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Principal Investigator: Tyler Steven Brown
Organization: BOSTON MEDICAL CENTER
Fiscal Year: 2024
Award: $193,752
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <AIDS Virus><Access to Care><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Address><Award><Bayesian Analysis><Bayesian computation><Bayesian inference><Bayesian network analysis><Bayesian spatial analysis><Bayesian statistical analysis><Bayesian statistical inference><Bayesian statistics><COVID-19><CV-19><Calibration><Cell Phone><Cellular Phone><Cellular Telephone><Cessation of life><Cities><Collection><Communicable Diseases><Computer Models><Computerized Models><Containment><Coronavirus Infectious Disease 2019><Data><Data Sources><Death><Detection><Development><Disease><Disease Outbreaks><Disorder><Drug Resistance Tuberculosis><Drug Resistant TB><Drug Resistant Tuberculosis><Drug resistance><Drug resistance in Mtb><Drug resistance in Mycobacterium Tuberculosis><Drug resistance in tuberculosis><Drug resistant M Tuberculosis><Drug resistant Mtb><Drug resistant Mycobacteria Tuberculosis><Drugs><Early Diagnosis><Early identification><Environment><Epidemic><Epidemiologic Research><Epidemiologic Studies><Epidemiological Studies><Epidemiologist><Epidemiology><Epidemiology Research><Evaluation><Evolution><Extensive Disease><Feedback><Funding><Future><Generalized Disease><Genetic><Genetic Diversity><Genetic Models><Genetic Variation><Geographic Area><Geographic Locations><Geographic Region><Geographical Location><Geography><Goals><HIV><Health Services Accessibility><Healthcare Delivery><Household><Human><Human Immunodeficiency Viruses><Individual><Infection><Infectious Disease Epidemiology><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Infectious Epidemiology><LAV-HTLV-III><Link><Location><Lymphadenopathy-Associated Virus><M tb><M tuberculosis><M tuberculosis infection><M. tb><M. tb infection><M. tuberculosis><M. tuberculosis infection><M.tb infection><M.tuberculosis infection><MDR Mtb><MDR Mycobacterium tuberculosis><MTB infection><Malaria><Maps><Math Models><Medication><Mentors><Mentorship><Methods><Migrant><Mobile Phones><Modeling><Modern Man><Movement><Mtb drug resistance><Multi-drug resistant M. Tuberculosis><Multi-drug resistant Mtb><Multi-drug resistant Mycobacterium tuberculosis><Multidrug resistant M. Tuberculosis><Multidrug resistant Mtb><Multidrug resistant Mycobacterium tuberculosis><Multiple drug resistance Mycobacteria Tuberculosis><Multiple drug resistant Mycobacteria Tuberculosis><Mycobacterium tuberculosis><Mycobacterium tuberculosis (MTB) infection><Mycobacterium tuberculosis infection><NIH><National Institutes of Health><Outbreaks><Paludism><Pattern><Pharmaceutical Preparations><Physicians><Plasmodium Infections><Population><Population Genetics><Predisposition><Process><Public Health><Public Health Schools><Research><Research Activity><Rural><Sampling><Science><Scientist><South Africa><Specific qualifier value><Specified><Survey Instrument><Surveys><Susceptibility><TB drug resistance><TB infection><Testing><Training><Training Activity><Transmission><Tuberculosis><Uncertainty><United States National Institutes of Health><Virus-HIV><Widespread Disease><Work><access to health services><access to services><access to treatment><accessibility to health services><anti-microbial resistant infection><antimicrobial resistant infection><availability of services><body movement><care access><career><career development><co-infection><coinfection><computational modeling><computational models><computer based models><computerized modeling><coronavirus disease 2019><coronavirus disease-19><coronavirus infectious disease-19><developmental><disseminated TB><disseminated tuberculosis><doubt><drug detection><drug resistance M Tuberculosis><drug resistance Mycobacteria Tuberculosis><drug resistance in TB><drug resistant><drug resistant M.tb><drug resistant in tuberculosis><drug testing><drug/agent><early detection><emerging epidemic><epidemiologic><epidemiologic investigation><epidemiological><epidemiology study><experience><forging><gene signatures><genetic signature><genomic data><genomic data-set><genomic dataset><genomic epidemiology><geographic site><health and care delivery><health care delivery><health delivery systems><health service access><health services availability><health services delivery><high risk><iPhone><improved><infection due to Mycobacterium tuberculosis><infectious disease model><innovate><innovation><innovative><insight><interdisciplinary approach><mathematic model><mathematical model><mathematical modeling><microbial><microbial genomics><mtb><multidisciplinary approach><multiple data sources><new approaches><new drug treatments><new drugs><new epidemic><new pharmacological therapeutic><new therapeutics><new therapy><next generation therapeutics><novel><novel approaches><novel drug treatments><novel drugs><novel epidemic><novel pharmaco-therapeutic><novel pharmacological therapeutic><novel strategies><novel strategy><novel therapeutics><novel therapy><prevent><preventing><public health relevance><public health research><resistance strain><resistance to Drug><resistant strain><resistant to Drug><rural area><rural location><rural region><rural to urban migration><rural-urban migration><service availability><skills><smart phone><smartphone><spatial epidemiology><surveillance strategy><training module><transmission process><treatment access><tuberculosis infection><tuberculous spondyloarthropathy><urban area><urban location><urban region>