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

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dc.contributor.authorBeckert, Patricken_ZA
dc.contributor.authorSanchez-Padilla, Elisabethen_ZA
dc.contributor.authorMerker, Matthiasen_ZA
dc.contributor.authorDreyer, Violaen_ZA
dc.contributor.authorKohl, Thomas A.en_ZA
dc.contributor.authorUtpatel, Christianen_ZA
dc.contributor.authorKoser, Claudio U.en_ZA
dc.contributor.authorBarilar, Ivanen_ZA
dc.contributor.authorIsmail, Naziren_ZA
dc.contributor.authorOmar, Shaheed V.en_ZA
dc.contributor.authorKlopper, Marisaen_ZA
dc.contributor.authorWarren, Robin M.en_ZA
dc.contributor.authorHoffmann, Haralden_ZA
dc.contributor.authorMaphalala, Guguen_ZA
dc.contributor.authorArdizzoni, Elisaen_ZA
dc.contributor.authorDe Jong, Bouke C.en_ZA
dc.contributor.authorKerschberger, Bernharden_ZA
dc.contributor.authorSchramm, Birgiten_ZA
dc.contributor.authorAndres, Sonkeen_ZA
dc.contributor.authorKranzer, Katharinaen_ZA
dc.contributor.authorMaurer, Florian P.en_ZA
dc.contributor.authorBonnet, Marylineen_ZA
dc.contributor.authorNiemann, Stefanen_ZA
dc.date.accessioned2021-04-29T10:21:24Z
dc.date.available2021-04-29T10:21:24Z
dc.date.issued2020-11-25
dc.date.updated2020-11-29T06:30:05Z
dc.descriptionCITATION: Beckert, P., et al. 2020. MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era. Genome Medicine, 12:104, doi:10.1186/s13073-020-00793-8.
dc.descriptionThe original publication is available at https://genomemedicine.biomedcentral.com
dc.description.abstractBackground: 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.en_ZA
dc.description.urihttps://genomemedicine.biomedcentral.com/articles/10.1186/s13073-020-00793-8
dc.description.versionPublisher's version
dc.format.extent11 pages
dc.identifier.citationBeckert, P., et al. 2020. MDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment era. Genome Medicine, 12:104, doi:10.1186/s13073-020-00793-8
dc.identifier.issn1756-994X (online)
dc.identifier.otherdoi:10.1186/s13073-020-00793-8
dc.identifier.urihttp://hdl.handle.net/10019.1/110368
dc.language.isoen_ZAen_ZA
dc.publisherBMC
dc.rights.holderAuthors retain copyright
dc.subjectMultidrug-resistant tuberculosis -- Prevention -- Eswatinien_ZA
dc.subjectMultidrug-resistant tuberculosis -- Diagnosis -- Eswatinien_ZA
dc.subjectGenomes -- Effect of drugs onen_ZA
dc.subjectWhole genome sequencingen_ZA
dc.subjectGene-Xpert tuberculosis testen_ZA
dc.titleMDR M. tuberculosis outbreak clone in Eswatini missed by Xpert has elevated bedaquiline resistance dated to the pre-treatment eraen_ZA
dc.typeArticle
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