Enterotoxigenic Escherichia coli (ETEC) diarrhea is hyperendemic among young Egyptian children, with a balanced distribution of toxin phenotypes from pathogenic isolates. These features make it logical to develop a field site for the evaluation of ETEC epidemiology and ETEC vaccines in Egypt. We have been engaged in a collaborative program of research in lower Egypt designed to characterize ETEC diarrhea in a pediatric cohort and to test the safety and immunogenicity of a promising killed oral ETEC vaccine candidate in preparation for a field trial of vaccine efficacy,which commenced in January 1999. We have followed a cohort of 397 children under 3 years with twice-weekly active surveillance in Abu Homos (Beheira governorate) to determine the age-specific incidence rate of ETEC diarrhea, by toxin and colonization factor (CFA) phenotypes. During 30 months of follow-up of the children, ETEC was isolated in 25% of diarrheal episodes; the incidence rates of ETEC (episodes per child-year) were 1.7, 1.6, and 0.7 in the first, second, and third years of life. Concurrent with establishment of this surveillance, we conducted randomized, placebo-controlled Phase 2 studies of killed oral ETEC vaccine, administered as a two-dose regimen to 76 adults, 107 children aged 6-12 years, 106 children aged 2-5 years, and 95 children aged 6-18 months in Benha, near Cairo. Each of these studies demonstrated the vaccine to be well-tolerated and to induce significant mucosal immune responses to vaccine antigens. In January 1999, a Phase III trial of the vaccine that will assess the safety, immunogenicity, and clinical efficacy of the vaccine, was initiated in Abu Homos. 192 children 6-18 months of age were randomized to receive either vaccine or placebo, and surveillance for potential adverse effects and diarrheal outcomes continues. In January 2000, an additional 161 children were randomized to receive either vaccine or placebo. The population was followed up for a two period. Results of the trial suggest that the vaccine failed to protect against diarrhea due to ETEC in this population, protective efficacy 20% (95%CI -29%;50%). In June 2000, a Phase II trial of the ETEC vaccine was initiated to evaluate its safety and immunogenicity when administered in conjunction with the expanded program on immunization (EPI) vaccines viz. DTP, Polio and Hepatitis B vaccines. Acute sera prior to immunization and sera after each vaccine dose were obtained for evaluation of antbody responses to each of the component vaccines. Data from this trial are currently being analyzed.
