Transmission of drug-resistant tuberculosis in a South African city with a high prevalence of HIV infection

项目概述：该申请是为Rebecca Berhanu MD申请的K08奖

PROJECT SUMMARY: This application is for a K08 award for Rebecca Berhanu MD, an Instructor in the Department of Global Health in the School of Public Health at Boston University, who is training to become an independent investigator in the field of tuberculosis (TB) transmission research, molecular epidemiology and social network analysis. TB is the leading infectious cause of death globally and the number one cause of death amongst people with HIV. New tools, including interventions designed to interrupt transmission, are required to stem the epidemic. The identification of recent TB transmission clusters by whole genome sequencing (WGS) and social network analysis offers unique insight into transmission patterns which cannot be obtained through traditional contact tracing methods. The overall research objective is to use phylogenetic analysis, molecular epidemiology and social network analysis to characterize recent transmission clusters of rifampin and multi-drug resistant (RR/MDR)TB in Johannesburg, South Africa. The aims of the study are to: 1) Use WGS to calculate the molecular clock of RR/MDR-TB 2) Evaluate the impact of HIV status and CD4 count on the likelihood of transmitting TB using cluster-based and source attribution analysis and 3) Conduct a pilot study to determine if social network analysis can be combined with WGS data to identify locations of recent transmission of RR/MDR-TB in a high TB burden setting. Dr Berhanu will receive mentorship from a team of inter-disciplinary experts in TB epidemiology, bioinformatics and TB genomics. Her primary mentor Dr Horsburgh is a Professor of Medicine and Epidemiology at Boston University and has over 30 years of experience in TB clinical and translational research. Her co- primary mentor Dr. Karen Jacobson, an Assistant Professor of Medicine at Boston University, is an expert in TB epidemiology in high burden settings and has worked extensively in South Africa using TB molecular data. Dr. Berhanu’s Advisory Board includes Dr. Maha Farhat, Assistant Professor of Biomedical Information at Harvard University, who has published extensively on WGS studies of Mycobacterium tuberculosis (MTB); Dr. Nazir Ismail, the head of the Centre for Tuberculosis of the NICD in Johannesburg, an expert in the molecular epidemiology of MTB and Dr. Evan Johnson, Associate Professor of Medicine and Biostatistics at Boston University, with expertise in bioinformatics analysis and interpretation. Dr. Berhanu’s training plan links to the proposed research aims: establish a solid foundation in epidemiology including social network analysis; develop skills in molecular epidemiology and phylogenetic analysis; and gain familiarity with WGS and biostatistical analysis. Training will be accomplished through a combination of didactic courses, workshops, and practicums. These training and research activities will allow Dr. Berhanu to mature into an independent investigator and provide a basis for a future R01 using molecular and social network data to identify TB transmission hotspots and areas for targeted case-finding.