Mamuda Kasimu, Aliyu Muhammad Sani, Suleman Mikailu, Ibrahim Abba Kasim, Maifada Asmau Ibrahim, Song Abubakar Mohammed, Garba Bala Yazeed, Aminu Dalhatu Abdullahi, Dan-Inna Muhammad Zaharaden, Jiya-Chitumu Eunice Nnaisa, Abdullahi Idris Nasir
National Tuberculosis and Leprosy Training Center, Zaria, Nigeria.
Department of Microbiology, Faculty of Life Sciences, Ahmadu Bello University, Zaria, Nigeria.
Acta Trop. 2025 Sep;269:107748. doi: 10.1016/j.actatropica.2025.107748. Epub 2025 Jul 17.
The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) is a critical-priority global health problem that requires molecular-based surveillance to understand its extent of transmission.
Sputa from 360 patients with pulmonary symptoms were collected and processed for culture and microscopy for Mycobacterium tuberculosis (MTB). Samples were confirmed positive for MTB by immunochromatographic test kits. The GenoType MTBDRplus was used to detect mutations in the rpoB, katG, and inhA promoters, which are responsible for rifampicin and isoniazid resistance.
Of the samples analyzed, 65.6% were confirmed MTB positive, while 48.9% had MDR-TB (both rifampicin and isoniazid resistant). Of the patients with MDR-TB, those aged > 60 years (54.3%), those with a tertiary education level (53.9%), and civil servants (68.4%) had the highest frequency of MDR-TB. Patients with a history of TB (68.3%), cigarette smokers (74.2%), those who consume alcohol (80.7%), diabetic mellitus (53.9%), those who had contact with TB patients (66.7%) had significantly high odds of MDR-TB (Odd Ratio range: 2.55-4.87, p < 0.05). MTBDRplus detected 144 (81.8%) of 176 culture-confirmed MDR-TB strains, of which 59.7%, 10.4%, and 9% point mutations in MUT3 (S531L), MUT2B (H526D), and MUT2A (H526Y), respectively, were found in the rpoB gene. Moreover, missing W8 (530-533), W6 (521-525), and W3 (513-517) were detected in 15.3%, 2.7% and 2.7% of rpoB gene, respectively. Furthermore, 55.6% and 33.3% mutations on the katG at MUT1 (S315T) and inhA MUT1 (C15T), conferring high-level isoniazid resistance and low-level isoniazid resistance among MDR-TB isolates.
Findings from this study revealed a high frequency and risk factors of MDR-TB mediated by multiple mutations in the rpoB gene and a relatively lesser frequency of mutations in the katG and inhA genes among the MTB isolates obtained from infected patients in the study area.
耐多药结核病（MDR-TB）的出现和传播是一个全球卫生重点问题，需要基于分子的监测来了解其传播程度。
收集360例有肺部症状患者的痰液，进行结核分枝杆菌（MTB）培养和显微镜检查。通过免疫层析检测试剂盒确认样本MTB呈阳性。使用GenoType MTBDRplus检测rpoB、katG和inhA启动子中的突变，这些突变与利福平及异烟肼耐药有关。
在分析的样本中，65.6%被确认为MTB阳性，而48.9%为耐多药结核病（对利福平和异烟肼均耐药）。在耐多药结核病患者中，年龄>60岁者（54.3%）、受过高等教育者（53.9%）和公务员（68.4%）耐多药结核病发生率最高。有结核病病史者（68.3%）、吸烟者（74.2%）、饮酒者（80.7%）、糖尿病患者（53.9%）、与结核病患者有接触者（66.7%）患耐多药结核病的几率显著较高（比值比范围：2.55 - 4.87，p<0.05）。MTBDRplus在176株培养确诊的耐多药结核菌株中检测到144株（81.8%），其中rpoB基因中分别有59.7%、10.4%和9%的点突变发生在MUT3（S531L）、MUT2B（H526D）和MUT2A（H526Y）。此外，分别在15.3%、2.7%和2.7%的rpoB基因中检测到缺失W8（530 - 533）、W6（521 - 525）和W3（513 - 517）。此外，耐多药结核分枝杆菌分离株中katG基因MUT1（S315T）和inhA基因MUT1（C15T）的突变分别导致高水平异烟肼耐药和低水平异烟肼耐药，发生率分别为55.6%和33.3%。
本研究结果显示，在研究区域感染患者的MTB分离株中，rpoB基因多重突变介导的耐多药结核病发生率较高，而katG和inhA基因的突变频率相对较低。
