Effectiveness of an oral cholera vaccine in Zanzibar: findings from a mass vaccination campaign and observational cohort study.

BACKGROUND: Zanzibar, in east Africa, has been severely and repeatedly affected by cholera since 1978. We assessed the effectiveness of oral cholera vaccination in high-risk populations in the archipelago to estimate the indirect (herd) protection conferred by the vaccine and direct vaccine effectiveness. METHODS: We offered two doses of a killed whole-cell B-subunit cholera vaccine to individuals aged 2 years and older in six rural and urban sites. To estimate vaccine direct protection, we compared the incidence of cholera between recipients and non-recipients using generalised estimating equations with the log link function while controlling for potential confounding variables. To estimate indirect effects, we used a geographic information systems approach and assessed the association between neighbourhood-level vaccine coverage and the risk for cholera in the non-vaccinated residents of that neighbourhood, after controlling for potential confounding variables. This study is registered with ClinicalTrials.gov, number NCT00709410. FINDINGS: Of 48,178 individuals eligible to receive the vaccine, 23,921 (50%) received two doses. Between February, 2009, and May, 2010, there was an outbreak of cholera, enabling us to assess vaccine effectiveness. The vaccine conferred 79% (95% CI 47-92) direct protection against cholera in participants who received two doses. Indirect (herd) protection was shown by a decrease in the risk for cholera of non-vaccinated residents within a household's neighbourhood as the vaccine coverage in that neighbourhood increased. INTERPRETATION: Our findings suggest that the oral cholera vaccine offers both direct and indirect (herd) protection in a sub-Saharan African setting. Mass oral cholera immunisation campaigns have the potential to provide not only protection for vaccinated individuals but also for the unvaccinated members of the community and should be strongly considered for wider use. Because this is an internationally-licensed vaccine, we could not undertake a randomised placebo-controlled trial, but the absence of vaccine effectiveness against non-cholera diarrhoea indicates that the noted protection against cholera could not be explained by bias. FUNDING: Bill & Melinda Gates Foundation, Swedish International Development Cooperation Agency, and the South Korean Government.

Safety of the recombinant cholera toxin B subunit, killed whole-cell (rBS-WC) oral cholera vaccine in pregnancy.

INTRODUCTION: Mass vaccinations are a main strategy in the deployment of oral cholera vaccines. Campaigns avoid giving vaccine to pregnant women because of the absence of safety data of the killed whole-cell oral cholera (rBS-WC) vaccine. Balancing this concern is the known higher risk of cholera and of complications of pregnancy should cholera occur in these women, as well as the lack of expected adverse events from a killed oral bacterial vaccine. METHODOLOGY/PRINCIPAL FINDINGS: From January to February 2009, a mass rBS-WC vaccination campaign of persons over two years of age was conducted in an urban and a rural area (population 51,151) in Zanzibar. Pregnant women were advised not to participate in the campaign. More than nine months after the last dose of the vaccine was administered, we visited all women between 15 and 50 years of age living in the study area. The outcome of pregnancies that were inadvertently exposed to at least one oral cholera vaccine dose and those that were not exposed was evaluated. 13,736 (94%) of the target women in the study site were interviewed. 1,151 (79%) of the 1,453 deliveries in 2009 occurred during the period when foetal exposure to the vaccine could have occurred. 955 (83%) out of these 1,151 mothers had not been vaccinated; the remaining 196 (17%) mothers had received at least one dose of the oral cholera vaccine. There were no statistically significant differences in the odds ratios for birth outcomes among the exposed and unexposed pregnancies. CONCLUSIONS/SIGNIFICANCE: We found no statistically significant evidence of a harmful effect of gestational exposure to the rBS-WC vaccine. These findings, along with the absence of a rational basis for expecting a risk from this killed oral bacterial vaccine, are reassuring but the study had insufficient power to detect infrequent events. TRIAL REGISTRATION: ClinicalTrials.gov NCT00709410.

Paperless registration during survey enumerations and large oral cholera mass vaccination in Zanzibar, the United Republic of Tanzania.

PROBLEM: Field trials require extensive data preparation and complex logistics. The use of personal digital assistants (PDAs) can bypass many of the traditional steps that are necessary in a paper-based data entry system. APPROACH: We programmed, designed and supervised the use of PDAs for a large survey enumeration and mass vaccination campaign. LOCAL SETTING: The project was implemented in Zanzibar in the United Republic of Tanzania. Zanzibar is composed of two main islands, Unguja and Pemba, where outbreaks of cholera have been reported since the 1970s. RELEVANT CHANGES: PDAs allowed us to digitize information at the initial point of contact with the respondents. Immediate response by the system in case of error helped ensure the quality and reliability of the data. PDAs provided quick data summaries that allowed subsequent research activities to be implemented in a timely fashion. LESSONS LEARNT: Portability, immediate recording and linking of information enhanced structure data collection in our study. PDAs could be more useful than paper-based systems for data collection in the field, especially in impoverished settings in developing countries.