This project entails continuing analyses of data derived from a large- scale, placebo-controlled field trial of B subunit-killed whole cell (BS-WC) and killed whole cell-only (WC) oral vaccines against cholera, conducted between 1985-90 in the Matlab field studies area of the International Center for Diarrheal Disease Research, Bangladesh. The trial enrolled ca. 89,000 subjects for study. Analyses of the first three years of follow-up revealed that each vaccine conferred ca. 50% protection against cholera episodes detected among patients seeking care at medical facilities. Specific goals of analyses conducted during the past year included: 1) evaluation of the efficacy of the vaccines during the fourth and fifth years of follow-up; 2) assessment of whether each vaccine protected against asymptomatic infections by V. cholerae 01, as well as infections causing diarrhea too mild to warrant solicitation of medical care; and 3) analyses of whether the incidence of cholera and death were correlated with participation in the trial per se. These analyses demonstrated that: 1) no protection was evident against treated cholera during the fourth and fifth years of follow-up; 2) during the first year of follow-up, when active surveillance permitted assessment of the comparative efficacy against V. cholerae 01 infections of all grades of severity, both vaccines conferred ca. 3O% protection against asymptomatic infections, and BS-WC (but not WC) both protected against V. cholerae 01 diarrhea and shifted the spectrum of such episodes from more severe to less severe disease; and 3) non-participants in the age-sex groups targeted for the trial exhibited a ca. 3O% higher incidence of both cholera and death than participants who ingested the placebo. Further analyses during the coming year will explore the implications of efficacy vs. effectiveness perspectives for estimates of vaccine protection, as well as other topics addressing the epidemiology of V. cholerae in this setting.
