Grant: Operating Grant

Vibrio cholerae is a waterborne pathogen that causes 3-5 million cases of cholera and over 100,000 deaths annually, mostly in Bangladesh. The increasing burden of cholera, the inability to achieve benchmarks for sanitation and safe water, and the emergence of pandemic strains of V. cholerae with increased virulence and environmental persistence underscore the need to understand and interrupt the transmission of cholera. Current cholera vaccines are only ~60-85% effective, and immunity lasts for only 2-3 years. Several lines of evidence suggest that V. cholerae was introduced into Haiti by asymptomatic carriers, but the reasons why some infections are asymptomatic, and other highly virulent, are still poorly understood. Also poorly understood is the relative importance of person-to-person (as opposed to waterborne) cholera transmission, and how V. cholerae evolves and adapts within individual infected patients. This research proposal will use whole genome sequencing of V. cholerae strains from cholera patients and their healthy household contacts in Bangladesh and Haiti in order to track the transmission and evolution of V. cholerae in real time. On an applied level, this research may lead to the identification of V. cholerae mutations associated with more severe disease and more effective transmission. These mutations could then be used to design field surveillance tests to identify strains with pandemic potential before they spread - both within endemic regions like Bangladesh, and also globally. Mapping and predicting immune-escape mutations will facilitate the design of a much-needed next generation of cholera vaccines capable of dealing with V. cholerae within-patient diversity and escape mutants. Finally, if person-to-person transmission is found to be an important factor in cholera transmission, this would suggest that more aggressive prophylactic treatment of household contacts may be a highly effective means of controlling epidemics.