Medical and biological significance of exhaled M. tuberculosis detected by community level face mask sampling in Pretoria.

在全球范围内，结核病（TB）是单一细菌病原体导致疾病和死亡的最大原因。据估计，超过四分之一的人类感染结核分枝杆菌（Mtb），即结核病的病原体；然而，超过80%的感染者从未发病，因为感染处于静止状态，不会产生症状。为了生存，结核分枝杆菌必须通过感染者呼出的飞沫在人与人之间传播。标准观点认为，这只发生在有咳嗽、体重减轻和发烧等肺结核症状的人身上。在这些人具有传染性后尽早发现、诊断和治疗，一直是全球根除结核病运动的主要优先事项。尽管如此，世界卫生组织（WHO）等权威机构承认，每年有数百万新感染病例被遗漏；这些无疑助长了持续的流行病。研究人员现在正在质疑患有静止性结核病的人是否也可能传播感染。这种“早期”形式结核病的证据来自复杂的肺部成像和在一些没有症状的个体中直接检测结核分枝杆菌。我们的研究团队多年来一直致力于使用改良口罩来检测呼出的结核杆菌。戴上含有莱斯特大学开发的合成采样基质的口罩30分钟，然后取出基质，在世卫组织推荐的Gene Xpert系统中检测其DNA，分析捕获的结核分枝杆菌。结合口罩采样（FMS）方法可以检测早期肺结核的证据，FMS的简单性、便利性和低成本促使我们研究是否可以将其用于社区采样规划中检测感染。在目前活跃的MRC项目中，莱斯特-比勒陀利亚团队发现了意想不到的高结核杆菌检出率：虽然先前的估计使我们期望检出率高达1%，但实际上这已经超过了15%。我们的研究是在Tshwane区进行的，比勒陀利亚团队在那里制定了一项面向社区的初级保健（COPC）方案，旨在以患者和家庭为中心促进健康。社区卫生工作者接受了FMS方面的培训，并收集了相关的人口和临床数据。youtube视频（Breathcatcher）向chw和客户解释了这种方法。我们的回应是将目前的研究重点重新放在照顾那些阳性样本上。虽然我们有明确的证据表明，fms检测到的Mtb患者可以在1-2个月内发展为常规识别的疾病，但在目前的研究中迄今尚未发现这一点，因为我们的随访能力非常有限。（COPC提供持续的临床支持）在这项新研究中，我们的目标是对50名提供结核杆菌阳性口罩（病例）的参与者进行一整年的详细随访，并将他们的临床和实验室状况与口罩结果为阴性的对照组（对照组）进行比较。FMS之外的测试（包括血液和肺部成像）将使我们能够将我们的评估与当前的诊断标准进行比较。病例检查每月一次，对照检查每月3次。这种方法将使我们能够检测个体随时间呼出结核分枝杆菌的不同模式，以及他们的感染是否进展为活动性疾病。我们的工作将由一个国际监测小组监督，该小组将审查我们的结果，并就如何对有疾病证据的个人进行最佳管理提出建议。通过这种方式，他们将得到符合公认标准的最早治疗。这项工作将提供在Tshwane社区呼出Mtb及其与临床疾病的关系的描述。如果正如我们所怀疑的那样，许多没有症状的人助长了感染的传播，那么就有必要重新重点关注控制和治疗。

Globally, tuberculosis (TB) is the greatest cause of disease and death by a single bacterial agent. Over one quarter of humanity is estimated to be infected with Mycobacterium tuberculosis (Mtb), the agent of TB; however, more than 80% of those infected never develop the disease because the infection remains quiescent and does not produce symptoms. In order to survive, Mtb must spread from person to person in droplets exhaled by infected individuals. The standard view has been that this only occurs in people who have symptoms of lung TB such as coughing, weight loss and fever. Detecting, diagnosing and treating these individuals as early as possible after they become infectious has been the major priority of the global campaign to eradicate TB. Nonetheless, authorities such as the World Health Organisation (WHO) recognise that many millions of newly infectious cases are missed every year; these undoubtedly fuel the continuing epidemic.Researchers are now questioning whether people with quiescent TB may also transmit the infection. Evidence for such 'incipient' forms of TB comes from sophisticated lung imaging and direct detection of Mtb in some individuals without symptoms. Our research team has been working for several years on the use of adapted face masks to detect exhaled Mtb. Masks containing a Leicester-developed synthetic sampling matrix are worn for 30 minutes then the matrix is taken out and analysed for captured Mtb by detecting its DNA in the WHO-recommended Gene Xpert system. Combined with evidence that the face mask sampling (FMS) approach can detect early lung TB, the simplicity, convenience and low cost of FMS led us to investigate whether it could be used to detect infection in a community sampling programme. In a currently active MRC project, the Leicester-Pretoria team have found an unexpectedly high Mtb detection rate: while prior estimates led us to expect a positive rate of up to 1%, in practice this has exceeded 15%. Our study is based in the Tshwane district where the Pretoria team have developed a community oriented primary care (COPC) programme directed to patient and household centred health promotion. Community Health Workers (CHWs) have been trained in FMS and gather relevant related demographic and clinical data. A youtube video (Breathcatcher) explains the approach to both CHWs and clients.. We have responded by refocussing the current study on caring for those with positive samples. Although we have clear evidence that people with FMS-detected Mtb can progress to conventionally recognised disease within 1-2 months, this has not been detected so far in the current study where our capacity for follow up is very limited. (Ongoing clinical support is provided by the COPC)In the new study we aim to provide detailed follow up on 50 participants providing Mtb positive masks (CASES) for a full year and to compare their clinical and laboratory status with a comparator group whose mask result is negative (CONTROLS). Tests additional to FMS (including blood and lung imaging) will allow us to compare our evaluations against current diagnostic standards. Review will be monthly for cases and 3 monthly for controls. This approach will allow us to detect different patterns with which individuals exhale Mtb over time and whether their infections progress to active disease. Our work will be supervised by an international monitoring group who will scrutinise our results and advise on the best management of individuals with evidence of disease. In this way they will receive the earliest treatment justified by accepted standards.This work will provide a description of exhaled Mtb in the Tshwane community and its relation to clinical disease. If, as we suspect, many people without symptoms are contributing to transmission of the infection, a major refocussing of control and treatment will be necessary.