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， 患有结核病，但从未通知公共卫生当局。越南和津巴布韦的研究表明， 研究表明，寻找未确诊结核病患者（“主动病例发现”，ACF）的密集努力， 减少结核病负担。然而，在高负担国家，重复人口水平的ACF不是一个可行的策略。 因此，了解ACF是否可以以既经济又安全的方式实施是至关重要的。 后勤上可行，流行病学上有效。此外，据估计，世界人口的23% 感染了M。结核病，越来越清楚的是，如果没有结核病，就无法实现全球结核病目标。 扩大结核病预防治疗。由于在提供TPT之前必须排除结核病，ACF 提供了一个独特的机会，通过筛查更广泛的人群结核病来扩大TPT;然而， 以往在高负担国家开展的艾滋病毒/艾滋病防治基金活动没有包括与TPT的联系。近期关键技术 创新，包括移动的胸部X射线设备、基于AI的X射线阅读和新型短程TPT 方案，使大规模ACF与TPT的联系首次可行，具有变革性的潜力， 对结核病负担的影响。在我们最初的R 01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有效性和实施情况， 基于场馆的ACF与TPT相联系的两种方法，每种方法都建立在STOMP的具体研究结果基础上- TB.具体而言，我们将进行一项多阶段、整群随机交叉试验（1型杂交 有效性-实施设计），将基于卫生设施的方法与ACF/TPT进行比较， 结合现有的基础设施和患者表达的偏好以及基于“热点”的方法， 将检测直接带到结核病负担最重的社区。在目标1中，我们将比较 在乌干达坎帕拉附近的八个地区，以热点为重点的ACF/TPT与以设施为基础的ACF/TPT的有效性。我们 主要结果是开始治疗确诊肺结核的人数。二次 分析将包括与TPT有关的人数以及八个干预地区的通知 与四个对照区相比。在目标2中，我们将比较实现（到达、实现和 维护）和以热点为重点的ACF/TPT相对于以设施为基础的ACF/TPT的增量成本效益。在目标3中， 我们将使用建模和模拟来估计干预措施对确诊病例比例、时间 结核病诊断率和10年结核病发病率和死亡率预测。这项研究将提供随机的， 支持结核病病例发现可行方法的实施和有效性的务实证据 和预防性治疗的关键时刻，当关键的创新（移动的胸部X光，基于人工智能的解释， 和短程TPT方案）正在使这种干预措施在高结核病负担环境中可扩展。

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.