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Enterotoxigenic Escherichia coli (ETEC), a major cause of infectious diarrhea, produce heat-stable and/or heat-labile enterotoxins and at least 25 different colonization factors that target the intestinal mucosa. The genes encoding the enterotoxins and most of the colonization factors are located on plasmids found across diverse E. coli serogroups. Whole-genome sequencing of a representative collection of ETEC isolated between 1980 and 2011 identified globally distributed lineages characterized by distinct colonization factor and enterotoxin profiles. Contrary to current notions, these relatively recently emerged lineages might harbor chromosome and plasmid combinations that optimize fitness and transmissibility. These data have implications for understanding, tracking and possibly preventing ETEC disease.

Helicobacter pylori colonizes the gastric and duodenal mucosa. The infection normally persists for life and causes peptic ulcers and gastric cancer in a subset of infected individuals. We hypothesized that the inability to clear the infection may be a consequence of H. pylori-specific regulatory T cells that actively suppress T-cell responses. Therefore, we characterized the T-cell responses to H. pylori in H. pylori-infected individuals without any subjective symptoms and in uninfected control subjects and investigated the role of regulatory CD4

A cohort of 321 children was followed from birth up to 2 years of age to determine the incidence of enterotoxigenic Escherichia coli (ETEC) in Bangladesh. The average number of diarrheal days and incidence rates were 6.6 and 2.3/child/year, respectively. ETEC was the most common pathogen and was isolated in 19.5% cases, with an incidence of 0.5 episode/child/year. The prevalence of rotavirus diarrhea was lower (10%). ETEC expressing the heat-stable enterotoxin (ST) was predominant. Strains isolated from diarrheal cases were positive for colonization factors (CFs) in higher frequency (66%) than from healthy children (33%) (P < 0.001). The heat-labile toxin (LT)-positive strains from healthy children were more often CF negative (92%) than those isolated from children with diarrhea (73%) (P < 0.001). In children with symptomatic or asymptomatic infections by CFA/I, CS1 plus CS3, CS2 plus CS3, or CS5 plus CS6 strains, a repeat episode of diarrhea or infection by the homologous CF type was uncommon. Repeat symptomatic infections were noted mostly for LTand ST-expressing ETEC. ETEC diarrhea was more prevalent in children in the A and AB groups than in those in the O blood group (P ‫؍‬ 0.032 to 0.023). Children with ETEC diarrhea were underweight and growth stunted at the 2-year follow-up period, showing the importance of strategies to prevent and decrease ETEC diarrheal morbidity in children.Enterotoxigenic Escherichia coli (ETEC) is a common cause of acute watery diarrhea in children in developing countries (25). ETEC is a multivalent pathogen producing the heatstable (ST) and/or heat-labile toxin (LT) as well as over 25 colonization factors (CFs). The ST phenotype of ETEC has been shown to be predominant (23,25), while the most common of the CFs are CFA/I and CS1 to CS6 (14,23,25,37). Studies in animals and in humans suggest that immunity against both LT and CFs may be important for protection against ETEC. However, results from different studies are conflicting regarding the relative importance of different toxin types and/or CFs on protection from further disease and infection (11,18,27,32), and data from different settings are needed to elucidate whether ETEC strains expressing these different virulence factors may prevent against repeated episodes of diarrhea. The first longitudinal study to determine the relationship between ETEC and other enteric pathogens and the incidence of diarrhea of children in a birth cohort was carried out in Mexico (10). In the present study, we have evaluated the natural history of ETEC infections, with emphasis on the different phenotypes, during the first 2 years of life in a birth cohort of 321 children in an urban slum area in Dhaka, Bangladesh. This included evaluation of the incidence, seasonality, and occurrence of symptomatic and asymptomatic ETEC infections. We have also evaluated whether blood group and nutritional factors may predispose to ETEC diarrhea. For comparison, we have also studied the incidence of other common enteric infections. MATERIALS AND METHODS Study popul...

