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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要背景：南非是一种独特的高风险环境，用于新型抗药性菌株的出现结核分枝杆菌（MTB）。新型耐药的MTB菌株通常仅在具有实现了持续的传播，并分散到远离其起源位置的较大地理区域。在爆发与流行病缺乏。候选人：我是传染病医师和流行病学家，有经验基因组流行病学，数学建模和现场公共卫生研究与卫生服务送货。我的研究采用了多种数据源（包括地理分解的微生物基因组数据和移动与电话相关的移动数据），以了解流行病的出现和传播。总体目标我的工作是改善和创新策略，以监视和遏制耐药性感染，专注于疟疾和结核病。培训：我正在寻求职业发展支持，以追求我的长期成为独立NIH资助的医师科学家的术语目标。为了实现我的研究和职业目标，我将在贝叶斯统计，空间人口遗传学，网络科学和研究中进行其他培训管理技能。导师与环境：Caroline Buckee博士，传染病的全球领导者流行病学和知名度具有传染病建模，将监督我的研究和培训活动作为主要导师。 Barun Mathema博士，结核病基因组流行病学的科学专家结核病的传播将作为我的联合委员会提供重点的科学支持。关键合作者项目包括Shaheed Vally Omar博士（南非耐药结核病的监视），Ted Cohen博士（结核病的数学建模和流行病学），Sheetal Silal博士（基于代理的传染性建模疾病动力学）和Sarita Shah博士（结核病监视和控制）。 MarcIpsitch博士，Yonatan毕业博士，博士路易丝·艾弗斯（Louise Ivers），尼尔·施卢格（Neil Schluger）博士和弗兰克·坦塞（Frank Tanser）博士将组成一个科学顾问委员会，他们将提供对我的研究和培训活动的年度反馈。我将在K08期间培训和开展研究活动哈佛大学奖陈公共卫生学院传染病动力学中心。研究：我将研究通过通过研究活动以三个特定目的：（1）使用地理位置的MTB基因组数据估算可能起源目前在南非循环的多种耐药MTB菌株的位置和传输中心；（2）在南非开发基于个人的MTB传播的计算模型移动性数据和MTB内部演变；（3）评估早期的多个候选监视策略使用基于个体的建模检测和遏制MTB的新型药物抗性菌株。