Molecular Epidemiology and Geospatial Analysis of TB Transmission in Uganda

描述(由申请人提供)：对艾滋病毒如何影响非洲结核病传播动态的不完全理解是知识上的一个重大差距，也是阻断结核病传播的一个重大障碍。确定最近的结核病传播网络的特征，确定正在进行的结核病传播的地点，以及了解艾滋病毒如何影响结核病传播，这些都是在非洲开发新的、战略性的强化结核病病例发现方法的关键步骤。我们的中心假设是，在这种艾滋病毒高流行环境下，大多数最近的结核病传播发生在社区聚集和卫生保健地点，而不是家庭，艾滋病毒感染者与未感染艾滋病毒的人相比，最近结核病传播的风险显著增加。本提案的目标如下：目标1：确定东非农村地区最近的结核病传播网络并确定其特点。我们将对托罗罗市3年来(~360年)所有确诊的、培养阳性的开始结核病治疗的病例进行分子流行病学分析，以确定由结核病分离株的基因聚集性定义的最新结核病传播网络。目的2：通过分析结核病基因聚集性发病病例的地理分布和社会网络，找出结核病频繁传播的地点。我们将结合分子流行病学、地理空间和社会网络数据来确定以高水平结核病传播为特征的结核病传播“热点”。这些“热点”可能发生在商业、社交(如市场、酒吧、教堂)或医疗保健场所。我们将调查艾滋病毒如何在社区一级影响结核病的传播地点目标3：在两个确定的结核病传播风险高的地点进行试点试验，一种以地点为基础的强化结核病病例发现战略。通过有重点的辅导培训和课程，候选人将在分子流行病学、地理信息系统(GIS)分析和流行病学数据的空间分析、社会网络分析以及在资源有限的情况下进行前瞻性临床研究方面培养高级技能。这些科学和事业目标将作为长期研究目标的基础，即在撒哈拉以南非洲进行大规模、全社区范围的定向强化结核病病例发现试验，以减少结核病在艾滋病毒感染者和未感染者中的死亡率和传播。 公共卫生相关性(由申请者提供)：该项目将增进我们对结核病如何在东非艾滋病毒普遍流行的农村社区传播的理解，并作为开发新方法的基础，通过早期诊断和加强病例发现来阻断结核病传播并降低结核病死亡率，这是一个具有重大科学和公共卫生重要性的目标。根据艾滋病毒状况确定结核病传播社区“热点”的位置，使我们有机会试点测试干预措施，以识别新的结核病病例并阻止结核病的后续传播。这项研究的数据将对未来R01研究在撒哈拉以南非洲设计和实施以社区为基础的强化结核病病例发现方法非常有用。

DESCRIPTION (provided by applicant): Incomplete understanding as to how HIV influences TB transmission dynamics in Africa represents a major gap in knowledge and a significant obstacle to disrupting TB transmission. Characterizing recent TB transmission networks, identifying sites of ongoing TB transmission, and understanding how HIV influences TB transmission are all critical steps in developing novel, strategic intensified TB case-finding approaches in Africa. Our central hypotheses are that the majority of recent TB transmission in this high HIV prevalence setting takes place in community gathering and health care sites, as opposed to households, and HIV-infected persons are at significantly increased risk of recent TB transmission compared to HIV-uninfected persons. The objectives of the current proposal are the following: Aim 1: Identify and characterize recent TB transmission networks in an East African rural setting. We will perform molecular epidemiologic analysis of all diagnosed, culture-positive TB cases initiating TB therapy in Tororo Municipality over 3 years (~360) in order to identify recent TB transmission networks defined by genotypic clustering of TB isolates. Aim 2: Locate sites of frequent TB transmission through analysis of the geographic distribution and social networks of genotype-clustered incident TB cases. We will combine molecular epidemiologic, geospatial and social network data to identify TB transmission "hot spots", characterized by high levels of TB transmission. These "hot spots" may occur in commercial, social (e.g. markets, bars, churches), or health care settings. We will investigate how HIV influences where TB is transmitted at a community level Aim 3: Pilot test a place-based intensified TB case-finding strategy at two identified locations of high TB transmission risk. Through a focused program of mentored training and coursework, the candidate will develop advanced skills in molecular epidemiology, Geographic Information System (GIS) analysis and the spatial analysis of epidemiologic data, social network analysis, and the conduct of prospective clinical studies in resource-limited settings. These scientific and career aims will serve as the basis for the long term research goal of conducting large, community-wide trials of targeted intensified TB case-finding in sub-Saharan Africa in order to reduce TB mortality and transmission among HIV-infected and uninfected persons. PUBLIC HEALTH RELEVANCE (provided by applicant): This project will advance our understanding of how TB is spreading through a rural community with a generalized HIV epidemic in East Africa and serve as the foundation for developing novel ways to disrupt TB transmission and reduce TB mortality through early diagnosis and intensified case-finding, a goal of significant scientific and public health importance. Identification of the location of community "hot-spots" of TB transmission by HIV status gives us the opportunity to pilot test interventions to identify new TB cases and stop subsequent transmission of TB. Data from this study will be highly useful to the design and implementation of community-based intensified TB case-finding approaches in sub-Saharan Africa for future R01 studies.