PROJECT SUMMARY Candidate: Dr. Kathleen Walsh is an Internal Medicine-trained physician scientist who has spent the past seven years conducting research in Haiti. She has gained first-hand experience in treating drug-resistant TB, learned Haitian Kreyol and trained a research team of Haitian physicians, nurses and lab technicians in the conduct of research in tuberculosis. She has authored 22 publications including 9 first author papers. She has preliminary data suggesting there is an emerging epidemic of isoniazid-resistant tuberculosis (INHr-TB), that adolescents are a sentinel population for INHr-TB in Haiti and that INHr-TB is predominantly being transmitted outside the household in community settings. She seeks to investigate the epidemiology of INHr-TB in Haiti. Career Goals: Dr. Walsh's goals are: 1. To gain skills in molecular epidemiology through utilization of whole genome sequencing to identify molecular disease clustering and INHr-TB transmission. 2. To gain expertise in geographic information systems (GIS) mapping of INHr- and DS-TB in Haiti 3. To acquire skills in biostatistics, specifically analysis of temporal trends and Poisson regression Career Development Plan: Dr. Walsh will have mentorship from Dr. Daniel Fitzgerald (clinical TB epidemiology), Dr. Jean W. Pape (TB disease mapping), Dr. Theodore Cohen (molecular epidemiology), Dr. Denis Nash (spatial epidemiology) and Dr. Myung Hee Lee (biostatistics). She will engage in courses and field work related to her proposed research. She will submit an R01 application based on this data. Environment: The proposed research will occur at Weill Cornell Medicine (New York, USA) and GHESKIO (Port-au-Prince, Haiti), which has 40 years of NIH-supported research and training in TB. Research: INHr-TB is the most common form of drug-resistant TB worldwide. Strains of Mtb typically acquire resistance to INH first and then sequentially to other drugs. Therefore, INH resistance is a precursor to multidrug-resistant TB. Since INH resistance is rarely diagnosed, there are large gaps in our understanding of this disease. Dr. Walsh hypothesizes that INHr-TB is an emerging epidemic in Haiti and adolescents are sentinel populations for this emergence. She further postulates that INHr-TB is predominantly transmitted in community settings and not in the household. She will test 5,183 diagnostic Mtb isolates from 2011 – 2021 to characterize temporal trends in INHr-TB prevalence in Haiti and determine if INHr-TB trends in adolescents precede INHr-TB trends in adults (Aim 1). She will prospectively investigate the conventional, molecular and spatial epidemiology of 360 INHr-TB and 360 DS-TB patients in Haiti and identify congregate settings where INHr-TB transmission is occurring (Aim 2). This project will provide critical insight into the epidemiology of INHr-TB so that we can improve detection and prevention of INHr-TB in Haiti and worldwide.

PROJECT NARRATIVE Isoniazid-resistant TB (INHr-TB) is the most common form of drug-resistant TB worldwide, and is a precursor to multidrug-resistant TB. INH resistance is rarely diagnosed leading to major gaps in our understanding of this disease. This project will provide critical insight into the epidemiology of INHr-TB including sentinel populations for the emergence of INHr-TB and congregate settings outside the household where INHr-TB is transmitted.