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In rural Bangladesh, family contacts of patients with cholera were studied prospectively to examine whether protection against colonization and disease due to Vibrio cholerae O1 was associated with circulating antibodies to V. cholerae. Family contacts (1,071) of 370 patients with cholera were visited daily for 10 days, cultured for V. cholerae, and queried about diarrhea. Sera collected on days 1 and 21 were assayed for vibriocidal antibodies, IgG and IgA antibodies to cholera toxin, and IgG antibodies to lipopolysaccharide (LPS). Vibriocidal titers of greater than or equal to 20 present in 50% of contacts by 20 years of age were associated with protection against both colonization and disease. An elevated level of IgG antitoxin was not associated with protection against colonization or disease but was the most sensitive indicator of recent symptomatic cholera and of immune response to the oral immunogen B subunit. IgG antibody to LPS and IgA antitoxin were of little value in predicting colonization or disease.

At the Matlab Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, the authors examined the blood groups of patients hospitalized between January and September 1979 for diarrheal disease due to a variety of bacterial and viral agents. A significant association was identified only for cholera, in which cholera patients were twice as likely to have blood group O and one-ninth as likely to have blood group AB as community controls. A follow-up study of family contacts of cholera patients, carried out between September 1980 and July 1982, indicated that blood group did not affect an individual's risk of having a culture-proven infection with V. cholerae 01 but was directly related to the severity of disease. Individuals with the most severe diarrhea compared with those with asymptomatic infection were more often of blood group O (68% versus 36%, p less than 0.01) and less often of AB (0% versus 7%, p less than 0.01). It was not possible to identify the molecular basis for this genetically related protection using biologic models of cholera that are currently available. The constant selective pressure of cholera against people of O blood group may account in part for the extremely low prevalence of O group genes and the high prevalence of B group genes found among the people living in the Gangetic Delta.

Enterotoxigenic Escherichia coli (ETEC) is one of the main causes of childhood diarrhea in developing countries and in travelers. However, this pathogen has often not been reported in surveys of diarrheal pathogens, due to lack of simple standardized methods to detect ETEC in many laboratories. ETEC expresses one or both of two different enterotoxin subtypes: heat-stable toxins, a heat-labile toxin (LT), and more than 22 different colonization factors (CFs) that mediate adherence to the intestinal cell wall. Here we compare established phenotypic and genotypic detection methods and newly developed PCR detection methods with respect to sensitivity, specificity, positive predictive value, and ease of performance. The methods include GM1-enzyme-linked immunosorbent assay and dot blot techniques using specific monoclonal antibodies (MAbs) for phenotypic detection of the toxins and CFs, respectively, as well as different PCR and DNA/DNA hybridization techniques, including new PCR assays, for genotypic identification of the toxin and CF genes, respectively. We found very good general agreement in results derived from genotypic and phenotypic methods. In a few strains, LT and CFs were identified genetically but not phenotypically. Based on our analyses, we recommend initial screening for ETEC in clinical samples by multiplex toxin gene PCR. Toxin-positive strains may then be analyzed by dot blot tests for detection of the CFs expressed on the bacterial surface and by PCR for determination of additional CFs for which MAbs are currently lacking as well as for strains that harbor silent CF genes.Enterotoxigenic Escherichia coli (ETEC) is one of the main causes of morbidity and mortality in children under the age of five in developing countries and in travelers and soldiers positioned in these areas (3,18,21,25). ETEC has, however, been grossly underestimated as the cause of diarrhea in many studies, mainly because few laboratories have suitable methods in place for ETEC diagnostics (18). Hence, it is of great importance to introduce simple and reliable methods for diagnosis of ETEC in all laboratories that are involved in identifying microbes associated with diarrhea. This study was undertaken to identify ETEC diagnostic methods that are suitable for more widespread introduction into research and clinical laboratories.ETEC expresses one or both of two types of toxin: heatstable toxin (ST) and heat-labile toxin (LT), both of which induce diarrhea. The ST toxin is encoded by two different genes, estA and st1, both of which code for small peptides (19 and 18 amino acids) with similar functions and gene sequences. The translated toxins are called STh (estA), originally found in ETEC isolated from humans, and STp (st1), found in ETEC isolated from pigs. The ST genes may be expressed alone or in combination with the LT genes eltA and eltB. Since eltAB may also be expressed alone, there are seven possible toxin combinations that can be expressed in individual ETEC strains: STh, STp, STh/LT, STp/LT, LT, and less commonly, STh/STp...