Evaluation of a Mask Aerosol Sampling System (MASS) as an Active Case Finding Approach Focused on Infectious TB in Low-Resource Settings.

在全球范围内，结核病（TB）是由单一细菌引起的死亡和疾病的最重要原因。结核病通过受感染者产生的气溶胶（咳嗽和其他呼吸活动排出的微小飞沫）传播。含细菌的飞沫被吸入肺部深处，经过数月和数年的时间，大约十分之一的初次感染者会产生疾病。超过四分之一的人类感染了导致结核病的细菌，结核分枝杆菌（Mtb），但只有那些继续发展肺部疾病的人才能传播感染。Mtb必须引起肺部疾病并通过气溶胶传播才能长期生存;如果我们阻止传播，最终有机体将灭绝，疾病将被消除。结核病是一种与贫穷有关的疾病，在资源有限的情况下，许多结核病病例得不到诊断。在撒哈拉以南非洲尤其如此，那里的卫生保健资源有限。在这里，检测具有提示性症状（例如长时间咳嗽）和Mtb阳性痰（咳出粘液）的个体提供了主要的诊断手段。然而，许多有症状的人没有获得医疗保健，即使社区卫生工作者（CHW）能够这样做，并且很大一部分（20-50%）无法产生痰液。莱斯特团队一直在开发使用适应性口罩捕获气溶胶的方法，以便在世界卫生组织推荐的结核分枝杆菌检测系统（称为Xpert MTB/RIF）中检测结核分枝杆菌。口罩样本允许以与痰液分析相似的频率检测Mtb阳性个体。但是，与痰液样本不同，每个可以佩戴口罩的人都会在我们的口罩气溶胶采样系统（MASS）中产生样本。MASS的成本非常低，只需要少量的专业知识来采集和分析样本。在这个项目中，我们将评估使用MASS作为一种低成本的社区筛查工具。我们的研究是基于南非的Tshwane区（估计约有1%的人患有肺结核），比勒陀利亚团队已经开发了一个面向社区的初级保健（COPC）计划（http：//www.up.ac.za/en/family-medicine/article/2077127/launch-video），旨在以患者和家庭（HH）为中心促进健康。在我们建立的结核病气雾剂合作（MRC和惠康信托基金资助）的基础上，在1670名COPC CHW的支持下，我们现在计划评估MASS作为Tshwane结核病筛查工具的应用。如果有利的话，这项评估将使我们能够开发一个大规模的干预试验，我们将在实践中比较基于MASS的筛查与传统的症状和痰液筛查方法检测感染病例的能力。如果能发现和治疗高比例的此类病例，该方法显然有可能降低该社区和其他贫困社区的结核病总体发病率。我们将首先在社区卫生工作者中测试MASS，以优化15分钟的程序，并为研究培训他们。然后，我们将使用标准的CHW审查程序来检测显示TB相关症状的个人的HHS。在知情同意后，将对5岁及以上的此类卫生保健人员的所有成员进行口罩采样。我们的目标是对120个有症状的人进行采样，并预计至少检测到20-40个阳性。与此同时，通过从COPC计划中注册的近30万人收集的数据，我们将确定120个与关键社会经济指标相匹配的HHS。这些卫生保健中心的所有成员将按上述方式进行抽样。有症状的个人和MASS阳性的个人都将被转介到当地诊所进行标准诊断和治疗。我们相信，MASS可以使资源有限的卫生系统将控制工作集中在最具传染性的结核病病例及其接触者身上，从而减少传播，从而减少疾病。

Globally, tuberculosis (TB) is the most important cause of death and disease due to a single bacterial agent. TB is transmitted by aerosols (tiny droplets expelled by coughing and other respiratory efforts) generated by infected individuals. The bacteria-containing droplets are breathed deep into the lungs where, over months and years, disease is produced in about one in ten of those who get the initial infection. Over one quarter of humanity is infected with the bacterium that causes TB, Mycobacterium tuberculosis (Mtb), but only people who go on to develop lung disease can spread the infection.Mtb must cause lung disease and be spread by aerosols to survive in the long term; if we prevent transmission, eventually the organism will die out and the disease will be eliminated. Thus, detection and treatment of infectious cases is of paramount importance.TB is a disease associated with poverty and, in resource constrained settings, many cases of TB go undiagnosed. This is particularly so in sub-Saharan Africa where healthcare is resource limited. Here, detection of individuals with suggestive symptoms (e.g. prolonged cough) and Mtb positive sputum (coughed up mucus) provides the main means of diagnosis. However, many symptomatic individuals do not access healthcare, even when enabled to do so by community health workers (CHWs) and a significant proportion (20-50%) are not able to produce sputum.The Leicester team have been developing the use of adapted face masks to capture aerosols in a way that allows detection of Mtb in the World Health Organisation-recommended Mtb detection system, called Xpert MTB/RIF. The mask samples allow detection of Mtb positive individuals at a similar frequency to sputum analysis. However, unlike sputum samples, everyone who can wear a mask produces a sample in our mask aerosol sampling system (MASS). MASS is very low cost and requires only modest expertise to take and analyse the samples. In this project we shall evaluate use of the MASS as a low cost community screening tool.Our study is based in the Tshwane district of South Africa (around 1% are estimated to have lung TB) where the Pretoria team have developed a community oriented primary care (COPC) programme (http://www.up.ac.za/en/family-medicine/article/2077127/launch-video) directed to patient and household (HH) centred health promotion. Building on our established TB aerosol collaboration (MRC and Wellcome Trust funded) and, critically, with the support of the 1670 COPC CHWs, we now plan to evaluate application of MASS as a TB screening tool in Tshwane. If favourable, this evaluation will enable us to develop a large scale intervention trial where we will compare the in-practice capacity of MASS-based screening to detect infectious cases with the conventional approach of symptom and sputum screening. If a high proportion of such cases can be detected and treated, the approach has clear potential to reduce the overall frequency of TB in this and other poor communities.We will first test MASS in the CHWs to optimise the 15 minute procedure and train them for the study. We will then use the standard CHW review programme to detect HHs with individuals showing TB-related symptoms. Following informed consent, all members of such HHs aged 5 years and above will be mask sampled. We aim to sample 120 HHs with symptomatic individuals and expect to detect at least 20-40 positives. In parallel, through data collected from the near 300,000 individuals registered on the COPC programme we will identify 120 HHs matched for key socioeconomic indicators. All members of these HHs will be sampled as above. Symptomatic individuals and MASS positive individuals will all be referred to local clinics for standard diagnosis and treatment.We believe MASS could enable resource-constrained health systems to focus control efforts on the most infectious TB cases and their contacts, thereby reducing transmission and consequently reducing disease.