Abstract:

Objective: To analyze the drug resistance profile and genetic diversity of Mycobacterium tuberculosis (MTB) in high-altitude regions of Sichuan Province (Sêrxü County, 4520 meters) and provide scientific data for formulating targeted tuberculosis (TB) prevention and control strategy, establishing MTB strain bank, and exploring influence of high altitude on MTB evolution in high altitude and alpine areas of China. Methods: A prospective study design was adopted, sputum samples from 189 pulmonary tuberculosis (PTB) patients, collected by designated medical institutions in Sêrxü County, Sichuan Province between June 2023 and April 2024, were obtained following standard procedures and subjected to modified Lowenstein-Jensen (LJ) solid culture, followed by genetic chip analysis and sequencing by a higher-level institution. Ultimately, a total of 75 valid strains were finally included in the study. An MTB sequence analysis platform was used to analyze the strain type, drug resistance, gene mutation, lineage, and clustering status of all strains. Results: Among the 75 strains, 33 strains were found to be resistant to 9 anti-tuberculosis drugs, with 33 resistant mutation sites and 35 types of resistant mutations. The total drug resistance rate was 44.00%. Among them, 10 strains (13.33%) were multidrug-resistant strains, 2 strains (2.67%) were pre-extensively drug-resistant strains, and 21 strains (28.00%) were other resistant strains. Among the 33 drug-resistant strains, 14 strains (42.42%) were single-mutation resistant, 12 strains (36.36%) had two resistance-related mutations, and 7 strains (21.21%) had three or more resistance-related mutations. For the 9 anti-TB drugs, the resistance rate to isoniazid was the highest (42.42%, 14/33), followed by rifampicin (39.39%, 13/33). In the lineage typing, the East Asian type (L2 type) accounted for 89.33% (67/75), mainly the Beijing East Asian type (94.03%, 63/67), while the other 8 strains were European-American type (L4 type, 10.67%). Fifty-one strains were clustered strains, with a clustering rate of 68.00%, and a total of 12 clusters were identified. The number of clustered strains ranged from 2 to 12, with 2 strains being the most common type (50.00%, 6/12). Conclusion: The proportion of drug-resistant tuberculosis in Sêrxü County, a high-altitude and cold area in Sichuan Province, is significantly higher than that in other regions. The main prevalent lineage is L2 type, and the clustering rate is relatively high, indicating a serious risk of recent tuberculosis transmission. The region should further strengthen tuberculosis prevention and control efforts to reduce the spread of MTB and the emergence of drug resistance.

Key words: Mycobacterium tuberculosis, Sequence-based typing, tandem repeat sequence, Tuberculosis, multi-drug resistant, Epidemiological research characteristics (subject), High altitude