POPULATION-BASED MOLECULAR EPIDEMIOLOGY OF TUBERCULOSIS

描述：(改编自申请人的摘要)：这项研究将 利用以人群为基础的分子流行病学来识别和评估 在不同情况下适合的结核病控制策略 流行病学情况。此外，我们还将测试几种不同的 结核分枝杆菌菌株的基因分型方法和意愿 确定技术的最佳组合，以提供最佳的 在追踪生物体的灵敏度和特异度之间取得平衡 人口。该项目的具体目标是根据 它们所涉及的研究的组成部分。组件1：1)使用 基于1S6110的RFLP图谱分析和/或基因分型方法组合 以确定结果是新的结核病病例的比例 最近感染了结核分枝杆菌。2)定义 因新近感染而患上肺结核的人的特征。 3)使用分子流行病学数据来建议和评估特定的 控制干预措施。4)利用本地数据构建数学模型 评估新的控制干预措施效果的模型。5)使用 来自研究网站的信息，以制定评估 候选结核病疫苗。综合起来，这组AIMS将 为结核病控制提供流行病学依据 针对特定流行病学的干预措施 处于危险中的环境或人群。组件2：1)识别两个 结核分枝杆菌的克隆性收集。2)使用各种技术来 对克隆菌株进行基因分型。3)找出最节俭的 可用于定义克隆的基因分型标记的组合。4) 比较克隆分析确定的流行病学联系和 基于IS6110的RFLP模式分析及其密集结果 流行病学调查。这些目标将有助于提供更多 准确、准确地识别和跟踪M。 结核病，从而提高了信息的质量 分子流行病学。这项研究是前瞻性的，以人群为基础。 学习地点将是旧金山、阿拉米达、科斯塔和圣马特奥 旧金山湾区的县和加州中部的六个农村县，索诺马， 索拉诺、尤洛、斯坦尼斯劳斯、圣华金和默塞德。手术方法 将从所有正在研究的新患者中分离出结核分枝杆菌 区域，对这些分离物进行RFLP图谱分析，识别聚集性 具有相同生物体的病例，并进行广泛详细的访谈 对于群集性病例和匹配的对照组，以确定流行病学 关系。

DESCRIPTION: (Adapted from the applicant's abstract): This study will utilize population-based molecular epidemiology to identify and evaluate tuberculosis control strategies that are appropriate under different epidemiologic circumstances. In addition, we will test several different methods for genotyping strains of Mycobacterium tuberculosis and will determine the optimum combination of techniques that provide the best balance of sensitivity and specificity for tracing the organism in a population. The specific aims of the project are grouped according to the component of the study to which they relate. Component 1: 1) To use 1S6110-based RFLP pattern analysis and/or combinations of genotyping methods to determine the proportions of new tuberculosis cases that are the result to recently-acquired infection with M. tuberculosis. 2) To define the characteristics of persons who develop tuberculosis from recent infection. 3) To use molecular epidemiologic data to suggest and evaluate specific control interventions. 4) To use local data to construct mathematical models to estimate the effects of new control interventions. 5) To use information from the study sites to develop approaches to the evaluation of candidate tuberculosis vaccines. Taken together this group of aims will serve to provide the epidemiologic basis for tuberculosis control interventions that are specifically targeted to particular epidemiologic circumstances or populations at risk. Component 2: 1) To identify two clonal collections of M. tuberculosis. 2) To use a variety of techniques to genotype the clonal strains. 3) To identify the most parsimonious combination of genotyping markers that can be used to define clonality. 4) To compare the epidemiologic links identified by clonal analysis and by IS6110-based RFLP pattern analysis with the results of intensive epidemiologic investigations. These aims will serve to provide a more accurate and precise means of identifying and tracking strains of M. tuberculosis thereby improving the quality of the information provided by molecular epidemiology. The study is prospective and population-based. Study sites will be San Francisco, Alameda, Contra Costa, and San Mateo counties in the Bay Area and six rural central California counties, Sonoma, Solano, Yolo, Stanislaus, San Joaquin, and Merced. The method of operation will be to obtain M. tuberculosis isolated from all new patients in study areas, perform RFLP pattern analysis on these isolates, identify clusters of cases having the same organism, and perform an extensive detailed interview for cases in clusters and a matched control group to identify epidemiologic connections.