Geospatial clustering and molecular and social epidemiology of drug resistant TB

描述（由申请人提供）：本申请是为Karen Jacobson， m.d., m.p.h.申请K01奖，她是马萨诸塞州总医院传染病科的医学助理，正在接受培训，以成为耐药结核病（TB）流行病学的独立调查员。结核病仍然是全球死亡的一个主要原因。目前减少结核病发病率的方法，即早期发现和治疗，正因耐药菌株的出现而受到损害。为了改善治疗效果，首先有必要确定耐药病例在哪里不成比例地发生，以及这些空间集群的特征是什么因素。这项拟议的研究将使用空间统计和分子流行病学的创新方法来确定耐药结核病“热点”，以促进对疾病传播和卫生保健服务失败发生的地方的了解。本研究的目的是：1)估计南非西开普省耐药结核病负担，并评估不同地理位置疾病负担的异质性；2)研究宿主危险因素和人口决定因素与耐药结核病高负担地区的关系；3)描述了我省耐药结核菌株的空间和分子聚集性。雅各布森博士的指导团队将由两位主要导师组成，一位在美国，另一位在南非：梅根·默里，医学博士，科学博士。从事结核病分子和社会流行病学研究的哈佛大学公共卫生学院流行病学副教授，以及研究结核病流行社区中结核病遗传学和疾病动态的Stellenbosch大学分子生物学和人类遗传学副教授Robin Warren博士。雅各布森博士的三位共同导师将是HSPH的人口学助理教授Marcia Castro博士，她曾使用空间方法研究传染病动力学；泰德·科恩，医学博士，公共卫生博士。HSPH流行病学助理教授，其研究重点是结核病传播动力学；Stellenbosch大学分子生物学和人类遗传学系副教授Thomas Victor博士，他在过去20年里一直在研究耐药结核病分子生物学。雅各布森博士制定了与她的研究目标相关的三个领域的培训计划：空间统计、调查和人口普查数据分析以及分子流行病学技术，她将在这些领域学习课程并接受指导。她将在项目实施期间接受的培训和指导将为Jacobson博士提供必要的技能和初步数据，以准备R01资助申请，研究拟议研究中确定的可修改因素，目标是制定旨在减少该地区和全球耐药结核病负担的干预措施。

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Tuberculosis (TB) continues to be a major cause of global mortality despite available therapies and DOTS (directly observed treatment, short course) strategy implementation, due, in part, to the emergence of drug resistant strains of the disease. The proposed research will use innovative spatial statistical and molecular epidemiologic techniques to identify regions of the Western Cape Province of South Africa with high drug resistant TB burden and will then investigate the social determinants and host risk factors associated with these regions. Improved understanding of the dynamics underlying transmission of this disease and the potentially modifiable sociodemographic factors associated with TB drug resistance will enable the development of improved interventions that can be applied both locally and globally.