Simplified Isoniazid Preventive Therapy (SPIRIT) Strategy to Reduce TB Burden

摘要 撒哈拉以南非洲艾滋病毒感染者（PLHIV）未能使用异烟肼（INH）预防性治疗（IPT） 非洲是当今世界证据与实践之间最大的执行差距之一， 应对艾滋病疫情。在艾滋病毒感染者中，结核病是导致死亡的主要原因，而IPT使结核病发病率降低了40%。 然而，在非洲，只有不到2%的合格个人获得IPT。鉴于两个国家都有指导方针， 推荐IPT，以及简单的临床算法，以确定IPT合格的人，其余的关键 扩大规模的要求是加强联系-在大多数卫生系统中由中层管理人员介导- 卫生部政策和诊所之间的关系。在乌干达，地区卫生官员是关键的中间人， 负责政策和执行之间联系的管理人员。我们建议测试一个全国性的多- “SPIRIT”（简化INH预防性治疗）干预的组成部分，目标是DHO-我们将其视为 关键传播媒介。SPIRIT基于行为改变的PRECEDE模型， 诱发（教学协作）;使（INH/B6/septrin单丸组合和SMS从DHO到 供应商）;和加强（报告协作）组件。对于这次重新提交，我们提供的数据显示， 通过对5个卫生组织及其诊所进行试点研究，确定SPIRT的可行性。在小的时候，小的时候， 协作并实施SPIRIT的关键组件，包括向前线发送双向文本消息 提供商接受IPT治疗的HIV阳性成人人数从基线时的0人增加到8周时的300人。 目的1：确定SPIRIT干预是否增加IPT启动。我们将组成20组5区 卫生官员和随机分配10人到SPIRIT干预组，10人到对照组（国家标准）， 随机试验主要结局是符合IPT资格的成年人开始IPT的比例。进行二次 结果，我们将衡量DHO之间有关IPT的知识、态度和实践的变化， 一线卫生工作者评估干预措施取得成果的机制。 目的2：评估SPIRIT干预对IPT完成率和结核病发病率的影响。即使 干预增加了IPT的使用，量化了患者实际使用IPT的情况以及对人群健康的影响 状况（如结核病减少），提供了一个重要的影响措施，使决策者能够优先考虑 这种干预更广泛。将采用两阶段调查抽样方法确定概率 有资格接受IPT的患者样本，其中通过INH的毛发水平测量依从性（直接测量 避孕药消费/坚持）和结核病发病率（人口健康措施） 目标3：评估SPIRIT的成本和成本效益。使用在Aims中获得的有效性措施 1和2，标准时间和运动和成本计算方法，我们将估计成本和成本效益， 目标2的抽样人群中的SPIRIT与标准治疗。感兴趣的结果将包括计划 以下各项的成本：a）IPT启动; B）IPT完成;以及c）TB病例避免。

ABSTRACT The failure to use isoniazid (INH) preventative therapy (IPT) in persons living with HIV (PLHIV) in Sub-Saharan Africa represents one of the single biggest implementation gaps between evidence and practice in today's response to the HIV epidemic. In PLHIV, TB is a lead cause of death, and IPT reduces TB incidence by 40%. Yet in Africa, less than 2% of eligible individuals receive IPT. Given the existence of both country guidelines recommending IPT, as well as simple clinical algorithms to identify IPT eligible persons, a remaining critical requirement for scale-up is strengthening the link - mediated by middle management in most health systems - between health ministry policy and clinics. In Uganda, District Health Officers (DHOs) serve as key middle managers working at the nexus between policy and implementation. We propose to test a countrywide multi- component “SPIRIT” (Simplified INH Preventive Therapy) intervention targeting DHOs – whom we view as critical dissemination agents. SPIRIT is based on the PRECEDE model of behavioral change that deploys predisposing (teaching collaborative); enabling (INH/B6/septrin single pill combination and SMS from DHO to provider); and reinforcing (reporting collaborative) components. For this resubmission, we provide data to show feasibility of SPIRT through a pilot study of 5 DHOs and their clinics. The DHOs engaged in the mini- collaborative and implemented key components of SPIRIT including bidirectional text messaging to front line providers. The number of HIV+ adults prescribed IPT increased from zero at baseline to 300 at 8 weeks. Aim 1: Determine if the SPIRIT intervention increases IPT initiation. We will form 20 groups of 5 District Health Officers and randomize 10 to the SPIRIT intervention and 10 to control (country standard) in a cluster- randomized trial. The primary outcome is proportion of IPT-eligible adults initiating IPT. For secondary outcomes, we will measure changes in knowledge, attitudes and practices regarding IPT among DHOs and front line health workers to assess mechanisms through which the intervention achieves outcomes. Aim 2: Evaluate the effect of the SPIRIT intervention on IPT completion and TB incidence. Even if the intervention increases IPT use, quantifying actual use of IPT by patients and effects on population health status (e.g. reduction in TB), provides an important impact measure that can enable policy makers to prioritize this intervention more widely. A two-stage survey sampling approach will be used to identify a probability sample of patients eligible for IPT in which to measure adherence through hair levels of INH (direct measure of pill consumption/adherence) and TB incidence (population health measure) Aim 3: Assess the cost and cost-effectiveness of SPIRIT. Using effectiveness measures obtained in Aims 1 and 2, standard time and motion and costing methods, we will estimate the cost and cost-effectiveness of SPIRIT vs standard of care in our sampled population from Aim 2. Outcomes of interest will include program costs per: a) IPT initiation; b) IPT completion; and c) TB case averted.