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

Abstract

SummaryBackgroundKilled whole-cell oral cholera vaccines (kOCVs) are becoming a standard cholera control and prevention tool. However, vaccine efficacy and direct effectiveness estimates have varied, with differences in study design, location, follow-up duration, and vaccine composition posing challenges for public health decision making. We did a systematic review and meta-analysis to generate average estimates of kOCV efficacy and direct effectiveness from the available literature.MethodsFor this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Review Library on July 9, 2016, and ISI Web of Science on July 11, 2016, for randomised controlled trials and observational studies that reported estimates of direct protection against medically attended confirmed cholera conferred by kOCVs. We included studies published on any date in English, Spanish, French, or Chinese. We extracted from the published reports the primary efficacy and effectiveness estimates from each study and also estimates according to number of vaccine doses, duration, and age group. The main study outcome was average efficacy and direct effectiveness of two kOCV doses, which we estimated with random-effect models. This study is registered with PROSPERO, number CRD42016048232.FindingsSeven trials (with 695 patients with cholera) and six observational studies (217 patients with cholera) met the inclusion criteria, with an average two-dose efficacy of 58% (95% CI 42–69, I2=58%) and effectiveness of 76% (62–85, I2=0). Average two-dose efficacy in children younger than 5 years (30% [95% CI 15–42], I2=0%) was lower than in those 5 years or older (64% [58–70], I2=0%; p<0·0001). Two-dose efficacy estimates of kOCV were similar during the first 2 years after vaccination, with estimates of 56% (95% CI 42–66, I2=45%) in the first year and 59% (49–67, I2=0) in the second year. The efficacy reduced to 39% (13 to 57, I2=48%) in the third year, and 26% (−46 to 63, I2=74%) in the fourth year.InterpretationTwo kOCV doses provide protection against cholera for at least 3 years. One kOCV dose provides at least short-term protection, which has important implications for outbreak management. kOCVs are effective tools for cholera control.FundingThe Bill & Melinda Gates Foundation.

Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects

“…Although kOCV with the B-subunit is less preferred for vaccine stockpile applications, our primary results present the kOCV efficacy profile with the B-subunit due to the biological plausibility of the estimates in the time-varying analysis [22] and the recent observation that two-dose vaccine efficacy with and without the B-subunit is likely indistinguishable. [23] Though in reality many other forces likely contributed to the Bentiu PoC Camp's susceptibility to the observed cholera outbreak, our case study shows that known key drivers (namely waning vaccine efficacy, a net influx of susceptible people through population mobility) alone are strong enough to produce the observation that the camp population sustained a cholera outbreak despite recent vaccination campaigns. Provided additional data on the cholera outbreak and the camp population, a complete cholera model fit to the epidemic may yield additional insights.…”

“…Cholera vaccine efficacy has been shown to vary by age of recipient, [22,23,27] however for simplicity and lack of detailed data we do not model this age structure. If children respond poorly to kOCV and are members of a mass vaccination campaign, we would expect herd immunity to wane more quickly, and especially so if children are disproportionate sources of transmission.…”

“…The population compartments of principal interest for this study are individuals who are fully susceptible to disease, S, and those who were vaccinated n-months ago, V n (Fig 1). To account for the observation that kOCV direct effects do not tend to wane exponentially, [22,23] we created an ensemble of n monthly stages (V 1 ,V 2 , . .…”

“…[22,27] Recent meta-analysis results found no differences in twodose efficacy for vaccines with and without the B-subunit. [23] To provide monthly estimates of vaccine efficacy, VE(t), we used published 6-month point estimates with linear interpolations between each. Efficacy after the 5 th year is assumed to be zero, as the estimated mean efficacy becomes negative.…”

The impact of geographic targeting of oral cholera vaccination in sub-Saharan Africa: a modeling study

“…Due to successful campaigns conducted in over 15 countries since 2013 [5], countries that regularly experience cholera are beginning to integrate vaccination with oral cholera vaccine (OCV) into regular public health activities, as recommended by the Global Task Force on Cholera Control (GTFCC) Roadmap to 2030 and general WHO guidance [6]. These vaccines have 49-67% efficacy in protecting vaccine recipients against cholera infection for up to five years [7], thus presenting an important near-term solution to rapidly reducing cholera risk while long-term improvements to safely managed and sustainable water and sanitation services are made. Moreover, killed whole-cell cholera vaccines are known to be very safe; trials for vaccines currently included in WHO stockpiles have not found evidence for vaccine-related adverse events in non-pregnant or pregnant populations [8,9].…”