Population Based Molecular Epidemiology of TB

描述(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基因分型 用流行病学方法阐明流行性感冒的分布和动态 旧金山的肺结核病例。在此期间，我们进行了改进和验证 分子流行病学方法，并系统地应用这些方法 一系列研究被用来指导针对 流行的流行病学情况。这项研究将扩展我们之前的研究 以人群为基础的结核病分子流行病学研究支持 旧金山消除结核病的广泛目标是由 通过旧金山结核分枝杆菌的传播。这 目标只有通过分子的长期应用才能测量 流行病学方法。此外，我们建议为此作出贡献 目的通过利用我们对动力学的详细了解 旧金山结核病检查宿主和患者的遗传因素 与结核分枝杆菌传播有关的微生物 结核病感染向临床结核病的进展。在建议的 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 目前对消除这一疾病的主要障碍。具体目标 被分为四个密切相关的组件，旨在研究 流行性出血热临床与流行病学特征之间的相互关系 结核病与人类宿主和微生物遗传事件之间的关系 这些发现可以迅速转化为结核病控制工作。这个 具体目标分为以下几个方面：1)识别和评估 结核病控制战略；2)接触和 传播；3)宿主基因表达反应的鉴定 区分敏感者和抗药性者；4)鉴定 分枝杆菌因子与接尘后的各种结局相关 传染性肺结核。这些目标的组成部分都与 阐明与结核分枝杆菌传播相关的因素和定向 旨在为旨在防止 变速箱。

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.