Sentinel populations and transmission hotspots of isoniazid-resistant tuberculosis

耐异烟肼结核病的哨兵人群和传播热点

• 批准号: 10644145
• 负责人: Kathleen F Walsh
• 金额: $ 19.55万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-13 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644145
• 关键词: Adolescent; Adult; Affect; Archives; Award; Biological Assay; Biometry; Cessation of life; Church; Clinical; Contact Tracing; Contracts; Country; Data; Detection; Development Plans; Diagnosis; Diagnostic; Disease; Disease Clusterings; Drug resistance; Drug resistance in tuberculosis; Elderly; Enrollment; Environment; Epidemiologist; Epidemiology; Genotype; Geographic Information Systems; Germany; Goals; Haiti; Haitian; Home; Household; Infection; Internal Medicine; Interview; Isoniazid resistance; Learning; Longitudinal Studies; Lung; Maps; Medicine; Mentorship; Molecular; Molecular Disease; Molecular Epidemiology; Multi-Drug Resistance; Multidrug-Resistant Tuberculosis; Mycobacterium tuberculosis; New York; Newly Diagnosed; Nurses; Paper; Patients; Persons; Pharmaceutical Preparations; Pharmacotherapy; Physicians; Population; Positioning Attribute; Predisposition; Prevalence; Prevention; Prevention program; Prevention strategy; Preventive; Preventive therapy; Publications; Pulmonary Tuberculosis; Research; Research Support; Resistance development; Resources; Rifampin; Risk; Scientist; Sentinel; Single Nucleotide Polymorphism; Testing; Time; Time trend; Training; Treatment Failure; Tuberculosis; United States National Institutes of Health; Work; Youth; aged; career; career development; community setting; experience; genome sequencing; high risk; improved; indexing; insight; mortality risk; new epidemic; prevent; programs; prospective; skill acquisition; skills; spatial epidemiology; transmission process; treatment center; trend; tuberculosis treatment; whole genome

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.

项目概要 候选人：凯瑟琳·沃尔什 (Kathleen Walsh) 博士是一位接受过内科医学培训的医师科学家，她在过去的 她在海地进行了七年的研究，获得了治疗耐药结核病的第一手经验。 学习海地Kreyol，并在该地区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 她发表了 22 篇出版物，其中包括 9 篇第一作者论文。 初步数据表明耐异烟肼结核病（INHr-TB）正在流行， 青少年是海地 INHr-TB 的哨兵人群，INHr-TB 的主要传播途径是 她试图在海地的家庭以外的社区环境中调查 INHr-TB 的流行病学。 职业目标：沃尔什博士的目标是： 1. 通过利用全基因组测序来识别分子流行病学技能 分子疾病聚类和 INHR-TB 传播。 2. 获得海地 INHr-和 DS-TB 地理信息系统 (GIS) 绘图方面的专业知识 3. 获得生物统计学技能，特别是时间趋势和泊松回归分析 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（结核病绘图）、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）她将从事课程和领域。 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），该中心在 NIH 的支持下在结核病领域开展了 40 年的研究和培训。 研究：INHR-TB 是全世界最常见的耐药结核病形式，通常由 Mtb 菌株感染。 首先对 INH 产生耐药性，然后再对其他药物产生耐药性，因此，INH 耐药性是 INH 耐药的先兆。 由于很少诊断出耐多药结核病，因此我们对耐多药结核病的认识存在很大差距。 Walsh 博士率先指出，INHr-TB 是海地的一种新流行病，青少年是这种疾病的流行者。 她进一步推测 INHr-TB 主要在以下人群中传播。 从 2011 年到 2021 年，她将在社区环境中而不是在家庭中测试 5,183 个诊断性结核分枝杆菌。 描述海地 INHr-TB 患病率的时间趋势，并确定青少年中 INHr-TB 的趋势是否存在 在成人 INHR-TB 趋势之前（目标 1），她将前瞻性地研究传统、分子和结核病的趋势。 对海地 360 名 INHr-TB 和 360 名 DS-TB 患者进行空间流行病学调查，并确定其中的聚集环境 INHr-TB 传播正在发生（目标 2）。 INHr-TB，以便我们能够改善海地和全世界 INHr-TB 的检测和预防。