Delayed culture conversion predicts poor outcomes for isoniazid mono-resistant TB in Uganda: a retrospective cross-sectional study from 2017- 2022.

Background: Isoniazid-resistant, Rifampicin-susceptible Tuberculosis (TB) is estimated to occur in 13% of new cases and 17% 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 to improve treatment success along with the reduction of the risk for further drug resistance development. This study was performed to determine the treatment outcomes and their associated factors among isoniazid mono-resistant TB patients in Uganda.

Methods: This was a cross-sectional study performed among newly diagnosed and retreatment TB patients whose sputum samples were referred to the National TB Reference Laboratory (NTRL)-Uganda from March 2017 to March 2022. Patient samples exhibiting Isoniazid mono-resistance as determined by phenotypic drug resistance testing (DST) were included in this study. Samples with data incompleteness and those whose treatment centers could not be traced were excluded from the study. Selected samples were tested for mutations associated with Isoniazid resistance using line probe. 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 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 isoniazid monoresistant isolates from different patients were analyzed in this study. In this study, most of the participants belonged to the category of newly diagnosed 35/85 (41.2%). Most of the participants 36/85, 42.3%) 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. There was no significant treatment outcome difference among the different age groups in this study when compared (unsuccessful Vs successful treatment, median age 35.4 years and 35.86 years, p = 0.078). However, the study found that most deaths were among people aged above 36 years 71.4%, (5/7 participants).

Conclusion: This study revealed Isoniazid mono-resistant TB as a significant factor associated with delayed culture conversion of beyond two (2) months. This emphasizes the need for prompt detection using routine point-of-care testing molecular diagnostic platforms to test for Isoniazid and Rifampicin resistance to improve TB treatment outcomes and reduce failures.

Clinical trial number: Not applicable.