Geospatial clustering and molecular and social epidemiology of drug resistant TB

项目摘要 这份申请是为了凯伦·雅各布森医学博士的K 01奖，M.P.H.一个部门的医学助理 马萨诸塞州总医院的传染病科主任，他正在接受培训，成为一名独立的 耐药结核病（TB）流行病学调查员。结核病仍然是导致 全球死亡率。目前降低结核病发病率的方法，即早期发现和治疗， 因为出现了耐药菌株为了改善治疗效果，首先 有必要确定耐药病例发生不成比例的地方以及这些病例的特征是什么 空间集群。拟议的研究将使用空间统计和分子生物学方面的创新方法。 流行病学，以确定耐药结核病“热点”，以促进了解疾病传播的地方 和医疗服务的失败。本研究的目的是：（1）估计药物负担 南非西开普省耐药结核病的研究，并评估 不同的地理位置; 2）检查宿主风险因素和人口决定因素之间的关联 高耐药结核病负担地区; 3）描述菌株的空间和分子聚类 耐药结核病的发病率雅各布森博士的导师团队将由两名主要导师组成，一名 一位在美国，一位在南非：梅根·默里，医学博士，科学博士，流行病学副教授， 哈佛公共卫生学院（HSPH），他对艾滋病的分子和社会流行病学进行了研究。 结核病和罗宾·沃伦博士，分子生物学和人类遗传学系副教授， 斯泰伦博斯大学的分子生物学家，他研究了结核病的遗传学和疾病动力学 流行病社区。雅各布森博士的三位共同导师将是马西娅·卡斯特罗博士，助理教授 HSPH的人口统计学，他使用空间方法研究传染病动力学; Ted Cohen， 医学博士，P.H.博士HSPH流行病学助理教授，其研究重点是结核病传播 动力学;和托马斯维克托，博士，分子生物学和人类学系副教授 在过去的20年里， 年雅各布森博士在三个领域制定了一项培训计划，这些领域与她的研究目标有关： 统计，调查和人口普查数据分析，分子流行病学技术，她将参加课程 并在每个领域接受指导。她将接受的培训和指导 该项目的实施将为雅各布森博士提供必要的技能和初步数据， 准备R 01资助申请，以研究拟议研究中确定的可修改因素，目标是 制定干预措施，旨在减少本区域和全球耐药结核病负担。

PROJECT SUMMARY This application is for a K01 award for Karen Jacobson, M.D., M.P.H., an Assistant in Medicine in the Division of Infectious Diseases at the Massachusetts General Hospital, who is training to become an independent investigator in the epidemiology of drug resistant tuberculosis (TB). TB continues to be a major cause of mortality globally. The current approach to decreasing TB incidence, early detection and treatment, is being compromised by the emergence of drug resistant strains. In order to improve treatment outcomes, it is first necessary to identify where drug resistant cases occur disproportionately and what factors characterize these spatial clusters. The proposed study will use innovative methods in spatial statistics and molecular epidemiology to identify drug resistant TB "hotspots" to advance understanding of where disease transmission and heath care delivery failure are occurring. The aims of the study are: 1) To estimate the burden of drug resistant TB in the Western Cape Province, South Africa, and assess the heterogeneity of disease burden in different geographic locations; 2) To examine the association of host risk factors and population determinants with regions of high drug resistant TB burden; and 3) To describe the spatial and molecular clustering of strains of drug resistant TB in this province. Dr. Jacobson's mentoring team will consist of two primary mentors, one in the U.S. and one in South Africa: Megan Murray, M.D., Sc.D., Associate Professor of Epidemiology at the Harvard School of Public Health (HSPH), who conducts research on the molecular and social epidemiology of TB, and Robin Warren, Ph.D., Associate Professor in the Division of Molecular Biology and Human Genetics at Stellenbosch University, a molecular biologist who has studied TB genetics and disease dynamics in TB epidemic communities. Dr. Jacobson's three co-mentors will be Marcia Castro, Ph.D., an Assistant Professor of Demography at HSPH, who has used spatial methods to study infectious disease dynamics; Ted Cohen, M.D., Dr.P.H., an Assistant Professor of Epidemiology at HSPH whose research focuses on TB transmission dynamics; and Thomas Victor, Ph.D., an Associate Professor in the Division of Molecular Biology and Human Genetics at Stellenbosch University, who has studied the drug resistant TB molecular biology for the past 20 years. Dr. Jacobson has developed a training plan in three areas that link to her research aims: spatial statistics, survey and census data analysis, and molecular epidemiologic techniques, and she will take courses and receive mentoring in each of these areas. The training and mentoring she will receive during the implementation of this project will provide Dr. Jacobson with the necessary skills and preliminary data to prepare an R01 grant application to study the modifiable factors identified in the proposed study, with the goal of developing interventions aimed at decreasing drug resistant TB burden in the region and globally.