Protective efficacy of the Shanchol oral cholera vaccine against cholera in a systematic review and meta-analysis of randomized controlled trials

Oral cholera vaccines (OCVs) have become a crucial part of global strategies for cholera prevention, working alongside water, sanitation, and hygiene (WASH) initiatives. However, estimates of vaccine efficacy can vary depending on the context. This systematic review and meta-analysis aimed to assess the protective efficacy of the killed whole-cell bivalent OCV, Shanchol, against laboratory-confirmed cholera. In accordance with PRISMA 2020 guidelines, a comprehensive search was conducted in PubMed, Scopus, the Cochrane Library, EMBASE, and ISI Web of Science for randomized controlled trials (RCTs) published up to February 2022. Eligible studies compared two doses of Shanchol with a placebo or no vaccination in either endemic or epidemic regions. Data were pooled using a random-effects model (DerSimonian–Laird method), with vaccine efficacy (VE) calculated using the formula VE = (1 − OR) × 100. A leave-one-out sensitivity analysis was performed to assess the robustness of the pooled estimate. The risk of bias was assessed using the Cochrane RoB 2 tool, and publication bias was assessed by visual inspection of funnel plots. Six RCTs conducted between 2011 and 2019 in India and Bangladesh met the inclusion criteria, involving a total of 627,982 participants (361,119 vaccinated and 266,863 controls). The pooled odds ratio was 0.41, translating to a vaccine efficacy of 59% (95% CI: 52–65%; p < 0.001). Between-study heterogeneity was moderate (I² = 40%, p = 0.09). All trials showed statistically significant protection in favor of vaccination. Leave-one-out sensitivity analysis confirmed the stability of the pooled estimate. The risk of bias was generally low, and visual inspection of the funnel plot showed no obvious asymmetry. Two doses of Shanchol provide substantial and consistent protection against laboratory-confirmed cholera, with a pooled vaccine efficacy of 59%. These findings support the World Health Organization’s recommendation to use OCVs as a complement to WASH interventions for both outbreak response and ongoing endemic control. Expanding vaccine access, combined with sustained improvements in sanitation and surveillance, is essential for achieving the Global Roadmap to 2030 goal of reducing cholera deaths by 90%.