Feasibility of Direct Sputum Molecular Testing for Drug Resistance as Part of Tuberculosis Clinical Trials Eligibility Screening
Feasibility of Direct Sputum Molecular Testing for Drug Resistance as Part of Tuberculosis Clinical Trials Eligibility Screening
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DOI：
10.3390/diagnostics9020056
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发表时间：
2019-06-01
期刊：
影响因子：
3.6
通讯作者：
Nahid, Payam
中科院分区：
文献类型：
--
作者：
Alipanah, Narges;Shete, Priya B.;Nahid, Payam
快速诊断耐药结核病（TB）对于早期启动有效治疗至关重要。使用线性探针检测法（MTBDRplus和MTBDRsl）对培养分离株进行分子检测已有一段时间，可显著缩短诊断耐药性的时间。然而，直接在痰液上常规使用该测试不太常见。作为在越南河内进行的结核病临床试验入组筛选程序的一部分，我们评价了直接对315名既往无结核病治疗史的受试者的痰液样本进行线探针检测（LPA）的可行性和性能。计算了与基于培养的药物敏感性试验（DST）参比标准品相比，检测利福平（RIF）和异烟肼（INH）耐药性的试验性能特征。LPA对耐药的诊断具有较高的敏感性和特异性。在高结核病负担环境中，作为时间敏感的临床试验筛查程序的一部分，扩大痰液分子检测是可行的，将减少开始适当治疗的时间和因微生物不合格而延迟排除的风险。
A rapid diagnosis of drug-resistant tuberculosis (TB) is critical for early initiation of effective therapy. Molecular testing with line probe assays (MTBDRplus and MTBDRsl) on culture isolates has been available for some time and significantly reduces the time to diagnosis of drug resistance. However, routine use of this test directly on sputum is less common. As part of enrollment screening procedures for tuberculosis clinical trials conducted in Hanoi, Vietnam, we evaluated the feasibility and performance of line probe assay (LPA) testing directly on sputum samples from 315 participants with no prior history of TB treatment. Test performance characteristics for the detection of rifampin (RIF) and isoniazid (INH) drug resistance as compared to culture-based drug susceptibility testing (DST) reference standard were calculated. LPA demonstrated high sensitivity and specificity for the diagnosis of drug resistance. Scaling up molecular testing on sputum as part of time-sensitive clinical trial screening procedures in high TB burden settings is feasible and will reduce both time to initiation of appropriate therapy and the risk of late exclusions due to microbiologic ineligibility.