Abstract

Limited recent molecular epidemiology data are available for pediatric Central Nervous System (CNS) infections in Europe. The aim of this study was to investigate the molecular epidemiology of enterovirus (EV) involved in CNS infections in children. Cerebrospinal fluid (CSF) from children (0–16 years) with suspected meningitis–encephalitis (ME) who were hospitalized in the largest pediatric hospital of Greece from October 2017 to September 2020 was initially tested for 14 common pathogens using the multiplex PCR FilmArray® ME Panel (FA-ME). CSF samples positive for EV, as well as pharyngeal swabs and stools of the same children, were further genotyped employing Sanger sequencing. Of the 330 children tested with FA-ME, 75 (22.7%) were positive for EV and 50 different CSF samples were available for genotyping. The median age of children with EV CNS infection was 2 months (IQR: 1–60) and 44/75 (58.7%) of them were male. There was a seasonal distribution of EV CNS infections, with most cases detected between June and September (38/75, 50.7%). EV genotyping was successfully processed in 84/104 samples: CSF (n = 45/50), pharyngeal swabs (n = 15/29) and stools (n = 24/25). Predominant EV genotypes were CV-B5 (16/45, 35.6%), E30 (10/45, 22.2%), E16 (6/45, 13.3%) and E11 (5/45, 11.1%). However, significant phylogenetic differences from previous described isolates were detected. No unusual neurologic manifestations were observed, and all children recovered without obvious acute sequelae. Specific EV circulating genotypes are causing a significant number of pediatric CNS infections. Phylogenetic analysis of these predominant genotypes found genetic differences from already described EV isolates.

Highlights

  • Enteroviruses (EVs) are members of the Picornaviridae family and consist of a nonenveloped positive single-stranded RNA [1]

  • During the 3-year study period, a total of 330 different Cerebrospinal fluid (CSF) samples were tested with the multiplex PCR FilmArray® ME panel and 13 (4%) bacterial and 92 (27.9%) viral Viruses 2021, 13, x FOR PEER REVIEWpathogens were detected

  • Except EVs, other viral pathogens were detected with FilmArray® Meningitis/Encephalitis (FA-ME) in 17 children: human herpesvirus 6 (HHV-6) in 11/92 (12%) and human parechovirus (HPeV) in 6/92 (6.5%)

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Summary

Introduction

Enteroviruses (EVs) are members of the Picornaviridae family and consist of a nonenveloped positive single-stranded RNA [1]. EV infections are frequently asymptomatic, they can present with a variety of clinical manifestations comprising fever, exanthems, headache, respiratory illness, sore throat, myocarditis, vomiting, diarrhea and sepsis-like illness in neonates and infants [3]. Several members of EVs are neurotropic pathogens with a wide spectrum of clinical disorders ranging from aseptic meningitis to more severe encephalitis [3]. Polio EVs have almost been eradicated due to systematic immunization, still circulating nonpolio EVs are associated with severe neurologic manifestations such as acute flaccid myelitis (AFM). Recent outbreaks associated with severe neurological complications and AFM have been reported in several countries from different continents including Europe and the USA, possibly attributed to EV-D68 and EV-A71 [4,5,6]

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