serval:BIB_4A2575D740A5
A cluster of multidrug-resistant Mycobacterium tuberculosis among patients arriving in Europe from the Horn of Africa: a molecular epidemiological study
10.1016/s1473-3099(18)30004-5
29326013
Walker
Timothy M
author
Merker
Matthias
author
Knoblauch
Astrid M
author
Helbling
Peter
author
Schoch
Otto D
author
van der Werf
Marieke J
author
Kranzer
Katharina
author
Fiebig
Lena
author
Kröger
Stefan
author
Haas
Walter
author
Hoffmann
Harald
author
Indra
Alexander
author
Egli
Adrian
author
Cirillo
Daniela M
author
Robert
Jérôme
author
Rogers
Thomas R
author
Groenheit
Ramona
author
Mengshoel
Anne T
author
Mathys
Vanessa
author
Haanperä
Marjo
author
Soolingen
Dick van
author
Niemann
Stefan
author
Böttger
Erik C
author
Keller
Peter M
author
Avsar
Korkut
author
Bauer
Christoph
author
Bernasconi
Enos
author
Borroni
Emanuele
author
Brusin
Sergio
author
Coscollá Dévis
Mireia
author
Crook
Derrick W.
author
Dedicoat
Martin
author
Fitzgibbon
Margaret
author
Gagneux
Sébastien
author
Geiger
Francisca
author
Guthmann
Jean-Paul
author
Hendrickx
David
author
Hoffmann-Thiel
Sabine
author
van Ingen
Jakko
author
Jackson
Sarah
author
Jaton
Katia
author
Lange
Christoph
author
Mazza Stalder
Jessica
author
O'Donnell
Joan
author
Opota
Onya
author
Peto
Tim E.A.
author
Preiswerk
Benjamin
author
Roycroft
Emma
author
Sato
Mariko
author
Schacher
Regina
author
Schulthess
Bettina
author
Smith
E. Grace
author
Soini
Hanna
author
Sougakoff
Wladimir
author
Tagliani
Elisa
author
Utpatel
Christian
author
Veziris
Nicolas
author
Wagner-Wiening
Christiane
author
Witschi
Mark
author
article
2018-04
The Lancet Infectious Diseases
1473-3099
journal
18
4
431-440
SummaryBackground 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).
Infectious Diseases
eng
60_published
true
University of Lausanne
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