Effect of pregnancy and HIV on the development of tuberculosis

项目摘要/摘要 候选人。Jyoti Mathad博士是一名受过传染病培训的内科科学家，在过去的五年里 多年来在印度进行研究。她帮助建立了一群孕妇，发展得很强大 与印度科学家的科学合作，培训了一个印度研究团队，并撰写了8本出版物 与她的研究有关。她已经证明，怀孕期间发生的免疫变化会影响 执行检测潜伏性结核病(TB)感染的测试。她假设这些变化 这是产后妇女活动性结核病发病率增加的原因之一。 职业发展计划。马萨德博士的近期和长期目标如下： 1)确定怀孕对结核分枝杆菌宿主免疫反应的影响 2)进行一项纵向研究，以确定孕期免疫相关因素，预测 产后HIV感染妇女活动性结核病的发展 3)成为研究孕妇传染病发病机制的专家 具有免疫学和大数据集统计分析方面的翻译实验室科学知识。 4)利用在此期间获得的知识和培训，成为一名独立的内科科学家 在本资助的第四年设计和提交R01建议书的授权期 5)成为美国和印度年轻调查人员的导师 Mathad博士将通过课程学习和在印度实施她的研究来发展这些技能。 环境拟议的研究和培训将在威尔·康奈尔医学院(美国)进行，地址为 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萨德博士提供强有力的指导。 研究。每年，全世界有20多万孕妇和产后患上活动性结核病。 了解怀孕增加患活动性结核病风险的免疫学机制 对孕妇及其子女的疾病预防战略具有重要影响。 目的1：比较北京地区600名孕妇和非孕妇对结核分枝杆菌的宿主免疫应答。 印度浦那。这一目标将检验这样一种假设，即孕妇拥有更多的调控 免疫细胞(CD_4+CD_(25)+FOXP_3+)及其细胞产物(转化生长因子-、IL-10)和辅助性T细胞的减少 结核分枝杆菌晚期妊娠采集的PBMC体外刺激产物(干扰素-、IL-2) 抗原。Mathad博士将招募感染艾滋病毒的女性(n=300)和未感染的女性(n=300)。目标2：确定 在300名感染艾滋病毒的孕妇队列中，免疫相关因素预测产后活动性结核病。这个 基本假设是干扰素-和其他细胞介导的免疫细胞因子的下降幅度 妊娠晚期与产后第一年活动性肺结核的发生有关。

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.