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.

项目摘要 候选人：Kathleen沃尔什博士是一位内科学专业的内科医生， 在海地做了七年的研究她获得了治疗耐药结核病的第一手经验， 学习了海地的Kreyol，并培训了一个由海地医生、护士和实验室技术人员组成的研究小组， 开展结核病研究。她发表了22篇论文，其中包括9篇第一作者论文。她有 初步数据表明，耐异烟肼结核病（INHr-TB）正在流行， 在海地，青少年是INHr-TB的哨点人群，INHr-TB主要通过以下途径传播： 在家庭之外的社区环境中。她试图调查海地INHr-TB的流行病学。 职业目标：沃尔什博士的目标是： 1.通过利用全基因组测序获得分子流行病学技能， 分子疾病聚集和INHr-TB传播。 2.获得海地INHr和DS-TB地理信息系统制图方面的专门知识 3.掌握生物统计学技能，特别是时间趋势和泊松回归分析 职业发展计划：沃尔什博士将接受丹尼尔菲茨杰拉德博士（临床结核病）的指导 流行病学），Jean W.佩普（结核病地图），西奥多科恩博士（分子流行病学），博士。 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 与她的研究计划有关的工作。她将根据这些数据提交R 01申请。 环境：拟议的研究将在威尔康奈尔医学（纽约，美国）和GHESKIO进行 （海地太子港），在NIH支持的结核病研究和培训方面拥有40年的经验。 研究：INHr-TB是全世界最常见的耐药结核病。结核分枝杆菌菌株通常获得 首先对INH耐药，然后依次对其他药物耐药。因此，INH抗性是 耐多药结核病由于INH耐药很少被诊断出来，我们对INH耐药的理解存在很大的差距。 这种疾病。沃尔什博士假设INHr-TB在海地是一种新兴的流行病， 为这一新兴的哨兵群体。她进一步假设INHr-TB主要在 社区环境，而不是家庭环境。她将在2011年至2021年期间测试5，183个诊断Mtb分离株， 描述海地INHr-TB患病率的时间趋势，并确定青少年INHr-TB的趋势 在成人INHr-TB趋势之前（目标1）。她将前瞻性地研究传统的，分子的和 海地360例INHr-TB和360例DS-TB患者的空间流行病学，并确定聚集环境， INHr-TB传播正在发生（目标2）。该项目将提供关键的洞察流行病学的 这样我们就可以在海地和全世界提高INHr-TB的检测和预防。