Whole genome sequencing of clinical samples reveals extensively drug resistant tuberculosis (XDR TB) strains from the Beijing lineage in Nigeria, West Africa

Idowu B Olawoye,Rosemary A Audu,Olabisi F Davies-Bolorunduro,Christian T Happi,Babatunde L Salako,Temitope A Abiodun,Chioma N Kunle-Ope,Jessica N Uwanibe

doi:10.1038/s41598-021-96956-7

Idowu B Olawoye, Rosemary A Audu + Show 6 more

Open Access

https://doi.org/10.1038/s41598-021-96956-7

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Abstract

Multi-drug (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) continues to be a global public health problem especially in high TB burden countries like Nigeria. Many of these cases are undetected and go on to infect high risk individuals. Clinical samples from positive rifampicin resistant Xpert®MTB/Rif assay were subjected to direct whole genome sequencing and bioinformatics analysis to identify the full antibiotics resistance and lineage profile. We report two (2) XDR TB samples also belonging to the East-Asian/Beijing family of lineage 2 Mycobacterium tuberculosis complex from clinical samples in Nigeria. Our findings further reveal the presence of mutations that confer resistance to first-line drugs (rifampicin, isoniazid, ethambutol and pyrazanimide), second-line injectables (capreomycin, streptomycin, kanamycin and/or amikacin) and at least one of the fluoroquinolones (ofloxacin, moxifloxacin, levofloxacin and/or ciprofloxacin) in both samples. The genomic sequence data from this study not only provide the first evidence of XDR TB in Nigeria and West Africa, but also emphasize the importance of WGS in accurately detecting MDR and XDR TB, to ensure adequate and proper management treatment regimens for affected individuals. This will greatly aid in preventing the spread of drug resistance TB in high burden countries.

Highlights

Mycobacterium tuberculosis complex (MTBC) which is responsible for tuberculosis (TB) remains a global public health concern especially in low-income countries as it is the leading cause of death from a bacterial infectious disease[1]
The updated definition of extensively drug-resistant TB (XDR TB) is a rare type of Multi-drug resistant TB (MDR TB) that is resistant to INH, RIF and any fluoroquinolone, and at least one additional Group A drug which are the most powerful second-line drugs used for drug resistant TB m anagement[15]
All samples (100%) tested positive to resistance to RIF using Xpert®MTB/Rif assay and 20% tested positive to resistance to INH and none of the samples tested positive to fluoroquinolones (FLQ) or second-line drug injectables using Hain Lifescience GenoType MTBDRplus and MTBDRsl line probe assays (Table 1)

Summary

Introduction

Mycobacterium tuberculosis complex (MTBC) which is responsible for tuberculosis (TB) remains a global public health concern especially in low-income countries as it is the leading cause of death from a bacterial infectious disease[1]. Just as many other West African countries, Nigeria has deployed rapid molecular techniques to detect RR-TB and MDR TB by using Xpert®MTB/Rif assay (Cephid, USA) and GenoType MTDRplus Line Probe Assay (Hain Lifescience GmbH, Germany)[18]. These techniques come with limitations when compared to whole genome sequencing (WGS), as the latter can detect drug resistant mutations outside the target zone of rapid tests and produce much more reliable and robust drug resistance profile of TB19.

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