DNA微阵列芯片法检测耐药结核分枝杆菌的临床应用价值研究

目的 评价DNA微阵列芯片法检测结核分枝杆菌及其对异烟肼和利福平耐药的检测效能。 方法 收集2011年1月至2017年5月间在江苏省灌云县疾病预防控制中心登记的814例涂阳肺结核患者的痰标本。利用传统罗氏培养法及比例法药物敏感性试验(简称“药敏试验”)和DNA微阵列芯片法,同时对患者的痰标本进行结核分枝杆菌检测,并检测其对异烟肼和利福平的耐药情况;分别以传统罗氏培养及比例法药敏试验为标准,评价DNA微阵列芯片法的检测效能。 结果 DNA微阵列芯片法对涂阳肺结核患者的结核分枝杆菌检出率为86.1%(701/814),高于传统罗氏培养法的82.4%(671/814),差异有统计学意义(χ ²=6.81,P<0.05)。以传统罗氏培养法为标准,DNA微阵列芯片法检测涂阳患者结核分枝杆菌的敏感度和特异度分别为92.4%(620/671)和43.4%(62/143),Kappa=0.39,阳性预测值和阴性预测值分别为88.4%(620/701)和54.9%(62/113)。以药敏试验为标准,对有完整的异烟肼和利福平耐药检测结果的620例患者进行分析,DNA微阵列芯片法检测初治涂阳患者是否对异烟肼与利福平耐药的敏感度分别为78.7%(37/47)和84.6%(22/26),阳性预测值分别为69.8%(37/53)和73.3%(22/30);检测复治涂阳患者是否对异烟肼与利福平耐药的敏感度分别为71.9%(23/32)和89.3%(25/28),阳性预测值分别为85.2%(23/27)和89.3%(25/28)。 结论 DNA微阵列芯片法对结核分枝杆菌的检出率高于传统罗氏培养;对结核分枝杆菌对异烟肼和利福平耐药性检测效果理想,具有较好的应用价值。

The study of clinical application value of DNA microarray chip in detection of drug-resistant Mycobacterium tubercu-losis

Objective To evaluate the performance of DNA microarray chip to detect Mycobacterium tuberculosis (MTB) and determine the susceptibility to isoniazid (INH) and rifampicin (RFP). A total of 814 specimens of sputum smear-positive (SS+) pulmonary tuberculosis cases registered in Guanyun County Center for Disease Control and Prevention between January 2011 and May 2017 were collected. Proportion method using L?wenstein-Jensen culture medium, drug susceptibility testing (DST) and DNA microarray chip were performed to detect MTB and to test the susceptibility to INH and RFP of the sputum specimens. The detection value of DNA microarray chip was assessed by using proportion method and DST as standard, respectively. DNA microarray chip showed a significant difference (χ ²=6.81, P<0.05) in the detection of MTB in SS+ cases with a detection rate of 86.1% (701/814), which was higher than that of proportion method (82.4%, 671/814). Taking proportion method as standard, the sensitivity and specificity of DNA microarray chip in detecting MTB were 92.4% (620/671) and 43.4% (62/143), Kappa value was 0.39, and positive predictive value (PPV) and negative predictive value (NPV) were 88.4% (620/701) and 54.9% (62/113), respectively. Taking DST as standard, analysis of 620 patients with complete results of INH- and RFP-resistance showed that the sensitivity of DNA microarray method for detecting INH and RFP resistance in new SS+ cases was 78.7% (37/47) and 84.6% (22/26), and the PPV was 69.8% (37/53) and 73.3% (22/30), respectively. The sensitivity of DNA microarray method for detecting INH and RFP resistance in relapse SS+ cases was 71.9% (23/32) and 89.3% (25/28), and the PPV were 85.2% (23/27) and 89.3% (25/28), respectively. Compared with proportion method, the detection rate of DNA microarray chip for MTB is higher. The testing performance of DNA microarray chip to detect INH- and RFP-resistance are sound regarding its high validity and reliability, which may be of great value in prevention and control of tuberculosis.