Frequency and patterns of first- and second-line drug resistance-conferring mutations in Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients in a cross-sectional study in Tigray Region, Ethiopia

Letemichael Negash Welekidan,Eystein Skjerve,Tsehaye Asmelash Dejene,Mengistu Welday Gebremichael,Ola Brynildsrud,Tone Tønjum,Solomon Abebe Yimer

doi:10.1016/j.jgar.2020.11.017

Abstract

ObjectivesTuberculosis (TB) is a preventable and treatable infectious disease, but the continuing emergence and spread of multidrug-resistant TB is threatening global TB control efforts. This study aimed to describe the frequency and patterns of drug resistance-conferring mutations of Mycobacterium tuberculosis (MTB) isolates detected from pulmonary TB patients in Tigray Region, Ethiopia. MethodsA cross-sectional study design was employed to collect sputum samples from pulmonary TB patients between July 2018 to August 2019. Culture and identification tests were done at Tigray Health Research Institute (THRI). Mutations conferring rifampicin (RIF), isoniazid (INH) and fluoroquinolone (FQ) resistance were determined in 227 MTB isolates using GenoType MTBDRplus and GenoType MTBDRsl. ResultsMutations conferring resistance to RIF, INH and FQs were detected in 40/227 (17.6%), 41/227 (18.1%) and 2/38 (5.3%) MTB isolates, respectively. The majority of mutations for RIF, INH and FQs occurred at codons rpoB S531L (70%), katG S315T (78%) and gyrA D94Y/N (100%), respectively. This study revealed a significant number of unknown mutations in the rpoB, katG and inhA genes. ConclusionHigh rates of mutations conferring resistance to RIF, INH and FQs were observed in this study. A large number of isolates showed unknown mutations, which require further DNA sequencing analysis. Periodic drug resistance surveillance and scaling-up of drug resistance testing facilities are imperative to prevent the transmission of drug-resistant TB in the community.

Highlights

Tuberculosis (TB) is a preventable and treatable infectious disease
This study aimed to describe the frequency and patterns of drug resistance-conferring mutations of Mycobacterium tuberculosis (MTB) isolates detected from pulmonary TB patients in Tigray Region, Ethiopia
The finding is in contrast to several other study reports. Double mutations at both katG and inhA regulatory regions in the same isolate were found in studies conducted at St Peter’s TB Specialized Hospital, Addis Ababa, Ethiopia (2%) [16], South India (0.1%) [28] and Shanghai, China (1.1%) [31]. These findings suggest that genetic strain background may influence the level of INH resistance conferred by particular mutations: MTB lineage 2 (Beijing genotype) was associated with any drug resistance and lineage 1 was associated with inhA promoter codon C15T mutations [34]

Summary

Introduction

Tuberculosis (TB) is a preventable and treatable infectious disease. The continuing emergence and spread of multidrug-resistant TB (MDR-TB) is threatening global TB control efforts. Among the 10 million incident TB cases reported in 2018, some 484 000 patients had rifampicin-resistant TB (RR-TB), and of these 78% were MDR-TB, defined as resistance to at least isoniazid (INH) and rifampicin (RIF), the two most potent first-line anti-TB drugs [1]. Among the reported MDR-TB cases in 2018, 6.2% were estimated to be extensively drug-resistant TB (XDR-TB) [1]. Ethiopia is one of the 14 high TB, TB/HIV and MDR-TB burden countries with incident TB, MDR/RR-TB cases and overall TB deaths of 165 000, 1600 and 26 200, respectively, in the year 2018 [1]

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