Innovative contact tracing strategies for detecting TB in mobile rural and urban South African populations

项目总结 尽管结核病在很大程度上是一种可以治愈的疾病，但它仍然是南非和 全球领先的单一病原体感染死因。然而，超过三分之一的结核病患者-AN 据估计，全世界有360万人--从未通知过卫生当局。人口统计小组： 结核病的最大风险也是大多数结核病传播的罪魁祸首是工作年龄的成年人 (尤其是男性)。这些人通常具有很高的流动性，这使得他们很难与传统的 结核病病例发现活动，如在医疗机构进行筛查或家庭接触者调查 营业时间。然而，他们的流动模式在整个撒哈拉以南非洲地区都高度规律化。 和世界其他地方：年轻人迁徙到城市工作，回到农村老家参观 节日期间的家庭。这些可预测的移动模式为创新创造了机会 干预措施使这些承受着巨大未确诊结核病负担的高危流动人口参与进来 并继续为许多社区的传播提供燃料。具体地说，流动的年轻人可以在 他们在城市的非工作时间(晚上和周末)回家，在农村看望家人 假日期间的设置。虽然大多数结核病传播发生在家庭之外，但家庭 被诊断患有结核病的人仍然是可以确定的最高风险人群，除了 聚集生活环境(例如，监狱)。因此，没有比这更好的地方来寻找“失踪的360万人” 比这些家庭中的结核病病例更多。我们建议对两种新的结核病病例发现干预措施进行随机试验 在被诊断为活动性结核病的患者的家庭成员中：在南方农村进行基于假期的筛查 非洲省(林波波省)和非高峰(周末/晚上)在许多人进入的城市居民点放映 林波波的居民为了工作而迁移。我们将登记2400例结核病索引病例，外加估计4800例 每个环境中的家庭联系人(每个环境7,200名参与者，总共14400名参与者)并随机 对他们进行新的接触调查和标准接触调查。在具体目标1中，我们将使用全基因组测序 在所有情况下，在传输树上覆盖有关人类活动的数据，以评估 这一人群中的流动性和结核病传播。在具体目标2中，我们将采用多学科方法 从以下几个方面比较每种情况下的新型接触调查与标准接触调查： 有效性(确诊的继发结核病病例数和开始治疗)；(B)执行(REACH， (C)成本效益(单位成本 (D)预计人口水平对结核病发病率的影响。 这些目标的成功完成将通过确定机动性在燃料中的作用而产生长期影响 结核病流行和测试两种量身定做的方法来改善高流动人口中的结核病控制- 服务不足的群体，越来越被认为在全球结核病传播中发挥着重要作用。

PROJECT SUMMARY Although largely a curable disease, tuberculosis (TB) remains the leading cause of death in South Africa and the leading single-agent infectious cause of death globally. Nevertheless, over one-third of people with TB – an estimated 3.6 million people worldwide – are never notified to health authorities. The demographic group at greatest risk for TB and also responsible for the majority of TB transmission consists of working-age adults (especially men). These individuals are often highly mobile, making it difficult to engage them with traditional TB case-finding activities such as screening at healthcare facilities or household contact investigation during business hours. Their patterns of movement, however, are highly regularized throughout sub-Saharan Africa and the rest of the world: young adults migrate to cities for work and travel home to rural homelands to visit families during the holidays. These predictable patterns of movement create an opportunity for innovative interventions to engage this high-risk, mobile population that bears a tremendous burden of undiagnosed TB and continues to fuel transmission in many communities. Specifically, mobile young adults can be found at their urban homes during non-working hours (on evenings and weekends) and visiting their families in rural settings during holiday times. Although most TB transmission occurs outside of households, household members of individuals diagnosed with TB remain the highest-risk population that can be identified, outside of congregate living settings (e.g., prisons). There is therefore no better place to look for the “missing 3.6 million” TB cases than in these households. We propose a randomized trial of two novel TB case-finding interventions among household members of patients diagnosed with active TB: holiday-based screening in a rural South African province (Limpopo) and off-peak (weekend/evening) screening in an urban settlement into which many residents of Limpopo migrate for work. We will enroll 2400 index cases of TB plus an estimated 4800 household contacts in each setting (7200 participants per setting, 14400 participants overall) and randomize them to novel versus standard contact investigation. In Specific Aim 1, we will use whole genome sequencing of all cases, overlaying transmission trees with data on human movement, to evaluate associations between mobility and TB transmission in this population. In Specific Aim 2, we will employ a multidisciplinary approach to compare novel versus standard contact investigation in each setting along the following dimensions: (a) effectiveness (number of secondary TB cases diagnosed and starting treatment); (b) implementation (reach, fidelity, and maintenance of contact investigation outside of business hours); (c) cost-effectiveness (cost per disability-adjusted life year) and budget impact; and (d) projected population-level impact on TB incidence. Successful completion of these aims will have long-term impact by characterizing the role of mobility in fueling TB epidemics and testing two tailored approaches to improve TB control in highly mobile populations – an underserved group that is increasingly recognized as playing a major role in global TB transmission.