The association between acute flaccid myelitis (AFM) and enterovirus D68 (EV-D68) – what is the evidence for causation?

Dyda, A; Stelzer-Braid, S; Adam, D; Chughtai, AA; Macintyre, CR

The association between acute flaccid myelitis (AFM) and enterovirus D68 (EV-D68) – what is the evidence for causation?

Dyda, A Stelzer-Braid, S

Adam, D Chughtai, AA Macintyre, CR

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Publication Type:: Journal Article
Citation:: Eurosurveillance, 2018, 23 (3)
Issue Date:: 2018-01-18

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Field	Value	Language
dc.contributor.author	Dyda, A	en_US
dc.contributor.author	Stelzer-Braid, S https://orcid.org/0000-0001-6037-9305	en_US
dc.contributor.author	Adam, D	en_US
dc.contributor.author	Chughtai, AA	en_US
dc.contributor.author	Macintyre, CR	en_US
dc.date.issued	2018-01-18	en_US
dc.identifier.citation	Eurosurveillance, 2018, 23 (3)	en_US
dc.identifier.issn	1025-496X	en_US
dc.identifier.uri	http://hdl.handle.net/10453/131043
dc.description.abstract	© 2018, European Centre for Disease Prevention and Control (ECDC). All rights reserved. Background: Enterovirus D68 (EV-D68) has historically been a sporadic disease, causing occasional small outbreaks of generally mild infection. In recent years, there has been evidence of an increase in EV-D68 infections globally. Large outbreaks of EV-D68, with thousands of cases, occurred in the United States, Canada and Europe in 2014. The outbreaks were associated temporally and geographically with an increase in clusters of acute flaccid myelitis (AFM). Aims: We aimed to evaluate a causal association between EV-D68 and AFM. ?Methods: Using data from the published and grey literature, we applied the Bradford Hill criteria, a set of nine principles applied to examine causality, to evaluate the relationship between EV-D68 and AFM. Based on available evidence, we defined the Bradford Hill Criteria as being not met, or met minimally, partially or fully. Results: Available evidence applied to EV-D68 and AFM showed that six of the Bradford Hill criteria were fully met and two were partially met. The criterion of biological gradient was minimally met. The incidence of EV-D68 infections is increasing worldwide. Phylogenetic epidemiology showed diversification from the original Fermon and Rhyne strains since the year 2000, with evolution of a genetically distinct outbreak strain, clade B1. Clade B1, but not older strains, is associated with AFM and is neuropathic in animal models. Conclusion: While more research is needed on dose–response relationship, application of the Bradford Hill criteria supported a causal relationship between EV-D68 and AFM.	en_US
dc.relation.ispartof	Eurosurveillance	en_US
dc.relation.isbasedon	10.2807/1560-7917.ES.2018.23.3.17-00310	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Enterovirus D, Human	en_US
dc.subject.mesh	Central Nervous System Viral Diseases	en_US
dc.subject.mesh	Myelitis	en_US
dc.subject.mesh	Enterovirus Infections	en_US
dc.subject.mesh	Neuromuscular Diseases	en_US
dc.subject.mesh	Disease Outbreaks	en_US
dc.title	The association between acute flaccid myelitis (AFM) and enterovirus D68 (EV-D68) – what is the evidence for causation?	en_US
dc.type	Journal Article
utslib.citation.volume	3	en_US
utslib.citation.volume	23	en_US
utslib.for	1117 Public Health and Health Services	en_US
utslib.for	0605 Microbiology	en_US
utslib.for	1199 Other Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.issue	3	en_US
pubs.publication-status	Published	en_US
pubs.volume	23	en_US

Abstract:

© 2018, European Centre for Disease Prevention and Control (ECDC). All rights reserved. Background: Enterovirus D68 (EV-D68) has historically been a sporadic disease, causing occasional small outbreaks of generally mild infection. In recent years, there has been evidence of an increase in EV-D68 infections globally. Large outbreaks of EV-D68, with thousands of cases, occurred in the United States, Canada and Europe in 2014. The outbreaks were associated temporally and geographically with an increase in clusters of acute flaccid myelitis (AFM). Aims: We aimed to evaluate a causal association between EV-D68 and AFM. ?Methods: Using data from the published and grey literature, we applied the Bradford Hill criteria, a set of nine principles applied to examine causality, to evaluate the relationship between EV-D68 and AFM. Based on available evidence, we defined the Bradford Hill Criteria as being not met, or met minimally, partially or fully. Results: Available evidence applied to EV-D68 and AFM showed that six of the Bradford Hill criteria were fully met and two were partially met. The criterion of biological gradient was minimally met. The incidence of EV-D68 infections is increasing worldwide. Phylogenetic epidemiology showed diversification from the original Fermon and Rhyne strains since the year 2000, with evolution of a genetically distinct outbreak strain, clade B1. Clade B1, but not older strains, is associated with AFM and is neuropathic in animal models. Conclusion: While more research is needed on dose–response relationship, application of the Bradford Hill criteria supported a causal relationship between EV-D68 and AFM.

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http://hdl.handle.net/10453/131043