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The association between acute flaccid myelitis (AFM) and Enterovirus D68 (EV-D68) - what is the evidence for

Amalie Dyda1, Sacha Stelzer-Braid2,3, Dillon Adam1

  • 1School of Public Health and Community Medicine, University of New South Wales (UNSW), Sydney, New South Wales (NSW), Australia.

Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin
|February 2, 2018
PubMed

Insights

Enterovirus D68 (EV-D68) is increasingly linked to acute flaccid myelitis (AFM). Applying the Bradford Hill criteria suggests a causal relationship between EV-D68 and AFM, particularly with the newer clade B1 strain.

Area of Science:

  • Virology
  • Neurology
  • Epidemiology

Background:

  • Enterovirus D68 (EV-D68) infections, historically mild, have seen increased global incidence.
  • Large EV-D68 outbreaks in 2014 coincided with a rise in acute flaccid myelitis (AFM) clusters.
  • The emergence of a distinct EV-D68 clade B1 strain correlates with AFM cases.

Purpose of the Study:

  • To investigate a potential causal association between EV-D68 and AFM.
  • To apply the Bradford Hill criteria to assess causality.
  • To evaluate the role of specific EV-D68 strains in AFM pathogenesis.

Main Methods:

  • Systematic review of published and grey literature.
  • Application of the nine Bradford Hill criteria for causality assessment.
  • Phylogenetic analysis of EV-D68 strains.

Main Results:

  • Six of nine Bradford Hill criteria were fully met, and two were partially met, supporting causality.
  • The EV-D68 clade B1 strain, unlike older strains, is associated with AFM and demonstrates neuropathic effects in animal models.
  • Increasing global incidence of EV-D68 infections noted.

Conclusions:

  • The Bradford Hill criteria provide strong support for a causal link between EV-D68 and AFM.
  • Further research is warranted to explore the dose-response relationship.
  • The neuropathic clade B1 strain is a key factor in the EV-D68-AFM association.
Keywords:
AFMBradford Hill CriteriaEV-D68Enterovirus D68acute flaccid myelitisacute flaccid paralysis

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