Sentinel populations and transmission hotspots of isoniazid-resistant tuberculosis

项目总结 候选人：凯瑟琳·沃尔什博士是一位受过内科训练的内科科学家，她过去 在海地进行了七年的研究。她在治疗耐药结核病方面获得了第一手经验， 学习了海地的Kreyol，并培训了一支由海地医生、护士和实验室技术人员组成的研究团队 开展结核病方面的研究。她撰写了22篇出版物，其中包括9篇第一作者论文。她有 初步数据表明，出现了一种新的耐异烟肼结核病(INHr-TB)， 青少年是海地INHr-TB的哨点人群，INHr-TB主要是通过 在家庭之外的社区环境中。她寻求调查海地INHr-TB的流行病学。 职业目标：沃尔什博士的目标是： 1.利用全基因组测序技术获得分子流行病学技能 分子疾病聚集性与INHr-TB传播。 2.获得海地非霍乱和结核病地理信息系统测绘方面的专门知识 3.掌握生物统计学技能，特别是时间趋势分析和泊松回归 职业发展计划：沃尔什博士将得到丹尼尔·菲茨杰拉德博士(临床结核病)的指导 流行病学)、Jean W.Pape博士(结核病疾病图谱)、Theodore Cohen博士(分子流行病学)、Dr. Denis Nash(空间流行病学)和Myung Hee Lee博士(生物统计学)。她将从事课程和实地考察 与她提出的研究相关的工作。她将根据这些数据提交R01申请。 环境：拟议的研究将在威尔·康奈尔医学院(美国纽约)和GHESKIO进行 (海地太子港)，它有40年的NIH支持的结核病研究和培训。 研究：INHr-TB是全球最常见的耐药结核病。结核分枝杆菌菌株通常会获得 首先对异烟肼耐药，然后依次对其他药物耐药。因此，异烟肼抗性是先兆 耐多药结核病。由于异烟肼耐药性很少被诊断出来，我们对异烟肼耐药性的理解存在很大差距。 这种病。沃尔什博士假设INHR-TB在海地是一种新的流行病，青少年 这一出现的哨兵种群。她进一步推测，INHr-TB主要是在 社区环境，而不是在家庭中。她将在2011-2021年检测5,183株诊断结核分枝杆菌 确定海地INHr-TB流行的时间趋势，并确定青少年中的INHr-TB趋势 在成人中先于INHr-TB趋势(目标1)。她将前瞻性地研究传统的、分子的和 海地360名INHr-TB和360名DS-TB患者的空间流行病学研究并确定聚集环境 正在发生INHr-TB传播(目标2)。该项目将提供对流行性感冒流行病学的重要洞察力 因此，我们可以改进海地和全世界对非霍乱结核病的检测和预防。

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.