title: A joint cross-border investigation of a cluster of multidrug-resistant tuberculosis in Austria, Romania and Germany in 2014 using classic, genotyping and whole genome sequencing methods: lessons learnt.
abstract: Molecular surveillance of multidrug-resistant tuberculosis (MDR-TB) using 24-loci MIRU-VNTR in the European Union suggests the occurrence of international transmission. In early 2014, Austria detected a molecular MDR-TB cluster of five isolates. Links to Romania and Germany prompted the three countries to investigate possible cross-border MDR-TB transmission jointly. We searched genotyping databases, genotyped additional isolates from Romania, used whole genome sequencing (WGS) to infer putative transmission links, and investigated pairwise epidemiological links and patient mobility. Ten isolates from 10 patients shared the same 24-loci MIRU-VNTR pattern. Within this cluster, WGS defined two subgroups of four patients each. The first comprised an MDR-TB patient from Romania who had sought medical care in Austria and two patients from Austria. The second comprised patients, two of them epidemiologically linked, who lived in three different countries but had the same city of provenance in Romania. Our findings strongly suggested that the two cases in Austrian citizens resulted from a newly introduced MDR-TB strain, followed by domestic transmission. For the other cases, transmission probably occurred in the same city of provenance. To prevent further MDR-TB transmission, we need to ensure universal access to early and adequate therapy and collaborate closely in tuberculosis care beyond administrative borders.
authors.affiliation: Respiratory Infections Unit, Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.|These authors contributed equally to this work.
authors.forename: Lena
authors.initials: L
authors.lastname: Fiebig
authors.affiliation: These authors contributed equally to this work.|Molecular and Experimental Mycobacteriology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Kohl
authors.affiliation: National Institute of Public Health - National Center for Communicable Diseases Surveillance and Control, Bucharest, Romania.
authors.forename: Odette
authors.initials: O
authors.lastname: Popovici
authors.affiliation: Local Public Health Office Ingolstadt, Ingolstadt, Germany.
authors.forename: Margarita
authors.initials: M
authors.lastname: Mühlenfeld
authors.affiliation: Austrian Reference Laboratory for Mycobacteria, Austrian Agency for Health and Food Safety (AGES), Vienna, Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Indra
authors.affiliation: Clinical Hospital of Pneumology, Tuberculosis National Reference Laboratory, Cluj-Napoca, Romania.
authors.forename: Daniela
authors.initials: D
authors.lastname: Homorodean
authors.affiliation: Pneumology Institute "Marius Nasta", Bucharest, Romania.
authors.forename: Domnica
authors.initials: D
authors.lastname: Chiotan
authors.affiliation: Labor Dr. Limbach, TB Laboratory, Heidelberg, Germany.
authors.forename: Elvira
authors.initials: E
authors.lastname: Richter
authors.affiliation: National Reference Center (NRC) for Mycobacteria, Research Center Borstel, Borstel, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Rüsch-Gerdes
authors.affiliation: Tuberculosis Patient Service, Health Service of the City of Vienna, Vienna, Austria.
authors.forename: Beatrix
authors.initials: B
authors.lastname: Schmidgruber
authors.affiliation: Molecular and Experimental Mycobacteriology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.|German Center for Infection Research, Partner Site Hamburg-Borstel-Lübeck, Borstel, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Beckert
authors.affiliation: Respiratory Infections Unit, Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hauer
authors.affiliation: Molecular and Experimental Mycobacteriology, Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.|National Reference Center (NRC) for Mycobacteria, Research Center Borstel, Borstel, Germany.|German Center for Infection Research, Partner Site Hamburg-Borstel-Lübeck, Borstel, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
authors.affiliation: Austrian Reference Laboratory for Mycobacteria, Austrian Agency for Health and Food Safety (AGES), Vienna, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Allerberger
authors.affiliation: Respiratory Infections Unit, Department for Infectious Disease Epidemiology, Robert Koch Institute, Berlin, Germany.
authors.forename: Walter
authors.initials: W
authors.lastname: Haas
mesh_terms: D000328:Adult; D000368:Aged; D001317:Austria / Q000453:epidemiology; D004196:Disease Outbreaks; D019143:Evolution, Molecular; D005260:Female; D016680:Genome, Bacterial; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000187:drug effects*; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000302:isolation & purification*; D012383:Romania / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D018088:Tuberculosis, Multidrug-Resistant / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*
keywords: Europe; contact tracing; genotyping; human migration; molecular epidemiology; multidrug-resistant; sequence analysis; transmission; tuberculosis