Geospatial clustering and molecular and social epidemiology of drug resistant TB

描述（由申请人提供）：本申请是为卡伦雅各布森，医学博士，M.P.H.马萨诸塞州总医院传染病科医学助理，正在接受培训，成为耐药结核病流行病学的独立调查员。结核病仍然是全球死亡的主要原因。目前降低结核病发病率、早期发现和治疗的方法正受到耐药菌株出现的影响。为了改善治疗结果，首先需要确定耐药病例不成比例地发生在哪里，以及这些空间集群的特征是什么因素。拟议的研究将使用空间统计学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医疗保健服务失败发生的理解。这项研究的目的是：1）估计南非西开普省耐药结核病的负担，并评估不同地理位置疾病负担的异质性; 2）检查宿主风险因素和人口决定因素与耐药结核病高负担地区的关联; 3）描述该省耐药结核菌株的空间和分子聚集。雅各布森博士的导师团队将由两名主要导师组成，一名在美国，一名在南非：梅根·默里，医学博士，科学博士，哈佛公共卫生学院（HSPH）流行病学副教授，他对结核病的分子和社会流行病学进行研究，罗宾·沃伦博士，斯泰伦博斯大学分子生物学和人类遗传学系副教授，分子生物学家，研究结核病流行社区的结核病遗传学和疾病动力学。雅各布森博士的三位共同导师将是马西娅·卡斯特罗博士，HSPH的人口统计学助理教授，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，斯泰伦博斯大学分子生物学和人类遗传学系副教授，他在过去20年中一直研究耐药结核病分子生物学。Jacobson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：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，她将参加这些领域的课程并接受指导。她将在本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R 01赠款申请，研究拟议研究中确定的可改变因素，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。 公共卫生相关性：尽管有可用的治疗方法和DOTS（直接观察治疗，短期）战略的实施，结核病（TB）仍然是全球死亡率的主要原因，部分原因是该疾病耐药菌株的出现。拟议的研究将使用创新的空间统计和分子流行病学技术来确定南非西开普省耐药结核病负担高的地区，然后调查与这些地区相关的社会决定因素和宿主风险因素。进一步了解这种疾病传播的动力学以及与结核病耐药性相关的潜在可改变的社会人口因素，将有助于制定可在当地和全球应用的改进干预措施。

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.