Anales de Pediatría (English Edition) Anales de Pediatría (English Edition)
Scientific Letter
Analysis of the clinical features of infections caused by enterovirus A71 (EV-A71) in Balearic Islands
Análisis de las características clínicas de las infecciones causadas por el enterovirus A71 (EV-A71) en las Islas Baleares
Jordi Reinaa,, , María Cabrerizob, Francesc Ferrésc
a Unidad de Virología, Servicio de Microbiología, Hospital Universitario Son Espases, Palma de Mallorca, Islas Baleares, Spain
b Unidad de Enterovirus, Centro Nacional de Microbiología, Madrid, Spain
c Sección de Urgencias, Servicio de Pediatría, Hospital Universitario Son Espases, Islas Baleares, Spain
Dear Editor:

Enteroviruses are a broad group of viruses with a wide geographical distribution. They predominantly affect children with respiratory, gastrointestinal, exanthematous, febrile and neurologic diseases. They are easily transmitted via person-to-person contact through faecal-oral route and have an incubation period of 1–3 days.1

Of the more than 100 known enteroviruses, enterovirus 71 (EV-A71) belongs to the Enterovirus A species, which comprehends more than 25 different serotypes, including coxsackievirus A16, which causes hand, foot and mouth disease (HFMD).1,2

Enterovirus 71 was first described in the context of outbreaks of infection with neurologic involvement between 1969 and 1972. Since then, it has been detected all over the world with a varying prevalence.1 It is generally considered to cause mild or moderate respiratory disease, HFMD and neurologic illness of varying severity (meningitis, encephalitis or flaccid paralysis).1,2 In some cases of HFMD, patients present with encephalitis at the level of the hindbrain, known as rhomboencephalitis, that may cause severe neurologic sequelae.1,2

After the outbreak of neurologic illness caused by EV-A71 in Catalonia,3 we thought it would be interesting to analyse the clinical characteristics of patients infected by this virus in the Balearic Islands.

We studied the presence of enteroviruses in respiratory samples (from pharyngeal swabs) of paediatric patients with clinical suspicion of acute respiratory tract infection (ARTI) between May 2015 and June 2016.

We performed viral detection by means of a gene amplification technique, a real-time RT-PCR assay capable of detecting and differentiating 16 viruses in one step (Allplex® Respiratory Full Panel Assay, Seegene; South Korea). This assay can differentiate between enterovirus and rhinovirus, but cannot be used to serotype enteroviruses. Samples that tested positive for enterovirus were submitted to the Centro Nacional de Microbiología (National Centre of Microbiology, Madrid), where the final serotyping was performed.

A total of 5772 respiratory samples were analysed during the period under study, of which 2788 (48.3%) tested positive for a virus. Of the latter, 148 (5.3%) were positive for enterovirus, and 8 strains (5.4%) were serotyped as EV-A71 (amounting to 0.1% of all tested specimens and 0.2% of positive specimens). All cases were sporadic community-acquired infections that did not occur in the context of an outbreak.

Of the 8 patients, 4 (50%) were boys and 4 (50%) girls; their median age was 17 months (range, 5 months-3 years). The timeline of the cases was: 1 case (12.5%) in November 2015, and 1 (12.5%) in March, 2 (25%) in May and 4 (50%) in June 2016. Table 1 details the main diseases detected in these patients. Two patients (12.5%) had underlying diseases and 4 (50%) required hospital admission.

Table 1.

Main characteristics of patients with infection by enterovirus A71.

Patient  Sex  Age  Symptoms  Underlying disease  Admission  Treatment 
Female  1 year  Fever, cold symptoms  None  No  Paracetamol 
Male  2 years  Fever, pharyngitis  None  No  Amoxicillin 
Female  1 year  Fever, petechiae  None  Yes  Amoxicillin 
4a  Female  5 months  Fever, cold symptoms  None  No  Paracetamol 
5a  Male  1 year  Fever, cold symptoms  None  No  Paracetamol 
6a  Female  1 year  Fever, bronchitis  Asthma  Yes  Salbutamol, amoxicillin 
Male  3 years  Fever, cold symptoms  Haemophagocytosis  Yes  Paracetamol, amoxicillin 
8b  Male  2 years  Fever, vomiting, ataxia  None  Yes  Salbutamol, ceftriaxone 
      Aseptic meningitis       
a

Co-infection with EV-D68.

b

Co-infection with bocavirus.

