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

项目概要：此应用程序是为丽贝卡Berhanu医学博士，在教师K 08奖 他是波士顿大学公共卫生学院全球卫生系的一名教授， 结核病传播研究、分子流行病学和 社会网络分析。结核病是全球主要的传染性死亡原因，也是导致 艾滋病毒感染者的死亡。新的工具，包括旨在中断传播的干预措施， 必须遏制疫情。利用全基因组鉴定结核病近期传播聚集群 测序（WGS）和社会网络分析提供了对传播模式的独特见解， 可以通过传统的接触者追踪方法获得。 总体研究目标是利用系统发育分析、分子流行病学和社会网络 分析表征利福平和多药耐药（RR/MDR）结核病的近期传播集群， 南非约翰内斯堡。本研究的主要目的是：1）利用WGS计算分子钟， 2）使用以下方法评估艾滋病毒状况和CD 4计数对结核病传播可能性的影响： 基于聚类和源归因分析和3）进行试点研究，以确定是否社会网络分析 可与WGS数据相结合，以确定结核病高负担地区最近发生RR/MDR-TB传播的地点 设置. Berhanu博士将接受结核病流行病学跨学科专家小组的指导， 生物信息学和结核病基因组学。她的主要导师Horsburgh博士是医学和流行病学教授 他在结核病临床和转化研究方面拥有30多年的经验。她的同事- 主要导师卡伦·雅各布森博士是波士顿大学医学助理教授，也是结核病专家 在高负担环境中进行流行病学研究，并利用结核病分子数据在南非开展了广泛的工作。博士 Berhanu的顾问委员会包括Maha Farhat博士，生物医学信息助理教授 在 哈佛 他在WGS关于结核分枝杆菌（MTB）的研究中发表了大量文章; Nazir博士 伊斯梅尔是约翰内斯堡NICD结核病中心的负责人， 波士顿大学医学和生物统计学副教授Evan约翰逊博士 大学，具有生物信息学分析和解释方面的专业知识。Berhanu博士的培训计划与 建议的研究目标：在流行病学包括社会网络分析方面建立坚实的基础; 分子流行病学和系统发育分析技能;熟悉WGS和生物统计学 分析.培训将通过教学课程，研讨会和实习相结合来完成。 这些培训和研究活动将使Berhanu博士成长为一名独立的研究者， 为未来R 01提供基础，使用分子和社会网络数据确定结核病传播热点 和有针对性的病例发现领域。

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.