Efficacy of a bivalent killed whole-cell cholera vaccine over five years: a re-analysis of a cluster-randomized trial

Youyi Fong, M Elizabeth Halloran, Jin Kyung Park, Florian Marks, John D Clemens, Dennis L Chao, Youyi Fong, M Elizabeth Halloran, Jin Kyung Park, Florian Marks, John D Clemens, Dennis L Chao

Abstract

Background: Oral cholera vaccine (OCV) is a feasible tool to prevent or mitigate cholera outbreaks. A better understanding of the vaccine's efficacy among different age groups and how rapidly its protection wanes could help guide vaccination policy.

Methods: To estimate the level and duration of OCV efficacy, we re-analyzed data from a previously published cluster-randomized, double-blind, placebo controlled trial with five years of follow-up. We used a Cox proportional hazards model and modeled the potentially time-dependent effect of age categories on both vaccine efficacy and risk of infection in the placebo group. In addition, we investigated the impact of an outbreak period on model estimation.

Results: Vaccine efficacy was 38% (95% CI: -2%,62%) for those vaccinated from ages 1 to under 5 years old, 85% (95% CI: 67%,93%) for those 5 to under 15 years, and 69% (95% CI: 49%,81%) for those vaccinated at ages 15 years and older. Among adult vaccinees, efficacy did not appear to wane during the trial, but there was insufficient data to assess the waning of efficacy among child vaccinees.

Conclusions: Through this re-analysis we were able to detect a statistically significant difference in OCV efficacy when the vaccine was administered to children under 5 years old vs. children 5 years and older. The estimated efficacies are more similar to the previously published analysis based on the first two years of follow-up than the analysis based on all five years.

Trial registration: ClinicalTrials.gov identifier NCT00289224.

Keywords: Cholera; Cluster randomized trial; Randomized control trial; Vaccination.

Conflict of interest statement

Ethics approval and consent to participate

The study protocol was approved by the Drugs Controller General of India, the ethics committee of the National Institute of Cholera and Enteric Diseases, the Health Ministry Screening Committee of India, and the International Vaccine Institute institutional review board.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdi stitutional affiliations.

Figures

Fig. 1
Fig. 1
Monthly number of culture-confirmed cholera cases during the study. The number of confirmed cases among all per-protocol study participants are indicated by the bars, with portions shaded gray to indicate the subset randomized to OCV. A large outbreak occurred in March–April 2010, and the bars representing these two months are indicated with black dots
Fig. 2
Fig. 2
Estimated protective efficacy of OCV over time. Panels plot vaccine efficacy for age groups 1 to under 5 years old (left), 5 to under 15 years old (middle), and 15 years old and older (right). Efficacy estimates are based on model B/T fit to the outbreak-free dataset. 95% point-wise confidence intervals are shown as dashed lines

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