Protection from Killed Whole-Cell Cholera Vaccines: A Systematic Review and Meta-Analysis

Author:

Xu Hanmeng,Tiffany Amanda,Luquero Francisco,Kanungo Suman,Bwire Godfrey,Qadri Firdausi,Garone Daniela,Ivers Louise C,Lee Elizabeth C,Malembaka Espoir BwengeORCID,Mendibourne Vincent,Bouhenia Malika,Breakwell Lucy,Azman Andrew S

Abstract

SummaryBackgroundKilled whole-cell oral cholera vaccines (kOCVs) are a standard prevention and control measure in cholera endemic areas, outbreaks, and humanitarian emergencies. Recently, new evidence has emerged and the ways in which the vaccines are used have changed. An updated synthesis of evidence on kOCV protection, is needed.MethodsWe systematically searched for randomized trials and observational studies that reported estimates of protection against confirmed cholera conferred by kOCVs. Eligible studies in English, French, Spanish or Chinese published through March 8, 2024, 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 summarized separately using random effects 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.FindingsTwenty-three publications from five randomized controlled trials and ten observational studies were included. Average two-dose efficacy one-year post-vaccination was 55% (95%CI: 46-62%), declining to 44% (95%CI: 25-59%) four years post-vaccination. Average two-dose effectiveness was 69% (95%CI: 58-78%) one-year post-vaccination declining to 47% (95%CI: 9-70%) four years post-vaccination. Only one randomized trial assessed one-dose efficacy and found sustained protection for two years (52%; 95%CI 8-75%). Average one-dose effectiveness one year after vaccination was 60% (95%CI: 51-68%) and 47% (95%CI: 34-58%) after two years. Through age-group specific meta-analysis average 2-dose efficacy in children under five years old was half that of older individuals.InterpretationTwo doses of kOCV provide protection against medically-attended cholera for at least four years post-vaccination. One-dose of kOCV provides protection for at least two years post-vaccination, but wanes faster than that of two doses. Children under five are less protected by kOCVs compared to those 5 years and older regardless of the number of doses received.FundingBill and Melinda Gates Foundation

Publisher

Cold Spring Harbor Laboratory

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