Feasibility of Direct Sputum Molecular Testing for Drug Resistance as Part of Tuberculosis Clinical Trials Eligibility Screening

• Main Authors: Narges Alipanah, Priya B. Shete, Hanh Nguyen, Nhung Viet Nguyen, Lien Luu, Thuong Pham, Hung Nguyen, Phuong Nguyen, Minh Chi Tran, Nam Pham, Ha Phan, Patrick P.J. Phillips, Adithya Cattamanchi, Payam Nahid
• Format: Article
• Language: English
• Published: MDPI AG 2019-05-01
• Series: Diagnostics
• Subjects: MTBDR<i>plus</i>; MTBDR<i>sl</i>; line probe assay; tuberculosis; DR-TB; Hain test; diagnostics; clinical trials; molecular testing
• Online Access: https://www.mdpi.com/2075-4418/9/2/56

A rapid diagnosis of drug-resistant tuberculosis (TB) is critical for early initiation of effective therapy. Molecular testing with line probe assays (MTBDR<i>plus</i> and MTBDR<i>sl</i>) 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.