One-dose cholera vaccine may be more effective during epidemic

When vaccine supplies are limited, a single dose of oral cholera vaccine may effectively prevent more cases and deaths than a standard two-dose strategy, according to recent findings.

Andrew S. Azman, PhD, research associate at Johns Hopkins Bloomberg School of Public Health, and colleagues used mathematical models to establish what they termed the “minimum relative single-dose efficacy” (MRSE) at which a single-dose vaccine campaign might equal or surpass the efficacy of a two-dose campaign using the same amount of vaccine during hypothetical epidemics. These were based upon outbreaks in Guinea, Haiti and Zimbabwe. They used data from published randomized and observational studies to estimate the average short-term effectiveness of one- and two-dose oral cholera vaccines (OCVs). For each country they considered scenarios in which either vaccination did not occur, a one-dose strategy was used or a two-dose strategy was used.

The researchers found that the MRSE for an OCV campaign in response to an epidemic depends largely on the timing and extent of the campaign. They estimated that early in an epidemic, the MRSE ranges between 35% and 56%, depending on the vaccine components and the percentage of population coverage. A single-dose campaign is most effective — or with the lowest MRSE — when a large percentage of the population can receive a single dose, thus optimizing the effects of early indirect protection, the investigators wrote. The least effective scenario — with the highest MRSE — for a single-dose campaign occurs when only a small percentage of the population is covered by the vaccine.

The researchers also found that the relative performance of a single-dose campaign increases over the duration of an epidemic. In the hypothetical epidemic scenario, they demonstrated that during epidemic growth, the MRSE decreased by roughly 1% every 3 days, falling to 17% to 32% by the peak of the epidemic. The MRSE continued to drop toward the end of the epidemic, reaching 15% to 25% after its peak.

In terms of short-term OCV efficacy, the researchers estimated that a two-dose protocol would have 77% (95% CI, 57%-88%) efficacy vs. 44% (95% CI, –27% to 76%) efficacy for one dose. This equated to a one-dose relative efficacy estimate of 57% (IQR, 13%-88%), which is above conservative estimates of MRSE. Azman and colleagues predicted that a single-dose vaccination campaign could potentially have averted 70,584 cases and 2,998 deaths in the Zimbabwe outbreak, 78,317 cases and 783 deaths in Haiti, and 2,826 cases and 51 deaths in Guinea. These projected cases are 1.1 to 1.2 times as many as would be avoided through a two-dose campaign. Sensitivity analyses evaluating potential outcomes of campaigns using alternative vaccination times and vaccine efficacy yielded consistent qualitative results.

According to Azman and colleagues, these findings may be useful to public health officials who will need to find ways to maximize limited OCV resources.

“Our analysis shows that there is a low bar for single-dose campaigns, with one dose of vaccine not needing to be more than 50% as efficacious, and perhaps much less, as two doses for a single dose to be preferred in reactive campaigns,” they wrote. “Current evidence suggests that a single dose of Shanchol [Shantha Biotechics] may meet this threshold. However, substantial uncertainty about one-dose efficacy remains, and field studies in areas with periodic outbreaks combined with careful evaluation of any one-dose campaigns should remain a priority.” – by Jen Byrne

Disclosure: The researchers report no relevant financial disclosures.

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Source:

Azman AS, et al. PLoS Med. 2015;doi:10.1371/journal.pmed.1001867.