Respiratory Infections by Enterovirus D68 in Outpatients and Inpatients Spanish Children.

The genus Enterovirus (belonging family Picornaviridae) comprises 10 species and 7 of them infect humans: enterovirus (EV) A–D and rhinovirus (RV) A–C. Human EV 68 (EV-D68) belongs to the EV species D together with 3 other EV types (EV-D70, EV-D94 and EV-D111).1 It was discovered in 1962 in respiratory samples2 and was earlier named human RV-87 on the basis of the optimal growth temperature, low pH sensitivity and antigenic characteristics being related to RV. It was later reclassified as EV-D68.3 During the following 40 years, human infection caused by EV-D68 was rarely reported. EV-D68 can be detected by generic reverse transcription-polymerase chain reactions (RT-PCRs) designed in the 5′ noncoding region (5′NCR), but the specific detection of EV-D68 requires genotyping using the gene that codifies the viral protein 1 (VP1) or the VP2–VP4 genome region. The phylogenetic analysis of circulating EV-D68 using VP1 gene sequences allowed its classification in 3 major genetic groups: major groups 1, 2 and 3 as was published by Meijer et al4 or clades B, C and A, respectively, published by Tokarz et al.5 In recent months, PCR techniques are being incorporated into the routine diagnosis of this virus.6 The spectrum of clinical disease comprises asymptomatic to acute respiratory infections, upper and mild to severe lower respiratory disease requiring hospitalization and occasionally neurological symptoms and eventually death.7–9 In the last 10 years, several EV-D68 outbreaks have been reported,10,11 mainly in 2010. After the 2010 outbreak, EV-D68 continues circulating in several countries like Netherlands,12 and the most important outbreak has occurred in US and Canada.13 From August to September 2014, a total of 220 people had a confirmed EV-D68 respiratory illness in 32 different US states, and in Canada there was an increase of severe respiratory infections associated to this virus. In these countries, the patient’s age ranged between 6 weeks and 16 years, and an important percentage needed admission to the intensive care unit (ICU). Asthma has been the underlying disease most frequently detected in these patients. In European countries, the laboratory-confirmed cases of infections by EV-D68 are low because respiratory infections of RV and nonpolio EV are not of mandatory notification in the European Union. Until now, only a few specialized laboratories perform the specific EV-D68 identification, and it is unknown which countries have established surveillance schemes for respiratory specimens with screening for EV. Based on the current information, the European Center for Disease Prevention and Control consider that European Union countries have a moderate risk of EV-D68 transmission because the circulation for this virus is low.14 As a part of a prospective study to identify the etiology and clinical characteristics of viral respiratory infections in children in Spain, we performed the analysis of the cases of EV infections in all children hospitalized in a secondary hospital in Madrid, during the epidemic respiratory season 2012–2013. Phylogenetic EV-D68 analysis was made using the VP1 gene. Clinical data of EV-D68 patients were compared with those infected by RV in the same period and population. The RV, belonged in the same genus Enterovirus, was chosen on the basis of similar clinical presentation.