Epidemiological investigation and comparison between phenotypic and whole-genome sequencing drug susceptibility testing in Mycobacterium tuberculosis isolates from The Republic of Korea
Background Whole genome sequencing (WGS) has been applied to tackle the major public health problem of tuberculosis (TB). The Republic of Korea has the highest rates of TB incidence of all OECD countries yet there has not yet been a comparison of phenotypic and WGS based TB drug susceptibility testing (DST) in this setting. Objectives A retrospective comparison of Mycobacterium tuberculosis (MTB) clinical isolates from 2015-2017 from two centres in the Republic of Korea using WGS to evaluate epidemiological links and compare phenotypic and WGS-based DST. Methods 57 MTB isolates had DNA extracted and were sequenced using the Illumina platform. The WGS analysis was performed using Artemis, Figtree and TB profiler. Phenotypic susceptibilities were carried out at the Supranational TB reference laboratory (Korean Institute of Tuberculosis). Results There were three clusters identified with single nucleotide polymorphism (SNP) difference less than 12. For first line anti-tuberculous drugs concordant with phenotypic DST for Rifampicin, Isoniazid, Pyrazinamide, Ethambutol were 98.25%, 92.98%, 87.72% and 85.96% respectively. The sensitivity of WGS-DST compared with pDST for rifampicin, isoniazid, pyrazinamide and ethambutol were 97.30%, 92.11%, 78.95% and 95.65% respectively. The specificity for the first line anti-tuberculous drugs was 100%, 94.74%, 92.11% and 79.41% respectively. The concordance with phenotypic DST for second line drugs varied from 85.96 to 100%. The sensitivity ranged from 66.67% to 100% and specificity ranged from 82.98 to 100%. Conclusions This study confirms the potential role for WGS in DST testing, but further larger studies are needed to ensure current databases of drug resistance mutations are reflective of the TB present in the Republic of Korea.