One patient presented with manifestations compatible with aseptic meningitis. The analysis of a cerebrospinal fluid specimen revealed a glucose concentration of 57mg/dL, a protein concentration of 0.34g/L, and counts of 5red blood cells/μL and 40 white blood cells/μL (10% neutrophils and 90% lymphocytes). The results of PCR for the detection of neurotropic and respiratory viruses were negative.

Fifty percent of patients had viral co-infection, which involved enterovirus D68 in 3 (75%) and a bocavirus in 1; the percentage of co-infection was of 16.8% for the rest of the detected enteroviruses. All patients had favourable outcomes, and none died due to the viral infection or complications from it.

In our study, neurologic involvement was found in only 1 (12.5%) out of all patients with ARTI caused by EV-A71. This patient developed aseptic meningitis, which caused no further complications. The proportion of central nervous system infections in which this virus is involved ranges between 10% and 15%, and increases slightly during outbreaks.1,2,4

In recent years, several large-scale outbreaks of HFMD have been reported, especially in Asia, associated with central nervous system complications.1 The virus has circulated less intensely in Europe, and in Spain there have been reports of outbreaks and sporadic cases of this disease.3–5

In the outbreak in Catalonia, there was a predominance of infections with neurologic involvement and in particular with rhomboencephalitis.3 The sporadic cases detected in our study were associated with less severe disease, as most of them presented as acute respiratory tract infections (ARTIs), with no significant neurologic complications,6 although the small number of cases did not allow reaching any firm conclusions. Some studies seem to suggest that there are different genetic lineages of EV-A71 that may determine its virulence.1,2,5

Given the sharp emergence of enteroviruses in respiratory and neurologic illnesses in the paediatric population in recent years, it is very important to carry out serotyping and follow-up studies of these infections.

References
1
P.C. Chang,S.C. Chen,K.T. Chen
The current status of the disease caused by enterovirus 71 infections: epidemiology, pathogenesis, molecular epidemiology, and vaccine development
Int J Environ Res Public Health, (2016), http://dx.doi.org/10.3390/ijerph13090890
pii: E890
2
P. McMinn,I. Stratov,L. Nagarajan,S. Davis
Neurological manifestations of enterovirus 71 infection in children during an outbreak of hand, foot and mouth disease in Western Australia
Clin Infect Dis, 32 (2001), pp. 236-242 http://dx.doi.org/10.1086/318454
3
European Centre for Disease Prevention and Control
Outbreak of enterovirus A71 with severe neurological symptoms among children in Catalonia, Spain
ECDC, (2016, June)
4
I. Schuffenecker,A. Mirand,D. Antona,C. Henquell,J.J. Chomel,C. Archimbaud
Epidemiology of human enterovirus 71 infections in France, 2000–2009
J Clin Virol, 50 (2011), pp. 50-56 http://dx.doi.org/10.1016/j.jcv.2010.09.019
5
M. Cabrerizo,D. Tarragó,C. Muñoz-Almagro,E. del Amo,M. Domínguez-Gil,J.M. Eiros
Molecular epidemiology of enterovirus 71, coxsackievirus A16 and A6 associated with hand, foot and mouth disease in Spain
Clin Microbiol Infect, 20 (2014), pp. 150-156
6
J. Reina,M. Cabrerizo,F. Aliaga
Infecciones respiratorias agudas comunitarias causadas por enterovirus en la población pediátrica
Enferm Infecc Microbiol Clin, (2016), http://dx.doi.org/10.1016/j.eimc.2016.05.007

Please cite this article as: Reina J, Cabrerizo M, Ferrés F. Análisis de las características clínicas de las infecciones causadas por el enterovirus A71 (EV-A71) en las Islas Baleares. An Pediatr (Barc). 2017;87:289–290.

Corresponding author. (Jordi Reina jorge.reina@ssib.es)
Copyright © 2016. Asociación Española de Pediatría
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