Field trial of oral cholera vaccines in Bangladesh

Abstract

The protective efficacy of oral B subunit killed whole-cell (BS-WC) and killed whole-cell (WC) cholera vaccines was assessed in 63 498 Bangladeshi children aged 2-15 years and women aged over 15 years. Each received three doses of BS-WC, WC, or placebo in a randomised, double-blinded fashion. Surveillance for cases seeking medical care up to six months after the third dose revealed 26 cases of confirmed cholera in the placebo group, 4 cases in the BS-WC group (protective efficacy 85%; p less than 0.0001), and 11 cases in the WC group (protective efficacy 58%; p less than 0.01). For each vaccine protective efficacy was consistent in different age-groups (2-10 years versus greater than 10 years) and for different severities of cholera.

PIP: The protective efficacy of oral B subunit killed whole-cell (BS-WC) and killed whole-cell (WC) cholera vaccines was investigated in 63,498 children aged 2-15 years and females over 15 years of age in Bangladesh. Study subjects received 3 doses of BS-WC, WC, or placebo in a randomized, double-blind fashion. Surveillance for cases seeking medical care up to 6 months after the 3rd dose revealed 26 cases of confirmed cholera in the placebo group, 4 cases in the BS-WC group, and 11 cases in the WC group. The protective efficacy was 85% for BS-WC vaccine and 58% for WC vaccine. The protective efficacy for both vaccines was consistent for both children and adult females. No significant decline in efficacy was noted when the follow-up period was divided into intervals of 14-83 days and 84-176 days. The BS-WC vaccine showed sustained efficacy for both severe and nonsevere cholera, whereas the WC vaccine seemed to be most protective against nonsevere cholera. Overall, these results show that oral vaccination with 3 doses of combined BS-WC vaccine induces high-grade, short-term protection against clinically important cholera and that vaccination with WC induces moderate protection. These data provide support for the concept that intestinal immunity is most relevant for protection against cholera. It remains to be determined whether fewer doses of the oral killed vaccines can yield comparable levels of protection in younger age groups. It is stressed that these results represent only a short-term evaluation of the efficacy of 3 doses of vaccine. Efficacy must be monitored over longer periods, and consideration should be given to testing formulations and dosing schedules that could realistically be incorporated into vaccination programs in developing countries.