Project Summary/Abstract Cholera is an ancient disease that has shown a remarkable ability to persist and spread in the modern world. On October 21, 2010, isolation of toxigenic Vibrio cholerae O1 from patients living along the Artibonite River was confirmed by the National Laboratory of Public Health of the Ministry of Public Health and Population (MSPP) in Haiti, the first cholera cases identified in Haiti in over 100 years. PFGE, VNTR, and sequence data subsequently demonstrated the essentially clonal relationship among strains, consistent with a point-source introduction of the microorganism. As of August 15, 2015, Haiti has reported a total of 746,469 cholera cases, with 427,841 hospitalizations and 8,985 deaths. After passage of the initial epidemic waves, the disease has moved into a chronic, endemic pattern, with periodic outbreaks associated with the rainy season and/or localized flooding; however, disease burden remains substantial, with 10,328 cholera cases, 8,124 hospitalizations, and 106 deaths reported in the first three months of 2015 alone. Cholera in Haiti, while a public health disaster, also represents a unique ?natural experiment,? where an epidemic has been caused by a single clone introduced onto an island: we have a complete characterization of the initial clone, and know exactly when and where it was introduced, permitting accurate assessments to be made of environmental persistence, transmission, and evolution of the microorganism. Our group from University of Florida has been involved in NIH-funded studies of cholera in a rural area of Haiti west of Port-au-Prince. However, to provide the data necessary for control of the disease in Haiti, we need comparable data from Port-au-Prince, where 1/3 of the Haitian population lives. While most work to date on cholera has been in rural settings, in Bangladesh and India, problems with the disease are increasingly centered in periurban slums/shantytowns in the global mega-cities, sites for which transmission data are limited. The current proposal, written in collaboration with GHESKIO (an organization which has been providing medical and public health services in the periurban slums of Port-au-Prince for over 30 years), seeks to make use of the unique situation in Haiti to address global issues relevant to cholera transmission in urban/periurban slum areas. Specific Aims include the following: Specific Aim 1: Establishment of systematic environmental surveillance for V. cholerae O1 in periurban slum areas of Port-au-Prince, and identification of risk factors for presence of the microorganism; Specific Aim 2: Characterization and identification of risk factors for household cholera transmission, including determination of rates of asymptomatic infection within households; and Specific Aim 3: Application of phylodynamic techniques to assess ongoing evolutionary changes in clinical and environmental V. cholerae O1 strains, and characterization of the evolutionary forces (such as vaccination) driving cholera epidemic waves.