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MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era.

Authors :
Beckert, Patrick
Sanchez-Padilla, Elisabeth
Merker, Matthias
Dreyer, Viola
Kohl, Thomas A.
Utpatel, Christian
Köser, Claudio U.
Barilar, Ivan
Ismail, Nazir
Omar, Shaheed Vally
Klopper, Marisa
Warren, Robin M.
Hoffmann, Harald
Maphalala, Gugu
Ardizzoni, Elisa
de Jong, Bouke C.
Kerschberger, Bernhard
Schramm, Birgit
Andres, Sönke
Kranzer, Katharina
Source :
Genome Medicine. 11/25/2020, Vol. 12 Issue 1, pN.PAG-N.PAG. 1p.
Publication Year :
2020

Abstract

Background: Multidrug-resistant (MDR) Mycobacterium tuberculosis complex strains not detected by commercial molecular drug susceptibility testing (mDST) assays due to the RpoB I491F resistance mutation are threatening the control of MDR tuberculosis (MDR-TB) in Eswatini. Methods: We investigate the evolution and spread of MDR strains in Eswatini with a focus on bedaquiline (BDQ) and clofazimine (CFZ) resistance using whole-genome sequencing in two collections ((1) national drug resistance survey, 2009–2010; (2) MDR strains from the Nhlangano region, 2014–2017). Results: MDR strains in collection 1 had a high cluster rate (95%, 117/123 MDR strains) with 55% grouped into the two largest clusters (gCL3, n = 28; gCL10, n = 40). All gCL10 isolates, which likely emerged around 1993 (95% highest posterior density 1987–1998), carried the mutation RpoB I491F that is missed by commercial mDST assays. In addition, 21 (53%) gCL10 isolates shared a Rv0678 M146T mutation that correlated with elevated minimum inhibitory concentrations (MICs) to BDQ and CFZ compared to wild type isolates. gCL10 isolates with the Rv0678 M146T mutation were also detected in collection 2. Conclusion: The high clustering rate suggests that transmission has been driving the MDR-TB epidemic in Eswatini for three decades. The presence of MDR strains in Eswatini that are not detected by commercial mDST assays and have elevated MICs to BDQ and CFZ potentially jeopardizes the successful implementation of new MDR-TB treatment guidelines. Measures to limit the spread of these outbreak isolates need to be implemented urgently. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
1756994X
Volume :
12
Issue :
1
Database :
Academic Search Index
Journal :
Genome Medicine
Publication Type :
Academic Journal
Accession number :
147198951
Full Text :
https://doi.org/10.1186/s13073-020-00793-8