McGill International TB Centre, Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada.
Centre National Hospitalier Universitaire de Pneumo-Pthisiologie de Cotonou, Cotonou, Benin.
Lancet Public Health. 2021 May;6(5):e272-e282. doi: 10.1016/S2468-2667(20)30261-9. Epub 2021 Mar 22.
Reaching the UN General Assembly High-Level Meeting on Tuberculosis target of providing tuberculosis preventive treatment to at least 30 million people by 2022, including 4 million children under the age of 5 years and 20 million other household contacts, will require major efforts to strengthen health systems. The aim of this study was to evaluate the effectiveness and cost-effectiveness of a health systems intervention to strengthen management for latent tuberculosis infection (LTBI) in household contacts of confirmed tuberculosis cases.
ACT4 was a cluster-randomised, open-label trial involving 24 health facilities in Benin, Canada, Ghana, Indonesia, and Vietnam randomly assigned to either a three-phase intervention (LTBI programme evaluation, local decision making, and strengthening activities) or control (standard LTBI care). Tuberculin and isoniazid were provided to control and intervention sites if not routinely available. Randomisation was stratified by country and restricted to ensure balance of index patients with tuberculosis by arm and country. The primary outcome was the number of household contacts who initiated tuberculosis preventive treatment at each health facility within 4 months of the diagnosis of the index case, recorded in the first or last 6 months of our 20-month study. To ease interpretation, this number was standardised per 100 newly diagnosed index patients with tuberculosis. Analysis was by intention to treat. Masking of staff at the coordinating centre and sites was not possible; however, those analysing data were masked to assignment of intervention or control. An economic analysis of the intervention was done in parallel with the trial. ACT4 is registered at ClinicalTrials.gov, NCT02810678.
The study was done between Aug 1, 2016, and March 31, 2019. During the first 6 months of the study the crude overall proportion of household contacts initiating tuberculosis preventive treatment out of those eligible at intervention sites was 0·21. After the implementation of programme strengthening activities, the proportion initiating tuberculosis preventive treatment increased to 0·35. Overall, the number of household contacts initiating tuberculosis preventive treatment per 100 index patients with tuberculosis increased between study phases in intervention sites (adjusted rate difference 60, 95% CI 4 to 116), while control sites showed no statistically significant change (-12, -33 to 10). There was a difference in rate differences of 72 (95% CI 10 to 134) contacts per 100 index patients with tuberculosis initiating preventive treatment associated with the intervention. The total cost for the intervention, plus LTBI clinical care per additional contact initiating treatment was estimated to be CA$1348 (range 724 to 9708).
A strategy of standardised evaluation, local decision making, and implementation of health systems strengthening activities can provide a mechanism for scale-up of tuberculosis prevention, particularly in low-income and middle-income countries.
Canadian Institutes of Health Research.
要实现联合国大会结核病问题高级别会议提出的目标，即在 2022 年之前向至少 3000 万人（包括 400 万 5 岁以下儿童和 2000 万其他家庭接触者）提供结核病预防性治疗，就需要大力加强卫生系统。本研究旨在评估一项卫生系统干预措施的效果和成本效益，该措施旨在加强对确诊结核病病例家庭接触者潜伏性结核病感染（LTBI）的管理。
ACT4 是一项在贝宁、加拿大、加纳、印度尼西亚和越南的 24 个卫生机构进行的集群随机、开放标签试验，这些机构被随机分为三个阶段的干预组（LTBI 方案评估、地方决策和强化活动）或对照组（标准 LTBI 护理）。如果常规不提供结核菌素和异烟肼，则向对照组和干预组提供。随机分组按国家分层，并进行限制，以确保按臂和国家平衡有结核病索引患者的数量。主要结局是在索引病例确诊后 4 个月内，每个卫生机构开始接受结核病预防治疗的家庭接触者数量，记录在我们 20 个月研究的前 6 个月或最后 6 个月。为便于解释，此数量按每 100 例新诊断的结核病索引患者标准化。分析采用意向治疗。协调中心和地点的工作人员无法进行掩蔽；然而，分析数据的人员对干预或对照的分配进行了掩蔽。同时进行了干预措施的经济分析。ACT4 在 ClinicalTrials.gov 注册，编号为 NCT02810678。
该研究于 2016 年 8 月 1 日至 2019 年 3 月 31 日进行。在研究的前 6 个月，干预点符合条件的家庭接触者中开始接受结核病预防治疗的比例为 0.21。在实施方案强化活动后，开始接受结核病预防治疗的比例增加到 0.35。总体而言，干预点每 100 例结核病索引患者开始接受结核病预防治疗的家庭接触者数量在研究阶段之间有所增加（调整后的速率差异为 60，95%CI 4 至 116），而对照组则没有统计学意义上的变化（-12，-33 至 10）。与干预相关的，每 100 例结核病索引患者开始预防治疗的接触者数量差异为 72（95%CI 10 至 134）。干预措施的总成本，加上每例额外开始治疗的 LTBI 临床护理，估计为 1348 加元（724 至 9708 加元）。
标准化评估、地方决策和实施卫生系统强化活动的策略可以为结核病预防提供一种扩大规模的机制，特别是在低收入和中等收入国家。
加拿大卫生研究院。
