Xu Hanmeng, Tiffany Amanda, Luquero Francisco J, Kanungo Suman, Bwire Godfrey, Qadri Firdausi, Garone Daniela, Ivers Louise C, Lee Elizabeth C, Malembaka Espoir Bwenge, Mendiboure Vincent, Bouhenia Malika, Breakwell Lucy, Azman Andrew S
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
Global Immunization Division, Centers for Disease Control and Prevention, Atlanta, GA, USA.
Lancet Glob Health. 2025 Jul;13(7):e1203-e1212. doi: 10.1016/S2214-109X(25)00107-X.
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.
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).
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.
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.
Bill & Melinda Gates Foundation.
灭活全细胞口服霍乱疫苗（kOCV）是霍乱流行地区以及疫情暴发和人道主义紧急情况期间的一项标准防控措施。新证据不断涌现，疫苗的使用方式也发生了变化。我们旨在提供关于kOCV所提供保护的最新证据综合分析。
在这项系统评价和荟萃分析中，我们采用与之前系统评价相同的检索程序，以识别报告kOCV针对就医确诊霍乱所提供保护估计值的随机临床试验（RCT）和观察性研究。纳入截至2024年3月8日发表的英文、法文、西班牙文或中文的符合条件的研究，包括之前评价中识别出的研究。提取了关于疗效和有效性的数据，以及剂量数、随访持续时间和年龄组的数据。使用随机效应模型分别汇总疗效和有效性估计值，以估计自接种以来不同时间的保护情况；使用meta回归模型估计按剂量划分的保护情况，作为自接种以来时间的函数。这项更新研究与原始评价一起在PROSPERO（CRD42016048232）上注册。
我们识别出截至2024年3月8日在线发表的8205条记录，包括之前评价中的6224篇文章和我们新检索（2016年1月1日之后）的1981篇文章。其中，53篇符合全文审查条件。纳入了来自23篇出版物的5项RCT和10项观察性研究。接种疫苗12个月后两剂的平均疗效为55%（95%CI 46 - 62），接种疫苗48个月后降至44%（25 - 59）。接种疫苗12个月后两剂的平均有效性为69%（58 - 78），接种疫苗48个月后降至47%（9 - 70）。只有一项RCT评估了单剂疗效，发现在5岁及以上人群中24个月内有持续保护（57%[42 - 69]），而年幼儿童中无显著保护。接种疫苗12个月后单剂的平均有效性为60%（51 - 68），24个月后为47%（34 - 58）。使用特定年龄组的荟萃分析，我们发现5岁以下儿童两剂的平均疗效是年龄较大个体的一半。
两剂kOCV在接种疫苗后至少4年内可预防就医确诊的霍乱。一剂kOCV在接种疫苗后至少2年内提供保护，但衰减速度比两剂快。无论接种剂量多少，5岁以下儿童比5岁及以上儿童受kOCV的保护作用小。
比尔及梅琳达·盖茨基金会。
