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: 10228725
• 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 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10228725
• 关键词: Acute; Adult; Antigens; Biological Assay; Cells; Cellular Immunity; Child; Clinical; Collaborations; Communicable Diseases; Data; 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; Peripheral Blood Mononuclear Cell; 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; immune reconstitution; improved; large datasets; medical schools; men; mortality; novel diagnostics; performance tests; pregnant; 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.

项目摘要/摘要 候选人。 Jyoti Mathad博士是经过传染病训练的医师科学家，他过去五个 多年在印度进行研究。她帮助建立了一群孕妇，发展强大 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个出版物 与她的研究有关。她已经记录了怀孕中发生的免疫变化影响 检测潜在结核病（TB）感染的测试的性能。她假设这些变化 有助于产后妇女的活跃结核病发病率增加。 职业发展计划。 Mathad博士的直接和长期目标如下： 1）确定怀孕对宿主免疫响应对结核分枝杆菌的影响 2）进行纵向研究以识别怀孕期间的免疫相关性，以预测 在产后感染的艾滋病毒的妇女中发展活性结核 3）通过获得传染病的发病机理，成为孕妇的发病机理 大型数据集的免疫学和统计分析的转化实验室科学知识。 4）使用在此期间获得的知识和培训成为独立的身体科学家 赠款期在本赠款的第4年设计和提交R01提案 5）成为美国和印度的年轻调查员的心理 Mathad博士将通过课程和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美国的威尔·康奈尔医学院（Weill Cornell Medical College）举行 Byramjee Jeejeebhoy医学院（印度）和结核病研究所（印度）。 这些机构之间的合作将为Mathad博士提供强烈的心态。 研究。每年，全世界有超过200,000名孕妇和产后妇女发展了活跃的结核病。 了解妊娠增加积极结核的风险的免疫机制 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名怀孕和非怀孕妇女的宿主免疫反应与结核分枝杆菌的免疫反应 印度浦那。这个目标将检验以下假设，即孕妇的调节性增加了 免疫细胞（CD4+CD25+FOXP3+）和细胞产物（TGF-，IL-10），辅助T细胞及其其降低 在三个月后期收集的PBMC刺激下，产物（IFN-，IL-2），结核分枝杆菌 抗原。 Mathad博士将同时注册HIV感染（n = 300）和未感染的（n = 300）女性。目标2：确定 免疫相关，可以预测300名HIV感染孕妇的队列中活跃的产后结核病。这 主要假设是IFN-和其他细胞介导的免疫细胞因子的减少幅度 在第三个中期，在产后第一年将与主动结核的发展相关。

项目成果

Screening and diagnosis of gestational diabetes in India: a systematic review and meta-analysis.

• DOI: 10.1007/s00592-018-1131-1
• 发表时间: 2018-06
• 期刊: Acta diabetologica
• 影响因子: 3.8
• 作者: Li KT;Naik S;Alexander M;Mathad JS
• 通讯作者: Mathad JS