Tuberculosis case finding by oral swab PCR

 描述(由申请人提供)：这项研究将评估结核病(TB)诊断和病例发现的新战略。肺结核的诊断通常包括对痰的分析，痰是一种来自患者呼吸道深处的粘性物质。痰很难收集，而且它的粘性使其难以加工、标准化、 并进行分析。为了解决另一种样本类型的需求，我们假设一些通过口腔的结核分枝杆菌细胞聚集在口腔上皮细胞的表面。这种细胞可以通过口腔拭子收集，并通过聚合酶链式反应(PCR)和/或其他标准的结核分枝杆菌检测方法进行检测。在对20例确诊结核病病例和20名匹配的健康对照采集的样本进行的一项试点病例对照研究中，口腔拭子的聚合酶链式反应分析相对于经批准的基于痰的方法显示出90%的敏感性和100%的特异性。目前的项目将1)在扩大的样本集(N=107个病例和107个对照)中验证这些发现；以及2)加强方法学，以进一步提高敏感性。口腔拭子样本是更简单、更清洁、侵入性更小、危害更小、体积更小、更均匀的痰的替代品。这种方法可以实现对痰可能不可行的护理点诊断策略。此外，因为它是非侵入性的，而且不需要活动性结核病症状，所以口腔拭子分析有可能使活动性结核病病例的发现成为可能。这样的工具将在结核病研究、护理和控制方面产生变革。

 DESCRIPTION (provided by applicant): This study will evaluate a novel strategy for tuberculosis (TB) diagnosis and case finding. Diagnosis of pulmonary TB usually includes analysis of sputum, a viscous material derived from deep in the airways of patients. Sputum is difficult and hazardous to collect, and its viscosity makes it challenging to process, standardize, and analyze. To address the need for an alternative sample type, we hypothesized that some of the Mycobacterium tuberculosis cells that pass through the oral cavity accumulate on the surfaces of oral epithelial cells. Such cells can be collected by using buccal swabs, and detected by using the polymerase chain reaction (PCR) and/or other standard M. tuberculosis detection methods. In a pilot case-control study conducted on samples collected from 20 confirmed TB cases and 20 matched healthy controls, PCR analysis of oral swabs exhibited 90% sensitivity and 100% specificity relative to approved sputum-based methods. The current project will 1) validate these findings in an expanded sample set (N = 107 cases and 107 controls); and 2) enhance the methodology to further improve sensitivity. Oral swab samples are simpler, cleaner, less invasive, less hazardous, smaller volume, and more uniform alternatives to sputum. This approach could enable point of care diagnostic strategies that might not be feasible with sputum. Moreover, because it is non- invasive and does not require active TB symptoms, oral swab analysis could potentially enable active TB case finding. Such a tool would be transformational in TB research, care, and control.