Whole genome sequencing for tuberculosis disease species identification, lineage determination, and drug resistance detection in Kashgar prefecture, China.

BACKGROUND

We aimed to use whole genome sequencing (WGS) to determine species and lineage composition and drug resistance profile in a high tuberculosis (TB)-burden region of China.

METHODS

We conducted WGS to 1791 acid-fast staining positive and culture-positive isolates collected from Kashgar prefecture in 2020. Bioinformatic analysis was applied to confirm species, lineage and drug resistant-related mutations. The drug susceptibility testing was performed on confirmed Mycobacterium tuberculosis complex (MTBC) isolates. We determined the accuracy of WGS prediction by comparing with phenotypes.

RESULTS

95.03% (1702/1791) were identified MTBC, 3.18% (57/1791) were nontuberculous mycobacteria (NTM), 0.61% (11/1791) were nocardia, 0.89% (16/1791) were gordonia and 0.056% (1/1791) were rhodococcus, the rest 4 isolations were identified as mixed infection. MTBC were composed of lineage 2 (45.83%, 780/1702), lineage 3 (462/1702, 27.14%), lineage 4 (455/1702, 26.73%), lineage 1(1/1702, 0.06%) and M.bovis (La1, 4/1702, 0.24%). Resistance to rifampicin, ethambutol, fluoroquinolones, aminoglycosides and ethionamide were accurately predicted with sensitivity of 96.43%, 83.33%,100%, 100% and 94.74% by WGS, while resistance to isoniazid with the sensitivity of 81.62%.

CONCLUSIONS

WGS can be an important approach in assessing TB control strategy and for determining therapeutic schemes in high TB-burden regions. The drug resistance TB of Kashgar prefecture is at low level and the application of WGS may prevent the increase of resistance rate.