Biomarker for XDR-TB Treatment Response and Drug Resistance in HIV Endemic Area

HIV 流行地区广泛耐药结核病治疗反应和耐药性的生物标志物

• 批准号: 8508846
• 负责人: Max O'Donnell
• 金额: $ 13.42万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-11 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8508846
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Antimycobacterial Agents; Applications Grants; Area; Bacteriophages; Bioethics; Biological Assay; Biological Markers; Biometry; Case Fatality Rates; Characteristics; Clinical; Clinical Trials; Collaborations; Colony-forming units; Communities; Complex; Data; Development; Development Plans; Diagnosis; Diagnostic; Drug Resistant Tuberculosis; Drug resistance; Drug resistance in tuberculosis; Early treatment; Engineering; Epidemiologist; Extreme drug resistant tuberculosis; Fluorescence; Foundations; Funding; Generations; Genus Mycobacterium; Goals; Gray unit of radiation dose; HIV; HIV drug resistance; Hour; In Vitro; Incidence; Infection; K-Series Research Career Programs; Laboratories; Manuscripts; Measures; Medicine; Mentors; Methyl Green; Microbiology; Molecular; Mycobacteriophages; Mycobacterium tuberculosis; Outcome; Patients; Pharmaceutical Preparations; Population; Predisposition; Process; Prospective Studies; Reaction; Regimen; Reporter; Reporter Genes; Research; Research Infrastructure; Research Institute; Research Personnel; Research Proposals; Resistance; Role; Sampling; Scientist; Signal Transduction; Solid; South Africa; Sputum; System; Testing; Time; Training; Treatment outcome; Tuberculosis; Validation; Virus; Work; base; career; career development; clinical application; clinical decision-making; clinical practice; college; comparative efficacy; experience; global health; improved; innovation; lectures; novel; programs; promoter; research and development; resistant strain; transmission process; treatment response; tuberculosis treatment

DESCRIPTION (provided by applicant): This proposal describes a career development plan and research proposal for Dr. Max O'Donnell, a pulmonologist at Albert Einstein College of Medicine. Working with collaborators and mentors at Einstein and in South Africa, Dr. O'Donnell is establishing himself as a translational investigator in drug-resistant tuberculosis (TB) and HIV research. Nowhere has drug-resistant TB generated more alarm than in South Africa, where synergies between endemic TB and HIV have caused 'explosive' increases in TB incidence and case-fatality rates. The most resistant form of TB, extensively drug resistant tuberculosis (XDR-TB), is increasingly prevalent in South Africa. An important obstacle to improving survival for XDR-TB is lack of a rapid, biomarker to serve as a surrogate outcome in clinical trials and guide clinician's by measuring treatment response. Fluoromycobacteriophage (FMP) assays use genetically modified mycobacteria-specific viruses to quantify viable M tuberculosis (Mtb) using a fluorescence reporter system. Utilizing a novel FMP assay with superior test characteristics, Dr. O'Donnell proposes to measure decrease in Mtb in XDR-TB patients' sputum as a biomarker for treatment response (Aim 1). Among XDR-TB patients who fail to respond to treatment Dr. O'Donnell proposes to use the same assay to rapidly diagnose emergent second-line drug resistance (Aim 2). This research component of this proposal is a result of an ongoing funded collaboration between researchers at Albert Einstein College of Medicine with researchers at the KwaZulu-Natal Research Institute for Research in Tuberculosis and HIV/AIDS (K-RITH), and the Centre for AIDS Programme of Research in South Africa (CAPRISA). The training component of this proposal involves developing the applicant as a TB molecular epidemiologist including training in the mentor's laboratory, coursework, seminars, lectures, and specific training in drug-resistant TB microbiology. Unique features include co-mentoring from a renowned TB basic scientist, TB epidemiologist, and translational researcher with additional support from career development committee with extensive TB and career development experience. This is an innovative approach with the potential to make substantial impact in our ability to rationally manage drug-resistant tuberculosis, rapidly evaluate the comparative efficacy of different drug regimens, and rapidly diagnose emergent drug-resistance among TB patients on treatment. This research will form the basis for a prospective study of the application of clinical biomarkers for treatment outcome in drug-resistant tuberculosis that will be proposed in an R01 grant application before the end of the K award.

描述（由申请人提供）：该提案描述了艾伯特·爱因斯坦医学院的肺科医生Max O'Donnell博士的职业发展计划和研究建议。 O'Donnell博士与爱因斯坦和南非的合作者和导师合作，成为耐药性结核病（TB）和HIV的转化调查员 研究。在南非，耐药结核病的抗药性TB在任何地方都没有更多的警报，在南非，地方性结核病和艾滋病毒之间的协同作用导致了结核病发病率和病例竞争率的“爆炸性”增加。在南非，结核病（XDR-TB）广泛的抗药性结核病（XDR-TB）的最具耐药性形式在南非越来越普遍。改善XDR-TB生存的重要障碍是缺乏快速的生物标志物，无法在临床试验中作为替代结果，并通过测量治疗反应来指导临床医生。荧光菌病菌（FMP）测定法使用经过转基因的分枝杆菌特异性病毒来量化可行的M结核病（MTB）（MTB）。 O'Donnell博士利用具有出色测试特征的新型FMP测定法提议测量XDR-TB患者痰液中MTB的降低，作为治疗反应的生物标志物（AIM 1）。在XDR-TB患者中，O'Donnell博士未能做出反应的患者建议使用相同的测定法来快速诊断出紧急的二线耐药性（AIM 2）。该提案的这一研究组成部分是阿尔伯特·爱因斯坦医学院研究人员与夸祖鲁 - 纳塔尔纳塔尔语研究研究所的艾伯特·爱因斯坦医学院研究人员之间持续资助的合作的结果。该提案的培训部分涉及将申请人作为结核病分子流行病学家开发，包括在导师的实验室，课程，研讨会，讲座和耐药性结核病微生物学方面的特定培训。独特的功能包括来自著名的结核病基础科学家，结核病流行病学家和翻译研究人员的同事，并获得了职业发展委员会的额外支持，并具有广泛的结核病和职业发展经验。这是一种创新的方法，有可能对我们合理管理耐药性结核病的能力产生重大影响，迅速评估比较疗效 在治疗中，不同药物方案以及结核病患者中迅速诊断出抗药性的抗药性。这项研究将构成对临床生物标志物在药物耐药结核病中的治疗结果应用的前瞻性研究的基础，该研究将在k奖结束之前在R01赠款申请中提出。