Detection of I491F and V170F rpoB mutations associated with misdiagnosis of rifampicin resistance among patients with drug-susceptible tuberculosis treatment failure, Myanmar, 2022

Objective: Detecting rifampicin (RIF) resistance is crucial in selecting tuberculosis (TB) treatment. Recently, several studies reported that I491F and V170F rpoB mutations were found with a varying prevalence. This study aimed to find out RIF resistance missed by routine diagnostic assays using nex...

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Main Authors: Phyu Win Ei, Mi Mi Htwe, Myat Htut Nyunt, Aye Su Mon, Zaw Myint, Wint Wint Nyunt, Su Mon Win, Sandar Aung, Wai Myat Thwe, Wah Wah Aung
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Journal of Global Antimicrobial Resistance
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213716525000013
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author Phyu Win Ei
Mi Mi Htwe
Myat Htut Nyunt
Aye Su Mon
Zaw Myint
Wint Wint Nyunt
Su Mon Win
Sandar Aung
Wai Myat Thwe
Wah Wah Aung
author_facet Phyu Win Ei
Mi Mi Htwe
Myat Htut Nyunt
Aye Su Mon
Zaw Myint
Wint Wint Nyunt
Su Mon Win
Sandar Aung
Wai Myat Thwe
Wah Wah Aung
author_sort Phyu Win Ei
collection DOAJ
description Objective: Detecting rifampicin (RIF) resistance is crucial in selecting tuberculosis (TB) treatment. Recently, several studies reported that I491F and V170F rpoB mutations were found with a varying prevalence. This study aimed to find out RIF resistance missed by routine diagnostic assays using next generation genome sequencing tool. Methods: Sputum specimens from first-line TB treatment failed patients attending Tuberculosis Centers in Yangon Region during 2022 were cultured in solid media. Phenotypic drug susceptibility testing was conducted using Mycobacterial Growth Indicator Tube method. Whole genome or Deeplex-targeted next-generation sequencing was performed using Illumina Miseq. Mutation analysis was done by PhyResSE and SAM-TB online platforms. Results: A total of 32 culture-positive isolates with DNA qualified for genome sequencing were included in the study. Those were diagnosed as rifampicin-susceptible by routine GeneXpert and line probe assays. RIF resistance-conferring mutations were found in 17/32 (53.1%) Mycobacterium tuberculosis isolates; 14 (43.7%) had mutations outside the RIF resistance determining region (I491F and V170F), two (6.3%) were S450L, mutation within RIF resistance determining region, and one isolate (3.1%) with interim resistance mutations S428T and S441A. Conclusion: This study highlighted the presence of rifampicin-resistant TB strains missed by current diagnostic strategies, and are circulating as treatment-failed patients. This demonstrates a gap in current World Health Organization-endorsed algorithms for capturing all multidrug-resistant-TB strains.
