 5 (table 1). Specimens were obtained between 0 and 73 days after the onset of symptoms (median 3 days, mode 1 day). Specimens were received by Leeds PHL between 0 and 45 days after being obtained (median 2 days, mode 1 day). Target organisms or toxins were identified in 54.9% of cases in the GP component and 36.9% in the cohort component (tables 2 and 3). Small round structured virus (SRSV) was the most commonly identified target organism in cases of IID in the community cohort (7% of cases positive). Campylobacter spp. and rotavirus group A were commoner than SRSV in cases in the GP component. The distribution of microorganisms
Aeromonas sp, Bacillus sp, Clostridium difficile, Salmonella sp, Shigella sp, Staphylococcus aureus, Vibro sp, Yersinia sp
Bacterial culture Direct microscopy
Escherichia coli O157, Giardia intestinalis
1-2g faeces to the PHLS Laboratory of Enteric Pathogens (DNA probes) Direct microscopy
Enterovirulent E. coli, Cryptosporidium parvum, Cyclospora cayetanensis
Virology (electron microscopy and enzyme immunoassay
Adenovirus, astrovirus, calicivirus rotavirus, SRSV (Norwalk-like)
Toxin tests culture counts for vegetative cells and spores
C. difficile, C. perfringens, B. cereus, S. aureus
Concentration and Protozoa and helminths for ova, cysts, and parasites
20% frozen suspension
Archiving at CAMR
COMMUNICABLE DISEASE AND PUBLIC HEALTH
undertaken to determine the true incidence of infectious intestinal disease (IID) in England and to estimate the incidence of gastrointestinal disease in the community attributable to a microbiological cause 7. The feasibility of the methodology adopted was confirmed in a pilot study 8. This paper presents the main microbiological results of the study. Further details of the methods are included in an accompanying article9, and other results including incidence, socioeconomic costs, and risk factors will be published in a detailed report 7.
VOL 2 NO 2 JUNE 1999
TABLE 2 Target organisms identified in the GP case control component Cases Number identified Bacteria Aeromonas spp Arcobacter cryaerophilus Bacillus spp (>104/g) Campylobacter spp Clostridium difficile cytotoxin C. perfringens enterotoxin Escherichia coli O157 Enterovirulent E. coli (DNA probes): Attaching and effacing Diffusely adherent Enteroaggregative Enteropathogenic Enterotoxigenic Vero cytotoxigenic (non-O157) Plesiomonas shigelloides Salmonella spp Shigella spp Staphylococcus aureus (>10 6/g) Vibrio spp Yersinia spp Protozoa Cryptosporidium parvum Giardia intestinalis Viruses Adenovirus types 40, 41 Astrovirus Calicivirus Rotavirus group A Rotavirus group C SRSV Organism or toxin not detected
Controls Percentage identified
164 1 4 353 38 114 3
2893 2893 2571 2893 2259 2871 2893
5.7 104/g) Campylobacter spp Clostridium difficile cytotoxin* C. perfringens enterotoxin Escherichia coli O157 Enterovirulent E. coli (DNA probes): Attaching and effacing Diffusely adherent Enteroaggregative Enteropathogenic Enterotoxigenic Vero cytotoxigenic (non-O157) Salmonella spp Shigella spp Staphylococcus aureus (>10 6/g) Vibrio spp Yersinia spp Protozoa Cryptosporidium parvum Giardia intestinalis Viruses Adenovirus types 40, 41 Astrovirus Calicivirus Rotavirus group A Rotavirus group C SRSV
Relative proportion identified (case/control)
95% confidence interval
1.35 0.42 17.31 6.05 5.96 NA
1.05-1.72 0.13-1.40 10.52-28.49 1.81-20.26 3.49-10.17
1.43 0.89 2.64 0.54 NA 0.54 11.43 NA 1.69 NA 0.71
1.06-1.92 0.68-1.17 1.88-3.69 0.15-1.90 0.19-1.50 6.03-21.63 0.58-4.94 0.49-1.04
22.84 13.03 8.46 18.86 NA 23.83
7.23-72.23 5.28-32.14 3.03-23.16 9.70-36.68 10.58-53.69
