Mass Oral Cholera Vaccination in Zanzibar
Mass Oral Cholera Vaccination in Zanzibar
The purpose of this study is to conduct cholera vaccinations in high-risk populations in
 Zanzibar in order to estimate herd protection conferred by the vaccine,estimate effectiveness
 of the vaccine, and describe the interaction of vaccination and improved water supply on the
 burden of cholera and diarrhoeal diseases.
The seventh cholera pandemic began in Indonesia in 1961 and spread quickly to other Asian
 countries. In 1970, the etiologic agent, Vibrio cholerae O1 El Tor, invaded sub-Saharan
 Africa, whose residents had not experienced cholera for more than 100 years. Outbreaks
 rapidly occurred and the disease has become endemic in several parts of the continent. In
 2006, Africa reported 234,349 cholera cases to the WHO, accounting for 99% of the
 officially-notified global cholera (1). Between 1995 and 2005, 66% of cholera outbreak
 reports to ProMed came from sub-Saharan Africa (2). There is growing evidence of the large
 and increasing burden of cholera in Africa.

 One African country that is severely and repeatedly affected by cholera is Zanzibar. After
 the first case of cholera was confirmed in the country in January 1978, regular outbreaks
 have been reported (3). These outbreaks cause human suffering, are socially disruptive, and
 divert resources from other essential services. Cholera control in Zanzibar has focused
 mainly on case management, water chlorination campaigns, and dissemination of hygiene
 messages. The Ministry of Health and Social Welfare (MOHSW) is eager to identify new and
 effective tools, such as oral cholera vaccination, that could be implemented in Zanzibar.

 In 2002, the World Health Organization (WHO) recommended the potential use of oral cholera
 vaccines in endemic and epidemic situations, but it was deemed necessary to gain more
 experience through demonstration projects (4). Since then, mass oral cholera vaccinations
 have been conducted in Beira, Mozambique (5), in Darfour, Sudan, and in Aceh, Indonesia which
 demonstrated the feasibility and effectiveness of vaccination under actual public health
 conditions. The only oral cholera vaccine available in the market consists of killed
 whole-cell V. cholerae O1 with purified recombinant B-subunit of cholera toxin (WC/rBS)
 administered with a buffer solution as two doses, at least a week apart. The vaccine is
 internationally-licensed (including in Zanzibar) for use in individuals 2 years of age and
 older. This vaccine, and its predecessor (BS-WC) that contained chemically extracted rather
 than recombinant cholera toxin B subunit, have been shown to be safe and protective in
 several trials conducted in cholera-endemic settings in Asia and South America (6-9) and in a
 sub-Saharan African setting with a high prevalence of HIV (5).

 An incompletely answered question regarding this vaccine is its potential to confer herd
 protection (10). The level of herd immunity would determine the minimum vaccine coverage
 required to produce widespread protection against cholera in a community. A recent study
 comparing cholera rates in sites in Asia and Africa has shown that the burden of cholera is
 greatest in young children (11); herd immunity would provide protection for children too
 young to receive the vaccine, as well as other unvaccinated members of the community.
 Although recent re-analysis of data from the large placebo-controlled field trials of the
 oral cholera vaccine in Bangladesh in the 1980s showed substantial herd protection from
 vaccination (12,13), there may be limitations to the applicability of these findings to other
 cholera endemic settings with different living conditions (14). Mathematical modelling of the
 same Bangladesh data found that cholera transmission could be controlled in endemic areas
 with 50% vaccine coverage. At this level of coverage, the model predicted that there would be
 an 89% reduction in cholera cases among the unvaccinated, and a 93% reduction overall in the
 entire population. A more modest coverage of 30% would result in a 76% reduction in cholera
 incidence for the population area covered (15). If confirmed in actual field studies, these
 mathematical predictions have major vaccine cost-effectiveness implications.

 We propose to carry out mass oral cholera vaccinations in populations at high risk for
 cholera in Zanzibar followed by an assessment of direct and indirect protection. The WHO was
 awarded a grant by the Bill and Melinda Gates Foundation entitled: "Pre-emptive use of a
 cholera vaccine in vulnerable populations at risk", under which this proposal will be funded.
 The 6 million US$ grant aims to address issues regarding the potential utilization and
 mechanism of pre-emptive delivery of the vaccine to prevent outbreaks in endemic regions. An
 important component is the potential creation of a "revolving" stock of vaccine and the
 financial sustainability of maintaining such a stockpile.

 The lessons learned from this project will be crucial for informed decisions about the
 potential wider use of cholera vaccination in Zanzibar and other cholera-endemic sub-Saharan
 African countries. The lessons learned from the effectiveness study will form part of the
 evidence for the possible establishment of a sustainable vaccine stockpile. The project would
 provide essential information on the vaccine coverage required to control cholera in endemic
 areas and additional data on vaccine effectiveness in a different setting in Africa.
Inclusion Criteria:

 -  Healthy residents of selected vaccination sites

 -  Aged 2 years and older

 -  non-pregnant

 Exclusion Criteria:

 -  Age less than 2 years

 -  Pregnant