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

项目摘要 此应用程序是一个K 08奖丽贝卡Berhanu医学博士，在波士顿大学的系讲师 公共卫生学院的全球健康，他正在接受培训，成为该领域的独立调查员 分子流行病学和结核病（TB）传播研究。结核病是导致 艾滋病是全球死亡的主要原因，也是艾滋病毒感染者的头号死因。近期结核病的识别 全基因组测序（WGS）方法的传播集群提供了对传播的独特见解 这是通过传统的接触追踪无法获得的模式。 总体的研究目标是利用WGS结合分子钟、遗传和传递簇 分析利福平和耐多药结核病在南非约翰内斯堡的传播特征 非洲本研究的目的是：1）使用WGS数据计算RR/MDR-TB的分子钟，2）使用 单核苷酸多态性（SNP）为基础的聚类分析和贝叶斯传播分析，以确定 最近的结核病传播集群或RR/MDR-TB，并评估艾滋病毒状况、CD 4计数和 抗逆转录病毒疗法（ART）对结核病传播可能性的影响，以及3）确定WGS传播是否聚集 利用人口统计和社交网络数据增强的识别可以识别 最近的RR/MDR-TB传播。 博士Berhanu将接受结核病流行病学、生物信息学、 和结核病基因组学。她的主要导师Horsburgh博士是波士顿的医学和流行病学教授 在结核病临床和转化研究方面拥有超过30年的经验。她的共同导师， 博士波士顿大学医学助理教授卡伦·雅各布森是结核病流行病学专家 在高负担环境中，并利用结核病分子数据在南非广泛开展工作。Berhanu博士的 顾问委员会包括Maha Farhat博士，生物医学信息助理教授 在 哈佛大学， 世卫组织发表了大量关于耐药性突变特征和最近传播标记的文章， 结核病基因组数据;约翰内斯堡NICD结核病中心主任Nazir Ismail博士是一位专家 和埃文约翰逊博士，医学和生物统计学副教授， 波士顿大学，拥有生物信息学方法学方面的专业知识。Berhanu博士的培训计划与拟议的 研究目标：建立流行病学的坚实基础;并发展生物信息学的新技能， 使用WGS数据进行遗传学和传播分析。培训将通过结合 在南非和波士顿的教学课程，研讨会和实习。这些训练和研究 活动将使Berhanu博士成长为一名独立的研究者，并为使用R 01提供基础。 分子和社会网络数据，以确定有针对性的病例发现的传播热点和地区。

PROJECT SUMMARY This application is for a K08 award for Rebecca Berhanu MD, an Instructor at Boston University’s Department of Global Health in the School of Public Health, who is training to become an independent investigator in the field of molecular epidemiology and tuberculosis (TB) transmission research. TB is the leading infectious cause of death globally and the number one cause of death amongst people with HIV. The identification of recent TB transmission clusters by whole genome sequencing (WGS) methods offers unique insight into transmission patterns which cannot be obtained through traditional contact tracing. The overall research objective is to use WGS coupled with molecular clock, phylogenic and transmission cluster analysis to characterize transmission of rifampin and multi-drug resistant (RR/MDR) TB in Johannesburg, South Africa. The aims of the study are to: 1) Use WGS data to calculate the molecular clock of RR/MDR-TB, 2) Use single-nucleotide polymorphism (SNP)-based cluster analysis and Bayesian transmission analysis to identify recent TB transmission clusters or RR/MDR-TB, and evaluate the impact of HIV status, CD4 count and antiretroviral therapy (ART) on the likelihood of transmitting TB and 3) Determine if WGS transmission cluster identification augmented with demographic and social-network data can identify non-household locations of recent RR/MDR-TB transmission. 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’ 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 resistance mutation characterization and markers of recent transmission using TB genomic data; Dr. Nazir Ismail, head of the Centre for Tuberculosis of the NICD in Johannesburg, is an expert in TB molecular epidemiology, and Dr. Evan Johnson, Associate Professor of Medicine and Biostatistics at Boston University, with expertise in bioinformatics methodology. Dr. Berhanu’s training plan links to the proposed research aims: establish a solid foundation in epidemiology; and develop new skills in bioinformatics, phylogenetics and transmission analysis using WGS data. Training will be accomplished through a combination of didactic courses, workshops, and practicums in South Africa and Boston. These training and research activities will allow Dr. Berhanu to mature into an independent investigator and provide a basis for an R01 using molecular and social network data to identify transmission hotspots and areas for targeted case-finding.