Elsevier

The Lancet

Volume 366, Issue 9479, 2–8 July 2005, Pages 44-49
The Lancet

Articles
Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis

https://doi.org/10.1016/S0140-6736(05)66550-6Get rights and content

Summary

Background

Decisions about the use of killed oral cholera vaccines, which confer moderate levels of direct protection to vaccinees, can depend on whether the vaccines also provide indirect (herd) protection when high levels of vaccine coverage are attained. We reanalysed data from a field trial in Bangladesh to ascertain whether there is evidence of indirect protection from killed oral cholera vaccines.

Methods

We analysed the first year of surveillance data from a placebo-controlled trial of B subunit-killed whole-cell and killed whole-cell-only oral cholera vaccines in children and adult women in Bangladesh. We calculated whether there was an inverse, monotonic trend for the relation between the level of vaccine coverage in a residential cluster and the incidence of cholera in individual vaccine recipients or placebo recipients residing in the cluster after controlling for potential confounding variables.

Findings

Vaccine coverage of the targeted population ranged from 4% to 65%. Incidence rates of cholera among placebo recipients were inversely related to levels of vaccine coverage (7·01 cases per 1000 in the lowest quintile of coverage vs 1·47 cases per 1000 in the highest quintile; p<0·0001 for trend). Receipt of vaccine by an individual and the level of vaccine coverage of the individual's cluster were independently related to a reduced risk of cholera. Moreover, after adjustment for the level of vaccine coverage of the cluster, vaccine protective efficacy remained significant (55% [95% CI 41–66], p<0·0001).

Interpretation

In addition to providing direct protection to vaccine recipients, killed oral cholera vaccines confer significant herd protection to neighbouring non-vaccinated individuals. Use of these vaccines could have a major effect on the burden of cholera in endemic settings.

Introduction

The public-health importance of a vaccine is related to the direct protection of vaccinated individuals and to additional indirect (herd) protection, which results from a reduction of the intensity of transmission of the target pathogen among members of vaccinated populations.1, 2, 3, 4 Phase III efficacy trials have typically used individually randomised designs to ensure that measurements of vaccine protective efficacy reflect only the direct effects of the vaccine.5 As a result, decisions about introduction of newly licensed vaccines into public-health programmes often do not consider the substantially greater protection that can occur when a vaccine is deployed in practice than when it is assessed in a trial setting.6

Killed whole-cell cholera vaccines given orally, either with or without cholera toxin B subunit, conferred about 50% protective efficacy against cases of cholera that occurred during 3 years of follow-up in a large-scale, individually randomised field trial in Bangladesh in the 1980s.7 That the vaccination of mothers seemed to reduce the risk of severe cholera in their non-vaccinated children led to the notion of the possible additional indirect protection from these vaccines.8 However, because the level of protective efficacy was moderate, there has been little enthusiasm for their introduction in populations with endemic cholera.

We reanalysed the data from the Bangladesh efficacy trial7 to ascertain whether there was evidence of indirect as well as direct vaccine protection of individuals. Although the trial was individually randomised, levels of vaccine coverage differed substantially within geographic subpopulations in the trial study site. This variation allowed us to analyse cholera risk by level of vaccine coverage and to assess whether there was evidence of indirect vaccine protection.

Section snippets

The Bangladesh trial

This trial was done in the Matlab field area of the International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B): Centre for Health and Population Research.7, 9 A study statistician randomly assigned all children aged 2–15 years and women older than 15 years one of three letter-codes, which corresponded to three agents identical in appearance. The statistician, who was masked to the identity of the codes, used a table of random numbers to allocate individuals to three roughly

Results

Among the vaccine trial target population living in the villages that were mapped with geographic information systems in 1994, there were 49 336 vaccine recipients and 24 667 placebo recipients. Vaccine coverage of baris ranged from 4 to 65%. Within a year of vaccination, 204 cholera cases were detected, 96 (47%) of whom had been vaccinated. 146 (72%) of these cases occurred in baris with only one case.

In simple analyses, the risk of cholera in recipients of two or more doses of either vaccine

Discussion

High levels of cholera vaccine coverage of baris were linked with a reduced risk of cholera both in bari residents who received placebo, for whom a strong inverse relation was observed, and in those who received vaccine, for whom a relation of borderline significance was recorded. These findings suggest that progressively higher levels of vaccine coverage can lead to increasing levels of indirect protection of non-vaccinated individuals and could also lead to progressively higher levels of

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    Citation Excerpt :

    An annual discount rate of 3% was applied to all future cost and DALYs calculations. To account for herd immunity in the analysis, we estimated an S curve of the coverage of the vaccine in relation to risk reduction of those who received no vaccines through a logistic model (Appendix Figure 1), using the prior data from Bangladesh [18] and following the same approach as Lee [12]. In the main analysis, herd immunity (risk reduction among not vaccinated) was included in relation to the population protected by different levels of vaccine coverage.

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