• Login
    View Item 
    •   Home
    • 1 Published Research and Commentary
    • TB
    • View Item
    •   Home
    • 1 Published Research and Commentary
    • TB
    • View Item
    Mar 04, 2021
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of MSFTitleAuthorsSubjectsPublisherJournalThis CollectionTitleAuthorsSubjectsPublisherJournal

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

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Beckert et al 2020 MDR M. ...
    Size:
    1.295Mb
    Format:
    PDF
    Download
    Authors
    Beckert, P
    Sanchez-Padilla, E
    Merker, M
    Dreyer, V
    Kohl, TA
    Utpatel, C
    Koser, CU
    Barilar, I
    Ismail, N
    Omar, SV
    Klopper, M
    Warren, RM
    Hoffmann, H
    Maphalala, G
    Ardizzoni, E
    de Jong, BC
    Kerschberger, B
    Schramm, B
    Andres, S
    Kranzer, K
    Maurer, FP
    Bonnet, M
    Niemann, S
    Show allShow less
    Issue Date
    2020-11-25
    Submitted date
    2021-01-14
    
    Metadata
    Show full item record
    Journal
    Genome Medicine
    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.
    Publisher
    BMC
    URI
    http://hdl.handle.net/10144/619835
    Language
    en
    Collections
    TB

    entitlement

     
    DSpace software (copyright © 2002 - 2021)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.