Increase in Enterovirus D68 Infections in Young Children, United Kingdom, 2006–2016

Everlyn Kamau; Heli Harvala; Soile Blomqvist; Dung Nguyen; Peter Horby; Richard Pebody; Peter Simmonds


Emerging Infectious Diseases. 2019;25(6):1200-1203. 

In This Article


The seroprevalence of EV-D68 approached 100% in adult UK populations in this study, consistent with previous seroepidemiology studies conducted in Finland and China.[11,12] Our findings provide further evidence for the wide circulation of EV-D68 infections before reported outbreaks in 2014 and 2016. We demonstrated high incidences of EV-D68 infection in young children; around one half are already infected by 2 years of age in both sampling periods. However, the seroprevalence of EV-D68 infection was consistently higher throughout childhood in 2016 samples than in 2006 samples (Figure 1).

Changes in population immunity, virus antigenicity, transmissibility, cellular tropism, and pathogenicity may contribute to the recent upsurge of severe EV-D68 infections worldwide. Concerning the first potential explanation, seroprevalences in age groups <40 years were consistently lower in 2006 than 2016 (Figure 1, panel B), although EV-D68 circulated extensively, and adults were almost always seropositive and immune before and after periods of greater disease severity in the United Kingdom and elsewhere.[4,13] Changes in NAb susceptibility and escape from population immunity appear unlikely to be a cause of changes in incidence; we found no evidence for major differences in antigenicity between Fermon, genotype D, or B3 isolates (Appendix Figure 1). Another possible cause is increased transmissibility of subgenotypes B2 and B3 in younger age groups (Figure 2, panel A), reflecting a possible change in tropism or persistence of virus shedding and longer periods of infectivity after changes in receptor use, cellular tropisms, or both. The Fermon prototype strain of EV-D68 isolated in 1962 has a stronger affinity to α2,6-sialic acid primarily in the airways than to α2,3-linked sialic acid present in the lower respiratory tract.[14] Whether the newer EV-D68 strains causing an outbreak of severe respiratory infections in 2008–2010 were evolved to use primarily α2,3-linked sialic acid or have switched to a sialic acid-independent mechanism of virus entry,[14] such as ICAM5,[15] needs further investigation. Of note, only contemporary EV-D68 strains were able to infect neuroblastoma-derived neuronal cell line SH-SY5Y and cause paralysis in a mouse model, indicating that additional changes in virus strains might have occurred around or after 2012,[8] although the relationship of this finding to increased transmissibility of EV-D68 has not been studied.

In summary, we document the greater circulation and force of EV-D68 infection in infants and young children in the United Kingdom over the period in which EV-D68 has emerged as an important respiratory pathogen and potential cause of paralytic disease, reflecting its changed transmissibility and pathogenic potential. Such rapid changes in virus behavior emphasize the importance of ongoing surveillance and appropriate diagnostics for emerging enteroviruses in the future.