Effect of pregnancy and HIV on the development of tuberculosis

怀孕和艾滋病毒对结核病发展的影响

• 批准号: 9409571
• 负责人: Jyoti S Mathad
• 金额: $ 19.28万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-04 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9409571
• 关键词: Acute; Adult; Antigens; Biological Assay; CD4 Positive T Lymphocytes; Cells; Cellular Immunity; Child; Clinical; Collaborations; Communicable Diseases; Data; Data Set; Development; Development Plans; Diagnosis; Diagnostic; Disease; Enrollment; Environment; FOXP3 gene; Flow Cytometry; Gap Junctions; Gene Expression; Goals; Grant; HIV; HIV Infections; HIV Seropositivity; Helper-Inducer T-Lymphocyte; High Risk Woman; IL2RA gene; Immune; Immune response; Immune system; Immunologics; Immunology; Immunosuppression; Incidence; India; Infant; Infection; Institution; Interferon Type II; Interferons; Interleukin-10; Interleukin-2; Knowledge; Laboratories; Lead; Life; Longitudinal Studies; Masks; Maternal Mortality; Mediating; Mentors; Mentorship; Mycobacterium tuberculosis; Nested Case-Control Study; Pathogenesis; Patients; Physicians; Population; Postpartum Period; Postpartum Women; Pregnancy; Pregnant Women; Prevention; Prevention strategy; Preventive care; Preventive therapy; Production; Publications; Publishing; Regulatory T-Lymphocyte; Reporting; Research; Research Institute; Research Personnel; Research Training; Risk; Science; Scientist; Statistical Data Interpretation; Symptoms; T-Lymphocyte; Testing; Third Pregnancy Trimester; Time; Training; Translational Research; Tuberculosis; Woman; base; career; career development; cell mediated immune response; clinical epidemiology; cohort; cytokine; design; disorder prevention; experience; high risk; implementation research; improved; medical schools; men; mortality; novel diagnostics; performance tests; pregnant; reconstitution; reproductive; response; skills; tool

PROJECT SUMMARY/ABSTRACT Candidate. Dr. Jyoti Mathad is an Infectious Diseases-trained physician-scientist who has spent the past five years conducting research in India. She helped establish a cohort of pregnant women, developed strong scientific collaborations with Indian scientists, trained an Indian research team, and authored 8 publications related to her research. She has documented that the immune changes that occur in pregnancy impact the performance of tests to detect latent tuberculosis (TB) infection. She hypothesizes that these changes contribute to the documented increase in active TB incidence in postpartum women. Career Development Plan. Dr. Mathad’s immediate and long-term goals are the following: 1) To determine the impact of pregnancy on the host immune response to M. tuberculosis 2) To conduct a longitudinal study to identify immune correlates during pregnancy that predict the development of active TB in postpartum HIV-infected women 3) To become an expert in the pathogenesis of infectious diseases in pregnant women by gaining knowledge in translational laboratory science in immunology and statistical analysis of large data sets. 4) To become an independent physician-scientist, using the knowledge and training obtained during this grant period to design and submit an R01 proposal in year 4 of this grant 5) To become a mentor to young investigators in the US and India Dr. Mathad will develop these skills through coursework and the implementation of her research in India. Environment. The proposed research and training will take place at Weill Cornell Medical College (USA), at Byramjee Jeejeebhoy Medical College (India) and the National Institute for Research in Tuberculosis (India). The collaborations between these institutions will provide Dr. Mathad with strong mentorship. Research. Each year, over 200,000 pregnant and postpartum women worldwide develop active TB. Understanding the immunologic mechanisms by which pregnancy increases the risk of developing active TB has important implications for disease prevention strategies for pregnant women and their children. Aim 1: Compare the host immune responses to M. tuberculosis in 600 pregnant and non-pregnant women in Pune, India. This aim will test the hypothesis that pregnant women have an increased abundance of regulatory immune cells (CD4+CD25+Foxp3+) and cell products (TGF-, IL-10) and a decrease in helper T cells and their products (IFN-, IL-2) after ex vivo stimulation of PBMCs collected in the late 3rd trimester with M. tuberculosis antigens. Dr. Mathad will enroll both HIV-infected (n=300) and –uninfected (n=300) women. Aim 2: Identify the immune correlates that predict active postpartum TB in a cohort of 300 HIV-infected pregnant women. The primary hypothesis is that the magnitude of decrease in IFN- and other cell-mediated immune cytokines during the 3rd trimester will correlate with the development of active TB in the first postpartum year.

项目概要/摘要 候选人乔蒂·马塔德 (Jyoti Mathad) 博士是一位接受过传染病培训的医师兼科学家，过去五年一直从事传染病研究。 她在印度进行了多年的研究，帮助建立了一批孕妇，她们发展得很坚强。 与印度科学家进行科学合作，培训了一支印度研究团队，并撰写了 8 篇出版物 她的研究表明，怀孕期间发生的免疫变化会影响身体。 进行检测潜伏性结核病 (TB) 感染的测试。 据记录，这导致产后妇女活动性结核病发病率增加。 Mathad 博士的职业发展计划如下： 1) 确定妊娠对宿主对结核分枝杆菌的免疫反应的影响 2) 进行一项纵向研究，以确定妊娠期间可预测的免疫相关因素 产后感染艾滋病毒的妇女发展为活动性结核病 3) 成为孕妇传染病发病机制的专家 免疫学和大数据集统计分析方面的转化实验室科学知识。 4）利用在此期间获得的知识和培训成为一名独立的医师科学家 在本拨款的第 4 年设计并提交 R01 提案的拨款期限 5）成为美国和印度年轻研究者的导师 马塔德博士将通过课程作业和在印度实施她的研究来培养这些技能。 环境。拟议的研究和培训将在威尔康奈尔医学院（美国）进行，地址： Byramjee Jeejeebhoy 医学院（印度）和国家结核病研究所（印度）。 这些机构之间的合作将为马塔德博士提供强有力的指导。 研究。全世界每年有超过 200,000 名孕妇和产后妇女患有活动性结核病。 了解怀孕增加患活动性结核病风险的免疫机制 对孕妇及其子女的疾病预防策略具有重要意义。 目标 1：比较 600 名孕妇和非孕妇对结核分枝杆菌的宿主免疫反应 印度浦那，这一目标将检验孕妇的监管更加丰富的假设。 免疫细胞（CD4+CD25+Foxp3+）和细胞产物（TGF-β、IL-10）以及辅助 T 细胞及其数量的减少 用结核分枝杆菌对妊娠第 3 个月末收集的 PBMC 进行离体刺激后的产物（IFN-α、IL-2） Mathad 博士将招募 HIV 感染者 (n=300) 和未感染者 (n=300) 目标 2：识别艾滋病毒感染者。 免疫相关性可预测 300 名感染 HIV 的孕妇会出现活动性产后结核病。 主要假设是 IFN-α 和其他细胞介导的免疫细胞因子的减少幅度 妊娠第三个月期间的感染与产后第一年活动性结核病的发展相关。