Agonafir Mulualem, Belay Gurja, Feleke Adey, Maningi Nontuthuko, Girmachew Feven, Reta Melese, Fourie P Bernard
Department of Microbial, Cellular and Molecular Biology, College of Natural and Computational Sciences, Addis Ababa University, Addis Ababa, Ethiopia.
Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa.
Infect Drug Resist. 2023 May 12;16:2953-2961. doi: 10.2147/IDR.S408567. eCollection 2023.
Advances in molecular tools that assess genes harboring drug resistance mutations have greatly improved the detection and treatment of drug-resistant tuberculosis (DR-TB). This study was conducted to determine the frequency and type of mutations that are responsible for resistance to rifampicin (RIF), isoniazid (INH), fluoroquinolones (FLQs) and second-line injectable drugs (SLIDs) in (MTB) isolates obtained from culture-positive pulmonary tuberculosis (TB) patients in the central, southeastern and eastern Ethiopia.
In total, 224 stored culture-positive MTB isolates from pulmonary TB patients referred to Adama and Harar regional TB laboratories between August 2018 and January 2019 were assessed for mutations conferring RIF, INH, FLQs and SLIDs resistance using GenoTypeMTBDRplus (MTBDRplus) and GenoTypeMTBDRsl (MTBDRsl).
RIF, INH, FLQs and SLIDs resistance-conferring mutations were identified in 88/224 (39.3%), 85/224 (38.0%), 7/77 (9.1%), and 3/77% (3.9%) of MTB isolates, respectively. Mutation codons S531L (59.1%) for RIF, S315T (96.5%) for INH, A90V (42.1%) for FLQs and WT1 (100%) for SLIDs were observed in the majority of the isolates tested. Over a 10th of mutations detected in the current study were unknown.
In this study, the most common mutations conferring drug resistance to RIF, INH, FLQs were identified. However, a significant proportion of RIF-resistant isolates manifested unknown mutations. Similarly, although few in number, all SLID-resistant isolates had unknown mutations. To further elucidate the entire spectrum of mutations, tool such as whole-genome sequencing is imperative. Furthermore, the expansion of molecular drug susceptibility testing services is critical for tailoring patient treatment and preventing disease transmission.
评估携带耐药性突变基因的分子工具的进展极大地改善了耐多药结核病（DR-TB）的检测和治疗。本研究旨在确定从埃塞俄比亚中部、东南部和东部的痰涂片阳性肺结核（TB）患者中分离出的结核分枝杆菌（MTB）菌株中，对利福平（RIF）、异烟肼（INH）、氟喹诺酮类（FLQs）和二线注射药物（SLIDs）耐药的突变频率和类型。
对2018年8月至2019年1月期间转诊至阿达马和哈勒尔地区结核病实验室的痰涂片阳性肺结核患者的224株保存的MTB菌株，使用GenoTypeMTBDRplus（MTBDRplus）和GenoTypeMTBDRsl（MTBDRsl）评估其对RIF、INH、FLQs和SLIDs耐药的突变情况。
分别在88/224（39.3%）、85/224（38.0%）、7/77（9.1%）和3/77（3.9%）的MTB菌株中鉴定出赋予RIF、INH、FLQs和SLIDs耐药的突变。在大多数检测的菌株中观察到RIF的S531L突变密码子（59.1%）、INH的S315T突变密码子（96.5%）、FLQs的A90V突变密码子（42.1%）和SLIDs的WT1突变密码子（100%）。本研究中检测到的超过十分之一的突变是未知的。
在本研究中，确定了赋予对RIF、INH、FLQs耐药的最常见突变。然而，相当一部分耐RIF菌株表现出未知突变。同样，虽然数量很少，但所有耐SLID菌株都有未知突变。为了进一步阐明突变的全谱，全基因组测序等工具势在必行。此外，扩大分子药敏试验服务对于定制患者治疗和预防疾病传播至关重要。
