We recruited 200 children shortly after birth and collected stool specimens weekly, irrespective of whether the children had diarrhea, until up to 2 years of age. All children were recruited during the first year of the study and were monitored for a median of 18.4 months. To measure pathogenicity, the odds ratio for diarrhea, adjusted for age, sex, and coinfections with other enteropathogens, was determined by logistic regression. Standard estimation of the population attributable risk indicated that rotavirus, enterotoxigenic Escherichia coli that produced only the heat-stable toxin ST, Isospora spp., Cryptosporidium parvum, Shiga toxin (Stx)-producing E. coli (STEC), and Shigella spp. or enteroinvasive E. coli were the most important contributors to diarrhea in this population. Stx2-but not Stx1-producing STEC strains were pathogenic. Enteroaggregative E. coli, diffusely adherent E. coli, and attaching-and-effacing E. coli strains, which were the most commonly isolated microorganisms, were not associated with diarrhea. For most of the microorganisms, primary infections did not confer protection against reinfection with the same organism, but some conferred protection against diarrhea from reinfection.Diarrheal diseases remain a major cause of childhood mortality and morbidity in developing countries. Although the mortality from diarrheal diseases is declining, diarrheal morbidity is not (27,48). In order to target preventive measures, it is essential to describe the natural history and the relative importance of the various diarrheagenic agents. Moreover, to guide vaccine development, it is important to estimate the protection against reinfection and disease that natural infections with the various enteropathogens may confer.Prospective cohort studies that investigate infections with diarrheal pathogens have been carried out for rotavirus (54), Campylobacter spp. (12)., Shigella spp. (20), Giardia lamblia (37), enterotoxigenic Escherichia coli (ETEC) (2), and other diarrheagenic E. coli strains (7,28,44). Longitudinal studies that describe a wide range of potential enteropathogens are few and were undertaken before the recognition of more recently described diarrheagenic agents, such as enteroaggregative E. coli (EAggEC) and diffusely adherent E. coli (DAEC) (14, 32).We used DNA-DNA colony hybridization to identify diarrheagenic E. coli, Salmonella, and Shigella spp. in a cohort of newborn children who were monitored until up to 2 years of age with weekly stool specimen collection. Furthermore, examinations for rotavirus, Yersinia spp., Campylobacter spp., and enteric parasites, including Cryptosporidium parvum, were undertaken. Our objectives were to identify from a wide range of potential enteropathogens those that were associated with diarrhea, to determine the age of primary infection, to quantify any protection that was induced by natural infection, and to estimate their relative contribution to the incidence of diarrhea in children of a developing country.
MATERIALS AND METHODSStudy design and assembly ...