Molecular epidemiology of an enterovirus A71 outbreak associated with severe neurological disease, Spain, 2016

Enterovirus 71 (EV-A71) is a small, non-enveloped, single-stranded RNA virus that belongs to the species Enterovirus A along with 24 other serotypes within the Enterovirus genus [1]. According to the VP1 protein sequence, EV-A71 is classified into six genogroups (A–F) and a number of subgenogroups (B0–B5, C1–C5) [2]. Although EV-A71 infection is often asymptomatic, it can cause disorders with a wide range of clinical manifestations from non-specific febrile illness, aseptic meningitis and mild mucocutaneous symptoms to severe neurological diseases such as brainstem encephalitis and acute flaccid paralysis (AFP) [3,4]. EV-A71 is distributed worldwide. However, the largest outbreaks associated with hand, foot and mouth disease (HFMD) with subsequent neurological and cardiopulmonary complications have been described in the Asia-Pacific region, especially in the past 20 years [2,5-7]. These outbreaks have been connected to the circulation of different subgenogroups (B3, B4, C1, C2 and C4) [8-14]. In Europe, although outbreaks of polio-like disease occurred in Hungary and Bulgaria in the 1970s [15,16], only sporadic cases have been reported from several countries in recent years, mainly caused by the C1 and C2 subgenogroups [2,17]. In 2015, a new recombinant EV-A71 variant was identified that affected at least 19 young children in different areas of Germany [18]. This infection was associated with neurological manifestations (cerebral seizures, myoclonia and ataxia) that required hospitalisation. There were no reports of fatal cases or clinical sequelae after hospital discharge. Moreover, a well-documented case, a 2-year-old girl, required hospitalisation and was diagnosed with brainstem encephalitis and cardiopulmonary complications with an outcome of a probable persistent neurological impairment [19]. In addition, 18 cases of severe neurological disease associated with EV-A71 infection, and phylogenetically closely related to the strains described in Germany, were reported in France between May and October 2016. ...