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：凯瑟琳·沃尔什（Kathleen Walsh）博士是一位经过内科培训的体育科学家，他已经度过了过去 在海地进行研究的七年。她在治疗耐药结核病方面获得了第一手经验， 在海地杂志学院学习了海地克雷尔，并培训了一支由海地医师，护士和实验室技术人员组成的研究团队 结核病的研究。她撰写了22个出版物，其中包括9篇第一篇论文。她有 初步数据表明，存在抗异念珠菌的结核病（INHR-TB）的流行病 青少年是海地INHR-TB的前哨种群，而INHR-TB主要是在传播 在社区环境中的家庭之外。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。通过利用整个基因组测序来识别分子流行病学的技能 分子疾病聚类和INHR-TB传播。 2。获得海地INHR和DS-TB的地理信息系统（GIS）映射的专业知识 3。要获得生物统计学的技能，特别分析临时趋势和泊松回归 职业发展计划：沃尔什博士将对丹尼尔·菲茨杰拉德（Daniel Fitzgerald）博士（临床结核病）产生心态 流行病学），Jean W. Pape博士（结核病疾病图），Theodore Cohen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）。她将参加课程和领域 与她提议的研究有关的工作。她将根据此数据提交R01申请。 环境：拟议的研究将在Weill Cornell Medicine（美国纽约）和Gheskio进行 （海地港太子港），在结核病中拥有40年的NIH支持研究和培训。 研究：INHR-TB是全球耐药性结核病的最常见形式。 MTB的菌株通常获得 首先对INH的抗性，然后依次与其他药物进行抗性。因此，INH抗性是 多药耐药结核病。由于很少诊断出INH抗性，因此我们对 这种疾病。沃尔什博士假设INHR-TB是海地的一种新兴流行，青少年是 哨兵人口的出现。她进一步假设INHR-TB主要传播 社区环境而不是家庭。她将从2011年至2021年测试5,183个诊断MTB分离株 表征海地INHR-TB患病率的临时趋势，并确定青少年的INHR-TB趋势是否 在成年人的INHR-TB趋势之前（AIM 1）。她可能会研究常规，分子和 海地360个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传输正在发生（AIM 2）。该项目将对有关流行病学的批判性见解 INHR-TB，以便我们可以改善海地和全世界对INHR-TB的检测和预防。