Association of Enterovirus D68 with Acute Flaccid Myelitis, Philadelphia, Pennsylvania, USA, 2009-2018

Abstract

Acute flaccid myelitis (AFM) is a polio-like disease that results in paralysis in previously healthy persons. Although the definitive cause of AFM remains unconfirmed, enterovirus D68 (EV-D68) is suspected based on 2014 data demonstrating an increase in AFM cases concomitant with an EV-D68 outbreak. We examined the prevalence in children and the molecular evolution of EV-D68 for 2009-2018 in Philadelphia, Pennsylvania, USA. We detected widespread EV-D68 circulation in 2009, rare detections in 2010 and 2011, and then biennial circulation, only in even years, during 2012-2018. Prevalence of EV-D68 significantly correlated with AFM cases during this period. Finally, whole-genome sequencing revealed early detection of the B1 clade in 2009 and continued evolution of the B3 clade from 2016 to 2018. These data reinforce the need to improve surveillance programs for nonpolio enterovirus to identify possible AFM triggers and predict disease prevalence to better prepare for future outbreaks.

Keywords: EV-D68; Pennsylvania; Philadelphia; United States; acute flaccid myelitis; children; enterovirus; enterovirus D68; viruses; whole-genome sequencing.

Figure 1

Association between AFM and EV-D68 prevalence, Philadelphia, Pennsylvania, USA, 2009–2018. A) The percentage of nasopharyngeal aspirate samples positive for RV/EV that typed as EV-D68 by real-time reverse transcription PCR. B) Comparison of confirmed AFM cases with the prevalence of EV-D68 during the same time period using Spearman correlation ρ and linear regression analysis (n = 10). AFM, acute flaccid myelitis; EV-D68, enterovirus D68; RV/EV, rhinovirus/enterovirus.

Figure 2

Phylogenetic relationships between Philadelphia whole enterovirus D68 (EV-D68) genomes, including AFM cases, Philadelphia, Pennsylvania, USA, 2009–2018. EV-D68 polyprotein sequences from GenBank (n = 55) and this study (n = 28) were used to build a maximum-likelihood tree. EV-D68 clades, defined in prior publications, are indicated. Sequences from this study are indicated in bold, and AFM cases are indicated with that prefix. AFM, acute flaccid myelitis. Scale bar indicates nucleotide substitutions per site.