INTERNATIONAL COLLABORATION IN INFECTIOUS DISEASES

该应用程序描述了一个联合计划，以研究两种常见和致命的 细菌性肠道疾病、志贺氏菌病和伤寒， 位于秘鲁的利马。 该计划将纳入正在进行的 约翰霍普金斯大学-秘鲁卡耶塔诺大学 埃雷迪亚急性腹泻病和营养计划。 有了这笔补助金 我们计划：1）描述这两种疾病的流行病学， 使用新的、高灵敏度和特异性的细菌学 技术，积极监测和病例控制方法; 2）制定， 根据描述性流行病学、干预战略， 卫生和免疫功能; 3）对重要细菌进行鉴定 毒力抗原，重点是那些引起局部或全身 免疫反应可能在保护宿主免受 再感染; 4）表征对自然感染的免疫应答 以及活疫苗（对于伤寒，我们将专注于细胞药物免疫 (CMI);对于志贺氏菌病，我们将侧重于局部肠道免疫）。 我们预计，拟议的 活动：1）开发实用和成本效益高的卫生 干预措施; 2）建议使用Ty 21 a伤寒疫苗; 3） 验证CMI反应作为保护研究的替代， 评估Ty 21 a疫苗的修改，并使未来的标准化 伤寒疫苗;和4）抗原和免疫的基本知识 在志贺氏菌病的反应，必要的发展成功的 疫苗

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.