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最重要的死亡和疾病原因。结核病是通过感染者产生的气雾剂(咳嗽和其他呼吸努力排出的微小飞沫)传播的。含有细菌的飞沫被深深地吸入肺部，在那里，在几个月甚至几年的时间里，大约十分之一的初始感染者会产生疾病。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)，但只有继续发展为肺部疾病的人才能传播感染。Mtb必须导致肺部疾病并通过气雾剂传播才能长期生存；如果我们阻止传播，最终有机体将死亡，疾病将被消灭。因此，发现和治疗感染病例至关重要。结核病是一种与贫困有关的疾病，在资源有限的情况下，许多结核病病例没有得到诊断。在撒哈拉以南非洲地区尤其如此，那里的医疗保健资源有限。在这里，检测有提示症状(如长期咳嗽)和结核分枝杆菌阳性痰(咳出粘液)的个人提供了主要的诊断手段。然而，许多有症状的人无法获得医疗保健，即使在社区卫生工作者(CHW)的允许下也是如此，而且很大一部分(20%-50%)无法产生痰。莱斯特团队一直在开发使用改装的口罩来捕获气雾剂，这种方式允许在世界卫生组织推荐的结核分枝杆菌检测系统中检测结核杆菌，称为Xpert MTB/RIF。口罩样本能够以类似于痰分析的频率检测结核分枝杆菌阳性个体。然而，与痰样本不同的是，每个戴口罩的人都会在我们的口罩气溶胶采样系统(MASS)中产生一个样本。质量成本非常低，只需要一般的专业知识就可以采集和分析样本。在这个项目中，我们将评估MASS作为一种低成本社区筛查工具的使用。我们的研究基于南非茨瓦内地区(估计约有1%患有肺结核病)，比勒陀利亚团队在那里开发了一项面向社区的初级保健计划(http://www.up.ac.za/en/family-medicine/article/2077127/launch-video)，旨在以患者和家庭(HH)为中心的健康促进。在我们已建立的结核病气雾剂合作(MRC和Wellcome Trust资助)的基础上，关键的是，在1670个COPC CHW的支持下，我们现在计划评估MASS作为结核病筛查工具在茨瓦内的应用。如果效果良好，这项评估将使我们能够开发一项大规模干预试验，在此试验中，我们将比较基于大规模筛查的实际能力，以发现感染病例与传统的症状和痰筛查方法。如果高比例的此类病例能够被发现和治疗，这种方法显然有潜力降低这个社区和其他贫穷社区的总体结核病发病率。我们将首先在社区卫生服务中心进行大规模测试，以优化15分钟的程序，并为研究对他们进行培训。然后，我们将使用标准的CHW审查计划来检测出现与结核病相关症状的个人的HHS。在知情同意后，所有5岁及以上的卫生健康服务人员将接受口罩抽样。我们的目标是对120名有症状的HHS进行抽样，预计至少检测到20-40例阳性。同时，通过从在COPC方案中登记的近300,000人收集的数据，我们将确定符合关键社会经济指标的120个HHS。这些卫生健康服务体系的所有成员都将如上进行抽样。有症状的个人和大规模阳性患者都将被转介到当地诊所进行标准诊断和治疗。我们相信，大规模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，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.