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。描述最近的结核病传播网络，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，都是在非洲制定新的战略性强化结核病病例发现方法的关键步骤。我们的中心假设是，在这种高艾滋病毒流行率的环境中，大多数最近的结核病传播发生在社区聚会和卫生保健场所，而不是家庭，艾滋病毒感染者与艾滋病毒未感染者相比，最近结核病传播的风险显着增加。本提案的目标如下：目标1：确定和描述东非农村地区最近的结核病传播网络。我们将对托罗罗市3年内（约360例）开始结核治疗的所有确诊、培养阳性结核病例进行分子流行病学分析，以确定最近由结核分离株基因型聚类定义的结核传播网络。目标二：通过分析基因型聚集性结核病病例的地理分布和社交网络，确定结核病频繁传播的地点。我们将联合收割机结合分子流行病学、地理空间和社会网络数据，以确定结核病传播“热点”，其特点是结核病传播水平高。这些“热点”可能发生在商业、社会（例如市场、酒吧、教堂）或医疗保健环境中。我们将调查艾滋病毒如何影响结核病在社区一级的传播目标3：在两个确定的结核病传播高风险地点试点测试一种基于地点的强化结核病病例发现战略。通过有针对性的指导培训和课程计划，候选人将发展分子流行病学，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环境中进行前瞻性临床研究的高级技能。这些科学和职业目标将作为长期研究目标的基础，即在撒哈拉以南非洲地区开展大规模的社区范围试验，有针对性地加强结核病病例发现，以降低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（由申请人提供）：该项目将促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，这是一个具有重要科学和公共卫生意义的目标。通过艾滋病毒状况确定结核病传播的社区“热点”位置，使我们有机会对干预措施进行试点测试，以确定新的结核病病例并阻止结核病的后续传播。本研究的数据将对撒哈拉以南非洲地区未来R01研究设计和实施以社区为基础的强化结核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.