Abstract

BackgroundAn unusually high incidence of aseptic meningitis caused by enteroviruses was noted in Alberta, Canada between March and October 2010. Sequence based typing was performed on the enterovirus positive samples to gain a better understanding of the molecular characteristics of the Coxsackie A9 (CVA-9) strain responsible for most cases in this outbreak.MethodsMolecular typing was performed by amplification and sequencing of the VP2 region. The genomic sequence of one of the 2010 outbreak isolates was compared to a CVA-9 isolate from 2003 and the prototype sequence to study genetic drift and recombination.ResultsOf the 4323 samples tested, 213 were positive for enteroviruses (4.93%). The majority of the positives were detected in CSF samples (n = 157, 73.71%) and 81.94% of the sequenced isolates were typed as CVA-9. The sequenced CVA-9 positives were predominantly (94.16%) detected in patients ranging in age from 15 to 29 years and the peak months for detection were between March and October. Full genome sequence comparisons revealed that the CVA-9 viruses isolated in Alberta in 2003 and 2010 were highly homologous to the prototype CVA-9 in the structural VP1, VP2 and VP3 regions but divergent in the VP4, non-structural and non-coding regions.ConclusionThe increase in cases of aseptic meningitis was associated with enterovirus CVA-9. Sequence divergence between the prototype strain of CVA-9 and the Alberta isolates suggests genetic drifting and/or recombination events, however the sequence was conserved in the antigenic regions determined by the VP1, VP2 and VP3 genes. These results suggest that the increase in CVA-9 cases likely did not result from the emergence of a radically different immune escape mutant.

Highlights

  • An unusually high incidence of aseptic meningitis caused by enteroviruses was noted in Alberta, Canada between March and October 2010

  • The enterovirus genome is comprised of a single open reading frame flanked by the 5’ and 3’ untranslated regions (UTRs), and the encoded polyprotein is cleaved to produce the structural and nonstructural proteins [1]

  • Non-polio enteroviruses were traditionally classified into serotypes, based on a neutralization assay and included 64 classical isolates consisting of Coxsackieviruses A, Coxsackieviruses B, echoviruses and several numbered enteroviruses [11]

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Summary

Introduction

An unusually high incidence of aseptic meningitis caused by enteroviruses was noted in Alberta, Canada between March and October 2010. Sequence based typing was performed on the enterovirus positive samples to gain a better understanding of the molecular characteristics of the Coxsackie A9 (CVA-9) strain responsible for most cases in this outbreak. Most infections are asymptomatic, non-polio enteroviruses are the most common infectious cause of aseptic meningitis [1]. Several outbreaks resulting from different enterovirus serotypes have been described including but not. Non-polio enteroviruses were traditionally classified into serotypes, based on a neutralization assay and included 64 classical isolates consisting of Coxsackieviruses A, Coxsackieviruses B, echoviruses and several numbered enteroviruses [11]. Typing methods based on sequencing have been previously described in the VP1 [12,13,14], VP2 [15,16], and VP4 [17] regions.

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