Background & objectives: There is a need for an affordable, easy, high-sensitivity test usable at the peripheral health facility for diagnosis of drug-resistant (DR) tuberculosis (TB) to interrupt disease transmission. Nucleic acid amplification tests (NAATs) for early detection of DR-TB are ideal to bring testing near to the patient. Truenat^TM MTB (Mycobacterium tuberculosis) and Truenat^TM MTB-RIF (rifampicin) is an indigenous chip-based real-time polymerase chain reaction (PCR) based test for detection of multidrug-resistant (MDR) TB. The test involves extraction of DNA using automated, battery operated Trueprep instrument and real-time PCR performed on the Truelab analyzer. We report here multicentric validation of Truenat MTB-RIF for detection of DR-TB in suspected DR-TB patients.
Methods: Consecutive patients aged 18-65 yr, with symptoms suggestive of TB and with a history of previous treatment, reporting to the National TB Elimination Programme (NTEP) clinics under four national institutes, namely AIIMS (All India Institute of Medical Sciences, New Delhi), NITRD (National Institute of Tuberculosis and Respiratory Diseases, New Delhi), NIRT (National Institute for Research in Tuberculosis, Chennai) and ICMR-National JALMA Institute for Leprosy and other Mycobacterial Diseases, Agra, were included in the study. Two sputum samples (one spot and one morning) were collected from each patient, after obtaining informed written consent. The samples were subjected to smear, GeneXpert and MGIT 960 culture (and drug susceptibility testing to RIF) (surrogate for MDR-TB) to serve as reference tests. The samples were coded to ensure blinding and subjected to Truenat MTB-RIF. Truenat MTB-RIF Version 1.5 was used for testing 1084 samples for RIF resistance, while Version 2.0 was used to test another 1201 samples.
Results: Truenat MTB-RIF Version 1.5 in comparison with comprehensive laboratory reference standards yielded sensitivity and specificity of 76.2 and 94.7 per cent, respectively for the detection of RIF resistance in 1084 samples, collected across four sites. Based on the analysis of discordant samples, Version 2.0 of Truenat was developed by the manufacturer and this was further tested on additional 1201 samples, yielding a sensitivity of 87.5 per cent and specificity of 99.5 per cent.
Interpretation & conclusions: Multicentric trial of Truenat^TM MTB-RIF demonstrated a great potential of this point of care NAAT for detection of MDR-TB. The test would be useful in limited resource settings and inaccessible areas without need for any additional infrastructure.

中文翻译：

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验证一种用于快速分子检测推定耐多药肺结核患者中利福平耐药性的本土化验

背景和目标：需要一种负担得起的、简单的、高灵敏度的测试，可在外围医疗机构中用于诊断耐药性 (DR) 结核病 (TB)，以阻断疾病传播。用于早期检测 DR-TB 的核酸扩增测试 (NAAT) 是将测试带到患者身边的理想选择。Truenat ^TM MTB（结核分枝杆菌） 和 Truenat ^TMMTB-RIF（利福平）是一种基于本土芯片的实时聚合酶链反应（PCR）测试，用于检测耐多药（MDR）结核病。该测试涉及使用自动、电池供电的 Trueprep 仪器提取 DNA，并在 Truelab 分析仪上执行实时 PCR。我们在此报告 Truenat MTB-RIF 用于检测疑似 DR-TB 患者中的 DR-TB 的多中心验证。
方法：18-65 岁的连续患者，有结核病症状和既往治疗史，向四个国家机构下属的国家结核病消除计划 (NTEP) 诊所报告，即 AIIMS（全印度医学科学研究所，新德里） ，NITRD（国家结核病和呼吸系统疾病研究所，新德里），NIRT（国家结核病研究所，钦奈）和 ICMR-国家 JALMA 麻风病和其他分枝杆菌疾病研究所，阿格拉，被包括在研究中。在获得书面知情同意后，从每位患者身上采集两份痰样本（一份和一份早晨）。对样本进行涂片、GeneXpert 和 MGIT 960 培养（以及对 RIF 的药物敏感性测试）（耐多药结核病的替代品）作为参考测试。对样品进行编码以确保致盲并经受 Truenat MTB-RIF。Truenat MTB-RIF 1.5 版用于测试 1084 个样品的 RIF 电阻，而 2.0 版用于测试另外 1201 个样品。
结果： Truenat MTB-RIF 1.5 版与综合实验室参考标准相比，在四个地点收集的 1084 个样本中检测 RIF 抗性的灵敏度和特异性分别为 76.2% 和 94.7%。基于对不一致样本的分析，制造商开发了 Truenat 2.0 版，并在另外 1201 个样本上进行了进一步测试，得出的灵敏度为 87.5%，特异性为 99.5%。
解释和结论： Truenat ^{TM的多中心试验}MTB-RIF 证明了这种护理点 NAAT 在检测耐多药结核病方面的巨大潜力。该测试在资源有限和无法进入的区域非常有用，无需任何额外的基础设施。