Background

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.

Methods

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.

Findings

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).

Interpretation

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.

Funding

Canadian Institutes of Health Research

中文翻译：

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卫生系统干预措施对潜伏性结核感染管理（ACT4）的有效性和成本效益：一项集群随机试验

背景

达到联合国大会结核病高级别会议的目标，即到2022年为至少3000万人提供结核病预防治疗，包括400万5岁以下的儿童和2000万其他家庭接触者，将需要做出巨大的努力来加强健康系统。这项研究的目的是评估卫生系统干预措施的有效性和成本效益，以加强已确诊结核病例家庭接触者对潜伏性结核感染（LTBI）的管理。

方法

ACT4是一项集群随机，开放标签的试验，涉及贝宁，加拿大，加纳，印度尼西亚和越南的24个卫生机构，被随机分配为三阶段干预（LTBI计划评估，本地决策和加强活动）或控制（标准LTBI护理）。如果不能常规获得结核菌素和异烟肼，则可用于控制和干预部位。随机分组按国家/地区进行分层，并限制了按机构和国家/地区来确保结核病索引患者的平衡。主要结果是在我们的20个月研究的头6个月或最后6个月内，在诊断出该病例后的4个月内，每个医疗机构中开始进行结核病预防治疗的家庭接触者的数量。为了简化解释，该数字是每100名新诊断的结核病患者标准化的。分析是按意向进行的。不可能在协调中心和现场掩盖工作人员；然而，那些分析数据被掩盖了干预或控制的分配。在试验的同时进行了干预的经济分析。ACT4已在ClinicalTrials.gov（NCT02810678）上注册。

发现

该研究在2016年8月1日至2019年3月31日之间进行。在研究的前6个月中，在干预场所符合资格的人群中，开始进行结核病预防治疗的家庭接触者的总总体比例为0·21。实施计划强化活动后，发起结核病预防治疗的比例增加到0·35。总体而言，在干预阶段的研究阶段之间，每100名患有结核病的患者开始进行结核病预防治疗的家庭接触者数量有所增加（调整率差异为60，95％CI为4至116），而对照地点则没有统计学上的显着变化（−12， -33至10）。每100名患有结核病的患者中，与干预措施相关的开始预防治疗的接触者的比率差异为72（95％CI 10至134）。干预的总费用加上每一次额外的接触引发治疗所需的LTBI临床护理估计为1348加元（范围为724至9708）。

解释

标准化评估，地方决策和实施卫生系统加强活动的战略可以提供扩大结核病预防的机制，特别是在低收入和中等收入国家。

资金

加拿大卫生研究所