Hotspot versus clinic-based active case finding for TB in Uganda: A pragmatic randomized trial

项目摘要 结核病(TB)是全球发病率和死亡率的主要原因；每年有近300万人 罹患结核病，但从未通知公共卫生当局。在越南和津巴布韦的研究表明 研究表明，集中努力寻找未确诊的结核病患者(“活跃病例发现”，ACF)可以极大地 降低结核病负担。然而，在高负担国家，重复人口水平的ACF不是一个可行的战略。 因此，了解ACF能否以既经济又实用的方式实施至关重要 在后勤上是可行的，在流行病学上也是有效的。此外，据估计，世界上23%的人口 感染了结核分枝杆菌，越来越清楚的是，如果不采取措施，全球消灭结核病的目标就无法实现。 扩大结核病预防治疗(TPT)。由于在提供TPT、ACF之前排除结核病是必不可少的 提供了一个独特的机会，通过筛查更广泛的人群来扩大TPT；然而，大多数 以前在高负担国家开展的ACF运动没有包括与TPT的联系。最新关键技术 创新，包括移动胸部X光设备，基于人工智能的X光阅读，以及新颖的短程TPT 方案，使大规模ACF与TPT的联系首次成为可能，具有变革的潜力 对结核病负担的影响。在我们最初的R01研究(STOMP-TB)中，我们将基于场所的筛查(VBS)确定为 乌干达城市社区ACF的有效方法；近3%的VBS参与者患有未诊断的结核病 疾病。在这个更新项目中，我们将严格评估比较效果和实施情况 连接到TPT的基于场馆的ACF的两种方法，每种方法都基于STOMP的具体发现- 结核病。具体地说，我们将进行一项多周期、整群随机交叉试验(类型1杂交 有效性-实施设计)将基于卫生设施的方法与ACF/TPT进行比较 整合了现有的基础设施和患者表达的偏好，并采用了基于热点的方法 将检测直接带到经历结核病负担最高的社区。在目标1中，我们将比较 在乌干达坎帕拉附近的八个地区，聚焦热点的ACF/TPT与基于设施的ACF/TPT的有效性。我们的 主要结果将是开始治疗确诊肺结核的人数。次要的 分析将包括与TPT有关的人数和八个干预地区的通知 与四个控制区进行比较。在目标2中，我们将比较实施(REACH、实施和 与基于设施的ACF/TPT相比，以热点为中心的ACF/TPT具有更高的成本效益。在《目标3》中， 我们将使用建模和模拟来估计干预对确诊病例比例、时间的影响 到结核病诊断，并预测10年内结核病发病率和死亡率。这项研究将提供随机化的 支持结核病病例发现可行方法的实施和有效性的实用证据 在关键时刻进行预防性治疗，关键创新(移动胸部X光、基于人工智能的解释、 和短程TPT方案)使此类干预措施在结核病负担高的环境中可推广。

Project Summary Tuberculosis (TB) is a leading cause of global morbidity and mortality; every year, nearly three million people develop TB disease but are never notified to public health authorities. Studies in Vietnam and Zimbabwe have shown that intensive efforts to find individuals with undiagnosed TB (“active case finding”, ACF) can greatly reduce TB burden. However, in high-burden countries, repeated population-level ACF is not a viable strategy. Therefore, it is critical to understand whether ACF can be implemented in a manner that is both economically/ logistically feasible and epidemiologically impactful. Additionally, as an estimated 23% of the world's population is infected with M. tuberculosis, it is increasingly clear that global targets to end TB cannot be achieved without scaling up TB preventive therapy (TPT). Since ruling out TB disease is essential before providing TPT, ACF offers a unique opportunity to expand TPT by screening a broader population for TB disease; however, most previous ACF campaigns in high-burden countries have not included linkage to TPT. Key recent technological innovations, including mobile chest X-ray devices, AI-based X-ray reading, and novel short-course TPT regimens, have made mass ACF with linkage to TPT feasible for the first time, with potential for transformative impact on TB burden. In our initial R01 study (STOMP-TB), we identified venue-based screening (VBS) as an efficient approach to ACF in an urban Ugandan community; nearly 3% of VBS attendees had undiagnosed TB disease. In this renewal project, we will rigorously evaluate the comparative effectiveness and implementation of two approaches to venue-based ACF with linkage to TPT, each building on specific findings from STOMP- TB. Specifically, we will conduct a multiple period, cluster randomized crossover trial (type 1 hybrid effectiveness-implementation design) comparing a health facility-based approach to ACF/TPT that incorporates existing infrastructure and patients' expressed preferences and a “hotspot”-based approach that brings testing directly to neighborhoods experiencing the highest burden of TB. In Aim 1, we will compare the effectiveness of hotspot-focused versus facility-based ACF/TPT in eight regions near Kampala, Uganda. Our primary outcome will be the number of individuals initiating treatment for confirmed pulmonary TB. Secondary analyses will include the number of people linked to TPT and notifications in the eight intervention regions compared to four control regions. In Aim 2, we will compare implementation (reach, implementation, and maintenance) and incremental cost-effectiveness of hotspot-focused versus facility-based ACF/TPT. In Aim 3, we will use modeling and simulation to estimate intervention effects on the proportion of cases diagnosed, time to TB diagnosis, and projected 10-year TB incidence and mortality. This study will provide randomized yet pragmatic evidence to support the implementation and effectiveness of feasible approaches to TB case-finding and preventive therapy at a critical moment when key innovations (mobile chest x-ray, AI-based interpretation, and short-course TPT regimens) are making such interventions scalable in high-TB-burden settings.