Rates and risk factors of monoresistance against isoniazid and multidrug-resistant tuberculosis in Almaty, Kazakhstan

BACKGROUND: Drug resistant tuberculosis (DR-TB) poses a massive threat to public health, and monoresistance to isoniazid (Hr-TB) is not often diagnosed. This study aims to determine rates of Hr-TB and multidrug resistance (MDR-TB) among TB isolates and assess risk factors for TB diagnosis and drug resistance in Almaty, Kazakhstan to inform public health policy. METHODS: From December 2021 to July 2022, sputum samples were collected from 1214 unique patients over age 18 with presumptive TB who were not currently on TB treatment. All samples were tested with both Mycobacterial Growth Indicator Tube (MGIT) liquid culture and the Becton-Dickinson real-time PCR (BD MAX™ MDR-TB) for detection of M. tuberculosis and drug resistance to isoniazid (INH), rifampicin (RIF), ethambutol (EMB), and pyrazinamide (PZA). Rates of monoresistance and MDR-TB were calculated, and univariate and multivariable logistic regression models were run to determine odds ratios for potential risk factors for TB, Hr-TB, and MDR-TB diagnosis using MGIT results. RESULTS: Any resistance to INH was found in 115 (43.7% [95% CI: 37.9-49.8%]) of 263 TB isolates diagnosed by MGIT, and Hr-TB was diagnosed in 34 MGIT TB isolates (12.9% [95% CI: 9.4-17.5%]). Among 359 BD MAX TB isolates, 51 (14.2% [95% CI: 11.0-18.2%]) were Hr-TB. MDR-TB was diagnosed in 70 MGIT TB isolates (26.6% [95% CI: 21.6-32.3%]) and 65 BD MAX TB isolates (24.7% [95% CI: 14.5-22.4%]). Male patients, those aged 35-44 and 45-54, and patients with self-reported diabetes mellitus had higher odds of TB diagnosis compared to female patients, those aged 65+, and those with no self-reported comorbid conditions, but no significant associations were found between patient characteristics and odds of Hr-TB or MDR-TB diagnosis. CONCLUSION: Rapid and accurate diagnosis of INH monoresistance is critical to understand national burdens of Hr-TB, improve treatment regimens, and prevent increases in MDR-TB in Kazakhstan. Current TB diagnostics that do not detect resistance to INH are inadequate to characterize Hr-TB. Therefore, high-burden MDR-TB countries should consider using diagnostics that detect resistance to both INH and RIF in national TB prevalence and drug resistance surveys. CLINICAL TRIAL: Not applicable.