title: Molecular and clinical epidemiology of norovirus outbreaks in Spain during the emergence of GII.4 2012 variant.
abstract: BACKGROUND
  Norovirus (NoV) is the most common cause of acute nonbacterial gastroenteritis outbreaks worldwide, but the impact of NoV infections in Spain remains underestimated.
  
  
  OBJECTIVE
  This study aimed to determine the prevalence and genetic diversity of NoVs causing outbreaks of acute gastroenteritis in Northeastern Spain (Catalonia) during 2010-2012, and to compare clinical features and levels of viral shedding of the most prevalent GII.4 2012 variant with its predecessor.
  
  
  METHODS
  NoVs were screened and genotyped in stools from gastroenteritis outbreaks. Genetic diversity over a region covering 50% of VP1, and viral loads were analyzed in stools belonging to GII.4 2009 and 2012 variants.
  
  
  RESULTS
  More than 50% of outbreaks were caused by genotype GII.4, although outbreaks caused by multiple strains, GII.6 and GII.1 were also prevalent. During 2012, GII.4 2012 strains clearly replaced GII.4 2009 strains. The first 2012 strain was detected in February 2011, representing the earliest isolate reported worldwide. Epidemiological features of GII.4 2012 and GII.4 2009 outbreaks were comparable, as well as levels of viral shedding in stools. Finally, analysis of the capsid gene showed a higher amino acid variability and diversification in GII.4 2012, affecting sites located at the P2 domain, but also in the shell domain.
  
  
  CONCLUSIONS
  Clinical features of outbreaks caused by different genotypes circulating in Spain, including outbreaks caused by GII.4 2012 and GII.4 2009 strains, were comparable. Although shed at similar levels than GII.4 2009 strains, GII.4 2012 strains have clearly replaced the previous predominant strain.
authors.affiliation: Enteric Virus Laboratory, Department of Microbiology, University of Barcelona, Avda Diagonal 643, 08028 Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA-UB), University of Barcelona, Avda Prat de la Riba 171, 08921 Santa Coloma de Gramanet, Spain.
authors.forename: Aurora
authors.initials: A
authors.lastname: Sabrià
authors.affiliation: Enteric Virus Laboratory, Department of Microbiology, University of Barcelona, Avda Diagonal 643, 08028 Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA-UB), University of Barcelona, Avda Prat de la Riba 171, 08921 Santa Coloma de Gramanet, Spain.
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Pintó
authors.affiliation: Enteric Virus Laboratory, Department of Microbiology, University of Barcelona, Avda Diagonal 643, 08028 Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA-UB), University of Barcelona, Avda Prat de la Riba 171, 08921 Santa Coloma de Gramanet, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Bosch
authors.affiliation: Laboratory of Microbiology, Hospital Universitari Vall d'Hebron, Pssg Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Bartolomé
authors.affiliation: Laboratory of Microbiology, Hospital Universitari Vall d'Hebron, Pssg Vall d'Hebron 119-129, 08035 Barcelona, Spain.
authors.forename: Thais
authors.initials: T
authors.lastname: Cornejo
authors.affiliation: Department of Health, Generalitat of Catalonia, Roc Boronat 81-95, 08005 Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Monforte de Lemos 5, 28029 Madrid, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Torner
authors.affiliation: Department of Health, Generalitat of Catalonia, Roc Boronat 81-95, 08005 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Martínez
authors.affiliation: Laboratory of the Public Health Agency, Pl. Lesseps 1, 08024 Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: de Simón
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Carlos III, Monforte de Lemos 5, 28029 Madrid, Spain; Department of Public Health, University of Barcelona, Casanova 143, 08036 Barcelona, Spain.
authors.forename: Angela
authors.initials: A
authors.lastname: Domínguez
authors.affiliation: Enteric Virus Laboratory, Department of Microbiology, University of Barcelona, Avda Diagonal 643, 08028 Barcelona, Spain; Nutrition and Food Safety Research Institute (INSA-UB), University of Barcelona, Avda Prat de la Riba 171, 08921 Santa Coloma de Gramanet, Spain. Electronic address: susanaguix@ub.edu.
authors.forename: Susana
authors.initials: S
authors.lastname: Guix
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017250:Caliciviridae Infections / Q000453:epidemiology* / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D004196:Disease Outbreaks; D005243:Feces / Q000821:virology; D005260:Female; D005759:Gastroenteritis / Q000453:epidemiology* / Q000821:virology*; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D029322:Norovirus / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D013030:Spain / Q000453:epidemiology; D017201:Virus Shedding; D055815:Young Adult
chemical_list: D012367:RNA, Viral
keywords: Gastroenteritis outbreak; Genetic variation; Human norovirus; Molecular epidemiology; Viral load