Objective: To detect the cell-free DNA of Mycobacterium tuberculosis (Cf-TB) in the cerebrospinal fluid (CSF) of patients with tuberculous meningitis (TBM), and to assess the diagnostic value of this method for TBM. Methods: We prospectively included patients with suspected meningitis from the Department of Tuberculosis, Beijing Chest Hospital, Department of Neurology, Beijing Chaoyang Hospital and Department of Neurology, 263 Hospital of the People's Liberation Army from September 2019 to March 2022. A total of 189 patients were included in this study. Among them, 116 were male and 73 were female, aged from 7 to 85 years, with an average of (38.5±19.1) years. The CSF specimens of the patients were collected for Cf-TB, MTB culture and Xpert MTB/RIF. SPSS 20.0 was used for statistical analysis and the difference was statistically significant with P<0.05. Results: Among the 189 patients, there were 127 patients in the TBM group and 62 patients in the non-TBM group. The sensitivity of Cf-TB was 50.4% (95%CI 41.4%-59.3%), the specificity was 100% (95%CI 92.7%-100.0%), the positive predictive value was 100% (95%CI 92.9%-100.0%), and the negative predictive value was 49.6% (95%CI 40.6%-58.6%). Using clinical diagnosis as the gold standard, the sensitivity of Cf-TB was 50.4% (64/127), which was significantly higher than that of MTB culture (8.7%, 11/127) and Xpert MTB/RIF (15.7%,20/127) (all P<0.001). Using etiology as the gold standard, the sensitivity of Cf-TB was 72.7% (24/33), which was significantly higher than that of MTB culture [33.3%, 11/33, (χ2=10.28, P=0.001)] and was similar to Xpert MTB/RIF (60.6%, 20/33) (χ2=1.091, P=0.296). Conclusion: The sensitivity of the Cf-TB test was significantly higher than that of CSF MTB culture and Xpert MTB/RIF. Cf-TB may provide evidence for earlier diagnosis and treatment of TBM.
目的： 探讨脑脊液结核分枝杆菌游离核酸（Cf-TB）检测方法对结核性脑膜炎的早期诊断价值。 方法： 前瞻性纳入2019年9月至2022年3月于首都医科大学附属北京胸科医院结核科、北京朝阳医院神经内科、解放军263医院神经内科就诊的疑诊为脑膜炎的患者189例，其中男性116例，女性73例，年龄7~85（38.5±19.1）岁。留取患者脑脊液标本分别进行Cf-TB检测、结核菌培养和利福平耐药实时荧光定量核酸扩增检测技术（Xpert MTB/RIF）检测，探讨不同检测方法对结核性脑膜炎的诊断价值。应用SPSS 20.0软件进行数据统计分析，以P<0.05差异有统计学意义。 结果： 189例患者中，TBM组患者127例，非TBM组患者62例。Cf-TB检测的敏感度为50.4%（95%CI 41.4%~59.3%），特异度为100%（95%CI 92.7%~100%），阳性预测值为100%（95%CI 92.9%~100%），阴性预测值为49.6%（95%CI 40.6%~58.6%）。在以临床诊断为金标准时，Cf-TB检测的敏感度为50.4%（64/127），显著高于结核菌培养（8.7%，11/127）和Xpert MTB/RIF检测（15.7%，20/127），差异均有统计学意义（均P<0.001）。在以病原学检测方法为金标准时，Cf-TB检测的敏感度为72.7 %（24/33），显著高于结核菌培养［33.3%（11/33），χ2=10.28，P=0.001］而与Xpert MTB/RIF检测相似（60.6%（20/33），χ2=1.091，P=0.296）。 结论： 脑脊液Cf-TB检测敏感度高于脑脊液结核菌培养和Xpert MTB/RIF检测，可以为TBM的早期、快速诊断提供可靠的证据支持。.