This application describes a joint program to study two common and lethal bacterial enteric diseases, shigellosis and typhoid fever, in an endemic area of Lima, Peru. This program will be integrated into the ongoing collaborative Johns Hopkins University - Universidad Peruana Cayetano Heredia program on Acute Diarrheal Diseases and Nutrition. With this grant we plan: 1) To describe the epidemiology of the two diseases within a defined population using new, highly sensitive and specific bacteriologic techniques, active surveillance and case control methods; 2) To develop, based on the descriptive epidemiology, strategies for interventions, both sanitary and immunoprophylatic; 3) To characterize the important bacterial virulence antigens with emphasis on those which elicit local or systemic immune responses that may play a role in protecting the host against reinfection; 4) To characterize the immune response to natural infection and to live vaccines (for typhoid, we will focus on cell medicated immunity (CMI); for shigellosis, we will focus on local intestinal immunity). We anticipate that the following benefits will accrue from the proposed activities: 1) the development of practical and cost effective sanitary interventions; 2) recommendations for use of the Ty21a typhoid vaccine; 3) validation of the CMI response as a surrogate for protection studies to evaluate modifications in the Ty21a vaccine and to standardize future typhoid vaccines; and 4) basic knowledge of the antigens and immune response in shigellosis necessary for the development of a successful vaccine.
