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

艾滋病毒感染率高的南非城市耐药结核病的传播

• 批准号: 10082653
• 负责人: Rebecca Hafkin Berhanu
• 金额: $ 17.88万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-04 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10082653
• 关键词: Africa South of the Sahara; Area; Award; Back; Bioinformatics; Biometry; Boston; CD4 Lymphocyte Count; Cause of Death; Church; Cities; Clinical; Clinical Research; Cluster Analysis; Communicable Diseases; Contact Tracing; Coupled; Data; Data Sources; Diagnosis; Drug resistance; Drug resistance in tuberculosis; Drug usage; Educational workshop; Enrollment; Epidemiology; Foundations; Funding; Future; Genome; Genomics; HIV; HIV Infections; Head; High Prevalence; Household; Housing; Institutes; International; Interruption; Intervention; Knowledge; Lead; Link; Literature; Location; Medicine; Mentors; Mentorship; Methodology; Methods; Minisatellite Repeats; Molecular; Molecular Epidemiology; Multi-Drug Resistance; Multidrug-Resistant Tuberculosis; Mutation; Participant; Patients; Pattern; Persons; Pharmaceutical Preparations; Phylogenetic Analysis; Population; Public Health Schools; Publishing; Research; Research Activity; Research Personnel; Resistance; Rifampin; Risk; Schools; Single Nucleotide Polymorphism; Site; Social Network; Solid; Source; South Africa; South African; Specific qualifier value; Specimen; Testing; Training; Training Activity; Translational Research; Transportation; Trees; Tuberculosis; Universities; Work; antiretroviral therapy; base; case finding; co-infection; cohort; density; experience; genome sequencing; genomic data; global health; insight; instructor; mid-career faculty; molecular clock; professor; programs; repository; resistance mutation; school health; skills; social; tool; transmission process; whole genome

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.

项目概要 本申请旨在为波士顿大学医学系讲师丽贝卡·伯哈努 (Rebecca Berhanu MD) 申请 K08 奖项 公共卫生学院的全球健康，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 结核病是导致结核病的主要原因。 全球死亡和艾滋病毒感染者的第一大死因 近期结核病的发现。 通过全基因组测序 (WGS) 方法进行的传播簇提供了对传播的独特见解 通过传统的接触者追踪无法获得模式。 总体研究目标是利用全基因组测序（WGS）与分子钟、系统发育和传播聚类相结合 分析南部约翰内斯堡利福平和多重耐药 (RR/MDR) 结核病的传播特征 非洲。该研究的目的是：1) 使用 WGS 数据计算 RR/MDR-TB 的分子钟，2) 使用 基于单核苷酸多态性 (SNP) 的聚类分析和贝叶斯传递分析来识别 最近的结核病传播集群或 RR/MDR-TB，并评估 HIV 状况、CD4 计数和 抗逆转录病毒治疗 (ART) 对传播结核病的可能性的影响以及 3) 确定 WGS 是否存在传播集群 通过人口统计和社交网络数据增强的身份识别可以识别非家庭位置 最近的 RR/MDR-TB 传播。 Berhanu 博士将接受结核病流行病学、生物信息学跨学科专家团队的指导 她的主要导师霍斯伯格博士是波士顿医学和流行病学教授。 她的共同主要导师，拥有 30 多年的结核病临床和转化研究经验。 波士顿大学医学助理教授凯伦·雅各布森博士是结核病流行病学专家 在高负担环境中，主要在南非使用 Berhanu 博士的结核病分子数据进行工作。 顾问委员会成员包括生物医学信息助理教授 Maha Farhat 博士 在 哈佛大学, 他主要发表了关于耐药突变特征和近期传播标记的文章 结核病基因组数据；约翰内斯堡 NICD 结核病中心主任纳齐尔·伊斯梅尔 (Nazir Ismail) 博士是一位专家 结核病分子流行病学博士，埃文·约翰逊博士，医学和生物统计学副教授 波士顿大学在生物信息学方法方面拥有专业知识，伯哈努博士的培训计划与拟议的相关。 研究目标：奠定流行病学的坚实基础；并发展生物信息学的新技能， 使用 WGS 数据的系统发育和传播分析将通过组合完成。 在南非和波士顿举办的教学课程、研讨会和实习 这些培训和研究。 活动将使 Berhanu 博士成长为一名独立研究者，并为使用 R01 提供基础 分子和社交网络数据，以确定传播热点和区域，以进行有针对性的病例发现。