Oral Wash for Nucleic Acid Diagnosis and Prognosis of TB in HIV-Infected Ugandans

描述（由申请人提供）：这是一份为加州大学旧金山分校弗朗西斯科（UCSF）的肺/重症监护医生Lucian Davis博士申请K23奖的申请。戴维斯博士是一名以患者为导向的临床研究人员，致力于在高负担、资源有限的环境中（RLS）对艾滋病毒相关结核病进行新的诊断。该K23奖将为戴维斯博士提供必要的支持，以实现以下目标：（1）成为以患者为导向的临床研究专家，以改善艾滋病毒感染者结核病的诊断和预后检测;（2）学习将实验室研究技术应用于临床标本的核酸扩增;（3）学习应用先进的生物统计方法评估诊断和预后测试;及（4）学习应用先进的分析方法评估诊断测试的功效和成本效益;（5）发展独立的临床研究事业。为了实现这些目标，戴维斯博士组建了一个指导团队，由主要导师，劳伦斯黄博士，医学教授在加州大学旧金山分校和国际公认的专家研究人员在艾滋病毒相关的肺部疾病;和两个共同导师：菲利普霍普韦尔博士，医学教授在加州大学旧金山分校和国际公认的权威，在全球结核病控制;以及加州大学旧金山分校流行病学和生物统计学教授、艾滋病毒及其呼吸系统并发症领域的流行病学专家丹尼斯·奥斯蒙德博士。缺乏快速、敏感和负担得起的结核病诊断方法是全球控制结核病的主要限制因素，特别是在艾滋病毒高流行地区。戴维斯博士的研究将确定一种广泛使用的结核分枝杆菌DMA测试与一种新的标本配对，口腔清洗，是否比目前的标准测试，痰涂片显微镜检查更准确地诊断艾滋病毒感染患者的结核病（目标1）;如果定量扩增抗原85 B mRNA，即与分枝杆菌生存力和TB治疗效果相关的转录物，可以在病程早期预测治疗失败（目标2）;以及在这种高负担环境中，口腔清洗加核酸检测对于诊断结核病是否具有成本效益。(Aim 3）Davis博士将利用国际HIV相关结核病研究（1 R 01 HL 090335 -01）的现有基础设施，招募并随访300名HIV感染的结核病疑似患者。这项研究将成为未来随机试验的基础，比较该地区结核病诊断的传统和新型诊断测试。公共卫生影响：我们正在研究在盐水漱口水上进行DNA指纹分析的快速新测试是否便宜且准确，用于诊断艾滋病毒感染者肺部的结核病。我们还试图找出类似的测试是否可以告诉这些患者一旦开始治疗是否会好转。

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Lucian Davis, a pulmonary/critical care physician at the University of California, San Francisco (UCSF). Dr. Davis is establishing himself as an investigator in patient-oriented clinical research on novel diagnostics for HIV-associated tuberculosis in high-burden, resource-limited settings (RLS). This K23 award will provide Dr. Davis with the support necessary to accomplish the following goals: (1) to become expert at patient-oriented clinical research into improved diagnostic and prognostic tests for TB in patients with HIV; (2) to learn to apply laboratory research techniques for nucleic acid amplification to clinical specimens; (3) to learn to apply advanced biostatistical methods for evaluating diagnostic and prognostic tests; and (4) to learn to apply advanced analytic methods for evaluating the efficacy and cost effectiveness of diagnostic tests; and (5) to develop an independent clinical research career. To achieve these goals, Dr. Davis has assembled a mentoring team comprised of a primary mentor, Dr. Laurence Huang, Professor of Medicine at UCSF and an internationally recognized expert researcher in HIV-associated pulmonary diseases; and two co-mentors: Dr. Philip Hopewell, Professor of Medicine at UCSF and an internationally recognized authority on global TB control; and Dr. Dennis Osmond, Professor of Epidemiology and Biostatistics at UCSF, and an expert epidemiologist in the field of HIV and its respiratory complications. A lack of rapid, sensitive, affordable diagnostics for TB is a major limitation to global control of the disease, especially in high HIV-prevalence areas. Dr. Davis' research will determine if a widely available DMA test for Mycobacterium tuberculosis paired with a novel specimen, the oral wash, is more accurate for diagnosis of TB in HIV-infected patients than the current standard test, sputum smear microscopy (Aim 1); if quantitative amplification of antigen 85B mRNA, a transcript associated both with mycobacterial viability and with TB treatment effects, can predict treatment failure early in the course of disease (Aim 2); and if the oral wash plus nucleic acid test is cost-effective for diagnosing TB in this high-burden setting. (Aim 3) Dr. Davis will use the existing infrastructure of the International HIV-associated Opportunistic Pneumonias study (1R01 HL090335-01) to enroll and follow 300 HIV-infected TB suspects. This research will form the basis for a future randomized trial comparing conventional and novel diagnostic tests for TB diagnosis in this region. Public Health Impact: We are studying if fast new tests that do DNA fingerprinting on salt water mouthwashes are cheap and accurate for diagnosing tuberculosis in the lungs of patients with HIV. We are also trying to find out if a similar test can tell if these patients are getting better once they start treatment.