Date of Award

January 2023

Document Type

Thesis

Degree Name

Master of Public Health (MPH)

Department

School of Public Health

First Advisor

Virginia Pitzer

Second Advisor

Inci Yildirim

Abstract

Introduction: Although killed whole-cell oral cholera vaccines (kOCVs) are widely used as a part of cholera control strategy, mixed evidence around the vaccine induced protection remains.Objectives: The primary objective of this systematic review was to update estimates of kOCV protection: vaccine efficacy and effectiveness. A secondary objective was to estimate the waning dynamic of kOCV protection by duration of follow-up. Methods: On August 15th, 2022, we searched for randomized control trials and observational studies that reported kOCV protection in low- and middle-income countries on PubMed, EMBASE, Scopus, ISI Web of Science, and The Cochrane Review Library with a start date of 1980 and a language restriction to English. For primary estimates, we extracted vaccine protection data at one year of follow-up and recalculated vaccine efficacy and/or effectiveness. We also performed secondary analyses by vaccine type, age, duration of follow-up, dosing schedules, and severity of dehydration. The waning dynamic of kOCV was estimated using a random-effects model. This systematic review adhered to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines and is registered with PROSPERO (CRD42022360028). Results: Seven trials and nine observational studies were included in this systematic review, with an average efficacy of 55% (95% Confidence Interval: 47–62%) and effectiveness of 73% (95% CI: 61–81%) at 1 year of follow-up. We found evidence of waning efficacy in our random-effects model. Vaccine efficacy was lower among children ≤5 years old (11% [95% CI: -26–49%]) than adults >5 years old, (55% [95% CI: 44–66%]). We observed higher efficacy against severe symptoms (61% [95% CI: 48–74%]) than against mild symptoms (54% [95% CI: 30–78%]). Conclusion: We found that one-dose, two-dose, and three-dose regimens of kOCV provide moderate protection for at least two years, with some evidence of longer vaccine protection varying in different age groups.

Comments

This thesis is restricted to Yale network users only. It will be made publicly available on 05/10/2025

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