Evaluation of new diagnostics for incident, active and recurrent TB (ENDx-Tb)

评估新发结核病、活动性结核病和复发性结核病的诊断方法 (ENDx-Tb)

• 批准号: 10418673
• 负责人: John T Belisle
• 金额: $ 150万
• 依托单位: STELLENBOSCH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-17 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10418673
• 关键词: Address; Adult; Affect; Africa; Age; Area; Asia; Biological; Biological Assay; Blood; Caring; Cessation of life; Child; Clinical; Clinical Research; Communities; Complement; Complex; Country; Detection; Diagnosis; Diagnostic; Diagnostic tests; Diagnostics Research; Disease; Early Diagnosis; Elements; Europe; Evaluation; Fingers; Future; Gambia; Geographic Locations; Goals; HIV; HIV Infections; Health Status; Health care facility; Healthcare; Healthcare Systems; Household; Incidence; Infection; Infrastructure; International; Laboratories; Liquid substance; Measures; Medical; Messenger RNA; Methods; Molecular; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Patients; Performance; Persons; Peru; Phase; Preventive therapy; Primary Health Care; Prophylactic treatment; Proteins; Quantitative Reverse Transcriptase PCR; Reagent; Recurrence; Relapse; Resource-limited setting; Resources; Risk; Rural; Sampling; Scientist; Shapes; Side; South Africa; South America; Southeastern Asia; Sputum; Symptoms; Testing; Time; Transcript; Treatment Efficacy; Treatment Protocols; Treatment outcome; Triage; Tuberculosis; Vietnam; Work; biosignature; clinical research site; co-infection; cohort; comorbidity; cost effective; diagnostic strategy; diagnostic tool; disorder prevention; drug-sensitive; experience; falls; follow-up; head-to-head comparison; health care settings; high risk; implementation barriers; improved; laboratory facility; latent infection; lipoarabinomannan; meetings; mortality; multidisciplinary; new technology; novel; novel diagnostics; novel strategies; pathogen; patient subsets; performance tests; point of care; predictive marker; predictive test; prevent; programs; progression risk; socioeconomics; standard of care; targeted treatment; transmission blocking; treatment duration; treatment response; treatment strategy; treatment stratification; tuberculosis treatment; urban area; urinary

PROJECT SUMMARY: ENDx-TB proposal A central component of WHO’s End TB Strategy is to diagnose approximately 3 million patients annually who are not diagnosed or treated due to inadequate tests that are not tailored towards specific needs for different levels or capabilities of health care facilities. Better tests are needed at point-of-care, where triage in low-resource settings is essential to prioritize those with the highest risk for tuberculosis disease to higher levels of care. On the other hand, more complex, resource-intensive tests aimed at specific phases of host-pathogen interaction, like at the end of treatment or during latent infection would complement community-based diagnosis in less- developed health care systems that have access to central, specialized laboratory facilities. Wide-ranging diagnostic capacities co-exist in different regions of the same country, for instance in rural vs urban areas and therefore, a comprehensive battery of diagnostic tests that are appropriate for specific settings are needed. Meeting the End TB Strategy targets will also require dramatically improved prevention of disease approaches to block transmission. With 1.7 billion people latently infected, it is not cost-effective to provide prophylaxis to all. Hence a test that could predict those most at risk of developing disease would enable targeted therapeutic approaches. Similarly, tests to enable personalized or stratified treatment strategies are urgently needed. The goal is to conduct a clinical research program across the globe to compare side-by-side the most promising new tests for a wide range of health care settings in experienced clinical sites in Africa (South Africa, The Gambia), Southeast Asia (Vietnam) and South America (Peru), and advanced laboratories in the USA and Europe. The cohorts include adults, children, and people living with HIV and with type 2 diabetes mellitus. The new assays include: 1) at point-of-care: sputum-free assys, including two triage tests, based on detection of host proteins and host transcripts, both on fingerstick blood, and a high-sensitivity urinary lipoarabinomannan assay; 2) at regional laboratories: a modified liquid culture method with TiKa reagent for increased sensitivity and faster performance, and the cycle threshold value of the Xpert Ultra test as a measure of bacterial load for tuberculosis treatment monitoring; and 3) at central laboratories: a multiplex qRT-PCR test for mRNA signatures for progression to tuberculosis, and a host 4-protein biosignature in blood for prediction of poor treatmeht outcome. The performance of these tests will be evaluated according to internationally established target product profiles for the respective health care levels. The proposal makes provision for the future inclusion of additional tests in the pipleline and the inclusion of additional cohorts for specialized diagnostic research questions. Together this approach will identify the best tests for different health care levels and for different phases of infection and disease. The multi-disciplinary team of test developers and clinical scientists, and the selection of cohorts are well suited to identify novel technologies towards meeting the End TB milestones.

项目摘要：ENDx-TB 提案 世卫组织终止结核病战略的核心组成部分是每年诊断大约 300 万患者 由于测试不充分，未针对不同人群的具体需求而未能得到诊断或治疗 医疗机构的水平或能力需要在资源匮乏的护理点进行更好的测试。 优先考虑那些结核病风险最高的人接受更高水平的护理至关重要。 另一方面，针对宿主与病原体相互作用的特定阶段的更复杂、资源密集型测试， 例如在治疗结束时或潜伏感染期间，将补充在较少的情况下基于社区的诊断 开发了可以使用广泛的中央专业实验室设施的医疗保健系统。 诊断能力在同一国家的不同地区共存，例如在农村与城市地区， 因此，需要适合特定环境的全面诊断测试。 实现终结结核病战略目标还需要大幅改进疾病预防方法 由于有 17 亿人处于潜伏感染状态，为所有人提供预防措施并不划算。 因此，一项能够预测那些最有可能罹患疾病的人的测试将能够实现靶向治疗 同样，迫切需要进行个性化或分层治疗策略的测试。 目标是在全球范围内开展临床研究计划，并排比较最有前途的新药物 在非洲（南非、冈比亚）经验丰富的临床地点对各种医疗保健环境进行测试， 东南亚（越南）和南美（秘鲁），以及美国和欧洲的先进实验室。 队列包括成人、儿童以及艾滋病毒感染者和 2 型糖尿病患者。 包括：1) 在护理点：无痰装配系统，包括基于宿主蛋白检测的两项分类测试 和宿主转录物，均采用指尖采血和高灵敏度尿液阿拉伯脂甘露聚糖测定法 2) 区域实验室：使用 TiKa 试剂改进的液体培养方法，提高灵敏度并加快速度 Xpert Ultra 测试的性能和循环阈值作为结核病细菌载量的衡量标准 治疗监测；3) 在中心实验室：针对 mRNA 特征的多重 qRT-PCR 测试 进展为结核病，以及血液中宿主 4 蛋白生物特征，用于预测不良治疗结果。 这些测试的性能将根据国际既定的目标产品概况进行评估 该提案为未来纳入额外的测试做出了规定。 管道和纳入专门诊断研究问题的其他队列一起。 该方法将确定针对不同医疗保健水平和不同感染阶段的最佳测试 由测试开发人员和临床科学家组成的多学科团队以及队列的选择 非常适合确定实现终结结核病里程碑的新技术。