Background
Cholera is a major global public health problem. In 1998, a total of 293,111 cases of cholera and 10,586 deaths from cholera were reported to the World Health Organization. As these numbers are based on official reports, and not all countries with cholera report to WHO, the data are regarded as major underestimates of the true morbidity and mortality due to cholera. Indeed, the public health importance of cholera appears to be increasing, because compared with previous years, these figures represent a significant increase in reported cholera morbidity and mortality worldwide. Also, new epidemics and major outbreaks are continuing to occur, and the number of countries affected by cholera is continuing to increase. In 1994, during an epidemic in a refugee camp in Goma, Democratic Republic of the Congo, an estimated 58,000 - 80,000 cases of cholera and 23,800 deaths from cholera occurred within one month. These worrisome developments have occurred despite persistent efforts to prevent cholera by providing clean drinking water and basic sanitation and by attempting to improve personal, community, and food hygiene. However, these measures to prevent cholera are not always easy to implement and are prone to lapses. Therefore, vaccines constitute an important potential additional tool to prevent cholera. In the past two decades, considerable progress has been made in the development of both live and killed oral cholera vaccines. A Swedish vaccine containing killed whole cells and the B subunit of the cholera toxin has been found to be safe and protective in field studies in Bangladesh and Peru. Another killed oral vaccine partly modeled on the Swedish vaccine but developed, produced, and tested in Vietnam has been found to be safe and protective against cholera. Several live vaccines have been developed or are in various stages of development.

Goals
Against this background, the 5-year goals adopted by the DOMI Program Cholera Working Group are a) to provide data and analyses necessary for rational targeting and implementation of vaccination against cholera in endemic areas; b) to generate the evidence, provide the technical assistance, and obtain the consensus and approvals necessary to introduce, in a rational fashion, killed oral cholera vaccine into the public health programs of at least two cholera-endemic countries in Asia; c) to facilitate and evaluate the use of a WHO-endorsed stockpile of killed oral cholera vaccine in refugee settings; and d) to provide Phase 3 evidence of the efficacy of at least 1 additional newer generation cholera vaccine in a cholera-endemic setting in Asia.

Projects
The Group's activities are being developed in collaboration with the Aga Khan University, Pakistan; the International Center for Diarrheal Disease Research, Bangladesh; the National Institute to Health Research and Development, Ministry of Health, Indonesia; the National Institute of Health and Epidemiology, Ministry of Health, Vietnam; EpiCenter, Paris, France; and MSF (Mecins sans fronties), Switzerland. Six projects are under development. These projects fall in three broad categories: demonstration projects, operational and feasibility study projects, and trials of new vaccines. The demonstration projects are randomized trials aimed at generating evidence about vaccine protective impact, cost-effectiveness, and acceptability to assist policymakers in deliberations about the introduction of the killed whole-cell oral cholera vaccine as a public health tool in cholera endemic areas. The operational and feasibility studies are designed to obtain relevant data to guide programmatic use of the killed whole-cell oral cholera vaccine in refugee, displaced, and endemic area populations at high risk of cholera. Finally, a series of planned trials of the experimental new live oral vaccine candidate, Peru-15, developed at the Harvard Medical School and produced by AVANT Immunotherapeutics are planned for implementation at the International Center for Diarrheal Disease Research, Bangladesh.

Making effective cholera vaccines available to the countries in the region at an affordable price is also a part of the DOMI Program strategy. IVI is engaged in facilitating technology transfer for vaccine production to qualified sites in developing countries with several developed country cholera vaccine producers (SBL Vaccin, Sweden, and AVANT Immunotherapeutics, USA).