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series Journal of Global Antimicrobial Resistance
spelling doaj-art-1a1bc7194edf440bb01fdfefdeb89bc12025-01-31T05:11:17ZengElsevierJournal of Global Antimicrobial Resistance2213-71652025-03-0141169172Detection of I491F and V170F rpoB mutations associated with misdiagnosis of rifampicin resistance among patients with drug-susceptible tuberculosis treatment failure, Myanmar, 2022Phyu Win Ei0Mi Mi Htwe1Myat Htut Nyunt2Aye Su Mon3Zaw Myint4Wint Wint Nyunt5Su Mon Win6Sandar Aung7Wai Myat Thwe8Wah Wah Aung9Department of Medical Research, Yangon, Republic of the Union of Myanmar; Corresponding author. Mailing address: Phyu Win Ei, Advanced Molecular Research Centre, No. 5, Ziwaka Rd, Dagon Tsp, 11191 Yangon, Myanmar.Department of Medical Research, Yangon, Republic of the Union of MyanmarDepartment of Medical Research, Yangon, Republic of the Union of MyanmarDepartment of Medical Research, Yangon, Republic of the Union of MyanmarNational Tuberculosis Program (Yangon Branch), Department of Public Health, Yangon, Republic of the Union of MyanmarNational TB Reference Laboratory, Yangon, Republic of the Union of MyanmarDepartment of Medical Research, Yangon, Republic of the Union of MyanmarDepartment of Medical Research, Yangon, Republic of the Union of MyanmarDepartment of Medical Research, Yangon, Republic of the Union of MyanmarDepartment of Medical Research, Yangon, Republic of the Union of MyanmarObjective: Detecting rifampicin (RIF) resistance is crucial in selecting tuberculosis (TB) treatment. Recently, several studies reported that I491F and V170F rpoB mutations were found with a varying prevalence. This study aimed to find out RIF resistance missed by routine diagnostic assays using next generation genome sequencing tool. Methods: Sputum specimens from first-line TB treatment failed patients attending Tuberculosis Centers in Yangon Region during 2022 were cultured in solid media. Phenotypic drug susceptibility testing was conducted using Mycobacterial Growth Indicator Tube method. Whole genome or Deeplex-targeted next-generation sequencing was performed using Illumina Miseq. Mutation analysis was done by PhyResSE and SAM-TB online platforms. Results: A total of 32 culture-positive isolates with DNA qualified for genome sequencing were included in the study. Those were diagnosed as rifampicin-susceptible by routine GeneXpert and line probe assays. RIF resistance-conferring mutations were found in 17/32 (53.1%) Mycobacterium tuberculosis isolates; 14 (43.7%) had mutations outside the RIF resistance determining region (I491F and V170F), two (6.3%) were S450L, mutation within RIF resistance determining region, and one isolate (3.1%) with interim resistance mutations S428T and S441A. Conclusion: This study highlighted the presence of rifampicin-resistant TB strains missed by current diagnostic strategies, and are circulating as treatment-failed patients. This demonstrates a gap in current World Health Organization-endorsed algorithms for capturing all multidrug-resistant-TB strains.http://www.sciencedirect.com/science/article/pii/S2213716525000013Rifampicin resistant TBrpoB mutationI491FV170FTreatment failureMyanmar
spellingShingle Phyu Win Ei
Mi Mi Htwe
Myat Htut Nyunt
Aye Su Mon
Zaw Myint
Wint Wint Nyunt
Su Mon Win
Sandar Aung
Wai Myat Thwe
Wah Wah Aung
Detection of I491F and V170F rpoB mutations associated with misdiagnosis of rifampicin resistance among patients with drug-susceptible tuberculosis treatment failure, Myanmar, 2022
Journal of Global Antimicrobial Resistance
Rifampicin resistant TB
rpoB mutation
I491F
V170F
Treatment failure
Myanmar
title Detection of I491F and V170F rpoB mutations associated with misdiagnosis of rifampicin resistance among patients with drug-susceptible tuberculosis treatment failure, Myanmar, 2022
title_full Detection of I491F and V170F rpoB mutations associated with misdiagnosis of rifampicin resistance among patients with drug-susceptible tuberculosis treatment failure, Myanmar, 2022
title_fullStr Detection of I491F and V170F rpoB mutations associated with misdiagnosis of rifampicin resistance among patients with drug-susceptible tuberculosis treatment failure, Myanmar, 2022
title_full_unstemmed Detection of I491F and V170F rpoB mutations associated with misdiagnosis of rifampicin resistance among patients with drug-susceptible tuberculosis treatment failure, Myanmar, 2022
title_short Detection of I491F and V170F rpoB mutations associated with misdiagnosis of rifampicin resistance among patients with drug-susceptible tuberculosis treatment failure, Myanmar, 2022
title_sort detection of i491f and v170f rpob mutations associated with misdiagnosis of rifampicin resistance among patients with drug susceptible tuberculosis treatment failure myanmar 2022
topic Rifampicin resistant TB
rpoB mutation
I491F
V170F
Treatment failure
Myanmar
url http://www.sciencedirect.com/science/article/pii/S2213716525000013
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