The study shows that in a densely populated urban housing area in Bangladesh, the majority of children suffer from diarrhea ranging from a minimum of 1 to 14 episodes and ETEC was the major cause. Almost half of the children suffered from ETEC diarrhea, and repeated infections were common. ETEC was also isolated from diarrheal and routine stools of mothers, showing that the fecal/oral route of transmission and carriage are factors that contribute to high rates of infection.
The incidence and prevalence of ETEC diarrhea were similar to the rates predicted in other settings (4
); furthermore, ETEC was detected in significantly higher frequencies in diarrheal children than from healthy children. In community-based studies in developing countries, spanning different continents, ETEC has also been found to be the one of the common pathogens isolated from young children in different studies (2
). However, in a cohort of children in Guinea Bissau (32
), where stools from both healthy and control children were analyzed, rotavirus was the most common.
In the present study, rates of isolation of V. cholerae
as well as Shigella
were low to negligible. The low isolation rates of these pathogens are probably not due to methodological problems, since the specimens were cultured within a few hours after collection and the microbiological techniques used in this study are similar to those used in the routine surveillance system of laboratories at ICDDR, B (3
). The low prevalences of V. cholerae
, and Salmonella
are possibly age related and have been observed in other studies (23
). Enteric parasites were isolated from diarrheal stools and control specimens. We used only routine microscopic examination for detection of parasites in this study and could not use more sensitive methods (15
) that can give a more accurate estimation of prevalence.
The seasonality of ETEC diarrhea in the community was similar to results of hospital-based studies in Bangladesh (3
). In addition, we observed seasonality for toxin types and the CFs CFA/I and CS5 plus CS6. In the spring months, the prevalence of the ST and prominent CFs was highest. A high preponderance of ST ETEC strains was seen in the spring in Egypt (26
). ETEC strains producing ST were most common in children with symptomatic infections (almost 80% were ST- or LT/ST-expressing strains), with CFs predominantly being present on these strains. ETEC strains expressing LT alone were, however, isolated frequently from routine monthly stools which were usually CF negative compared to the LT/ST or ST toxin phenotypes. The low prevalence of CFs on LT ETEC strains has been observed in Argentina, Bangladesh, and Egypt (23
A considerably higher proportion of ETEC strains isolated from diarrheal stools were CF positive in comparison to controls, supporting the concept that possession of CFs is needed for induction of virulence and studies are needed to determine if there are clones that are pathogenic (1
). We also found a high frequency of ETEC reinfections. However, initial infections with ETEC strains expressing CFA/I, CS5 plus CS6, and combinations of CS1 to CS3 were not followed by symptomatic or asymptomatic infections with ETEC strains expressing the homologous CF. Our data on the capacity of major CFs to prevent reinfection fit in well with those available from animal and human studies and support the present strategy of including them in ETEC vaccines (28
). However, this is discordant with results observed from epidemiological studies in Guinea Bissau, which focused on both weekly isolations from children and infections rather than disease (27
Symptomatic or asymptomatic infection with LT ETEC was often followed by reinfection of the same toxin type. Although studies (9
) show that vaccination or natural infection by the LT phenotype is protective, our study was unable to demonstrate a role of LT ETEC in preventing reinfection. The reasons for these discrepant results are obscure, but they may be explained by the different study designs and community settings and also because strains in different locations may produce different levels of toxins and disease severity. We also observed that ETEC of the ST or the ST/LT phenotype did not protect from further ETEC infections of the same toxin phenotype.
Studies including those in Bangladesh (8
) and Mexico (11
) have suggested that breast-feeding is associated with a reduced risk of ETEC diarrhea in infancy. However, it has also been shown that this protection does not last over the first 2 to 3 years of life (8
). In the present cohort, all children were breast-fed in the first 6 months after birth and we also observed that the rate of ETEC diarrhea was lower during this period compared to rest of the study period, which suggests an overall protective effect of breast-feeding only in infancy.
We could not detect rates of ETEC diarrhea in the children in our cohort who were exclusively breast-fed lower than those in children given other types of liquid and weaning food together with breast milk in the initial 6 months. No difference was seen in the rates of diarrhea among these two groups of children in the rest of the 2-year study period.
ETEC diarrhea appeared to be associated with the nutritional status of the children. Thus, those children who had experienced one or more episodes of diarrhea due to ETEC as a single pathogen were significantly more malnourished and growth stunted by 2 years of age than those without any episode of ETEC disease. This is in agreement with earlier studies which have also shown that ETEC diarrheal episodes in early childhood may have a negative effect on the growth of the children (6
). However, additional factors that may dispose these children to malnutrition include other enteric infections as well their overall lower socioeconomic living conditions and contaminated environment (11
In our study, we found ETEC diarrheal episodes were more common in children in the AB or A group than those in the O blood group. A higher incidence of Entamoeba histolytica
-associated diarrhea has been seen in those in the O and AB groups (16
), while a relationship has been found with cholera and the O blood group but not ETEC diarrhea (7
). It has recently been shown that CFA/I binds to glycospingolipids that are associated with blood group antigens that may be expressed on epithelial cells in the small intestine in humans (5
). Thus, the presence of certain blood group antigens on intestinal epithelial cells may predispose to ETEC expressing certain CFs.
An improved understanding of the natural history of ETEC disease during early childhood in areas of high endemicity and factors that may predispose to these diarrheas may assist in the development of interventions such as effective vaccines for developing countries. The results from this study may contribute to such knowledge.