Impact of maternal HIV on Mycobacterium tuberculosis infection among peripartum women and their infants

孕产妇HIV感染对围产期妇女及其婴儿结核分枝杆菌感染的影响

• 批准号: 9137077
• 负责人: Sylvia LaCourse
• 金额: $ 17.12万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-15 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9137077
• 关键词: Address; Affect; Age-Months; Algorithms; Area; Award; Benefits and Risks; Biological Assay; Centers for Disease Control and Prevention (U.S.); Characteristics; Child; Clinical; Clinical Investigator; Clinical Research; Clinical Trials; Clinical Trials Design; Cohort Studies; Communicable Diseases; Complex; Cost Effectiveness Analysis; Crowding; Data; Data Analyses; Data Collection; Development Plans; Diagnostic; Diagnostic tests; Disease; Economic Models; Employment; Enrollment; Epidemiologic Methods; Epidemiologic Studies; Epidemiology; Evaluation; Exposure to; Foundations; Funding; Future; Goals; HIV; Household; Hypersensitivity; Immunologics; Incidence; Individual; Infant; Infection; Institution; Interferon Type II; Internal Medicine; International; Intervention; Intervention Trial; Kenya; Lead; Learning; Logistic Regressions; Maternal and Child Health; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; Modeling; Morbidity - disease rate; Mothers; Outcome; Paternal Exposure; Pathogenesis; Pediatrics; Performance; Physicians; Pilot Projects; Population; Positioning Attribute; Postpartum Period; Predisposition; Pregnancy; Pregnant Women; Prevalence; Prevention; Prevention strategy; Prevention trial; Preventive therapy; Publications; Recording of previous events; Research; Research Personnel; Research Proposals; Research Training; Resources; Risk; Role; Staging; Testing; Time; Training; Tuberculin Test; Tuberculosis; Universities; Washington; Woman; Women' s Health; antiretroviral therapy; base; career; career development; clinically relevant; cofactor; cohort; cost; cost effectiveness; design; diagnostic screening; effectiveness clinical trial; epidemiologic data; evidence base; evidence based guidelines; experience; health economics; health seeking behavior; improved; infant outcome; infectious disease model; instructor; isoniazid; mortality; performance tests; pregnant; programs; prospective; public health relevance; screening; skills; trial design

 DESCRIPTION (provided by applicant): This K23 Mentored Patient-Oriented Research Career Development Award proposal describes a training and research program that will enable the Candidate to achieve her goal of becoming an independent clinical investigator with expertise in HIV/tuberculosis (TB) and maternal and child health. The Candidate is an Infectious Disease physician trained in Internal Medicine and Pediatrics, with experience in evaluating TB diagnostics, and implementation and evaluation of HIV and TB screening algorithms. For this K23 award, the career development plan will provide the Candidate with mentored learning in advanced epidemiologic, biostatistical, and health economics modeling methods while investigating whether maternal HIV is associated with increased risk of Mycobacterium tuberculosis (Mtb) infection in peripartum women and their infants, and if HIV and pregnancy stage influence latent tuberculosis (LTBI) infection test discordance. HIV-infected individuals and infants have an increased risk of progression from Mtb infection to TB disease. Pregnant and postpartum periods have also been associated with increased risk of TB. Whether maternal HIV increases susceptibility to Mtb infection among peripartum women and their infants, and the dual roles of HIV and peripartum stage on latent TB testing are unknown. The investigator proposes to develop new parallel prospective cohorts enrolling HIV-infected and uninfected pregnant women and their infants. Research Specific Aims are to determine the: (Aim 1) effect of maternal HIV on risk and timing of maternal peripartum Mtb infection, (Aim 2) influence of maternal HIV on risk of infant Mtb infection, and (Aim 3) effect of maternal HIV status and peripartum stage on LTBI test performance, including interferon gamma-release assays (IGRA) and tuberculin skin tests (TST). The incidence of maternal Mtb infection will be estimated and compared between HIV-infected and HIV-uninfected pregnant women using IGRA in pregnancy, and at 6 weeks, and 1 year postpartum. The prevalence of Mtb infection in HIV-exposed and HIV-unexposed infants will be compared at 6 and 12 months of age by IGRA. TST and IGRA discordance will be compared in pregnancy, early postpartum, and late postpartum within each maternal cohort and between HIV-infected and uninfected women. Potential cofactors for maternal and infant Mtb infection and maternal LTBI test discordance will be evaluated. The Candidate proposes training designed to provide her skills in implementing prospective cohort studies and conducting complex longitudinal data analysis in maternal-infant cohorts as part of her research proposal, as well as in interventional trial design, cost-effectiveness and outcomes modeling to provide a foundation for future directions including submitting an R01 proposal. Skills will be gained through directed mentorship, didactic coursework, the proposed research plan, as well as additional mentor-identified opportunities to collaborate on international HIV/TB trials. Her specific goals over the training period are to 1) gain proficiency in advanced logistic regression and linear mixed models, 2) develop content expertise in key areas of HIV/TB-related research in maternal child health settings, 3) lead a longitudinal epidemiologic study, 4) contribute to understanding epidemiologic correlates of Mtb infection in HIV-infected mothers and their children, 5) build a foundation in cost-effectiveness modeling including the use of composite risk-benefit maternal-infant outcomes, and 6) generate original data and scientific questions while expanding her publication record in order to successfully compete for independent funding at the R01 level. The Candidate has identified an interdisciplinary team of mentors (Drs. John-Stewart, Gupta, Kinuthia, Richardson) and collaborators (Drs. Horne, Maleche-Obimbo, Cain, Levin) from University of Washington, Johns Hopkins University, University of Nairobi, and CDC with expertise in HIV and TB epidemiology in women and children, longitudinal cohort studies and clinical trials, TB diagnostics, cost-effectiveness and infectious disease modeling. The Candidate's institution has a long-standing history of collaborative research in Kenya. Her mentors and institution have committed the resources needed to successfully advance her research independence. The research findings will provide important data regarding TB epidemiology and pathogenesis, and inform future TB interventional trials and models in the context of maternal/child health. This proposed project will provide the groundwork for the Candidate's career goal to become an independent clinical researcher with a focus on improving the health of women and their children in areas of high HIV/TB burden through evidence- based preventive strategies.

