Objective: To evaluate the performance of Mycobacterium tuberculosis and rifampicin resistance mutation detection kit (InnowaveDX MTB/RIF, referred to as "InnowaveDX") in diagnosing tuberculosis and rifampicin resistance using sputum samples. Methods: From June 19, 2020 to May 16, 2022, patients with suspected tuberculosis were prospectively and consecutively enrolled in Hunan Provincial Tuberculosis Prevention and Control Institute, Henan Provincial Hospital of Infectious Diseases and Wuhan Jinyintan Hospital. A total of 1 328 patients with suspected tuberculosis were finally included. According to the inclusion and exclusion criteria, 1 035 pulmonary tuberculosis patients (357 were confirmed tuberculosis cases and 678 were clinically diagnosed tuberculosis cases) and 180 non-tuberculosis patients were finally included. Sputum samples were collected from all patients for routine sputum smear acid-fastness tests, mycobacterial culture and drug susceptibility testing. Moreover, the diagnostic value of Xpert®MTB/RIF (referred to as "Xpert") and InnowaveDXin detecting tuberculosis and rifampicin resistance was evaluated. Clinical diagnosis and culture results of Mycobacterium tuberculosis were used as reference standards to assess tuberculosis diagnosis, and phenotypic drug sensitivity and Xpert were used as reference standards to assess rifampicin resistance. The sensitivity, specificity, positive predictive value and negative predictive value of the two methods for tuberculosis diagnosis and rifampicin resistance were analyzed. The consistency of the two techniques was analyzed usingkappa test. Results: Taking clinical diagnosis as the reference standard, the detection sensitivity of InnowaveDX [58.0% (600/1 035)] was higher than that of Xpert [51.7% (535/1 035)] in 1035 patients with pulmonary tuberculosis, and the difference was statistically significant (P<0.001). In 270 pulmonary tuberculosis patients with culture-positive pulmonary tuberculosis identified as M.tuberculosis-complex, the positive rates of InnowaveDX and Xpert were both high [99.6%(269/270)and 98.2%(265/270), respectively] and there was no statistical difference. In culture-negative patients with pulmonary tuberculosis, the sensitivity of InnowaveDX was 38.8% (198/511), which was higher than that of Xpert (29.4%, 150/511), and the difference was statistically significant (P<0.001). Taking phenotypic drug-susceptibility testing (DST) as reference, the sensitivity of InnowaveDX to rifampicin resistance was 99.0% (95%CI: 94.7%-100.0%) and the specificity was 94.0%(95%CI: 88.5%-97.4%). With Xpert as the reference, the sensitivity and specificity of InnowaveDX were 97.1% (95%CI: 93.4%-99.1%) and 99.7% (95%CI: 98.4%-100.0%), respectively, and the kappa value was 0.97 (P<0.001). Conclusions: InnowaveDX show a high sensitivity for detecting Mycobacterium tuberculosis, especially in pulmonary tuberculosis patients with a clinical diagnosis and negative culture results. It also showed high sensitivity in detecting rifampicin resistance with DST and Xpert as reference respectively. InnowaveDX is an early and accurate diagnostic tool for TB and drug-resistant TB, particularly suitable for application in low- and middle-income countries.
目的： 评估结核分枝杆菌（MTB）和利福平耐药突变检测试剂盒（InnowaveDX MTB/RIF，简称InnowaveDX）检测痰液对MTB复合群及利福平耐药的诊断价值。 方法： 前瞻性连续纳入2020年6月19日至2022年5月16日湖南省结核病防治所、河南省传染病医院和武汉市金银潭医院就诊的具有结核病体征的患者1 328例，依据纳入及排除标准，最终纳入1 035例肺结核患者（确诊患者357例，临床诊断患者678例）和180例非结核患者。收集所有患者的痰液样本，进行常规痰涂片、痰培养、药敏试验，并评价Xpert®MTB/RIF（简称Xpert）和InnowaveDX对肺结核和利福平耐药的诊断价值。对肺结核的诊断分别以临床诊断和MTB培养结果为参考标准，对利福平耐药的评价分别以表型药敏试验和Xpert为参考标准，分析两种检测方法对结核病诊断和利福平耐药的敏感度、特异度、阳性预测值、阴性预测值。两种检测技术的一致性分析行kappa检验。 结果： 以临床诊断为参考标准，InnowaveDX对1 035例临床诊断肺结核患者检测敏感度［58.0%（600/1 035）］高于Xpert［51.7%（535/1 035）］，差异有统计学意义（P<0.001）。对270例培养阳性且鉴定为MTB复合群的肺结核患者，InnowaveDX和Xpert阳性率均高，分别为99.6%（269/270）和98.2%（265/270），差异无统计学意义；而在培养阴性的肺结核患者中，InnowaveDX检测敏感度为38.8%（198/511），明显高于Xpert（29.4%，150/511），差异有统计学意义（P<0.001）。以表型药敏试验结果为金标准，InnowaveDX对利福平耐药的敏感度为99.0%（95%CI：94.7%~100.0%），特异度为94.0%（95%CI：88.5%~97.4%）。以Xpert为金标准，InnowaveDX对利福平耐药敏感度为97.1%（95%CI：93.4%~99.1%），特异度为99.7%（95%CI：98.4%~100.0%），两种检测方法一致性kappa值为0.97（P<0.001）。 结论： InnowaveDX检测MTB复合群敏感度较高，尤其表现在结核病临床诊断和痰培养阴性肺结核患者。在利福平耐药检测方面，分别以表型药敏试验和Xpert结果为参考标准，InnowaveDX均显示了较高的利福平耐药检测敏感度，与Xpert的一致性高。InnowaveDX检测具有敏感度高和检测周期短的特点，可有效提升结核病病原学阳性率和预测耐药性，尤其适用于在中低收入国家推广应用。.