When is Helicobacter pylori acquired in populations in developing countries? A birth-cohort study in Bangladeshi children

Abstract

Helicobacter pylori colonization is prevalent throughout the world, and is predominantly acquired during childhood. In developing countries, >70% of adult populations are colonized with H. pylori and >50% of children become colonized before the age of 10 years. However, the exact timing of acquisition is unknown. We assessed detection of H. pylori acquisition among a birth cohort of 105 children in Mirzapur, Bangladesh. Blood samples collected at time 0 (cord blood), and at 6, 12, 18, and 24 months of life were examined for the presence of IgG and IgA antibodies to whole cell H. pylori antigen and for IgG antibodies to the CagA antigen using specific ELISAs and immunoblotting. Breast milk samples were analyzed for H. pylori-specific IgA antibodies. Cord blood was used to establish maternal colonization status. H. pylori seroprevalence in the mothers was 92.8%. At the end of the two-year follow-up period, 50 (47.6%) of the 105 children were positive for H. pylori in more than one assay. Among the colonized children, CagA prevalence was 78.0%. A total of 58 children seroconverted: 50 children showed persistent colonization and 8 (7.6%) children showed transient seroconversion, but immunoblot analysis suggested that the transient seroconversion observed by ELISA may represent falsely positive results. Acquisition of H. pylori was not influenced by the mother H. pylori status in serum or breastmilk. In this population with high H. pylori prevalence, we confirmed that H. pylori in developing countries is detectable mainly after the first year of life.

Keywords: CagA; acquisition; breast feeding; developing countries; epidemiology; seroconversion; serological diagnostic testing; seroprevalence; transmission.

Figure 1.

Western blot of H. pylori antigen preparations with human and rabbit serum samples. Panel A. Whole cell preparation of H. pylori 26695; Panel B. Water extracted whole cell antigen (WEWCA), as described. Panel C. Recombinant CagA protein, as described. Sera are: Lane 1, H. pylori⁺/CagA⁺ patient (H, human serum), lane 2, H. pylori⁺/CagA⁻ patient. Lane 3, H. pylori⁻/CagA⁻ patient, and Lane 4, serum from rabbit immunized with purified H. pylori CagA antigen (R, rabbit).

Figure 2.

Serum pepsinogen I (PGI) levels of 18 birth-cohort children. Panel A. PGI levels of samples (n = 20) from children who never seroconverted compared to children with seroconversion (split into samples from children before (n = 21) and after (n = 23) seroconversion). Horizontal bars indicate the mean.**p = 0.001; Panel B. Serum PGI levels over time (mean±SEM ng/ml) in five children who were persistently H. pylori sero-negative and were followed from birth; n = 5 per time point. Panel C. Changes in PGI levels (mean±SEM ng/ml) associated with H. pylori seroconversion in children who became persistently sero-positive. n = 9, 12, 13, 9, 3 for the indicated time points respectively;