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: 9981167
• 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 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9981167
• 关键词: Address; Adult; Affect; Africa; Age; Americas; Area; Asia; 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; 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; Microbiology; Molecular; Monitor; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Patients; Performance; Peru; Phase; Preventive therapy; Primary Health Care; Prophylactic treatment; Proteins; Quantitative Reverse Transcriptase PCR; Reagent; Recurrence; Relapse; Resources; Risk; Rural; Sampling; Scientist; Side; South Africa; South America; Southeastern Asia; Sputum; Symptoms; Testing; Time; Transcript; Treatment Efficacy; Treatment Protocols; Treatment outcome; Triage; Tuberculosis; Vietnam; Work; base; biosignature; clinical research site; co-infection; cohort; comorbidity; cost effective; disorder prevention; drug-sensitive; experience; falls; follow-up; head-to-head comparison; health care settings; high risk; 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; socioeconomics; standard of care; targeted treatment; tool; transmission process; treatment duration; treatment response; treatment strategy; 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.

项目总结：ENDx-TB提案 世卫组织终止结核病战略的一个核心组成部分是每年诊断约300万患者， 由于不适当的测试，没有针对不同的特定需求进行诊断或治疗， 卫生保健设施的水平或能力。在护理点需要更好的测试，在那里， 为了将结核病风险最高的人优先考虑到更高水平的护理，环境至关重要。对 另一方面，针对宿主-病原体相互作用的特定阶段的更复杂的、资源密集型的测试， 如在治疗结束时或潜伏感染期间， 发达的卫生保健系统可以使用中央专门的实验室设施。广泛的 诊断能力在同一国家的不同地区共存，例如农村地区与城市地区， 因此，需要一套适合于特定环境的综合诊断测试。 实现终结结核病战略的目标还需要大大改进疾病预防方法 以阻止传播。由于有17亿人潜伏感染，向所有人提供预防措施不符合成本效益。 因此，一项可以预测那些最有可能患上疾病的人的测试将使靶向治疗成为可能。 接近。同样，迫切需要能够实现个性化或分层治疗策略的测试。的 我们的目标是在地球仪进行一项临床研究计划， 在非洲（南非、冈比亚）经验丰富的临床地点进行广泛的卫生保健环境测试， 东南亚（越南）和南美（秘鲁），以及美国和欧洲的先进实验室。的 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。新的检测方法 包括：1）在护理点：基于宿主蛋白质检测，包括两个分类测试的无肿瘤ASSY 和宿主转录物，两者均在手指针刺血和高灵敏度尿脂阿拉伯甘露聚糖测定中; 2）在 区域实验室：使用TiKa试剂的改良液体培养法，可提高灵敏度， 性能和Xpert Ultra test的循环阈值作为结核菌载量的指标 治疗监测;和3）在中心实验室：多重qRT-PCR检测mRNA特征， 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公认的目标产品概况进行评估 在各自的医疗水平。该提案为今后在《公约》中列入更多的测试作出了规定。 管道和纳入专门诊断研究问题的额外队列。一起这么 该方法将确定不同卫生保健水平和不同感染阶段的最佳检测方法， 疾病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是 非常适合确定实现终结结核病里程碑的新技术。