Kabugo Joel, Sande Obondo James, Kabahita Jupiter Marina, Namutebi Joanita, Mujuni Dennis, Oundo Hellen Rosette, Kisakye Daniel, Batte Dorothy Nassozi, Joloba Moses, Mboowa Gerald
The WHO Supranational Tuberculosis Reference Laboratory, Ministry of Health, Kampala, Uganda.
Department of Immunology and Molecular Biology, School of Biomedical Sciences, College of Health Sciences, Makerere University, P. O Box 7072, Kampala, Uganda.
BMC Infect Dis. 2025 Jul 1;25(1):821. doi: 10.1186/s12879-025-11218-5.
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.
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.
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).
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.
Not applicable.
耐异烟肼、对利福平敏感的结核病（TB）估计在13%的新发病例和17%的既往治疗病例中出现。世界卫生组织（WHO）现行指南推荐，对于单纯耐异烟肼结核病（Hr-TB）患者，采用利福平（RFP）、乙胺丁醇（EMB，E）、吡嗪酰胺（PZA，Z）和左氧氟沙星（LFX，Q）治疗6个月，但其他治疗方案在管理Hr-TB方面的有效性和应用尚未得到证实。需要更加关注及时识别Hr-TB患者，以提高治疗成功率，并降低进一步产生耐药性的风险。本研究旨在确定乌干达单纯耐异烟肼结核病患者的治疗结局及其相关因素。
这是一项横断面研究，研究对象为2017年3月至2022年3月期间痰标本被送至乌干达国家结核病参比实验室（NTRL）的新诊断和复治结核病患者。通过表型耐药性检测（DST）确定为单纯耐异烟肼的患者样本纳入本研究。数据不完整的样本以及无法追溯治疗中心的样本被排除在研究之外。使用线性探针检测所选样本中与异烟肼耐药相关的突变。患者人口统计学数据来自国家结核病参比实验室（NTRL）电子数据系统以及带有其他数据的申请表，如治疗方案、不良反应和从治疗登记册中获取的治疗开始日期。将可用的自变量（年龄、性别、使用的治疗方案、结核分枝杆菌异烟肼突变基因，特别是InhA和KatG、结核病病史、HIV状态和报告年份）作为Hr-TB与治疗成功之间关系的可能因素进行评估。
本研究共分析了来自不同患者的85株耐异烟肼分离株。在本研究中，大多数参与者属于新诊断类别，35/85（41.2%）。大多数参与者36/85（42.3%）在开始治疗后的第1个月痰培养转阴。本研究结果表明，最主要的结核分枝杆菌突变发生在KatG MUT1区域，核苷酸变化为S315T1。本研究中不同年龄组之间的治疗结局无显著差异（治疗失败与成功，中位年龄分别为35.4岁和35.86岁，p = 0.078）。然而，研究发现大多数死亡病例发生在36岁以上人群中，占71.4%（5/7名参与者）。
本研究揭示单纯耐异烟肼结核病是与延迟超过两个月痰培养转阴相关的重要因素。这强调了需要使用常规即时检验分子诊断平台进行快速检测，以检测异烟肼和利福平耐药性，从而改善结核病治疗结局并减少治疗失败。
不适用。
