Evaluation of new diagnostic methodology for the detection of second-line drug resistance in Mycobacterium tubercolosis clinical isolates

Abstract

The World Health Organization (WHO) Global Report, 2017, confirms that tuberculosis (TB) is the primary cause of death globally caused by an infectious agent. Drug-resistant TB (DR-TB) is reported by the WHO to affect at least 600 000 people globally and is the primary obstacle in the fight against the elimination of TB disease. The prompt identification and treatment of DR-TB is essential. Conventional culturebased diagnostic tests for TB require substantial laboratory capacity and result availability can take up to 3 - 4 months. The implementation of rapid molecular diagnostic tests such as line probe assays (LPA) and the Xpert MTB/RIF® (Cepheid, USA) have led to an improvement in reporting turnaround times. GenoType® MTBDRsl VER 2.0 LPA is designed for molecular detection of second-line drug resistance-conferring mutations in genes encoding resistance to fluoroquinolones (FLQ) (gyrA and gyrB) and second-line injectable drugs (SLID) (rrs and eis). This study evaluated the diagnostic performance of the Genotype® MTBDRsl VER 2.0 compared to phenotypic drug susceptibility testing (DST) as the gold standard, on clinical samples and Mycobacterium tuberculosis complex clinical isolates from South Africa. The performance indices (sensitivity and specificity estimates) for the assay when tested on clinical samples were as follows respectively: FLQ 77.2% (95% CI, 67.2% - 85.3%); 85.4% (95% CI, 79.0% - 90.5%) and SLID 81.9% (95% CI, 75.5% - 87.2%), 91.5% (95% CI, 86.6% - 95.5%). For clinical isolates the performance indices were as follows respectively: FLQ 100% (95% CI, 95.8% - 100%); 98.9% (95% CI, 96.1% - 99.9%) and SLID 89.2% (95% CI, 79.1% - 95.6%); 98.5% (95% CI, 95.7% - 99.7). The incorporation of the assay into the TB diagnostic algorithm will improve South Africa’s TB Control Program in prompt identification and appropriate treatment of drugresistant TB cases.