NA: not applicable (no positive control) SRSV: small round structured virus (Norwalk-like) * aged over 1 year
was licensed for use in the United States in August 199818 and approval for use in the United Kingdom is awaited. C. jejuni was the most frequently identified target organism in the GP component, with group A rotavirus the runner-up, reflecting patterns seen in national surveillance data 2 , although the two sources cannot be compared directly. In routine diagnostic practice many of the target organisms
0 1 2 3 4
GP component Community cases (%) cohort (%) (n=2893) cases (n=761)
Controls (%) (n=2819)
1305 (45.1) 1261 (43.6) 276 (9.5) 48 (1.7) 3 (0.1)
2296 478 41 4
480 (63.1) 232 (30.5) 48 (6.3) 1 (0.1)
Total (%) (n=6473)
(81.4) 4081 (63.0) (17.0) 1971 (30.5) (1.5) 53 (0.8) (0.1) 53 (0.8) 3 (0.1)
and toxins are sought only when travel history, food history, or clinical features indicate a need for specific tests. The relationship between the results of this study, including results of other aspects of this study, and national surveillance data are presented elsewhere 7,19. Salmonellas were isolated more frequently from cases in the GP component (5%) than from cases in the community cohort component (1.1%), reflecting the severity of disease associated with this pathogen. VTEC O157 was isolated and also detected by DNA probes in three cases only in the GP component (0.1%), indicating that cases occur rarely, although affected individuals may have severe disease. Enteroaggregative E.coli, a heterogeneous group associated with diarrhoea in children and adults20, was the most commonly detected enterovirulent E.coli in GP component cases. The rarity of recognised enteropathogens in control subjects was expected, but the relatively high rates of detection of aeromonas, yersinia, diffusely adherent E. coli, and attaching and effacing E.coli in controls in both components of the study suggests that their detection in cases was not always related to IID. Typing of these organisms did not help to identify pathogenic subsets. Aeromonas and yersinia in most cases and controls were isolated only after enrichment, indicating that these microorganisms were present in small numbers in stool specimens. Further studies on archived isolates may help to identify differences in virulence characteristics and improve our understanding of the role of these microorganisms in IID.
TABLE 6 Percentage of stools positive, by age group, for cases with selected target organisms in the GP case control (GPCC) and population cohort (PC) components < 1 year Number of cases submitting specimen: Campylobacter spp Clostridium difficile cytotoxin Clostridium perfringens enterotoxin Salmonella spp Cryptosporidium parvum Adenovirus types 40, 41 Astrovirus Rotavirus group a SRSV and calicivirus
> 74 years
2.0 7.2* 4.0 2.3 0.7 6.9 1.9 21.3 14.7
6.4 28.6* 0.0 0.0 0.0 7.1 7.1 10.3 17.8
5.4 1.7 5.6 2.5 2.8 10.3 6.7 17.3 14.8
6.4 0.9 1.9 1.9 1.3 6.1 4.0 8.8 13.5
11.3 0.6 4.5 5.9 5.0 1.0 3.0 6.7 6.0
3.2 0.0 1.6 2.4 0.8 1.8 0.9 4.5 9.9
16.9 0.7 3.2 6.7 0.5 0.2 1.8 2.3 6.0
3.5 0.3 0.9 0.5 0.0 0.0 1.2 2.0 5.2
9.6 7.6 5.4 0.0 0.0 1.1 1.1 4.4 10.1
4.2 5.3 0.0 0.0 0.0 0.0 0.0 0.0 4.5
* percentage in controls GPCC 16.6, PC 21.0 SRSV: Small round structured virus (Norwalk-like)
VOL 2 NO 2 JUNE 1999
COMMUNICABLE DISEASE AND PUBLIC HEALTH
Acknowledgements We thank the staff of the laboratories that took part in the study, the many individuals who provided helpful comments and guidance, and the surgeries in the MRC’s General Practice Research Framework (listed on page 107) 9.
