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: 9088299
• 负责人: Max O'Donnell
• 金额: $ 13.42万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 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 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9088299
• 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 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; HIV/TB; Hour; In Vitro; Incidence; K-Series Research Career Programs; Laboratories; Light; Manuscripts; Measures; Medicine; Mentors; 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; Surrogate Markers; System; Testing; Time; Training; Treatment outcome; Tuberculosis; Validation; Virus; Work; base; career; career development; clinical biomarkers; clinical decision-making; clinical practice; co-infection; college; comparative efficacy; experience; extensive drug resistance; global health; improved; innovation; laboratory experience; lectures; molecular marker; novel; novel therapeutics; 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）：本计划书描述了爱因斯坦医学院肺科医生Max O'Donnell博士的职业发展计划和研究计划。O'Donnell博士与爱因斯坦大学和南非的合作者和导师合作，正在确立自己在耐药结核病和艾滋病毒方面的转化研究员地位

项目成果

Clofazimine in the treatment of extensively drug-resistant tuberculosis with HIV coinfection in South Africa: a retrospective cohort study.

• DOI: 10.1093/jac/dku235
• 发表时间: 2014-11
• 期刊: The Journal of antimicrobial chemotherapy
• 作者: N. Padayatchi;M. Gopal;R. Naidoo;L. Werner;K. Naidoo;I. Master;M. O’Donnell

Primary Capreomycin Resistance Is Common and Associated With Early Mortality in Patients With Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal, South Africa.

• DOI: 10.1097/qai.0000000000000650
• 发表时间: 2015-08-15
• 期刊: Journal of acquired immune deficiency syndromes (1999)
• 作者: OʼDonnell MR;Pillay M;Pillay M;Werner L;Master I;Wolf A;Mathema B;Coovadia YM;Mlisana K;Horsburgh CR;Padayatchi N
• 通讯作者: Padayatchi N

Turning the tide against tuberculosis.

扭转结核病的颓势。

• DOI: 10.1016/j.ijid.2017.01.012
• 发表时间: 2017
• 期刊: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
• 作者: Padayatchi,Nesri;Naidu,Naressa;Friedland,Gerald;Naidoo,Kasavan;Conradie,Francesca;Naidoo,Kogieleum;O'Donnell,MaxRoe
• 通讯作者: O'Donnell,MaxRoe

Emergence, Epidemiology, and Transmission Dynamics of 2009 Pandemic A/H1N1 Influenza in Kampala, Uganda, 2009-2015.

2009-2015 年乌干达坎帕拉 2009 年甲型 H1N1 流感大流行的出现、流行病学和传播动态。

• DOI: 10.4269/ajtmh.17-0524
• 发表时间: 2018
• 期刊: The American journal of tropical medicine and hygiene
• 作者: Cummings,MatthewJ;Bakamutumaho,Barnabas;Yang,Wan;Wamala,JosephF;Kayiwa,John;Owor,Nicholas;Namagambo,Barbara;Byaruhanga,Timothy;Wolf,Allison;Lutwama,JuliusJ;Shaman,Jeffrey;O'Donnell,MaxR
• 通讯作者: O'Donnell,MaxR

Effect of Antiretroviral Therapy on Treatment Outcomes in a Prospective Study of Extensively Drug-Resistant Tuberculosis (XDR-TB) HIV Coinfection Treatment in KwaZulu-Natal, South Africa.

• DOI: 10.1097/qai.0000000000001833
• 发表时间: 2018-12-01
• 期刊: Journal of acquired immune deficiency syndromes (1999)
• 作者: Yuengling KA;Padayatchi N;Wolf A;Mathema B;Brown T;Horsburgh CR;OʼDonnell MR
• 通讯作者: OʼDonnell MR