Evidence map›Paper›PMID 33239092›Full record

ArticleGenome medicine2020

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

Patrick Beckert, Elisabeth Sanchez-Padilla, Matthias Merker, Viola Dreyer, Thomas A Kohl, Christian Utpatel, Claudio U Köser, Ivan Barilar, Nazir Ismail, Shaheed Vally Omar and 13 more

Open access · goldAbstract read
In one paragraph

Article in Genome medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

53 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.

  1. Pooled it
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  6. Transmission of bedaquiline-resistant Mycobacterium tuberculosis in KwaZulu-Natal, South Africa.American journal of respiratory and critical care medicine · 2026
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  14. Letter to the Editor: First detection of aEuro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2024
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  17. First detection of aEuro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 12 institutions in 7 countries.

Patrick BeckertMolecular and Experimental Mycobacteriology, Research Center Borstel, Parkallee 1, 23845, Borstel, Germany.
Elisabeth Sanchez-PadillaEpicentre, Paris, France.
Matthias MerkerMolecular and Experimental Mycobacteriology, Research Center Borstel, Parkallee 1, 23845, Borstel, Germany.
Viola DreyerMolecular and Experimental Mycobacteriology, Research Center Borstel, Parkallee 1, 23845, Borstel, Germany.
Thomas A KohlMolecular and Experimental Mycobacteriology, Research Center Borstel, Parkallee 1, 23845, Borstel, Germany.
Christian UtpatelMolecular and Experimental Mycobacteriology, Research Center Borstel, Parkallee 1, 23845, Borstel, Germany.
Claudio U KöserDepartment of Genetics, University of Cambridge, Cambridge, UK.
Ivan BarilarMolecular and Experimental Mycobacteriology, Research Center Borstel, Parkallee 1, 23845, Borstel, Germany.
Nazir IsmailCentre for Tuberculosis, National TB Reference Laboratory, WHO TB Supranational Laboratory Network, National Institute for Communicable Diseases/National Health Laboratory Services, Johannesburg, South Africa.
Shaheed Vally OmarCentre for Tuberculosis, National TB Reference Laboratory, WHO TB Supranational Laboratory Network, National Institute for Communicable Diseases/National Health Laboratory Services, Johannesburg, South Africa.
Marisa KlopperDST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Robin M WarrenDST/NRF Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
Harald HoffmannSYNLAB Gauting, Gauting, Germany, IML red GmbH, Institute of Microbiology and Laboratory Medicine, WHO Supranational Reference Laboratory of TB, Gauting, Germany.
Gugu MaphalalaNational Tuberculosis Reference Laboratory (NTRL), Ministry of Health, Mbabane, Swaziland.
Elisa ArdizzoniMycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Bouke C de JongMycobacteriology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine, Antwerp, Belgium.
Bernhard KerschbergerMédecins Sans Frontières (MSF) - Eswatini, Mbabane, Eswatini.
Birgit SchrammEpicentre, Paris, France.
Sönke AndresNational and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany.
Katharina KranzerNational and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany.
Florian P MaurerNational and WHO Supranational Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany.
Maryline BonnetEpicentre, Paris, France.
Stefan NiemannMolecular and Experimental Mycobacteriology, Research Center Borstel, Parkallee 1, 23845, Borstel, Germany. sniemann@fz-borstel.de.ORCID 0000-0002-6604-0684
Research Center Borstel - Leibniz Lung Center · DEInstituut voor Tropische Geneeskunde · BENational Health Laboratory Service · ZASouth African Medical Research Council · ZAGerman Center for Infection Research · DEInserm · FRMinistry of Health · SZSouthern Africa Nazarene University · SZUniversität Hamburg · DEUniversity of Cambridge · GBUniversity of London · GBUniversity of Namibia · NA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundMultidrug-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.

methodsWe 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).

resultsMDR 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.

conclusionThe 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.

Indexed as

Antitubercular AgentsBacterial ProteinsClone CellsDiarylquinolinesDisease OutbreaksEswatiniHumansMicrobial Sensitivity TestsMutationMycobacterium tuberculosisTuberculosis, Multidrug-ResistantAntitubercular AgentsBacterial ProteinsbedaquilineDiarylquinolinesDiagnostice escapeMDR outbreak strainsMultidrug resistanceResistance evolutionTreatment escapeTreatment failureTuberculosis

Identifiers

PMID33239092
PMCPMC7687760
OpenAlexW3108748143

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.