Population Based Molecular Epidemiology of TB

描述（由申请人提供）：自1991年1月以来，我们一直在使用 结核分枝杆菌基因分型与常规 流行病学的方法来阐明的分布和动态 结核病在旧金山弗朗西斯科。在此期间，我们已经完善和验证了 分子流行病学方法，并应用这些方法在一个系统的 一系列研究，已被用来指导干预措施， 流行病学的现状。这项研究将扩展我们以前的研究。 以人群为基础的结核病分子流行病学研究， 在旧金山弗朗西斯科消除结核病的广泛目标是， 结核分枝杆菌在旧金山弗朗西斯科的传播。这 只有通过长期应用分子生物学， 流行病学方法。此外，我们建议为此作出贡献， 目标，利用我们对动态的详细了解， 结核病在旧金山弗朗西斯科检查宿主和 与M.结核病和 结核病感染进展为临床结核病。拟议 我们将结合最先进的分子流行病学和 分子生物学、基因组学和计算生物学的最新进展， 制定有效的结核病控制计划，以解决一些 目前消除这种疾病的主要障碍。具体目标 分为四个密切相关的组成部分，旨在审查 临床和流行病学特征之间的相互关系 结核病和人类宿主和微生物遗传事件，其中 调查结果可以迅速转化为结核病控制工作。的 具体目标如下：1）识别和评价 结核病控制战略; 2）暴露和 3）鉴定宿主基因表达反应， 区分易感者和耐药者; 4）识别 与暴露后各种结果相关的分枝杆菌因素 传染性肺结核这些目标的组成部分都与以下方面有关： 阐明了与M.结核病和定向 旨在为旨在预防的措施提供科学依据， 传输

DESCRIPTION (provided by applicant): Since January 1991 we have been using genotyping ot Mycobacterium tuberculosis together with conventional epidemiological approaches to elucidate the distribution and dynamics of tuberculosis in San Francisco. During this time we have refined and validated molecular epidemiological methods and applied these methods in a systematic series of studies that have been used to guide interventions tailored to the prevailing epidemiological circumstances. This study will extend our previous population-based, molecular epidemiologic studies of tuberculosis in support of the broad objective of eliminating tuberculosis in San Francisco that is caused by the transmission of Mycobacterium tuberculosis in San Francisco. This objective can be measured only by long-term application of molecular epidemiological methods. In addition, we propose to contribute to this objective by utilizing our detailed understanding of the dynamics of tuberculosis in San Francisco to examine genetic factors in both host and microbe that are associated with transmission of M. tuberculosis and progression of tuberculosis infection to clinical tuberculosis. In the proposed studies we will be combining state-of-the-art molecular epidemiology with recent advances in molecular biology, genomics, and computational biology in the setting of an effective tuberculosis control program to address some of the major current impediments to the elimination of the disease. The specific aims have been divided into four closely related components, intended to examine the interrelationships between clinical and epidemiological features of tuberculosis and human host and microbial genetic events in a setting wherein findings can be translated quickly to tuberculosis control efforts. The specific aims are divided as follows: 1) Identification and evaluation of tuberculosis control strategies; 2) Quantification of exposure and transmission; 3) Identification of host gene expression responses that distinguish susceptible and resistant persons; 4) Identification of mycobacterial factors associated with various outcomes following exposure to infectious tuberculosis. The components of these aims are all related to elucidating the factors related to transmission of M. tuberculosis and directed toward providing the scientific basis for measures designed to prevent transmission.