Molecular approaches for understanding TB dynamics

描述（由申请人提供）：本提案详细介绍了Theodore H. Cohen在传染病流行病学学术生涯发展的5年培训计划。他完成了杜克大学的医学博士学位和北卡罗来纳大学公共卫生学院的公共卫生硕士学位，现在将通过哈佛大学公共卫生学院流行病学系的教学和研究培训来提高他的研究技能。拟议的项目将侧重于开发新的分析工具来评估结核病患者的分子数据。结核病和公共卫生研究的领导者Barry Bloom博士将指导首席研究员的科学发展。他是哈佛大学公共卫生学院院长，培养了许多研究生和博士后研究员。对于相关流行病学方法的高级培训，该计划包括共同导师Megan Murray助理教授和James Robins教授。Murray博士开发了结核病传播的随机模型，并广泛使用分子流行病学数据。詹姆斯·罗宾斯教授是因果推理和流行病学方法方面的主要专家，并在这些技术方面培训了许多学生和博士后。作为结核病研究和流行病学方法的中心，哈佛大学公共卫生学院为这项培训提供了独特的环境。自从开发出结核分枝杆菌DNA指纹鉴定方法以来，分子技术已被用于估计可归因于近期传播的病例比例，记录外源性再感染，确定疾病传播的宿主和菌株特定风险因素。这些研究的方法学问题可能会损害其可解释性，特别是在高发地区。虽然人们越来越认识到这些问题，但在发现改进分子研究分析的方法方面却做得很少。本研究的具体目的是：1)描述结核病在南非和俄罗斯联邦高发地区的传播动态；2)描述耐药菌株在耐药高发地区的传播动态，并确定耐药流行菌株。我们希望，更好的分析技术将允许对治疗和预防进行更准确的评估。

DESCRIPTION (provided by applicant): This proposal details a 5-year training program for the development of Theodore H. Cohen's academic career in infectious disease epidemiology. He has completed a MD at Duke University and a MPH at the UNC School of Public Health and will now enhance his research skills through didactic and research training in the Epidemiology Department at the Harvard School of Public Health. The proposed program will focus on the development of new analytic tools to evaluate molecular data from tuberculosis patients. Dr. Barry Bloom, a leader in tuberculosis and public health research, will mentor the principal investigator's scientific development. He is the Dean of the Harvard School of Public Health and has trained numerous graduate students and post-doctoral fellows. For advanced training in relevant epidemiological methods, the program includes co-mentors, Asst. Prof. Megan Murray and Professor James Robins. Dr. Murray has developed stochastic models of tuberculosis transmission and worked extensively with molecular epidemiological data. Professor James Robins is a leading expert in causal inference and epidemiological methods and has trained many students and post-doctoral fellows in these techniques. As a center of TB research and epidemiological methods, the Harvard School of Public Health offers a unique setting for this training. Since the development of methods for DNA fingerprinting of M. tuberculosis, molecular techniques have been used to estimate the fraction of cases attributable to recent transmission, to document exogenous reinfection, to identify host and strain specific risk factors for disease spread. Methodological problems in these studies may impair their interpretability, especially in high incidence areas. While there is increasing recognition of these problems, little work has been done to discover methods for improving the analysis of molecular studies. The specific aims of this research are: 1) To describe the transmission dynamics of tuberculosis in high incidence areas of South Africa and the Russian Federation and 2) To describe the transmission dynamics of drug-resistant strains in high-incidence areas with a high prevalence of drug-resistance and to identify drug-resistant epidemic strains. It is our hope that better analytic techniques will allow for more accurate assessments of treatment and prevention.