Research Training on Pathogenesis and Diagnosis of HIV-TB

HIV-TB发病机制和诊断研究培训

• 批准号: 9049560
• 负责人: Suman Laal
• 金额: $ 30.44万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-25 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9049560
• 关键词: Basic Science; Bedside Testings; Bioinformatics; Cessation of life; Clinic; Clinical; Clinical Management; Diagnosis; Diagnostic; Diagnostic tests; Doctor of Philosophy; Faculty; Fostering; Foundations; Goals; HIV; HIV Infections; HIV/TB; Immune System Diseases; Immune response; Immunologic Deficiency Syndromes; Immunologic Techniques; India; Individual; Institutes; Institution; International AIDS; Lung; Medical Education; Medical Research; Mentors; Molecular; Morbidity - disease rate; Mycobacterium tuberculosis; Parents; Pathogenesis; Patients; Performance; Pharmaceutical Preparations; Population; Predisposition; Research; Research Infrastructure; Research Project Grants; Research Training; Scientist; Specimen; Students; Techniques; Testing; Training; Training Programs; clinical care; education research; improved; member; mortality; pathogen; programs; tool

DESCRIPTION (provided by applicant): India has the largest number of individuals co-infected with HIV and M. tuberculosis in the world, and TB is the most important cause of morbidity and mortality in HIV+ patients in India. The immune dysfunction caused by HIV-infection alters clinical and radiological presentation of TB; HIV+ TB patients are often asymptomatic, about half the patients are paucibacillary, and over 50% of the patients have extrapulmonary TB. Paucibacillary pulmonary and extrapulmonary TB in HIV+ patients is difficult to diagnose due to lack of affordable diagnostic tests, often poor accessibility to the ste from which the specimen has to be obtained for testing, and the invasive techniques required to obtain the specimen for diagnosis. The poor performance of insensitive diagnostic tests currently used for TB diagnosis in TB-endemic settings like India leads to significant under- diagnosis of TB in the very population where TB progression is rapid and often fatal. Thus, despite being totally treatable with the existing drugs, the lack of appropriate diagnostic tools results in identification of less than half of the HIV+ TB patients being diagnosed before death. The goal of this HIV Research Training Program (HRTP) is to provide training and capacity building for fostering basic research on understanding the pathogenesis of pulmonary and extrapulmonary TB in HIV+ patients, with the ultimate goal of devising rapid, simple and accurate point-of-care tests for diagnosis of active and subclinical, pulmonary and various forms of extrapulmonary TB. Facilitate new research efforts aimed at understanding the pathogenesis, immune responses and host-pathogen interaction in pulmonary and extrapulmonary TB in HIV+ patients (Aim 1); provide training in specific cellular, molecular and immunological techniques and the related troubleshooting, and in bioinformatics required for initiating the research project defined in aim 1 (Aim 2); mentor and support trainees for developing research projects in their parent lab (Aim 3), and establish long-term collaborative relationships between NYU and scientists in the partner institute (Aim 4). Training will be provided to young tenured faculty members and PhD students from the Post Graduate Institute for Medical Education and Research (PGIMER), Chandigarh, India. PGIMER was one of the seven collaborating institutions on the NYU AIDS International Training and Research Program (AITRP, since 2001; NCE till 2014). The training of 10 (9 faculty and one PhD student) under the former AITRP has resulted in i) training to 5 clinicians in clinical care of HIV/TB and TB patients; ii) establishmet of an immunodeficiency clinic for providing clinical care to HIV+ patients, that is now designated as Center of Excellence for Clinical management of HIV+ patients, and provides ART to >4000 patients from 6 states in northern India; iii) training of 3 clinical mycobacteriologists who now rn accredited TB labs for culture and drug susceptibility testing, and iv) trained two basic science faculty with whom collaborative research has been ongoing or initiated. PGIMER is rapidly improving its research infrastructure and staff. The proposed HIV Research Training Program proposes to build on this already strong foundation that has been established over the last decade.

描述（由申请人提供）：印度是世界上艾滋病毒和结核分枝杆菌混合感染人数最多的国家，结核病是印度艾滋病毒+患者发病和死亡的最重要原因。 HIV 感染引起的免疫功能障碍改变了结核病的临床和放射学表现； HIV+结核病患者通常无症状，大约一半的患者为少杆菌，超过50%的患者患有肺外结核。 HIV+患者中的少杆菌性肺结核和肺外结核很难诊断，因为缺乏负担得起的诊断测试，通常难以获得检测样本的场所，以及获取诊断样本所需的侵入性技术。目前，在印度等结核病流行地区，用于结核病诊断的不敏感诊断测试性能不佳，导致结核病进展迅速且往往致命的人群中结核病诊断严重不足。因此，尽管现有药物完全可以治疗，但由于缺乏适当的诊断工具，导致在死亡前被诊断出的艾滋病毒+结核病患者中不到一半被识别出来。该艾滋病毒研究培训计划 (HRTP) 的目标是提供培训和能力建设，以促进了解艾滋病毒阳性患者肺结核和肺外结核发病机制的基础研究，最终目标是设计快速、简单和准确的现场检测，以诊断活动性和亚临床、肺结核和各种形式的肺外结核。促进旨在了解 HIV+ 患者肺结核和肺外结核的发病机制、免疫反应和宿主-病原体相互作用的新研究工作（目标 1）；提供特定细胞、分子和免疫学技术以及相关故障排除以及启动目标 1（目标 2）中定义的研究项目所需的生物信息学方面的培训；指导和支持学员在其母实验室开发研究项目（目标 3），并在纽约大学与合作伙伴研究所的科学家之间建立长期合作关系（目标 4）。将为印度昌迪加尔医学教育与研究研究生院 (PGIMER) 的年轻终身教职人员和博士生提供培训。 PGIMER 是纽约大学艾滋病国际培训和研究计划（AITRP，自 2001 年起；NCE 至 2014 年）的七个合作机构之一。在前 AITRP 下对 10 名（9 名教师和 1 名博士生）进行了培训，结果是 i) 5 名临床医生接受了艾滋病毒/结核病和结核病患者临床护理方面的培训； ii) 建立一个免疫缺陷诊所，为 HIV+ 患者提供临床护理，该诊所现被指定为 HIV+ 患者临床管理卓越中心，并向印度北部 6 个州的超过 4000 名患者提供 ART； iii) 培训了 3 名临床分枝杆菌学家，他们现在在经过认可的结核病实验室进行培养和药物敏感性测试，以及 iv) 培训了两名正在进行或已启动合作研究的基础科学教师。 PGIMER 正在迅速改善其研究基础设施和人员。拟议的艾滋病毒研究培训计划旨在建立在过去十年已经建立的坚实基础上。