title: Key Role of Sequencing to Trace Hepatitis A Viruses Circulating in Italy During a Large Multi-Country European Foodborne Outbreak in 2013.
abstract: BACKGROUND
  Foodborne Hepatitis A Virus (HAV) outbreaks are being recognized as an emerging public health problem in industrialized countries. In 2013 three foodborne HAV outbreaks occurred in Europe and one in USA. During the largest of the three European outbreaks, most cases occurred in Italy (>1,200 cases as of March 31, 2014). A national Task Force was established at the beginning of the outbreak by the Ministry of Health. Mixed frozen berries were early demonstrated to be the source of infection by the identity of viral sequences in patients and in food. In the present study the molecular characterization of HAV isolates from 355 Italian cases is reported.
  
  
  METHODS
  Molecular characterization was carried out by PCR/sequencing (VP1/2A region), comparison with reference strains and phylogenetic analysis.
  
  
  RESULTS
  A unique strain was responsible for most characterized cases (235/355, 66.1%). Molecular data had a key role in tracing this outbreak, allowing 110 out of the 235 outbreak cases (46.8%) to be recognized in absence of any other link. The data also showed background circulation of further unrelated strains, both autochthonous and travel related, whose sequence comparison highlighted minor outbreaks and small clusters, most of them unrecognized on the basis of epidemiological data. Phylogenetic analysis showed most isolates from travel related cases clustering with reference strains originating from the same geographical area of travel.
  
  
  CONCLUSIONS
  In conclusion, the study documents, in a real outbreak context, the crucial role of molecular analysis in investigating an old but re-emerging pathogen. Improving the molecular knowledge of HAV strains, both autochthonous and circulating in countries from which potentially contaminated foods are imported, will become increasingly important to control outbreaks by supporting trace back activities, aiming to identify the geographical source(s) of contaminated food, as well as public health interventions.
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bruni
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Taffon
authors.affiliation: Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Equestre
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Chionne
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Madonna
authors.affiliation: National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Rizzo
authors.affiliation: National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Tosti
authors.affiliation: National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Alfonsi
authors.affiliation: National Centre for Epidemiology, Surveillance and Health Promotion, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Ricotta
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: De Medici
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Pasquale
authors.affiliation: Department of Veterinary Public Health and Food Safety, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Scavia
authors.affiliation: Reparto tecnologia acidi nucleici applicata agli alimenti, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Brescia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Pavoni
authors.affiliation: Reparto tecnologia acidi nucleici applicata agli alimenti, Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Brescia, Italy.
authors.forename: Marina Nadia
authors.initials: MN
authors.lastname: Losio
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Romanò
authors.affiliation: Department of Biomedical Sciences for Health, University of Milan, Milan, Italy.
authors.forename: Alessandro Remo
authors.initials: AR
authors.lastname: Zanetti
authors.affiliation: Azienda Ospedaliero-Universitaria Policlinico di Bari, Bari, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Morea
authors.affiliation: Microbiology and Virology Unit, Padua University Hospital, Padua, Italy.
authors.forename: Monia
authors.initials: M
authors.lastname: Pacenti
authors.affiliation: Department of Molecular Medicine, University of Padua, Padua, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.affiliation: Laboratory of Virology, Istituto Nazionale per le Malattie Infettive "L. Spallanzani", Rome, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Capobianchi
authors.affiliation: Azienda Ospedaliero-Universitaria Policlinico di Bari, Bari, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Chironna
authors.affiliation: Directorate General for Preventive Health Care, Ministry of Health, Rome, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Pompa
authors.affiliation: Department of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità (ISS), Rome, Italy.
authors.forename: Anna Rita
authors.initials: AR
authors.lastname: Ciccaglione
mesh_terms: D019943:Amino Acid Substitution; D016358:Contact Tracing; D004196:Disease Outbreaks; D005060:Europe; D014644:Genetic Variation; D005838:Genotype; D006506:Hepatitis A / Q000453:epidemiology* / Q000635:transmission / Q000821:virology*; D030041:Hepatitis A virus / Q000235:genetics*; D006801:Humans; D007558:Italy; D010802:Phylogeny; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D062211:Spatio-Temporal Analysis; D015678:Viral Structural Proteins / Q000235:genetics
chemical_list: C096539:VP1 protein, hepatitis A virus; D015678:Viral Structural Proteins