Geographic origins and dispersal of drug-resistant M. tuberculosis in South Africa: Advancing strategies for early detection

南非耐药结核分枝杆菌的地理起源和传播：推进早期检测策略

• 批准号: 10523608
• 负责人: Tyler Steven Brown
• 金额: $ 19.84万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-02 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10523608
• 关键词: Address; Award; Bayesian Analysis; COVID-19; Car Phone; Cessation of life; Cities; Collection; Communicable Diseases; Computer Models; Containment; Data; Data Sources; Detection; Development; Disease; Disease Outbreaks; Drug resistance; Drug resistance in tuberculosis; Drug resistant Mycobacteria Tuberculosis; Early Diagnosis; Early identification; Environment; Epidemic; Epidemiologist; Epidemiology; Evaluation; Evolution; Feedback; Funding; Future; Genetic; Genetic Models; Genetic Variation; Geographic Locations; Geography; Goals; HIV; Health Services Accessibility; Household; Human; Individual; Infection; Infectious Disease Epidemiology; Link; Location; Malaria; Maps; Mentors; Mentorship; Methods; Migrant; Modeling; Movement; Multiple drug resistant Mycobacteria Tuberculosis; Mycobacterium tuberculosis; Pattern; Pharmaceutical Preparations; Pharmacoepidemiology; Physicians; Population; Population Genetics; Predisposition; Process; Public Health; Public Health Schools; Research; Research Activity; Rural; Sampling; Science; Scientist; South Africa; Specific qualifier value; Surveys; Testing; Training; Training Activity; Tuberculosis; Uncertainty; United States National Institutes of Health; Widespread Disease; Work; antimicrobial resistant infection; base; career; career development; co-infection; experience; genetic signature; genomic data; genomic epidemiology; health care delivery; high risk; improved; infectious disease model; innovation; insight; interdisciplinary approach; mathematical model; microbial; microbial genomics; multiple data sources; novel; novel strategies; novel therapeutics; prevent; public health relevance; public health research; resistant strain; rural area; rural-urban migration; skills; spatial epidemiology; surveillance strategy; transmission process; urban area

PROJECT SUMMARY Background: South Africa is a unique, high-risk environment for the emergence of novel drug-resistant strains of Mycobacterium tuberculosis (Mtb). Novel drug-resistant Mtb strains are often identified only after they have achieved sustained transmission and dispersed into larger geographic areas away from their origin location. Strategies for early detection of drug-resistant Mtb strains, at the critical juncture between outbreak and epidemic, are lacking. Candidate: I am infectious disease physician and epidemiologist, with experience in genomic epidemiology, mathematical modeling, and field-level public health research and health service delivery. My research employs multiple data sources (including geolocated microbial genomic data and mobile phone-associated movement data) to understand how epidemics emerge and spread. The overarching objective of my work is to improve and innovate strategies for surveillance and containment of drug-resistant infections, focused on malaria and tuberculosis. Training: I am seeking career development support to pursue my long- term goal of becoming an independent NIH-funded physician scientist. To achieve my research and career goals, I will pursue additional training in Bayesian statistics, spatial population genetics, network science, and research management skills. Mentors and Environment: Dr. Caroline Buckee, a global leader in infectious disease epidemiology and mobility-informed infectious disease modeling, will oversee my research and training activities as primary mentor. Dr. Barun Mathema, a scientific expert in the tuberculosis genomic epidemiology and tuberculosis transmission, will provide focused scientific support as my co-mentors. Key collaborators on this project include Dr. Shaheed Vally Omar (surveillance for drug-resistant TB in South Africa), Dr. Ted Cohen (mathematical modeling and epidemiology of tuberculosis), Dr. Sheetal Silal (agent-based modeling of infectious disease dynamics), and Dr. Sarita Shah (TB surveillance and control). Dr. Marc Lipsitch, Dr. Yonatan Grad, Dr. Louise Ivers, Dr. Neil Schluger, and Dr. Frank Tanser will form a Scientific Advisory Board, who will provide annual feedback on my research and training activities. I will train and conduct research activities during the K08 award at the Harvard T.H. Chan School of Public Health Center for Communicable Disease Dynamics. Research: I will examine novel strategies for early detection of drug-resistant Mtb in South Africa through research activities under three specific aims: (1) Using geolocated Mtb genomic data to estimate likely origin locations and transmission hubs for multiple drug-resistant Mtb strains currently circulating in South Africa; (2) Developing an individual-based computational model of Mtb transmission in South Africa incorporating human mobility data and Mtb within-host evolution; (3) Evaluating multiple candidate surveillance strategies for early detection and containment of novel drug-resistant strains of Mtb using individual-based modeling.

项目总结 背景：南非是出现新型耐药菌株的独特、高风险环境 结核分枝杆菌(Mtb)。新的耐药结核分枝杆菌菌株通常是在它们具有 实现了持续传播，并分散到远离其原产地的更大地理区域。 在疫情和结核病爆发之间的关键时刻及早检测耐药结核分枝杆菌菌株的战略 流行病，都是缺乏的。应聘者：我是传染病内科医生和流行病学家，有 基因组流行病学、数学建模、实地公共卫生研究和卫生服务 送货。我的研究使用了多种数据来源(包括地理定位的微生物基因组数据和移动数据 电话相关的移动数据)，以了解流行病是如何出现和传播的。总体目标 我的工作之一是改进和创新监测和遏制耐药感染的战略， 重点关注疟疾和结核病。培训：我正在寻求职业发展支持，以追求我的长期- 学期目标是成为美国国立卫生研究院资助的独立内科科学家。为了实现我的研究和职业目标， 我将继续学习贝叶斯统计学、空间种群遗传学、网络科学和研究方面的其他培训。 管理技能。导师与环境：传染病领域的全球领导者Caroline Buckee博士 流行病学和流动性知情的传染病建模，将监督我的研究和培训活动 作为主要导师。巴伦·马特玛博士，结核病基因组流行病学和 结核病传播，将为我提供有针对性的科学支持，作为我的共同导师。这方面的主要合作者 项目包括Shaheed Vally Omar博士(南非耐药结核病监测)、Ted Cohen博士 (结核病的数学模型和流行病学)，Shetal Silal博士(基于试剂的传染病模型 疾病动力学)和Sarita Shah博士(结核病监测和控制)。马克·利普西奇博士、约纳坦·格拉德博士、 路易丝·艾弗斯、尼尔·施卢格博士和弗兰克·坦瑟博士将组成一个科学顾问委员会，该委员会将提供 对我的研究和培训活动的年度反馈。我将在K08期间进行培训和研究活动 在哈佛大学公共卫生学院传染病动力学中心获奖。 研究：我将通过以下途径检查南非早期发现耐药结核杆菌的新策略 三个特定目标下的研究活动：(1)使用地理定位的结核分枝杆菌基因组数据来估计可能的起源 南非目前流行的多种耐药结核分枝杆菌菌株的地点和传播中心；(2) 在南非建立基于个人的结核分枝杆菌传播计算模型 移动数据和Mtb在宿主内的进化；(3)早期评估多个候选监视策略 使用基于个体的建模检测和遏制结核分枝杆菌的新型耐药菌株。