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Original article
Extensive global movement of multidrug-resistant M. tuberculosis strains revealed by whole-genome analysis
  1. Keira A Cohen1,
  2. Abigail L Manson2,
  3. Thomas Abeel2,3,
  4. Christopher A Desjardins2,
  5. Sinead B Chapman2,
  6. Sven Hoffner4,
  7. Bruce W Birren2,
  8. Ashlee M Earl2
  1. 1 Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  2. 2 Broad Institute of Harvard and M.I.T, Cambridge, Massachusetts, USA
  3. 3 Delft Bioinformatics Lab, Technische Universiteit Delft Faculteit Technische Natuurwetenschappen, Delft, Netherlands
  4. 4 Department of Public Health Sciences, Karolinska Institute, Stockholm, Sweden
  1. Correspondence to Dr Ashlee M Earl, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; aearl{at}broadinstitute.org

Abstract

Background While the international spread of multidrug-resistant (MDR) Mycobacterium tuberculosis strains is an acknowledged public health threat, a broad and more comprehensive examination of the global spread of MDR-tuberculosis (TB) using whole-genome sequencing has not yet been performed.

Methods In a global dataset of 5310 M. tuberculosis whole-genome sequences isolated from five continents, we performed a phylogenetic analysis to identify and characterise clades of MDR-TB with respect to geographic dispersion.

Results Extensive international dissemination of MDR-TB was observed, with identification of 32 migrant MDR-TB clades with descendants isolated in 17 unique countries. Relatively recent movement of strains from both Beijing and non-Beijing lineages indicated successful global spread of varied genetic backgrounds. Migrant MDR-TB clade members shared relatively recent common ancestry, with a median estimate of divergence of 13–27 years. Migrant extensively drug-resistant (XDR)-TB clades were not observed, although development of XDR-TB within migratory MDR-TB clades was common.

Conclusions Application of genomic techniques to investigate global MDR migration patterns revealed extensive global spread of MDR clades between countries of varying TB burden. Further expansion of genomic studies to incorporate isolates from diverse global settings into a single analysis, as well as data sharing platforms that facilitate genomic data sharing across country lines, may allow for future epidemiological analyses to monitor for international transmission of MDR-TB. In addition, efforts to perform routine whole-genome sequencing on all newly identified M. tuberculosis, like in England, will serve to better our understanding of the transmission dynamics of MDR-TB globally.

  • tuberculosis
  • clinical epidemiology

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Footnotes

  • Contributors This study was designed and conducted by KAC, ALM and AE. Analysed the data: KAC, ALM, TA and CAD. Interpreted results: KAC, ALM. Wrote the manuscript: KAC, ALM, AE. Involved in sample acquisition and handling, including oversight of these activities: AME, BWB, SH, SBC. All authors have read the manuscript and confirm that they meet ICMJE criteria for authorship.

  • Funding National Institute of Allergy and Infectious Diseases Contract No: HHSN272200900018C and Grant Number U19AI110818 to ALM, TA, CAD, BWB, AE; National Heart, Blood, and Lung Institute T32HL007633 and K08HL139994 to KAC and Burroughs Wellcome Fund Career Award for Medical Scientists to KAC. This research used infrastructure resources from the Broad Institute, the Delft University of Technology, Internet2 and SURFnet (the Dutch research and education network), supported under the Enlighten Your Research Global program.

  • Disclaimer The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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