TY - JOUR
T1 - The association between acute flaccid myelitis (AFM) and enterovirus D68 (EV-D68)
T2 - what is the evidence for causation?
AU - Dyda, Amalie
AU - Stelzer-Braid, Sacha
AU - Adam, Dillon
AU - Chughtai, Abrar A.
AU - Macintyre, C. Raina
N1 - Copyright the Author(s) 2018. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2018/1/18
Y1 - 2018/1/18
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85041924107&partnerID=8YFLogxK
U2 - 10.2807/1560-7917.ES.2018.23.3.17-00310
DO - 10.2807/1560-7917.ES.2018.23.3.17-00310
M3 - Review article
C2 - 29386095
AN - SCOPUS:85041924107
SN - 1025-496X
VL - 23
SP - 1
EP - 9
JO - Eurosurveillance
JF - Eurosurveillance
IS - 3
M1 - 17-00310
ER -