Protection from killed whole-cell cholera vaccines: a systematic review and meta-analysis

BACKGROUND

Killed whole-cell oral cholera vaccines (kOCVs) are a standard prevention and control measure in cholera-endemic areas and during outbreaks and humanitarian emergencies. New evidence has emerged and the ways in which the vaccines are used have changed. We aimed to provide an updated synthesis of evidence on protection conferred by kOCV.

METHODS

In this systematic review and meta-analysis, we used the same search procedure as a previous systematic review to identify randomised clinical trials (RCTs) and observational studies that reported estimates of protection conferred by kOCVs against medically attended, confirmed cholera. Eligible studies in English, French, Spanish, or Chinese published up until March 8, 2024, including those identified in the previous review, were included. Data on efficacy and effectiveness were extracted, as were the number of doses, duration of follow-up, and age group. Efficacy and effectiveness estimates were summarised separately using random-effect models to estimate protection by time since vaccination; meta-regression models were used to estimate protection, by dose, as a function of time since vaccination. This updated study is registered along with the original review with PROSPERO (CRD42016048232).

FINDINGS

We identified 8205 records published online up until March 8, 2024, including 6224 articles from the previous review and 1981 articles from our new search (after Jan 1, 2016). Of these, 53 were eligible for full-text review. Five RCTs and ten observational studies from 23 publications were included. Average two-dose efficacy 12 months after vaccination was 55% (95% CI 46-62), declining to 44% (25-59) 48 months after vaccination. Average two-dose effectiveness was 69% (58-78) 12 months after vaccination, declining to 47% (9-70) 48 months after vaccination. Only one RCT assessed one-dose efficacy and found sustained protection for 24 months (57% [42-69]) among those 5 years and older with no significant protection in younger children. Average one-dose effectiveness 12 months after vaccination was 60% (51-68) and after 24 months was 47% (34-58). Using age group-specific meta-analysis, we found that average two-dose efficacy in children younger than 5 years was half that of older individuals.

INTERPRETATIONS

Two doses of kOCV provide protection against medically attended cholera for at least 4 years after vaccination. One dose of kOCV provides protection for at least 2 years after vaccination, but wanes faster than that of two doses. Children younger than 5 years are less protected by kOCVs than those aged 5 years and older, regardless of the number of doses received.