A new method for active tuberculosis case finding

项目总结 2035年结束结核病战略的一个关键组成部分是制定改进的 以前未诊断的结核病的活动性病例发现(ACF)方法。多数 国家结核病控制项目进行的ACF是基于检测 远程获得但新诊断的结核病病例的家庭接触者(HC) 疾病。这种方法通常在2-4%的情况下检测到以前未诊断出的结核病 HCS的。 我们建议测试一种全新的基于测试HCS的ACF方法 最近获得和新诊断的结核病感染的青少年。这是一项创新 ACF方法的优点是，由于感染是最近获得的， 源病例可能仍在新的IGRA转换器的密切接触范围内。为 因此，我们假设将找到多达50%的来源病例 这些新的转换器。 这种方法是基于我们最近三年的系列测试研究结果。 坦桑尼亚650名青春期学龄儿童中结核病感染情况。这项研究是基于 关于使用干扰素伽马释放试验(IGRA)进行结核病感染的年度检测。 我们表明这种测试是可行的，并检测到2.9%的年率 感染。 在拟议的新的5年研究中，我们将对以下项目进行基线IGRA测试 1200坦桑尼亚青少年紧随其后的第四季度IGRA测试x4估计 基线时IGRA阴性的1020人。我们预计将发现新的结核病感染病例 (IGRA转换为阳性)50名参与者。然后我们将测试他们的200个 家庭和其他密切接触者(统称为他们的密切接触者，CC)并预测 我们将在至少25个或更少的时间内确定以前未诊断出的结核病的来源病例 在这50例新的青少年感染中，有50%。预计新发结核病的比率 因此，CCS中的检测率为25/200或12.5%，比 目前检测结核病患者红细胞压积的方法。成本效益将是 与国家计划目前使用的方法进行分析和比较 肺结核和麻风病。 圆满完成拟议研究并取得假定成果 有可能对全球结核病的结果产生重大影响。这是意料之中的 正在开发的众多新的医疗点IGRA测试将使系列 在低收入国家进行方案层面的测试是可行和经济的。 这项研究将利用全面的DarDar进行 研究计划，穆亨比利大学之间长达20年的研究合作 健康和联合科学(坦桑尼亚，MUHAS)和盖泽尔医学院 达特茅斯(美国)，将包括两名具有广泛经验的流行病学家顾问 评估结核病控制计划(霍斯堡、惠伦)的经验。

PROJECT SUMMARY A critical component of the 2035 End TB Strategy is development of improved methods for Active Case Finding (ACF) of previously undiagnosed TB disease. Most ACF conducted by national tuberculosis control programs is based on testing household contacts (HCs) of remotely-acquired but newly-diagnosed cases of TB disease. This approach typically detects previously undiagnosed TB disease in 2-4% of HCs. We propose to test an entirely new method of ACF based on testing HCs of adolescents with recently-acquired and newly-diagnosed TB infection. This innovative method of ACF has the advantage that, since infections were recently acquired, the source cases are likely still among the close contacts of the new IGRA convertor. For this reason, we hypothesize that a source case will be found for as many as 50% of these new convertors. This approach is based on results of our recent 3-year study of serial testing for TB infection among 650 adolescent schoolchildren in Tanzania. The study was based on annual testing for TB infection using an interferon gamma release assay (IGRA). We showed that such testing was feasible and detected a 2.9% annual rate of infection. In the proposed new 5-year study we will perform baseline IGRA testing on 1200 Tanzanian adolescents followed by Q4 month IGRA testing x4 on the estimated 1020 who are IGRA negative at baseline. We anticipate detecting new TB infection (IGRA conversion to positive) in 50 participants. We will then test 200 of their household and other close contacts (collectively, their close contacts, CC) and predict that we will identify a source case of previously undiagnosed TB in a minimum of 25 or 50% of these 50 new adolescent infections. The predicted rate of new TB disease detection among CCs is therefore 25/200 or 12.5%, which is 3-6 times higher than the current approach for testing HCs of patients with TB disease. Cost-effectiveness will be analyzed and compared to the current approach used by the National Program on Tuberculosis and Leprosy. Successful completion of the proposed study with the hypothesized outcomes has the potential for a major impact on global tuberculosis outcomes. It is expected that the numerous new point-of-care IGRA tests under development will make serial testing feasible and economical at a programmatic level in low income countries. The research study will be conducted with the comprehensive DarDar Research Program, a 20-year research collaboration between Muhimbili University of Health and Allied Sciences (MUHAS, Tanzania) and the Geisel School of Medicine at Dartmouth (USA) and will include two consultant epidemiologists with extensive experience in evaluating TB control programs (Horsburgh, Whalen).