Herd immunity conferred by killed oral cholera vaccines in Bangladesh: A reanalysis

Background: Decisions about the use of killed oral cholera vaccines, which confer moderate levels of direct protection to vaccinees, can depend on whether the vaccines also provide indirect (herd) protection when high levels of vaccine coverage are attained. We reanalysed data from a field trial in Bangladesh to ascertain whether there is evidence of indirect protection from killed oral cholera vaccines. Methods: We analysed the first year of surveillance data from a placebo-controlled trial of B subunit-killed whole-cell and killed whole-cell-only oral cholera vaccines in children and adult women in Bangladesh. We calculated whether there was an inverse, monotonic trend for the relation between the level of vaccine coverage in a residential cluster and the incidence of cholera in individual vaccine recipients or placebo recipients residing in the cluster after controlling for potential confounding variables. Findings: Vaccine coverage of the targeted population ranged from 4% to 65%. Incidence rates of cholera among placebo recipients were inversely related to levels of vaccine coverage (7·01 cases per 1000 in the lowest quintile of coverage vs 1·47 cases per 1000 in the highest quintile; p<0·0001 for trend). Receipt of vaccine by an individual and the level of vaccine coverage of the individual's cluster were independently related to a reduced risk of cholera. Moreover, after adjustment for the level of vaccine coverage of the cluster, vaccine protective efficacy remained significant (55% [95% CI 41-66], p<0·0001). Interpretation: In addition to providing direct protection to vaccine recipients, killed oral cholera vaccines confer significant herd protection to neighbouring non-vaccinated individuals. Use of these vaccines could have a major effect on the burden of cholera in endemic settings.