References 1. Feldman RA, Banatvala N. The frequency of culturing stools from adults with diarrhoea in Great Britain. Epidemiol Infect 1994; 113: 41-4. 2. Wall PG, de Louvois J, Gilbert RJ, Rowe B. Food poisoning: Notifications, laboratory reports and outbreaks – where do the statistics come from and what do they mean? Commun Dis Rep CDR Rev 1996; 6: R93-100. 3. Hunt DA, Shannon R, Palmer SR, Jephcott AE. Cryptosporidium in an urban community. BMJ 1984; 289: 814-6. 4. Skirrow MB. A demographic survey of campylobacter, salmonella and shigella infections in England. Epidemiol Infect 1987; 99: 647-57. 5. PHLS Study Group: Cryptosporidium in England and Wales; prevalence and clinical and epidemiological features. BMJ 1990; 300: 774-7. 6. The Committee on the Microbiological Safety of Food. The microbiological safety of food: part 1. London; HMSO, 1990. 7. Report of the study of infectious intestinal disease in
COMMUNICABLE DISEASE AND PUBLIC HEALTH
England. London: HMSO, 1999 (in press). 8. Roderick P, Wheeler J, Cowden J, Sockett P, Skinner R, Mortimer P, et al. A pilot study of infectious intestinal disease in England. Epidemiol Infect 1995; 114: 277-88. 9. Sethi D, Wheeler JG, Cowden JM, Rodrigues LC, Sockett PN, Roberts JA, et al. A study of infectious intestinal disease in England: plan and methods of data collection. Commun Dis Public Health 1999; 2: 101-7. 10. Smith HR, Scotland SM. Recent developments in laboratory techniques for the detection of diarrhoeagenic Escherichia coli. PHLS Microbiology Digest 1994; 11: 7-12. 11. Hudson MJ, Hill MJ, Elliott PR, Berghouse L, Burnham WR, Lennard-Jones JE. The microbial flora of the rectal mucosa and faeces of patients with Crohn’s disease before and during antimicrobial therapy. J Med Microbiol 1984; 18: 335-45. 12. Bartholomew BA, Stringer MF, Watson GN, Gilbert RJ. Development and application of an enzyme linked immunosorbent assay for Clostridium perfringens type A enterotoxin. J Clin Pathol 1985; 38: 222-8. 13. Caul EO. Viral gastroenteritis: small round structured viruses, caliciviruses and astroviruses. Part II. The epidemiological perspective. J Clin Pathol 1996; 49: 959. 14. Kapikian AZ. Overview of viral gastroenteritis. Arch Virol 1996; 12 [suppl]: 7-19. 15. DeWit MAS, et al. Gastroenteritis in sentinel practices in the Netherlands. In: Proceedings of the 4th world congress on foodborne infections and intoxications. Berlin: Federal Institute for Health Protection of Consumers and Veterinary Medicine, 1998: vol 1: 226-31. 16. Abbink F, et al. A population cohort study with a nested casecontrol study; a study design to estimate the incidence and aetiology of gastroenteritis in the Netherlands. In: Proceedings of the 4th world congress on foodborne infections and intoxications. Berlin: Federal Institute for Health Protection of Consumers and Veterinary Medicine, 1998: vol 2: 766-9. 17. Ryan MJ, Ramsay M, Brown D, Gay NJ, Farrington CP, Wall PG. Hospital admissions attributable to rotavirus infection in England and Wales. J Infect Dis 1996; 174(suppl 1): S12-8. 18. Centers for Disease Control and Prevention, Rotavirus vaccine for the prevention of rotavirus gastroenteritis among children: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1999; 48 (RR-2): 1-23. 19. Wheeler JG, Cowden JM, Sethi D, Wall PG, Rodrigues LC, Tompkins DS, et al. Study of infectious intestinal disease in England: rates in the community, presenting to GPs, and reported to national surveillance. BMJ 1999; 318: 1046-50. 20. Law D, Chart H. Enteroaggregative Escherichia coli. J Appl Microbiol 1998; 84: 685-97. 21. Joint DH/PHLS Working Group. The prevention and management of Clostridium difficile infection. London, Department of Health/PHLS, 1994. 22. Standing Medical Advisory Committee, Sub-Group on Antimicrobial Resistance. The path of least resistance. London: Department of Health, 1998. 23. Goosens H, Sprenger MJW. Community acquired infections and bacterial resistance. BMJ 1998; 317: 654-7.
VOL 2 NO 2 JUNE 1999
C. perfringens enterotoxin was confirmed as an important cause of IID in the community and was commoner in GP patients (4%) than in the population cohort (1.2%). C. difficile cytotoxin was most frequently identified in both cases and controls under 2 years of age, when the organism is a common feature of normal faecal flora21, but was also found in 21 older cases who presented to GPs, associated with prior use of antibiotics 7. Current efforts to reduce unnecessary prescribing of antibiotics may reduce the frequency of associated episodes of diarrhoea 22,23. This study has helped to improve understanding of the microbial causes of IID in England and highlighted the differences between the spectrum of disease in the community as a whole and among those who present to GPs. Results of this study will help medical microbiologists to optimise laboratory protocols for the investigation of stool specimens submitted by GPs. The relative numerical importance of different microorganisms has been clarified but this should be considered alongside the severity of illness that they cause7. Work on archived stool specimens and bacterial isolates will help to provide further useful information.