常用实验室技术诊断结核性脑膜炎效能的比较研究

目的 对常用实验室技术诊断结核性脑膜炎(tuberculous meningitis,TBM)的效能进行比较研究,以提高临床早期诊断TBM的水平。方法 采用BACTEC MGIT 960液体培养(简称“MGIT 960法”)、改良抗酸染色(简称“MZN法”)、GeneXpert MTB/RIF(简称“GeneXpert法”)、荧光探针法聚合酶链式反应(简称“PCR-荧光探针法”)和结核感染T细胞斑点试验(T-SPOT.TB)等5种实验室检测技术对西安市胸科医院2017年1月至2018年4月期间收治的244例成年疑似结核性脑膜炎患者脑脊液进行检测。包括71例TBM组患者(确诊组36例,很有可能组23例,可能组12例)及33例非TBM组患者。评价上述5种实验室技术诊断TBM的效能,并探讨细菌学方法组(MGIT 960和MZN法)、分子生物学方法组(GeneXpert和PCR-荧光探针法)、免疫学方法组(T-SPOT.TB),以及上述5种技术联合诊断组(简称“联合诊断组”)在TBM早期诊断中的价值,并比较5种实验室技术之间、4种方法组之间诊断TBM敏感度的差异。结果 以临床诊断为标准,5种检测技术诊断TBM的特异度和阳性预测值均为100.0%;MGIT 960法、MZN法、GeneXpert 法、PCR-荧光探针法和T-SPOT.TB检测技术诊断TBM的敏感度分别为19.7%(14/71)、26.8%(19/71)、42.3%(30/71)、35.2%(25/71)、29.6%(21/71);GeneXpert法和PCR-荧光探针法的敏感度均高于MGIT 960法,差异均有统计学意义(χ ²=8.43,P=0.004;χ ²=4.28,P=0.039)。细菌学方法组、分子生物学方法组、免疫学方法组及联合诊断组的敏感度分别为31.0%(22/71)、50.7%(36/71)、29.6%(21/71)、73.2%(52/71);分子生物学方法组和联合诊断组的敏感度高于细菌学方法组,差异均有统计学意义(χ ²=5.71,P=0.017;χ ²=73.20,P=0.000)。 结论 在TBM的早期诊断中,GeneXpert法与PCR-荧光探针法的敏感度高于MGIT 960法;各实验方法联合检测有助于提高诊断TBM的敏感度,并且与细菌学方法组相比,分子生物学方法组以及联合诊断组的敏感度更高。

Comparative analysis of common laboratory diagnostic methods for tuberculous meningitis

Objective To compare the performance of common laboratory techniques in the diagnosis of tuberculous meningitis (TBM) in order to improve early diagnosis of TBM.Methods Five techniques including BACTEC MGIT 960 liquid culture method (MGIT 960 method), modified acid-fast staining (MZN method), GeneXpert MTB/RIF (GeneXpert method), fluorescent probe polymerase chain method (PCR-fluorescence probe method), and tuberculosis infection T cell spot test (T-SPOT.TB) were conducted with cerebrospinal fluids of 224 adult suspected TBM patients who admitted in Xi’an Chest Hospital from January 2017 to April 2018. There were 71 patients in the TBM group (36 in the confirmed group, 23 in the strongly probable group, and 12 in the possible group) and 33 in the non-TBM group. Performance of the above five laboratory techniques for diagnosing TBM were assessed. The values of bacteriological method (MGIT 960 and MZN methods), molecular biology method (GeneXpert and PCR-fluorescence probe method), immunology method (T-SPOT.TB), and combination of all five techniques in early diagnosis of TBM were compared.Results Taking the clinical diagnosis results as standard, the specificity and positive predictive value of the five detection techniques for TBM diagnosis were all 100.0%. The sensitivity of MGIT 960, MZN, GeneXpert, PCR-fluorescence probe and T-SPOT.TB method were 19.7% (14/71), 26.8% (19/71), 42.3% (30/71), 35.2% (25/71), and 29.6% (21/71), respectively. The sensitivity of the GeneXpert method and the PCR-fluorescence probe method was higher than that of the MGIT 960 method, and the differences were statistically significant (χ ²=8.43, P=0.004; χ ²=4.28, P=0.039). The sensitivity of the bacteriological method, molecular biology method, the immunology method, and the combined method were 31.0% (22/71), 50.7% (36/71), 29.6% (21/71), and 73.2% (52/71), respectively. The sensitivity of the molecular biology method and the combined diagnosis method were higher than that of the bacteriological method, and the differences were statistically significant (χ ²=5.71, P=0.017; χ ²=73.20, P=0.000). Conclusion In the early diagnosis of TBM, the sensitivity of GeneXpert and PCR-fluorescence probe method is higher compared with MGIT 960 method. The combined detection of experimental methods can improve the sensitivity of TBM diagnosis. Compared with the bacteriological method, the sensitivity of the biological method and combined diagnosis method is higher.