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The association between acute flaccid myelitis (AFM) and Enterovirus D68 (EV-D68) - what is the evidence for causation?
Euro Surveill. 2018 01; 23(3)ES

Abstract

BackgroundEnterovirus 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 world-wide. 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.

Authors+Show Affiliations

School of Public Health and Community Medicine, University of New South Wales (UNSW), Sydney, New South Wales (NSW), Australia.Division of Serology and Virology, South Eastern Area Laboratory Services, Prince of Wales Hospital, Sydney, Australia. School of Medical Sciences, University of New South Wales (UNSW), Sydney, New South Wales (NSW), Australia.School of Public Health and Community Medicine, University of New South Wales (UNSW), Sydney, New South Wales (NSW), Australia.School of Public Health and Community Medicine, University of New South Wales (UNSW), Sydney, New South Wales (NSW), Australia.College of Public Service and Community Solutions and College of Health Solutions, Arizona State University, Tempe, Arizona, United States. School of Public Health and Community Medicine, University of New South Wales (UNSW), Sydney, New South Wales (NSW), Australia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

29386095

Citation

Dyda, Amalie, et al. "The Association Between Acute Flaccid Myelitis (AFM) and Enterovirus D68 (EV-D68) - what Is the Evidence for Causation?" Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin, vol. 23, no. 3, 2018.
Dyda A, Stelzer-Braid S, Adam D, et al. The association between acute flaccid myelitis (AFM) and Enterovirus D68 (EV-D68) - what is the evidence for causation? Euro Surveill. 2018;23(3).
Dyda, A., Stelzer-Braid, S., Adam, D., Chughtai, A. A., & MacIntyre, C. R. (2018). The association between acute flaccid myelitis (AFM) and Enterovirus D68 (EV-D68) - what is the evidence for causation? Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin, 23(3). https://doi.org/10.2807/1560-7917.ES.2018.23.3.17-00310
Dyda A, et al. The Association Between Acute Flaccid Myelitis (AFM) and Enterovirus D68 (EV-D68) - what Is the Evidence for Causation. Euro Surveill. 2018;23(3) PubMed PMID: 29386095.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The association between acute flaccid myelitis (AFM) and Enterovirus D68 (EV-D68) - what is the evidence for causation? AU - Dyda,Amalie, AU - Stelzer-Braid,Sacha, AU - Adam,Dillon, AU - Chughtai,Abrar A, AU - MacIntyre,C Raina, PY - 2018/2/2/entrez PY - 2018/2/2/pubmed PY - 2019/1/19/medline KW - AFM KW - Bradford Hill Criteria KW - EV-D68 KW - Enterovirus D68 KW - acute flaccid myelitis KW - acute flaccid paralysis JF - Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin JO - Euro Surveill. VL - 23 IS - 3 N2 - BackgroundEnterovirus 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 world-wide. 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. SN - 1560-7917 UR - https://www.unboundmedicine.com/medline/citation/29386095/The_association_between_acute_flaccid_myelitis__AFM__and_Enterovirus_D68__EV_D68____what_is_the_evidence_for_causation L2 - http://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2018.23.3.17-00310 DB - PRIME DP - Unbound Medicine ER -