Treatment outcomes of isoniazid mono-resistant mycobacterium tuberculosis patients in Uganda: a retrospective cross-sectional study from 2017 to 2022

Abstract

Globally, isoniazid-resistant, rifampicin-susceptible TB is estimated to occur in 13.1% (95% confidence interval [CI]: 9.9–16.9%) of new cases and 17.4% (95% CI: 0.5–54.0%) of previously treated cases. Current WHO guidelines recommend treatment with Rifampicin (RFP), ethambutol (EMB, E), pyrazinamide (PZA, Z), and levofloxacin (LFX, Q) for 6 months in patients with isoniazid mono-resistant TB (Hr-TB) but the effectiveness and use of other regimens in managing Hr-TB has not been established. There is a need to pay increased attention to the timely identification of Hr-TB patients in order to improve treatment success along with reduction of the risk for further drug resistance development Methodology: Selected isolates were tested for mutations associated with isoniazid resistance. Patient demographic data was obtained from the National TB Reference Laboratory (NTRL) electronic data system and request forms with additional data, such as treatment regimen, adverse effects, and treatment start dates obtained from treatment registers. The main outcome was dichotomized as unsuccessful treatment outcome (failed, died, lost to follow-up and not evaluated) vs successful treatment outcome (cured or completed). The independent variables available (age, sex, regimen used, M. tuberculosis mutation genes for isoniazid specifically InhA and KatG, history of TB, HIV status, and reporting year) were assessed as possible factors in the relationship between Hr-TB and treatment success. Results: A total of 85 isolates from different patients were analyzed in this study. Most of the participants 36(42.4%) turned culture negative at month one upon initiation of treatment. The findings from this study show that the most dominant Mycobacterium tuberculosis mutation occurred in the KatG MUT1 region with a nucleotide change of S315T1 and with inhA MUT2, MUT3A, and 3B region being registered with no mutations in this study. However, the study found that the majority of deaths were among people aged above 36 years 71.4% (5/7 participants). Conclusion: This study revealed delayed culture conversation of beyond 2 months as a significant factor associated with unsuccessful treatment of isoniazid mono-resistant TB and this can be used as a predictor in routine patient management. The study found a higher proportion of mutations known to confer high-level isoniazid drug resistance among patients with isoniazid drug resistance but the treatment outcome across the different mutations never varied. Hr-TB was commonest among the male and also mainly among participants who previously had TB and had been initiated on anti-TB treatment. In this study Majority of the patients had successful treatment outcome.