Patterns of Mycobacterium tuberculosis genotypes and resistance mutations in patients with pulmonary multidrug resistant tuberculosis in Sverdlovsk oblast, Russia

Tatiana Umpeleva¹Elena Mazurina¹Leonid Lavrenchuk¹Sven Gudmund Hinderaker^2*Einar Heldal³Andrei Mariandyshev⁴Diana Vakhrusheva¹Irina Vasilieva5¹

• ¹National Medical Research Center for Phthisiopulmonology and Infection Disease, Yekaterinburg, Russia, Yekaterinburg, Russia
• ²University of Bergen, Bergen, Norway
• ³LHL International, Oslo, Oslo, Norway
• ⁴Northern State Medical University, Arkhangelsk, Arkhangelsk Oblast, Russia

Background. Nearly half of new tuberculosis patients in Sverdlovsk oblast had multidrug resistant tuberculosis (MDR-TB) who often also had resistance to fluoroquinolones (FQ-R). The aim of this study was to 1) describe how many of the MDR-TB patients had M. tuberculosis with the same pattern (a combination of genotype and mutations in genes associated with drug resistance) by the Russian microarray assay TB-TEST, and 2) assess the correlation between groups of these patterns and patients' characteristics.We analyzed 345 MDR-TB DNA samples from patients with pulmonary TB in Sverdlovsk oblast between 2017 and 2020 using «TB-TEST». We assumed that isolates with unique patterns seen in only one patient represented minimal M. tuberculosis transmission, and the more isolates with the same pattern the more recent transmission had probably taken place. All patients were categorized into three groups so that the groups would be approximately the same size:Group 1 -unique patterns; Group 2 (low-frequency pattern group) shared by 2-6 patients in the pattern; and Group 3 (high-frequency patterns group, "dominant") shared by 7-18 patients.Results. 174 distinct genetic patterns were identified: group 1 with unique patterns (36.8%); group 2 with low-frequency pattern (31.0%); and group 3 with high-frequency patterns (32.2%). The Beijing B0/W148 genotype was found in 72.4% of cases and was significantly less frequent in patients with unique patterns (59.1% vs 66.4% vs 93.7%). Mutations in gyrA/B genes were found in 50.4% of all samples, but were significantly more common in the group with unique patterns (73% vs 43.9% and 30.6%) suggesting that mutations in gyrA/B genes had developed over the past years as a result of inadequate chemotherapy regimens but had not yet circulated widely, possibly due to lower transmission potential or recent emergence. Patients with M. tuberculosis-positive sputum and with treatment duration exceeding 12 months had a significantly higher proportion of unique patterns and exhibited higher rates of fluoroquinolone resistance.