Abstract
IntroductionEnterovirus A71 (EV-A71) is an emerging pathogen that causes a wide range of disorders including severe neurological manifestations. In the past 20 years, this virus has been associated with large outbreaks of hand, foot and mouth disease with neurological complications in the Asia-Pacific region, while in Europe mainly sporadic cases have been reported. In spring 2016, however, an EV-A71 outbreak associated with severe neurological cases was reported in Catalonia and spread further to other Spanish regions.AimOur objective was to investigate the epidemiology and clinical characteristics of the outbreak.MethodsWe carried out a retrospective study which included 233 EV-A71-positive samples collected during 2016 from hospitalised patients. We analysed the clinical manifestations associated with EV-A71 infections and performed phylogenetic analyses of the 3’-VP1 and 3Dpol regions from all Spanish strains and a set of EV-A71 from other countries.ResultsMost EV-A71 infections were reported in children (mean age: 2.6 years) and the highest incidence was between May and July 2016 (83%). Most isolates (218/233) were classified as subgenogroup C1 and 217 of them were grouped in one cluster phylogenetically related to a new recombinant variant strain associated with severe neurological diseases in Germany and France in 2015 and 2016. Moreover, we found a clear association of EV-A71-C1 infection with severe neurological disorders, brainstem encephalitis being the most commonly reported.ConclusionAn emerging recombinant variant of EV-A71-C1 was responsible for the large outbreak in 2016 in Spain that was associated with many severe neurological cases.
Highlights
Enterovirus A71 (EV-A71) is an emerging pathogen that causes a wide range of disorders including severe neurological manifestations
We investigated the clinical manifestations of EV-A71 infections and the molecular epidemiology and geographical spread of the strains detected in Spain in 2016, comparing them to strains circulating in Spain and other countries in recent years
During 2016, the Spanish National Reference Laboratory for Enterovirus (SNRLE) received 1,113 EV-positive samples from 1,029 patients admitted to different Spanish hospitals with clinical pictures of fever without source (FWS) (n = 174; 16.9%), HFMD/exanthema (n = 52; 5.1%), respiratory illnesses (n = 270; 26.2%), the neurological diseases described above (n = 470; 45.7%), and others (n = 63; 6.1%)
Summary
Enterovirus A71 (EV-A71) is an emerging pathogen that causes a wide range of disorders including severe neurological manifestations. In the past 20 years, this virus has been associated with large outbreaks of hand, foot and mouth disease with neurological complications in the Asia-Pacific region, while in Europe mainly sporadic cases have been reported. In spring 2016, an EV-A71 outbreak associated with severe neurological cases was reported in Catalonia and spread further to other Spanish regions. Most isolates (218/233) were classified as subgenogroup C1 and 217 of them were grouped in one cluster phylogenetically related to a new recombinant variant strain associated with severe neurological diseases in Germany and France in 2015 and 2016. Conclusion: An emerging recombinant variant of EV-A71-C1 was responsible for the large outbreak in 2016 in Spain that was associated with many severe neurological cases. EV-A71 infection is often asymptomatic, 95 C1-variant C1
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