 描述（由申请人提供）： 这项K23指导了以患者为导向的研究职业发展奖提案，描述了一项培训和研究计划，该计划将使候选人能够实现她成为具有艾滋病毒/结核病专业知识（TB）和孕产妇和儿童健康专业知识的独立临床研究者的目标。 候选人是一位受过内科和儿科培训的传染病医师，具有评估结核病诊断的经验，以及对HIV和TB筛查算法的实施和评估。为了获得这一K23奖，职业发展计划将为候选人提供高级流行病学，生物统计学和健康经济学建模方法的指导学习方法，同时研究了母体HIV是否与周期妇女及其儿童及其婴儿及其IF HIM和IF HIM和IF HIM和IF HIST CAPETIONS LATENCENCENT（LITENCEDSBIDER）（MTB）感染的结核病风险增加有关。 感染HIV的个体和婴儿从MTB感染到结核病疾病的进展风险增加。孕妇和产后时期也与结核病风险增加有关。孕产妇的艾滋病毒是否会增加围产期妇女及其婴儿中MTB感染的敏感性，以及在潜在结核病测试中艾滋病毒和周期阶段的双重作用。 研究者的建议是开发新的平行前瞻性人群，以招募受HIV感染和未感染的孕妇及其婴儿。 Research Specific Aims are to determine the: (Aim 1) effect of maternal HIV on risk and timing of maternal peripheralum Mtb infection, (Aim 2) influence of maternal HIV on risk of infant Mtb infection, and (Aim 3) effect of maternal HIV status and peripheralum stage on LTBI test performance, including interferon gamma-release Assays (IGRA) and tuberculin skin tests (TST).将估计并比较产妇MTB感染的事件，并在怀孕期间使用IGRA，6周和产后1年的HIV感染和HIV未感染的孕妇进行比较。 IGRA将在6个月和12个月大时比较艾滋病毒暴露和艾滋病毒无暴露的婴儿中MTB感染的患病率。在每个母校队列中以及HIV感染的妇女和未感染的妇女之间，将比较TST和IGRA不一致的怀孕，产后早期和产后晚期的不一致。将评估母体和婴儿MTB感染和母体LTBI测试不一致的潜在辅助因子。 旨在为她的研究建议的一部分以及介入的试验设计，成本效益和成果建模的候选提案培训旨在提供她实施前瞻性队列研究和进行复杂的纵向数据分析的技能，并为未来的方向提供基础，包括提交R01提案。技能将通过指导的指导职位，教学课程，拟议的研究计划以及在国际艾滋病毒/结核病试验上进行合作的其他机会。 她在培训期间的特定目标是1）在高级逻辑回归和线性混合模型中提高能力，2）在孕产妇儿童健康环境中与HIV/TB相关研究的关键领域建立内容专业知识，3）领导一个领导纵向流行病学研究，4）有助于了解MTB的构建模型，以促进MTB的建立，以促进HIV-INFERTION in HIV-INFERTION-MOTHERS-MONDERS-MONSTER-5）5）5）复合风险效益产妇的结果，以及6）产生原始数据和科学问题，同时扩大了她的出版记录，以便成功地在R01级别争夺独立资金。 The Candidate has identified an interdisciplinary team of mentors (Drs. John-Stewart, Gupta, Kinuthia, Richardson) and collaborators (Drs. Horne, Maleche-Obimbo, Cain, Levin) from University of Washington, Johns Hopkins University, University of Nairobi, and CDC with expertise in HIV and TB epidemiology in women and children, longitudinal cohort studies and clinical试验，结核病诊断，成本效益和传染病建模。候选人的机构在肯尼亚拥有长期的合作研究历史。她的导师和机构已承诺成功地推进她的研究独立性所需的资源。 研究结果将提供有关结核病流行病学和发病机理的重要数据，并在孕产妇健康的背景下为未来的结核病介入试验和模型提供信息。这 拟议的项目将为候选人的职业目标提供基础，以成为一名独立的临床研究人员，重点是通过基于证据的预防策略来改善妇女及其子女的健康。