ETEC EPIDEMIOLOGY AND VACCINE RESEARCH IN LOWER EGYPT

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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 begun a collaborative program to develop a field site near Alexandria for the study of pediatric ETEC diarrhea, and to evaluate the safety and immunogenicity of a promising killed oral ETEC vaccine candidate in preparation for a field trial of vaccine efficacy. This program of projects has followed two pediatric cohorts, one in Abees (Alexandria governorate) and the other in Abu Homos (Beheira governorate) to determine the age-specific incidence rate of ETEC diarrhea from birth to 35 months, by toxin and colonization factor (CFA) phenotype; and to evaluate the protective relationship between titers of serum IgG antibodies to ETEC toxins and CFAs and the risk of diarrhea due to ETEC manifesting these virulence factors. During two years of follow-up of 242 children in Abees, the incidence of ETEC diarrhea was found to be .9 episodes per child-year, and 88% of isolates expressed LT-only or ST-only. Approximately one-fourth of cases were due to an ETEC that expressed a recognized CFA antigen. Among the 286 children followed for one-year in Abu Homos, the incidence of ETEC was 1.4 episodes per child-year, with 80% of isolates expressing LT-only or ST-only, and ca. 40% of isolates expressed a CFA. A randomized, placebo-controlled Phase 2 study of killed oral ETEC vaccine, administered as a two-dose regimen to 76 adults in Benha, near Cairo, demonstrated the vaccine to be well-tolerated and to induce signficant musosal immune responses to vaccine antigens. A similarly designed trial of the vaccine, administered to 110 children aged 6-12 years in the same site was recently conducted. No serious reactions were noted, but definitive analyses await unblinding of the codes.