Application value of whole genome sequencing in the diagnosis of drug-resistant tuberculosis
WU Lianpeng1, 2, XIA Dandan1, 2, XU Ke1, 2
1.Department of Clinical Laboratory Medicine, the Ding Li Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou 325000, China; 2.Key Laboratory for Diagnosis and Treatment of New and Recurrent Infectious Diseases of Wenzhou, Wenzhou 325000, China
WU Lianpeng,XIA Dandan,XU Ke. Application value of whole genome sequencing in the diagnosis of drug-resistant tuberculosis[J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2024, 54(1): 42-46,52.
Abstract：Objective: To evaluate the whole genome sequencing (WGS) in the diagnosis of drug resistant tuberculosis. Methods: The strains of 65 tuberculosis patients treated in Wenzhou Central Hospital from January 2021 to September 2022 were collected. MGIT960 liquid drug sensitivity test and WGS were used to detect the drug resistance of streptomycin, rifampicin, isoniazid and ethambutol. The result of MGIT960 liquid drug sensitivity test was used as reference criteria to evaluate the diagnostic efficacy of WGS in drug-resistant tuberculosis. Results: After WGS detection, it was found that the main mutation types of streptomycin resistance gene were rpsL_K43R (62.07%, 18/29) and rpsL_K43R+rrs_A1401G (13.79%, 4/29), while those of rifampicin resistance gene were rpoB_S450L (48.15%, 26/54) and rpoB_D435V (9.26%, 5/54). The main mutation types of isoniazid resistance gene were katG_S315T (78.72%, 37/47) and fabG1_C-15T (8.51%, 4/47). The main mutation types of ethambutol resistance gene were embB_M306V (52.38%, 11/21) and embB_M306I (14.29%, 3/21). Taking the MGIT960 test results as the reference standard, the sensitivity of WGS to streptomycin, rifampicin, isoniazid and ethambutol resistance was 93.10%, 98.11%, 95.92% and 81.25%, respectively and the specificity was 94.44%, 83.33%, 100.00% and 83.67%, respectively; and the kappa values were 0.875, 0.842, 0.920 and 0.578,respectively. The sensitivity of WGS in the diagnosis of multidrug resistant tuberculosis (MDR-TB) was 93.10%,the specificity was 100.00%, and the Kappa value was 0.887. Conclusion: WGS has high sensitivity, specificity and consistency in the diagnosis of streptomycin, rifampicin and isoniazid resistance, and effective in the diagnosis of MDR-TB, which can serve as reference for the early diagnosis of drug resistant tuberculosis.
