Department of Pulmonology and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.
Department of Human, Biological and Translational Medical Sciences, School of Medicine, University of Namibia, Windhoek, Namibia.
Microbiol Spectr. 2022 Jun 29;10(3):e0025922. doi: 10.1128/spectrum.00259-22. Epub 2022 Jun 7.
Treatment of tuberculosis requires rapid information about Mycobacterium tuberculosis () drug susceptibility to ensure effective therapy and optimal outcomes. At the tuberculosis referral hospital in Windhoek, Namibia, a country of high tuberculosis incidence, we evaluated the diagnostic accuracy of a line-probe-assay (LPA), GenID, for the molecular diagnosis of infection and drug resistance in patients with suspected tuberculosis (cohort 1) and confirmed rifampin (RIF)-resistant tuberculosis (cohort 2). GenID test results were compared to Xpert MTB/RIF and/or culture and antimicrobial suceptibilty testing. GenID LPA was applied to 79 and 55 samples from patients in cohort 1 and cohort 2, respectively. The overall sensitivity of GenID LPA for the detection of DNA in sputum from patients with detectable and undetectable acid-fast bacilli by sputum smear microscopy was 93.3% (56/60; 95% confidence interval = 83.8-98.2) and 22.7% (5/22; 7.8-45.4). The sensitivity/specificity for the detection of drug resistance was 84.2% (32/38; 68.7-94.0)/100% (19/19; 82.4-100.0) for RIF, 89.7% (26/29; 72.6-97.8)/91.7% (22/24; 73.0-99.0) for isoniazid, and 85.7% (6/7; 42.1-99.6)/94.7% (18/19; 74.0-99.9) for fluoroquinolones; 23.6% of tests for second-line injectable resistance were invalid despite repeat testing. The diagnosis of tuberculosis by detection of DNA in sputum by GenID LPA depends strongly on the detection of acid-fast bacilli in sputum specimen. Prediction of drug resistance by GenID did not reach the World Health Organization (WHO) target product profile. Mycobacterium tuberculosis () drug-resistance detection is crucial for successful control of tuberculosis. Line-probe assays (LPA) are frequently used to detect resistance to rifampin, isoniazid, fluoroquinolones (FQs), and second-line injectables (SLIs). GenID RIF/isoniazid (INH), FQ, and SLI LPA have not been widely tested and used so far. This study tested the diagnostic performance of the GenID LPA in a high-incidence TB/HIV, real-world setting in Namibia. The LPA demonstrates only an acceptable diagnostic performance for and drug-resistance detection. The diagnostic sensitivity and specificity fall short of the WHO suggested target product profiles for LPA.
结核病的治疗需要快速了解结核分枝杆菌（）对药物的敏感性，以确保有效治疗和最佳疗效。在纳米比亚温得和克的结核病转诊医院，该国有很高的结核病发病率，我们评估了线探针分析（LPA），GenID，对疑似结核病患者（队列 1）和确诊利福平（RIF）耐药结核病（队列 2）患者的 感染和药物耐药性的分子诊断的诊断准确性。GenID 测试结果与 Xpert MTB/RIF 和/或 培养和抗菌药物敏感性测试进行比较。GenID LPA 分别应用于队列 1和队列 2中 79 和 55 例患者的样本。GenID LPA 检测可检测和不可检测的抗酸杆菌痰液中 DNA 的总体敏感性分别为 93.3%（56/60；95%置信区间=83.8-98.2）和 22.7%（5/22；7.8-45.4）。检测耐药性的敏感性/特异性分别为 84.2%（32/38；68.7-94.0）/100%（19/19；82.4-100.0），38.7%（26/29；72.6-97.8）/91.7%（22/24；73.0-99.0）用于异烟肼，85.7%（6/7；42.1-99.6）/94.7%（18/19；74.0-99.9）用于氟喹诺酮类药物；尽管进行了重复测试，但仍有 23.6%的二线注射药物耐药性检测无效。GenID LPA 通过检测痰液中的 DNA 对结核病的诊断很大程度上取决于痰液中抗酸杆菌的检测。GenID 预测药物耐药性未达到世界卫生组织（WHO）目标产品概况。结核分枝杆菌（）药物耐药检测对于成功控制结核病至关重要。线探针分析（LPA）常用于检测利福平、异烟肼、氟喹诺酮类（FQs）和二线注射剂（SLIs）的耐药性。GenID RIF/异烟肼（INH）、FQs 和 SLI LPA 尚未广泛测试和使用。本研究在纳米比亚高发病率的结核病/艾滋病毒现实环境中测试了 GenID LPA 的诊断性能。LPA 仅对 和耐药性检测具有可接受的诊断性能。诊断灵敏度和特异性均未达到世界卫生组织建议的 LPA 目标产品概况。
