Effect of pregnancy and HIV on the development of tuberculosis

项目总结/摘要 候选人Jyoti Mathad博士是一位受过传染病培训的医生兼科学家， 多年来，在印度进行研究。她帮助建立了一个孕妇群体， 与印度科学家进行科学合作，培训了一个印度研究团队，并撰写了8篇出版物 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 检测潜伏性结核病（TB）感染的测试性能。她假设这些变化 有助于产后妇女活动性结核病发病率的增加。 职业发展计划。马萨德博士的近期和长期目标如下： 1)目的探讨妊娠对宿主抗支原体免疫应答的影响。结核 2)进行一项纵向研究，以确定怀孕期间的免疫相关性，预测 艾滋病毒感染妇女产后活动性结核病的发展 3)通过获得孕妇传染病发病机制的专家 在免疫学和大型数据集统计分析方面的转化实验室科学知识。 4)成为一个独立的物理学家，科学家，利用在此期间获得的知识和培训， 在本资助的第4年设计并提交R 01提案的资助期 5)成为美国和印度年轻研究人员的导师 博士Mathad将通过课程和她在印度的研究实施来发展这些技能。 环境拟议的研究和培训将在威尔康奈尔医学院（美国）进行， 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Mathad博士提供强有力的指导。 Research.每年，全世界有超过20万名孕妇和产后妇女患上活动性结核病。 了解妊娠增加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战略具有重要意义。 目的1：比较宿主对M. 600名孕妇和非孕妇的肺结核 印度浦那。这一目标将检验孕妇体内的调节性激素水平增加这一假设。 免疫细胞（CD 4 + CD 25 + Foxp 3+）和细胞产物（TGF-β，IL-10）减少，辅助性T细胞及其 用M.结核 抗原Mathad博士将招募HIV感染（n=300）和未感染（n=300）的女性。目标2：确定 300例HIV感染孕妇中预测活动性产后结核免疫相关性的 主要假设是IFN-γ和其他细胞介导的免疫细胞因子减少的幅度 妊娠晚期的肺结核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.