Molecular approaches for understanding TB dynamics

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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.