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.

Objectives: 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.

Study design: 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.

Keywords: Gastroenteritis outbreak; Genetic variation; Human norovirus; Molecular epidemiology; Viral load.