title: Outbreak investigation for toxigenic Corynebacterium diphtheriae wound infections in refugees from Northeast Africa and Syria in Switzerland and Germany by whole genome sequencing.
abstract: Toxigenic Corynebacterium diphtheriae is an important and potentially fatal threat to patients and public health. During the current dramatic influx of refugees into Europe, our objective was to use whole genome sequencing for the characterization of a suspected outbreak of C. diphtheriae wound infections among refugees. After conventional culture, we identified C. diphtheriae using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and investigated toxigenicity by PCR. Whole genome sequencing was performed on a MiSeq Illumina with >70×coverage, 2×250 bp read length, and mapping against a reference genome. Twenty cases of cutaneous C. diphtheriae in refugees from East African countries and Syria identified between April and August 2015 were included. Patients presented with wound infections shortly after arrival in Switzerland and Germany. Toxin production was detected in 9/20 (45%) isolates. Whole genome sequencing-based typing revealed relatedness between isolates using neighbour-joining algorithms. We detected three separate clusters among epidemiologically related refugees. Although the isolates within a cluster showed strong relatedness, isolates differed by >50 nucleotide polymorphisms. Toxigenic C. diphtheriae associated wound infections are currently observed more frequently in Europe, due to refugees travelling under poor hygienic conditions. Close genetic relatedness of C. diphtheriae isolates from 20 refugees with wound infections indicates likely transmission between patients. However, the diversity within each cluster and phylogenetic time-tree analysis suggest that transmissions happened several months ago, most likely outside Europe. Whole genome sequencing offers the potential to describe outbreaks at very high resolution and is a helpful tool in infection tracking and identification of transmission routes.
authors: Clinical Microbiology, University Hospital Basel, Basel, Switzerland; Bavarian Health and Food Safety Authority (LGL), Oberschleissheim, Germany; Applied Microbiology Research, Department of Biomedicine, University Basel, Basel, Switzerland.
authors: D M
authors: DM
authors: Meinel
authors: Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors: R
authors: R
authors: Kuehl
authors: Institute for Medical Microbiology, University of Zurich, Zurich, Switzerland.
authors: R
authors: R
authors: Zbinden
authors: Computational Evolution, D-BSSE, ETH Zurich, Basel, Switzerland.
authors: V
authors: V
authors: Boskova
authors: Department of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano, Switzerland.
authors: C
authors: C
authors: Garzoni
authors: Internal Medicine, Ospedale di Mendrisio, Mendrisio, Switzerland.
authors: D
authors: D
authors: Fadini
authors: Clinical Microbiology, EOLAB, Bellinzona, Switzerland.
authors: M
authors: M
authors: Dolina
authors: Institute of Medical Microbiology and Hygiene, University Medical Centre Freiburg, Freiburg, Germany.
authors: B
authors: B
authors: Blümel
authors: Clinical Microbiology, Labor Team W, Saint Gallen, Switzerland.
authors: T
authors: T
authors: Weibel
authors: Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors: S
authors: S
authors: Tschudin-Sutter
authors: Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors: A F
authors: AF
authors: Widmer
authors: Paediatric Infectious Diseases, University of Basel Children's Hospital, Basel, Switzerland.
authors: J A
authors: JA
authors: Bielicki
authors: Paediatric Infectious Diseases, University of Basel Children's Hospital, Basel, Switzerland.
authors: A
authors: A
authors: Dierig
authors: Paediatric Infectious Diseases, University of Basel Children's Hospital, Basel, Switzerland.
authors: U
authors: U
authors: Heininger
authors: Bavarian Health and Food Safety Authority (LGL), Oberschleissheim, Germany; German National Consiliary Laboratory on Diphtheria, Oberschleissheim, Germany.
authors: R
authors: R
authors: Konrad
authors: Bavarian Health and Food Safety Authority (LGL), Oberschleissheim, Germany; German National Consiliary Laboratory on Diphtheria, Oberschleissheim, Germany.
authors: A
authors: A
authors: Berger
authors: Clinical Microbiology, University Hospital Basel, Basel, Switzerland.
authors: V
authors: V
authors: Hinic
authors: Clinical Microbiology, University Hospital Basel, Basel, Switzerland.
authors: D
authors: D
authors: Goldenberger
authors: Clinical Microbiology, University Hospital Basel, Basel, Switzerland.
authors: A
authors: A
authors: Blaich
authors: Computational Evolution, D-BSSE, ETH Zurich, Basel, Switzerland.
authors: T
authors: T
authors: Stadler
authors: Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland.
authors: M
authors: M
authors: Battegay
authors: Bavarian Health and Food Safety Authority (LGL), Oberschleissheim, Germany; German National Consiliary Laboratory on Diphtheria, Oberschleissheim, Germany.
authors: A
authors: A
authors: Sing
authors: Clinical Microbiology, University Hospital Basel, Basel, Switzerland; Applied Microbiology Research, Department of Biomedicine, University Basel, Basel, Switzerland. Electronic address: adrian.egli@usb.ch.
authors: A
authors: A
authors: Egli
mesh_terms: D000293:Adolescent; D000328:Adult; D000349:Africa / Q000453:epidemiology; D001427:Bacterial Toxins / Q000235:genetics* / Q000378:metabolism; D015373:Bacterial Typing Techniques; D003353:Corynebacterium diphtheriae / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D004165:Diphtheria / Q000188:drug therapy / Q000453:epidemiology*; D004196:Disease Outbreaks; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008297:Male; D005810:Multigene Family; D058885:Multilocus Sequence Typing; D010802:Phylogeny; D012036:Refugees; D013557:Switzerland / Q000453:epidemiology; D013593:Syria / Q000453:epidemiology; D014946:Wound Infection / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D055815:Young Adult
chemical_list: D001427:Bacterial Toxins
keywords: Corynebacterium diphtheriae; Emerging diseases; Outbreak investigation; Refugee; Toxin-production; Typing; Whole genome sequencing