Enterovirus-A71 Rhombencephalitis Outbreak in Catalonia: Characteristics, Management and Outcome

Abstract

Background: Between April and June 2016, an outbreak of rhombencephalitis (RE) caused by enterovirus (EV) A71 was detected in Catalonia, Spain—the first documented in Western Europe. The clinical characteristics and outcome of patients with this condition differed from those reported in outbreaks occurring in Southeast Asia. Methods: Observational, multicenter study analyzing characteristics, treatment and outcome of patients with EV-A71 rhombencephalitis diagnosed in 6 publicly funded hospitals within the Catalonian Health Institute. A review of clinical characteristics, diagnosis, treatment and outcome of these patients was conducted. Results: Sixty-four patients met the clinical and virologic criteria for rhombencephalitis caused by EV-A71. All patients had symptoms suggesting viral disease, mainly fever, lethargy, ataxia and tremor, with 30% of hand-foot-mouth disease. Intravenous immunoglobulin therapy was given to 44/64 (69%) patients and methylprednisolone to 27/64 (42%). Six patients (9%) required pediatric intensive care unit admission. Three patients had acute flaccid paralysis of 1 limb, and another had autonomic nervous system (ANS) dysfunction with cardiorespiratory arrest. Outcome in all patients (except the patient with hypoxic-ischemic encephalopathy) was good, with complete resolution of the symptoms. Conclusions: During the 2016 outbreak, rhombencephalitis without ANS symptoms was the predominant form of presentation and most patients showed no hand-foot-mouth disease. These findings contrast with those of other patient series reporting associated ANS dysfunction (10%–15%) and hand-foot-mouth disease (60%–80%). Complete recovery occurred in almost all cases. In light of the favorable outcome in untreated mild cases, therapies for this condition should be reserved for patients with moderate-severe infection. The main relevance of this study is to provide useful information for setting priorities, management approaches and adequate use of resources in future EV-A71 associated rhombencephalitis outbreaks.

Enteroviruses: epidemic potential, challenges and opportunities with vaccines

“…Sporadic cases and epidemics of EV-A71 infections have been reported across Europe [ 101 – 107 ]. In 2016, Catalonia was hit by an outbreak that later spread across Spain, resulting in 57 children suffering from severe neurological disease instead of HMFD [ 17 , 108 ]. The largest outbreak of EV-A71 in the Americas was observed in 2018, during which 43 children showed symptoms of meningitis, encephalitis, AFM or seizures [ 18 ].…”

The Repurposing of Cellular Proteins during Enterovirus A71 Infection

“…Waves of infections occurred in the Netherlands, France, and Germany from 2007–2013 [ 5 ]. Most recent incidences of EV-A71 infection include several cases in Spain in 2016 and around 13,000 cases in Gansu Province, China in 2018 [ 6 , 7 ]. Also in 2018, the Children’s Hospital of Colorado reported a 2.75 percent increase in confirmed cases as compared to the average from the past 5 years (2013–2017) [ 8 ].…”

Investigating the mechanism of Echovirus 30 cell invasion

“…Although most EVs infections are asymptomatic, there are more than 20 clinically recognized disorders associated with many EVs types, with millions of people being infected annually (Caroline et al, 2013;Hoang et al, 2019). Clinically, EVs infections can cause a variety of symptoms, such as hand-foot-and-mouth disease (Zhang et al, 2010;Huang et al, 2018), acute hemorrhagic conjunctivitis (Leveque et al, 2010), poliomyelitis (World Health Organization Country Office Tajikistan et al, 2010;Hall et al, 2019), encephalitis (Worner et al, 2021), and aseptic meningitis (AM), while cardiac illness may ultimately result in death (Caroline et al, 2013;Zell et al, 2017;Del Cuerpo et al, 2022). Over 90% of cases of viral meningitis cases are caused by EVs, while CNS involvement is frequently associated with systemic infections, liver cell death, and myocarditis (Caroline et al, 2013).…”