Molecular diversity and biennial circulation of enterovirus D68: a systematic screening study in Lyon, France, 2010 to 2016

Abstract

BackgroundUnderstanding enterovirus D68 (EV-D68) circulation patterns as well as risk factors for severe respiratory and neurological illness is important for developing preventive strategies. Methods: Between 2010 and 2016, 11,132 respiratory specimens from hospitalised patients in Lyon, France, were screened for EV-D68 by PCR. Phylogenetic relationships of the viral-protein-1 sequences were reconstructed using maximum-likelihood and Bayesian-Markov-Chain-Monte-Carlo approaches. Results: Overall, 171 infections with a biennial pattern were detected, including seven, one, 55, none, 42, one and 65 cases annually during 2010–16. Children (< 16 years-old; n = 150) were mostly affected and 71% (n = 121) of the total patients were under 5 years-old. In 146 patients with medical reviews, 73% (n = 107) presented with acute respiratory distress. Among paediatric patients with medical reviews (n = 133), 55% (n=73) had an asthma/wheezing history, while among adults (n = 13), 11 had underlying diseases. In total, 45 patients had severe infections and 28 patients needed intensive care unit stays. No acute flaccid myelitis (AFM) was detected. We found genotypes A, B1, B2 B3 and D circulating, and no associations between these and clinical presentations. During the study, new genotypes continuously emerged, being replaced over time. We estimated that ancestors of currently circulating genotypes emerged in the late-1990s to 2010. Rises of the EV-D68 effective population size in Lyon coincided with infection upsurges. Phylogenetic analyses showed ongoing diversification of EV-D68 worldwide, coinciding with more infections in recent years and increases of reported AFM paediatric cases. Conclusions: Reinforcement of diagnostic capacities and clinical-based surveillance of EV-D68 infections is needed in Europe to assess the EV-D68 burden.

Co-circulation of multiple enterovirus D68 subclades, including a novel B3 cluster, across Europe in a season of expected low prevalence, 2019/20

“…Enterovirus D68 (EV-D68) is primarily a respiratory virus. Previously published data have suggested circulation with a biennial epidemic cycle in Europe and North America [1][2][3], but surveillance is not consistent. The Danish enterovirus surveillance detected two cases of EV-D68 infection in August 2019 and a further case in early September.…”

Detection of Enterovirus D68 in wastewater samples from the United Kingdom during outbreaks reported globally between 2015 and 2018

“…The first known large outbreak of severe respiratory illness associated with EV-D68 infection occurred in the USA between August and December 2014 (Holm-Hansen et al 2016). Genetically related EV-D68 strains were also found during the same period in Canada, Europe and Asia with more than 2,000 cases reported in 20 countries (Kramer et al 2018). These outbreaks were temporally and geographically associated with an increase in AFM cases, particularly in the USA, and a similar association was observed in Europe, Argentina and the USA in 2016 (Cassidy et al 2018).…”

“…Infection with enterovirus D68 (EV-D68) has been associated with severe respiratory disease in humans with increasing evidence of its link to neurological complications causing acute flaccid myelitis (AFM), a polio-like syndrome resulting in long-term or permanent disability (Cassidy et al 2018). Although EV-D68 was first identified in 1962, it was rarely reported until 2008 when small outbreaks started to emerge in what appears to be mostly a biannual distribution (Kramer et al 2018). The first known large outbreak of severe respiratory illness associated with EV-D68 infection occurred in the USA between August and December 2014 (Holm-Hansen et al 2016).…”

Molecular Pathogenicity of Enteroviruses Causing Neurological Disease

“…Recent epidemiological criteria using the Bradford-Hill analyses showed strong support that AFM is primarily caused by EV-D68 (Dyda et al, 2018;Messacar et al, 2018). The particular cyclical and biennial patterns of EV-D68 infections correlated well with outbreaks of AFM in children occurring in 2014(Dyda et al, 2018Kramer et al, 2018). However, detecting the virus from clinical samples remains a challenge and contributed to skepticism surrounding EV-D68 as a cause of AFM.…”