Tuberculosis case finding by oral swab PCR

 描述（由申请人提供）：本研究将评价结核病（TB）诊断和病例发现的新策略。肺结核的诊断通常包括痰液分析，痰液是一种来自患者气道深处的粘性物质。痰液的收集是困难和危险的，其粘度使其难以处理，标准化， 分析。为了解决对替代样本类型的需求，我们假设一些通过口腔的结核分枝杆菌细胞积聚在口腔上皮细胞的表面上。这些细胞可以通过使用口腔拭子收集，并通过使用聚合酶链反应（PCR）和/或其他标准M.结核病检测方法。在对从20例确诊结核病例和20例匹配的健康对照中收集的样本进行的一项试点病例对照研究中，相对于批准的基于结核病的方法，口腔拭子的PCR分析显示出90%的灵敏度和100%的特异性。当前项目将1）在扩大的样本集（N = 107例病例和107例对照）中验证这些发现; 2）增强方法学以进一步提高灵敏度。口腔拭子样本是痰液的更简单、更清洁、侵入性更小、危害更小、体积更小且更均匀的替代品。这种方法可以实现对痰液可能不可行的护理点诊断策略。此外，由于它是非侵入性的，不需要活动性结核病症状，口腔拭子分析可能有助于发现活动性结核病病例。这种工具将在结核病研究、护理和控制方面具有变革性意义。

 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.