Vadakunnel Maria Jose, Nehru Vijayalakshmi Jawaharlal, Brammacharry Usharani, Ramachandra Venkateswari, Palavesam Suganthi, Muthukumar Anbazhagi, Mani Balasundaram Revathi, Pradhabane Gunavathy, Sriramkumar S R, Venkatchalam Kanagavel, Muthaiah Muthuraj
Institute of Basic Medical Sciences, University of Madras, Chennai, Tamil Nadu, India.
Department of Environmental Science, Central University, Kasaragod, Kerala, India.
Sci Rep. 2025 Aug 4;15(1):28335. doi: 10.1038/s41598-025-13227-5.
Enhancing treatment outcomes for drug-resistant tuberculosis is a major global priority for tuberculosis control programs. India has the highest number of Multidrug-resistant Tuberculosis cases worldwide, yet no longitudinal studies have assessed the factors affecting treatment outcomes in public sector conditions. This study aimed to evaluate factors associated with ineffective treatment outcomes in patients with Multidrug-resistant Tuberculosis receiving outpatient care under the National Tuberculosis Elimination Programme in Puducherry, India, from January 2020 to December 2023. We employed multivariate regression methods to calculate odds ratios with 95% confidence intervals to identify factors linked to unsuccessful treatment outcomes. Clinical data from patients with Multidrug-resistant Tuberculosis revealed an overall treatment success rate of 60.42%. The findings showed that patients undergoing retreatment were more likely to experience unsuccessful outcomes. Additionally, co-infection with HIV, as well as the use of alcohol or tobacco, increased the odds of treatment failure. Patients with heteroresistant patterns had 2.72 times higher odds of unsuccessful treatment outcomes compared to those with inferred and true-resistant patterns. Furthermore, patients living in rural areas typically experienced worse treatment outcomes than those in urban areas, with higher rates of loss to follow-up. Patients on longer treatment regimens were also more likely to be lost to follow-up compared to those on shorter regimens. Notably, true resistance due to rpoB gene mutations accounted for 65.9% (29 out of 44) of total deaths, with mutations at codon S450L contributing to 47.7% of these fatalities, a finding that has not been reported elsewhere. The study highlighted a strong association between heteroresistance in the rpoB gene and poor treatment outcomes. These results emphasize the need for detailed molecular-level studies to improve treatment outcomes by ensuring appropriate drug selection for MDR/RR Tuberculosis. Additionally, further research is necessary to determine the impact of heteroresistance on treatment outcomes in individual patients.
提高耐多药结核病的治疗效果是全球结核病控制项目的一项主要优先事项。印度是全球耐多药结核病病例数最多的国家，但尚无纵向研究评估公共部门环境下影响治疗效果的因素。本研究旨在评估2020年1月至2023年12月在印度本地治里市国家结核病消除计划下接受门诊治疗的耐多药结核病患者中，与治疗效果不佳相关的因素。我们采用多变量回归方法计算比值比及95%置信区间，以确定与治疗失败相关的因素。耐多药结核病患者的临床数据显示总体治疗成功率为60.42%。研究结果表明，接受再次治疗的患者更有可能治疗失败。此外，合并感染艾滋病毒以及使用酒精或烟草会增加治疗失败的几率。与推断性耐药和真正耐药模式的患者相比，具有异质性耐药模式的患者治疗失败的几率高出2.72倍。此外，农村地区的患者通常比城市地区的患者治疗效果更差，失访率更高。与治疗方案较短的患者相比，治疗方案较长的患者也更有可能失访。值得注意的是，rpoB基因突变导致的真正耐药占总死亡人数的65.9%（44例中的29例），其中密码子S450L处的突变占这些死亡病例的47.7%，这一发现尚未在其他地方报道。该研究强调了rpoB基因异质性耐药与治疗效果不佳之间的密切关联。这些结果强调需要进行详细的分子水平研究，以通过确保为耐多药/利福平耐药结核病患者选择合适的药物来改善治疗效果。此外，有必要进一步研究以确定异质性耐药对个体患者治疗效果的影响。
