Maynard-Smith Laura, Larke Natasha, Peters Jurgens A, Lawn Stephen D
Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, UK.
BMC Infect Dis. 2014 Dec 31;14:709. doi: 10.1186/s12879-014-0709-7.
Although the evidence base regarding the use of the Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis (TB) when testing respiratory samples is well established, the evidence base for its diagnostic accuracy for extrapulmonary and sputum-scarce pulmonary TB when testing non-respiratory samples is less clearly defined.
A systematic literature search of 7 electronic databases (Medline, EMBASE, ISI Web of Science, BIOSIS, Global Health Database, Scopus and Cochrane Database) was conducted to identify studies of the diagnostic accuracy of the Xpert assay when testing non-respiratory samples compared with a culture-based reference standard. Data were extracted and study quality was assessed using the QUADAS-2 tool. Sensitivities and specificities were calculated on a per-sample basis, stratified by sample type and smear microscopy status and summarised using forest plots. Pooled estimates were calculated for groups with sufficient data.
Twenty-seven studies with a total of 6,026 non-respiratory samples were included. Among the 23 studies comparing Xpert and culture done on the same samples, sensitivity was very heterogeneous with a median sensitivity of 0.83 (IQR, 0.68-0.94) whereas specificities were typically very high (median, 0.98; IQR, 0.89-1.00). The pooled summary estimates of sensitivity when testing smear-positive and smear-negative samples were 0.95 (95% CI 0.91-1.00) and 0.69 (95% CI 0.60-0.80), respectively. Pooled summary estimates of sensitivity varied substantially between sample types: lymph node tissue, 0.96 (95% CI, 0.72-0.99); tissue samples of all types, 0.88 (95% CI, 0.76-0.94); pleural fluid, 0.34 (95% CI, 0.24-0.44); gastric aspirates for diagnosis of sputum-scarce pulmonary TB, 0.78 (IQR, 0.68 - 0.85). Median sensitivities when testing cerebrospinal fluid and non-pleural serous fluid samples were 0.85 (IQR, 0.75-1.00) and 0.67 (IQR, 0.00-1.00), respectively.
Xpert detects with high specificity the vast majority of EPTB cases with smear-positive non-respiratory samples and approximately two-thirds of those with smear-negative samples. Xpert is a useful rule-in diagnostic test for EPTB, especially when testing cerebrospinal fluid and tissue samples. In addition, it has a high sensitivity for detecting pulmonary TB when using gastric aspirate samples. These findings support recent WHO guidelines regarding the use of Xpert for TB diagnosis from non-respiratory samples.
尽管关于在检测呼吸道样本时使用Xpert MTB/RIF检测法诊断肺结核（TB）的证据基础已得到充分确立，但在检测非呼吸道样本时，其对肺外结核和痰少性肺结核的诊断准确性的证据基础尚不太明确。
对7个电子数据库（Medline、EMBASE、ISI Web of Science、BIOSIS、全球健康数据库、Scopus和Cochrane数据库）进行系统的文献检索，以确定与基于培养的参考标准相比，Xpert检测法在检测非呼吸道样本时的诊断准确性研究。提取数据并使用QUADAS-2工具评估研究质量。按样本类型和涂片显微镜检查状态分层，逐样本计算敏感性和特异性，并使用森林图进行汇总。对有足够数据的组计算合并估计值。
纳入了27项研究，共6026份非呼吸道样本。在对相同样本进行Xpert检测和培养比较的23项研究中，敏感性差异很大，中位敏感性为0.83（四分位间距，0.68 - 0.94），而特异性通常非常高（中位值，0.98；四分位间距，0.89 - 1.00）。检测涂片阳性和涂片阴性样本时敏感性的合并汇总估计值分别为0.95（95%可信区间0.91 - 1.00）和0.69（95%可信区间0.60 - 0.80）。不同样本类型之间敏感性的合并汇总估计值差异很大：淋巴结组织为0.96（95%可信区间，0.72 - 0.99）；所有类型的组织样本为0.88（95%可信区间，0.76 - 0.94）；胸腔积液为0.34（95%可信区间，0.24 - 0.44）；用于诊断痰少性肺结核的胃抽吸物为0.78（四分位间距，0.68 - 0.85）。检测脑脊液和非胸腔浆液性液体样本时的中位敏感性分别为0.85（四分位间距，0.75 - 1.00）和0.67（四分位间距，0.00 - 1.00）。
Xpert能以高特异性检测出绝大多数涂片阳性非呼吸道样本的肺外结核病例以及约三分之二涂片阴性样本的病例。Xpert是一种用于肺外结核的有用的确诊诊断检测方法，尤其是在检测脑脊液和组织样本时。此外，使用胃抽吸物样本检测肺结核时它具有高敏感性。这些发现支持了世界卫生组织最近关于使用Xpert从非呼吸道样本诊断结核病的指南。
