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: 10460953
• 负责人: Rebecca Hafkin Berhanu
• 金额: $ 17.88万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 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/10460953
• 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; 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; Tuberculosis diagnosis; 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.

项目摘要 该申请是波士顿大学的讲师丽贝卡·贝哈努（Rebecca Berhanu）医学博士的K08奖 公共卫生学院的全球健康，他正在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。 全球死亡和艾滋病毒识别的人的第一名死亡。 通过整个基因组测序（WGS）方法的传输簇为传播提供了独特的见解 传统的接触跟踪无法获得的模式。 总体研究目标是使用与分子时钟，系统和传播群集的WGS双交流 分析以转移利福平和南部约翰内斯堡的多药耐药（RR/MDR）结核 非洲。研究的目的是：1）使用WGS数据计算RR/MDR-TB的分子时钟 基于单核苷酸多态性（SNP）基于聚类分析和贝叶斯交易分析以识别 最近的结核病传输簇或RR/MDR-TB，并评估HIV状况，CD4计数和 抗逆转录疗法（ART）关于传输结核病的可能性和3）确定WGS传输群是否是否 通过人口统计和社会网络数据增强的识别可以识别非房屋的位置 最近的RR/MDR-TB传输。 Berhanu博士将获得TB流行病学专家的指导，生物信息学 AndTB基因组学。 大学，在TB临床和翻译研究方面拥有30多年的经验。 波士顿大学医学助理教授Karen Jacobson博士是TB Epidemiorogy的专家 在高昂的环境中，使用TB分子数据在南非进行了广泛的工作 顾问委员会包括生物医学信息助理教授Maha Farhat博士 在 哈佛大学 谁广泛发表了有关电阻突变表征和最近传播的标记 TB基因组数据； TB分子流行病学和医学与生物统计学协会的Evan Johnson博士在 波士顿大学，具有生物信息学方法的专业知识。 研究目的：在流行病学上建立坚实的基础； 系统发育学和使用WGS数据的传播分析将通过组合完成 在南非和波士顿的教学课程，讲习班和实践。 活动将使Berhanu博士能够成熟Intuture缩进调查员，并为R01提供基础 分子和社交网络数据，以识别用于针对性案例调查的传输热点和区域。