Novel clinic-based TB diagnostics and testing algorithms for persons with HIV

针对艾滋病毒感染者的基于临床的新型结核病诊断和检测算法

• 批准号: 9896773
• 负责人: ADRIENNE E SHAPIRO
• 金额: $ 18.68万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-20 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9896773
• 关键词: Address; Adopted; Adult; Africa; Africa South of the Sahara; Algorithms; Bedside Testings; Biological Assay; Body mass index; CD4 Lymphocyte Count; Caring; Classification; Clinic; Clinical; Clinical Research; Consumption; Cost Analysis; Data; Decision Analysis; Detection; Diagnosis; Diagnostic; Diagnostic tests; Epidemiologic Methods; Epidemiology; Equipment; Evaluation; Foundations; Generations; Goals; HIV; HIV/TB; Health; Hospitals; Impact evaluation; In Vitro; Inpatients; Laboratories; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Modeling; Morbidity - disease rate; Outpatients; Patient Dropouts; Patient Selection; Patients; Performance; Peripheral; Persons; Physicians; Population; Positioning Attribute; Property; Randomized Controlled Trials; Research; Research Institute; Resources; Rural; Science; Scientist; Services; South Africa; Specificity; Specimen; Sputum; Symptoms; Testing; Time; Training; Training Programs; Translating; Tuberculosis; Urine; Validation; World Health Organization; base; budget impact; care seeking; career; clinically relevant; cohort; cost; diagnostic accuracy; economic evaluation; effective intervention; epidemiology study; evaluation/testing; follow-up; health economics; implementation science; implementation strategy; improved; infectious disease model; innovation; lipoarabinomannan; meetings; microcosting; minimal risk; mortality; mycobacterial; next generation; novel; novel diagnostics; point of care; predictive modeling; primary outcome; prospective; regression trees; rural South Africa; screening; secondary outcome; skills; standard of care; tool; transmission process; tuberculosis diagnostics; tuberculosis treatment; uptake; validation studies

PROJECT SUMMARY/ABSTRACT Tuberculosis (TB) is the leading cause of mortality in people with HIV (PWH) in sub-Saharan Africa, due in part to delays in diagnosis and timely treatment. While HIV-infected persons often first seek care at peripheral clinics, TB diagnostic testing equipment located in centralized laboratories require time-consuming specimen transport and processing, resulting in delayed diagnosis and patient drop-out from care. Use of a point-of-care urine-based test detecting mycobacterial lipoarabinomannan (LAM) has been successful in reducing mortality in a hospital setting, but the existing test is insensitive in ambulatory patients. The largest burden of undiagnosed TB is in PWH in non-hospital settings, and clinic-based testing assays and improved algorithms are urgently needed. A promising novel, rapid, urine-based tests (nuLAM) has been developed that may overcome many barriers to TB diagnosis, but has not yet been tested in a clinical setting. My central hypothesis is that rational use of next- generation POC LAM testing will be an effective intervention for PWH in South Africa. I will test this hypothesis with the following specific aims: 1) To develop an optimized clinical algorithm to identify HIV-infected outpatients for TB testing using POC uLAM and guide evaluation of nuLAM. 2) To determine the diagnostic accuracy of the next-generation LAM tests to detect TB in a population of HIV-infected outpatients attending a rural clinic in South Africa, compared to rigorous validation standards of TB culture and GeneXpert. 3) To estimate the population-level impact of nuLAM testing of outpatient PWH through costing and decision analysis. My career goal is to become a physician-scientist with a focus on developing and implementing diagnostic approaches to ultimately reduce morbidity and mortality from HIV-associated TB. I will use the opportunity of the K23 award to obtain mentorship in predictive modeling, implementation science, and diagnostics science. These skills are highly complementary to my strong background in epidemiologic methods and clinical research, and will enable me to translate epidemiologic research findings into tools to help clinicians and policymakers improve approaches to TB diagnosis. At the completion of the research and mentoring outlined, I will be well-positioned to launch an independent research career with the ultimate goal of improving diagnosis, treatment, and care of HIV-associated TB in sub-Saharan Africa.

项目摘要/摘要 结核病是撒哈拉以南非洲艾滋病毒携带者(PWH)死亡的主要原因，部分原因是 延误诊断和及时治疗。虽然艾滋病毒感染者往往首先在外围诊所寻求治疗， 位于集中实验室的结核病诊断检测设备需要耗时的样本运输 和处理，导致延迟诊断和病人退出护理。使用以尿液为基础的护理点 检测分枝杆菌脂阿拉伯甘露聚糖(LAM)在医院成功降低死亡率 设置，但现有的测试是不敏感的门诊患者。未确诊结核病的最大负担是在 迫切需要非医院环境下的PWH，以及基于诊所的检测分析和改进的算法。一个 有希望的新型快速尿液检测(NuLAM)已经被开发出来，它可能会克服许多结核病的障碍 诊断，但尚未在临床环境中进行测试。我的中心假设是合理使用NEXT- 代POC LAM测试将是对南非PWH的有效干预。我将检验这一假设 具体目标如下：1)开发一种优化的临床算法来识别HIV感染的门诊患者 使用POC ULAM进行结核病检测，并指导NuLAM的评估。2)以确定诊断的准确性 下一代LAM测试在年一家农村诊所就诊的艾滋病毒感染门诊患者中检测结核病 南非，与结核病培养和基因Xpert的严格验证标准相比。3)评估 通过成本计算和决策分析对门诊威斯康星医院NULAM检测的人群水平影响。我的职业生涯 目标是成为一名内科科学家，专注于开发和实施诊断方法 最终降低艾滋病毒相关结核病的发病率和死亡率。我将利用K23奖的机会来 获得预测建模、实施科学和诊断科学方面的指导。这些技能是 与我在流行病学方法和临床研究方面的强大背景具有很强的互补性，并将使 我将把流行病学研究成果转化为工具，帮助临床医生和政策制定者改进 结核病诊断的方法。在完成概述的研究和指导后，我将处于有利地位 开始独立的研究事业，最终目标是改善诊断、治疗和护理 撒哈拉以南非洲的艾滋病毒相关结核病。