A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012–14): a retrospective cohort study

In 2014, there was an outbreak of enterovirus D68 throughout the United States. This outbreak was linked to severe respiratory infection, and also occurred at around the same time as an increase in the number of cases of acute flaccid paralysis, or acute flaccid myelitis (AFM). Enterovirus D68 has previously been detected in people with AFM. Individuals with AFM have myelitis, or inflammation of the spinal cord, but the inflammation is located largely in the gray matter of the spinal cord rather than in the white matter as in transverse myelitis. They also have flaccid paralysis, which means their limbs are weak and have reduced muscle tone.

A study by Greninger et al looked to see if there was a link between the 2014 enterovirus D68 outbreak and AFM. They included individuals with AFM who went to Children’s Hospital Colorado or Children’s Hospital Los Angeles from November 24, 2013 to October 11, 2014, or individuals who were identified by the California Department of Public Health between January 1, 2012 and October 4, 2014. Different types of samples (for example, nasopharyngeal and oropharyngeal, blood, cerebrospinal fluid, and stool) were taken from individuals during their time in the hospital. A total of 48 individuals were included in the study, 25 of whom were diagnosed with AFM, two with enterovirus-associated encephalitis (inflammation of the brain), five with enterovirus D68-associated upper respiratory illness, and 16 with aseptic meningitis or encephalitis and also tested positive for enterovirus. Of the 25 individuals with AFM, 11 were part of a cluster of AFM cases, and 14 were not. A cluster occurs when a group of individuals get the same illness at around the same time and in close geographic proximity to one another.

Most individuals with AFM were children and had a median age of 7 years. More than half (60%) of the cases reported were male and most (80%) reported upper respiratory illness before the symptoms of AFM started. 48% of nasopharyngeal and oropharyngeal samples from individuals with AFM tested positive for enterovirus D68. 64% of the 11 individuals who were part of a cluster tested positive for enterovirus D68.

None of the 25 individuals had enterovirus D68 present in their cerebrospinal fluid, but viruses like enterovirus are not usually detected in cerebrospinal fluid. Only one person had enterovirus D68 present in their whole blood and stool samples, but the virus was present in lower numbers than in their nasopharyngeal and oropharyngeal samples.

Those with AFM, whether or not they had enterovirus D68, had similar outcomes.  All continued to have neurological deficits 30 days after onset and in 77% of the individuals, there was no or minimal improvement in paralysis.

The authors believe that the data from this study shows that there is probably an association between enterovirus D68 and AFM. This is because over a third of individuals with AFM had enterovirus D68 present in their samples, and 80% of individuals with AFM had an upper respiratory illness before their AFM, and upper respiratory illness is commonly associated with enterovirus D68. Also, enterovirus D68 was the most common virus that was detected in samples and no other enteroviruses that have been previously linked with AFM were detected. The authors also noted that the samples were collected more than a week after the onset of URI (upper respiratory infection) which probably decreased the numbers of the virus present in samples. Also individuals who were negative for enterovirus D68 had their samples collected later than those who were positive, so this may have made it less likely that the virus would be detected. They also identified a pair of siblings who had the same strain of enterovirus D68. Both siblings had an upper respiratory illness, but one went on to develop AFM. The authors state that this indicates that the way individuals react to enterovirus D68 and how severe their reaction varies from person to person.

Greninger AL, Naccache SN, Messacar K et al. A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012–14): a retrospective cohort study. Lancet Infec Dis. 2015;15:671-82.