Serial IGRA testing of Tanzanian adolescents to detect TB in household contacts

项目总结 坦桑尼亚是世界上结核病负担最重的国家之一。实现 2035年结束结核病战略下的全球消除结核病将需要扩大重点 关于活动性结核病病例的发现。当前病例查找战略的一个关键组成部分是 检测最近远程感染的新病例的家庭接触者(HCS) 诊断为结核病(首发病例)以发现可能同时患有结核病的HCS。仅限 2%-4%的家庭通常被发现有以前未发现的结核病病例 疾病。这是因为结核病通常需要2-5年的时间才能发展。 暴露和感染，这表明如果在家庭中发生传播， 来源：HC可能已接受治疗、康复或死于结核病。 我们假设，对最近获得的(事件)结核病感染病例进行HCS检测 很可能会导致检测到显著更高比例的HC 青少年感染源，且仍有未确诊的活动性结核病。 在最近在坦桑尼亚完成的一项为期3年的前瞻性研究中，我们开发了 对青少年进行以学校为基础的系列检测，以检测新感染的结核病。这个 试验使用T斑点干扰素伽马分析(IGRA)检测新的感染，以及 确定年新发感染率为2.9%。在拟议的2年期中 研究我们将对800名青春期学童进行筛查，并跟踪估计680名IGRA- 阴性参与者在1.5年内发现了25例新的结核病感染病例。我们 假设他们的25个家庭(以及他们的100个HC)中有 以前未发现的结核病病例将高达14%，因此将确定 新的、更强有力的全球积极病例发现战略。控制家庭将 包括25名感染结核病青少年(100名儿童)和家庭 在25名未感染结核病的青少年中(100人)。这项试验将在 全面的DarDar研究计划，两国之间长达20年的研究合作 穆亨比利卫生与联合科学大学(坦桑尼亚穆哈斯大学)和盖泽尔 达特茅斯医学院(美国)。这项创新的研究有可能 确定一种改变游戏规则的战略，以便更有效地发现活跃的结核病病例。

PROJECT SUMMARY Tanzania has one of the highest burdens of tuberculosis (TB) in the world. Achieving global TB elimination under the 2035 End TB Strategy will require an expanded focus on active TB case finding. A key component of the current case finding strategy is testing household contacts (HCs) of new cases of remotely-acquired but recently diagnosed TB disease (index case) to find HCs who may also have TB disease. Only 2-4% of households are typically found to have a previously undetected case of TB disease. This is because TB disease typically requires 2-5 years to develop after exposure and infection, suggesting that if transmission occurred in the household the source HC may have already been treated, recovered or died from TB. We hypothesize that testing HCs of recently acquired (incident) cases of TB infection is likely to result in detection of a significantly higher proportion of HCs who were the source of the adolescent infection and still have undiagnosed active TB disease. In a recently completed 3-year prospective study in Tanzania we developed methods for school-based serial testing of adolescents to detect newly acquired TB infection. The trial used the T spot interferon gamma assay (IGRA) assay to detect new infection, and determined that the annual rate of new infection was 2.9%. In the proposed 2-year study we will screen 800 adolescent schoolchildren and follow the estimated 680 IGRA- negative participants for 1.5 years to detect >25 new incident TB infections. We hypothesize that the proportion of their 25 households (and their 100 HCs) with a previously undetected case of TB will be as high as 14%, and will therefore identify a new and more robust global strategy for active case finding. Control households will include those of 25 adolescents with prevalent TB infection (100 HCs) and households of 25 adolescents with no TB infection (100 HCs). The trial will be conducted under 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). This innovative study has the potential to identify a game-changing strategy for more effective active TB case finding.