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

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. On April 29 and May 30, 2016, the Swiss and German...

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Vydáno v:	The Lancet infectious diseases Ročník 18; číslo 4; s. 431 - 440
Hlavní autoři:	Walker, Timothy M, Merker, Matthias, Knoblauch, Astrid M, Helbling, Peter, Schoch, Otto D, van der Werf, Marieke J, Kranzer, Katharina, Fiebig, Lena, Kröger, Stefan, Haas, Walter, Hoffmann, Harald, Indra, Alexander, Egli, Adrian, Cirillo, Daniela M, Robert, Jérôme, Rogers, Thomas R, Groenheit, Ramona, Mengshoel, Anne T, Mathys, Vanessa, Haanperä, Marjo, Soolingen, Dick van, Niemann, Stefan, Böttger, Erik C, Keller, Peter M, Avsar, Korkut, Bauer, Christoph, Bernasconi, Enos, Borroni, Emanuele, Brusin, Sergio, Coscollá Dévis, Mireia, Crook, Derrick W., Dedicoat, Martin, Fitzgibbon, Margaret, Gagneux, Sébastien, Geiger, Francisca, Guthmann, Jean-Paul, Hendrickx, David, Hoffmann-Thiel, Sabine, van Ingen, Jakko, Jackson, Sarah, Jaton, Katia, Lange, Christoph, Mazza Stalder, Jessica, O'Donnell, Joan, Opota, Onya, Peto, Tim E.A., Preiswerk, Benjamin, Roycroft, Emma, Sato, Mariko, Schacher, Regina, Schulthess, Bettina, Smith, E. Grace, Soini, Hanna, Sougakoff, Wladimir, Tagliani, Elisa, Utpatel, Christian, Veziris, Nicolas, Wagner-Wiening, Christiane, Witschi, Mark
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	United States Elsevier Ltd 01.04.2018 Elsevier Limited New York, NY : Elsevier Science ; The Lancet Pub. Group, 2001 Elsevier Science ;, The Lancet Pub. Group
Témata:	Adolescent Adult Africa Algorithms Animals Antitubercular Agents - pharmacology Bacteriology Boundaries Child Cluster Analysis Colleges & universities Disease Transmission, Infectious Drug resistance Emigrants and Immigrants Epidemics Epidemiology Europe - epidemiology Female Genome, Bacterial Genomes Humans Infectious diseases Information sharing Life Sciences Lungs Male Medical research Microbial Sensitivity Tests Microbiology and Parasitology Migration Minisatellite Repeats Molecular Epidemiology Molecular Typing Multidrug resistance Multidrug resistant organisms Mycobacterium tuberculosis Mycobacterium tuberculosis - classification Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - genetics Mycobacterium tuberculosis - isolation & purification Polymorphism, Single Nucleotide Public health Systematic review Tuberculosis Tuberculosis, Multidrug-Resistant - epidemiology Whole Genome Sequencing Young Adult Europe Africa Somalia Italy Horn of Africa
ISSN:	1473-3099, 1474-4457, 1474-4457
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Shrnutí:	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. 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. 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. 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. 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).
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 PMCID: PMC5864516 Members listed at the end of the paper Contributed equally
ISSN:	1473-3099 1474-4457 1474-4457
DOI:	10.1016/S1473-3099(18)30004-5