Cohort Study of Guinean Children: Incidence, Pathogenicity, Conferred Protection, and Attributable Risk for Enteropathogens during the First 2 Years of Life

Abstract

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 ...

Pediatric Diarrhea in Southern Ghana: Etiology and Association with Intestinal Inflammation and Malnutrition

“…In support of this notion, almost all prior studies recover EAEC from controls [47][48][49] and from individuals with diarrhea. 17,50 Pathogenic factors may influence the initiation of a symptomatic phase, determined by and include distinct mechanisms as reviewed by Kaper and others.…”

Clonal Relatedness of Enterotoxigenic Escherichia coli Strains Isolated from a Cohort of Young Children in Guinea-Bissau

“…The stool specimens were inoculated and incubated on Statens Serum Institut solid enteric medium (2). Up to 12 (mean, 11.4) individual colonies from each dish were analyzed by DNA-DNA colony hybridization for the presence of the structural genes encoding STp, STh, LT, Shiga-like toxins 1 and 2 (Stx1 and Stx2, respectively), intimin (eae), and invasion plasmid antigen H (ipaH), in addition to the genetic markers for enteroaggregative E. coli and diffusely adherent E. coli (23,25). For each specimen, colonies that were positive for the same gene probes were considered to represent the same strain, and only one was kept for further analyses.…”

Induction of Increased Permeability of Polarized Enterocyte Monolayers by Enterotoxigenic Escherichia coli Heat-Labile Enterotoxin

“…4 Among populations of infants and children in resource-poor areas, infections with ST-producing strains are more strongly associated with illness. 3 Strains producing only LT are often not associated with diarrhea in such settings, 5,6 although first encounters with the pathogen likely result in diarrhea. 3 Importantly, however, colonization with LT-ETEC in the absence of symptoms commonly occurs among those previously exposed to LT, and possibly among some with no immunologic experience.…”

“…3 Strains producing only LT are often not associated with diarrhea in such settings, 5,6 although first encounters with the pathogen likely result in diarrhea. 3 Importantly, however, colonization with LT-ETEC in the absence of symptoms commonly occurs among those previously exposed to LT, and possibly among some with no immunologic experience. 6 The large number of asymptomatic colonization events makes it important to understand the potential ill effects of ETEC exposure, other than fluid and ion secretion.…”

“…[1][2][3] The current paradigm of ETEC pathogenesis suggests that the organism colonizes the small intestine by virtue of proteinaceous colonization factors, previously called colonization factor antigens, followed by the elaboration of heat-stable (ST) enterotoxin and/or heat-labile enterotoxin (LT). 4 Among populations of infants and children in resource-poor areas, infections with ST-producing strains are more strongly associated with illness.…”