Seid Aynias, Berhane Nega, Nureddin Semira
Department of Medical Biotechnology, Institute of Biotechnology, University of Gondar, Gondar, Ethiopia.
Department of Biology, Faculty of Natural and Computational Science, Debre-Tabor University, Debre-Tabor, Ethiopia.
Interdiscip Perspect Infect Dis. 2022 Jun 16;2022:1967675. doi: 10.1155/2022/1967675. eCollection 2022.
Tuberculosis (TB) is one of the top 10 causes of mortality and the first killer among infectious diseases of poverty (IDoPs) worldwide. It disproportionately affects on-third of the world's low-income countries including Ethiopia. One of the factors driving the TB epidemic is the global rise of MDR/XDR-TB and their low detection affect the global TB control progress. Recently, the resistance-associated genetic mutations in MTBC known to confer drug resistance have been detected by rapid molecular diagnostic tests and sequencing methods. In this article, the published literature searched by PubMed database from 2010 to 2021 and English language were considered. The aim of this systematic review was to assess the prevalence of the most common rpoB, katG, and inhA gene mutations associated with multidrug resistance in MTBC clinical strains among TB patients in Ethiopia. Though 22 studies met our eligibility criteria, only 6 studies were included in the final analysis. Using the molecular GenoType MTBDRplus and MTBDRsl line probe assay and sequencing procedures, a total of 932 culture-positive MTBC isolates were examined to determine RIF, INH, and MDR-TB resistance patterns along with rpoB, katG, and inhA gene mutation analysis. As a result, among the genotypically tested MTBC isolates, 119 (12.77%), 83 (8.91%), and 73 (7.32%) isolates were INH, RIF, and MDR-TB resistant, respectively. In any RIF-resistant MTBC strains, the most common single point mutations were in codon 531 (S531L) followed by codon 526 (H526Y) of the rpoB gene. Besides, the most common mutations in any INH-resistant MTBC were strains observed at codon 315 (S315T) and WT probe in the katG gene and at codon C15T and WT1 probe in the inhA promoter region. Detection of resistance allele in rpoB, KatG, and inhA genes for RIF and INH could serve as a marker for MDR-TB strains. Tracking the most common S531L, S315T, and C15T mutations in rpoB, katG, and inhA genes among RIF- and INH-resistant isolates would be valuable in TB diagnostics and treatment regimens, and could reduce the development and risk of MDR/XDR-TB drug-resistance patterns.
结核病（TB）是全球十大死因之一，也是全球贫困相关传染病（IDoPs）中的头号杀手。它对包括埃塞俄比亚在内的世界三分之一低收入国家造成了尤为严重的影响。耐多药/广泛耐药结核病（MDR/XDR-TB）在全球范围内的增加及其低检出率是推动结核病流行的因素之一，影响了全球结核病控制进程。最近，通过快速分子诊断测试和测序方法已经检测到结核分枝杆菌复合群（MTBC）中已知赋予耐药性的与耐药相关的基因突变。在本文中，考虑了通过PubMed数据库搜索到的2010年至2021年发表的英文文献。本系统评价的目的是评估埃塞俄比亚结核病患者MTBC临床菌株中与耐多药相关的最常见rpoB、katG和inhA基因突变的流行情况。虽然有22项研究符合我们设定的标准，但最终分析仅纳入了6项研究。使用分子GenoType MTBDRplus和MTBDRsl线性探针分析及测序程序，共检测了932株培养阳性的MTBC分离株，以确定利福平（RIF）、异烟肼（INH）和耐多药结核病的耐药模式以及rpoB、katG和inhA基因突变分析。结果，在进行基因分型检测的MTBC分离株中，分别有119株（12.77%）、83株（8.91%）和73株（7.32%）对INH、RIF和耐多药结核病耐药。在任何耐RIF的MTBC菌株中，最常见的单点突变位于rpoB基因的第531密码子（S531L），其次是第526密码子（H526Y）。此外，在任何耐INH的MTBC菌株中，最常见的突变见于katG基因的第315密码子（S315T）和野生型探针，以及inhA启动子区域的第C15T密码子和野生型1探针。检测rpoB、KatG和inhA基因中RIF和INH的耐药等位基因可作为耐多药结核菌株的标志物。追踪耐RIF和耐INH分离株中rpoB、katG和inhA基因中最常见的S531L、S315T和C15T突变，对于结核病的诊断和治疗方案具有重要价值，并可降低MDR/XDR-TB耐药模式的发生和风险。
