A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study - 26/03/18

Doi : 10.1016/S1473-3099(18)30004-5

Timothy M Walker, MRCP ^a,^{^{*
Contributed equally}}, Matthias Merker, PhD ^h,^{^{*
Contributed equally}}, Astrid M Knoblauch, PhD ^b,^{^{*
Contributed equally}}, Peter Helbling, MD ^c, Otto D Schoch, ProfMD ^d, Marieke J van der Werf, PhD ^e, Katharina Kranzer, MD ⁱ, Lena Fiebig, PhD ^j, Stefan Kröger, PhD ^j, Walter Haas, ProfMD ^j, Harald Hoffmann, MD ^k, Alexander Indra, MD ^l, Adrian Egli, MD ^m,ⁿ, Daniela M Cirillo, MD ^o, Jérôme Robert, ProfMD ^p, Thomas R Rogers, ProfDMed ^q,^r, Ramona Groenheit, PhD ^s, Anne T Mengshoel, MD ^t, Vanessa Mathys, PhD ^u, Marjo Haanperä, PhD ^v,^w, Dick van Soolingen, ProfPhD ^f,^g, Stefan Niemann, ProfDSc ^h,^{^{†
Contributed equally}}, Erik C Böttger, ProfMD ^x,^{^{†
Contributed equally}}, Peter M Keller, MD ^x,^⁎,^{^{†
Contributed equally}}
and the
MDR-TB Cluster Consortium^{^‡}
Members listed at the end of the paper

Korkut Avsar, Christoph Bauer, Enos Bernasconi, Emanuele Borroni, Sergio Brusin, Mireia Coscollá Dévis, Derrick W. Crook, Martin Dedicoat, Margaret Fitzgibbon, Sébastien Gagneux, Francisca Geiger, Jean-Paul Guthmann, David Hendrickx, Sabine Hoffmann-Thiel, Jakko van Ingen, Sarah Jackson, Katia Jaton, Christoph Lange, Jessica Mazza Stalder, Joan O’Donnell, Onya Opota, Tim E.A. Peto, Benjamin Preiswerk, Emma Roycroft, Mariko Sato, Regina Schacher, Bettina Schulthess, E. Grace Smith, Hanna Soini, Wladimir Sougakoff, Elisa Tagliani, Christian Utpatel, Nicolas Veziris, Christiane Wagner-Wiening, Mark Witschi

^a Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK

^b Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland

^c Division of Communicable Diseases, Federal Office of Public Health, Bern, Switzerland

^d University of Zurich and Tuberculosis Center of the Swiss Lung Association, Zurich, Switzerland

^e European Centre for Disease Prevention and Control, Solna, Sweden

^f National Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment, Bilthoven, Netherlands

^g Center for Infectious Disease Research, Diagnostics and Perinatal Screening, Center for Infectious Disease Research, Diagnostics and Perinatal Screening, Bilthoven, Netherlands

^h Molecular and Experimental Mycobacteriology, Research Center Borstel, Borstel, Germany

ⁱ National Reference Center for Mycobacteria, Research Center Borstel, Borstel, Germany

^j Respiratory Infections Unit, Department of Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany

^k SYNLAB Gauting and Institute of Microbiology and Laboratory Medicine, World Health Organization Supranational Reference Laboratory of Tuberculosis, Munich-Gauting, Germany

^l Austrian Reference Laboratory for Mycobacteria, Austrian Agency for Health and Food Safety, Vienna, Austria

^m Clinical Microbiology, University Hospital Basel, Basel, Switzerland

ⁿ Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland

^o Emerging Bacterial Pathogens Unit, Division of Immunology and Infectious Diseases, San Raffaele Scientific Institute, San Raffaele Hospital, Milan, Italy

^p Assistance publique-Hôpitaux de Paris, Centre National de Référence de Mycobactéries et de la Résistance des Mycobactéries aux Antituberculeux, Bactériologie-Hygiène, Hôpitaux Universitaires Pitié Salpêtrière and Sorbonne Universités, Centre d’Imagerie Médicale Italie-Paris, CR7, Institut national de la santé et de la recherche médicale U1135, Paris, France

^q Irish Mycobacteria Reference Laboratory, St James’s Hospital Dublin, Ireland

^r Department of Clinical Microbiology, Trinity College Dublin, Dublin, Ireland

^s Department of Microbiology, Public Health Agency of Sweden, Solna, Sweden

^t National Reference Laboratory for Mycobacteria, Norwegian Institute of Public Health, Oslo, Norway

^u Program Tuberculosis and Mycobacteria, Operational Direction Communicable and Infectious Diseases, Scientific Institute of Public Health (Site Ukkel), Ukkel, Belgium

^v National Institute for Health and Welfare, Department of Infectious Diseases Surveillance and Control, Turku, Finland

^w Department of Health Security, National Institute for Health and Welfare, Helsinki, Finland

^x Institute of Medical Microbiology, National Center for Mycobacteria, University of Zurich, Zurich, Switzerland

^* Correspondence to: Dr Peter M Keller, Institute of Medical Microbiology, National Center for Mycobacteria, University of Zurich, 8006 Zurich, Switzerland Correspondence to: Dr Peter M Keller, Institute of Medical Microbiology National Center for Mycobacteria University of Zurich Zurich 8006 Switzerland

Summary

Background

The risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan.

Methods

On April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control.

Findings

Between Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation.

Interpretation

Our data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto.

Funding

The Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG).

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Vol 18 - N° 4

P. 431-440 - avril 2018 Retour au numéro

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A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study - 26/03/18

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