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

对坦桑尼亚青少年进行系列 IGRA 检测，以检测家庭接触者中的结核病

• 批准号: 10592476
• 负责人: Maryam Amour
• 金额: $ 16.33万
• 依托单位: MUHIMBILI UNIVERSITY/ ALLIED HLTH SCIS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10592476
• 关键词: 15 year old; Adolescent; Africa South of the Sahara; Agreement; Ally; Biological Assay; Cause of Death; Cessation of life; Child; Clinical Trials; Collaborations; Communicable Diseases; Country; Data; Detection; Diagnosis; Disease; Ensure; Goals; Health; Health Policy; Household; Incidence; Infection; Interferon Type II; Methods; Monitor; Newly Diagnosed; Notification; Participant; Persons; Population; Prospective Studies; Public Health; Relapse; Reporting; Research; Schools; Science; Source; Spottings; Tanzania; Testing; Time; Tuberculosis; Tuberculosis diagnosis; Universities; active method; case finding; improved; indexing; innovation; low and middle-income countries; medical schools; novel; point of care; programs; screening; transmission process; treatment guidelines

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.

项目摘要 坦桑尼亚是世界上结核病负担最高的国家之一。实现 根据2035年终止结核病战略，全球消除结核病需要扩大重点 活动性肺结核病例的发现目前病例发现战略的一个关键组成部分是 检测新的远程感染病例的家庭接触者，但最近 诊断为结核病（指示病例），以发现可能也患有结核病的HC。只 通常发现2-4%的家庭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年的发展后， 暴露和感染，这表明，如果在家庭中发生传播， 源HC可能已经接受治疗、康复或死于TB。 我们假设，检测最近获得的（事件）结核感染病例的HC 很可能导致检测到更高比例的HC， 青少年感染源，仍然有未确诊的活动性结核病。 在坦桑尼亚最近完成的一项为期3年的前瞻性研究中，我们开发了 以学校为基础的青少年系列检测，以发现新获得的结核病感染。的 试验使用T点干扰素γ测定（IGRA）测定来检测新的感染， 新感染率为2.9%。在拟议的两年期内 我们将对800名青少年学童进行筛查，并跟踪估计的680名IGRA- 阴性参与者1.5年，以检测>25例新发结核病感染。我们 假设他们的25个家庭（和他们的100个HC）中有一个 以前未发现的结核病例将高达14%，因此将确定一个 新的、更强大的主动病例发现全球战略。控制户将 包括25名青少年结核病流行感染者（100例HC）和家庭 25例无结核感染的青少年（100例HC）。试验将根据 全面的DarDar研究计划，这是一项为期20年的研究合作， Muhimbili健康和相关科学大学（坦桑尼亚MUHAS）和Geisel 达特茅斯医学院（美国）。这项创新研究有可能 为更有效地发现活动性结核病例确定一种改变游戏规则的战略。