Acute flaccid myelitis (AFM) appears to have a viral etiology, but
exactly which virus is causing the polio-like illness remains unknown,
according to an analysis of pediatric cases reported to the CDC from
2015 to 2017.
Among 193 children with
confirmed AFM,
79% reported a respiratory or febrile illness from 2 to 7 days before
limb weakness set in, and the cases tended to cluster in the late summer
or fall, reported Tracy Ayers, PhD, of the CDC in Atlanta, Georgia, and
colleagues.
Although no single pathogen was identified as the driving force
behind these cases, viral pathogens were found in almost half of
patients (47%), with coxsackievirus A16 detected in the cerebrospinal
fluid and serum of one patient and enterovirus D68 — the most
predominant pathogen detected in the
2014 outbreak — detected in serum of another, they wrote in
Pediatrics.
Together, these findings “strongly suggest a viral etiology, including [enteroviruses],” the authors stated.
AFM, a rare condition characterized by acute onset of focal limb
weakness and spinal cord gray matter lesions, was classified as such
during the 2014 outbreak, in which 120 individuals contracted the
disorder from August through December of that year.
AFM made national news in 2018, with a total of
228 confirmed cases
in 41 U.S. states, and four confirmed cases in 2019. The spike in
reported cases in 2018 was so dramatic that the CDC announced they would
start
tracking AFM cases.
Importantly, 143 cases (74%) in this study occurred in 2016, “fitting
within the larger epidemiological context of a biennial pattern of AFM
outbreaks in the U.S. documented from 2014 to 2018,” wrote Samuel
Dominguez, MD, PhD, of Children’s Hospital Colorado in Aurora, and
colleagues, in an
accompanying commentary.
However, myelitis in the grey matter of the spinal cord has been
associated with poliovirus, non-polio enteroviruses, flaviviruses, and
autoantibody conditions, Dominguez and colleagues noted.
“As such, a single etiology to explain all cases of the clinical
syndrome of AFM at all times would not be expected,” they wrote.
Although enterovirus D68 appears to be the most likely driving force
behind AFM, widespread enterovirus circulation makes it difficult to
establish a causal relationship when collected from nonsterile sites,
the authors reported.
“Serologic evidence of widespread infection with EV-D68, even before
the first notable increase of AFM in 2014, suggests that if EV-D68 was
the primary cause of AFM in 2014 and 2016, other factors must play a
role in the development of this rare outcome,” they wrote.
AFM outbreaks need to be analyzed separately from the “background
noise” of endemic AFM, Dominguez’s group wrote. Developing intrathecal
enterovirus antibody tests for cerebrospinal fluid could also improve
the ability to diagnose cases, they added.
All cases in this analysis were confirmed to be AFM by an expert
panel of pediatricians and neurologists. The CDC requested sterile site
and nonsterile-site specimens from each of the patients with confirmed
AFM, which were tested for poliovirus, enteroviruses, rhinoviruses, and
parechoviruses.
Overall, 305 incidents were reported from 43 states, of which 193
pediatric cases were confirmed. Children tended to be white (53%) and
male (61%) with a median age of 6 years.
Across the 3-year study period, the majority of cases occurred from
August through November (61%). In 2016 when the number of cases peaked,
88% of cases occurred from August through November, the authors
reported.
At the time of limb weakness onset, one-third of patients had cranial
nerve findings (33%), quadriplegia (36%), or required mechanical
ventilation (33%), the authors reported. Over one-quarter presented with
an altered mental status at this time (28%).
Poliovirus was not detected in any cases, and enterovirus D68 was
found in about one-quarter of confirmed cases from 2015 through 2017
(24%), although it was also found in patients with misclassified AFM.
In CDC laboratories, 32 of 90 children with upper respiratory
specimens were positive for enterovirus and rhinovirus (36%) and 15 of
77 kids with stool samples were positive for enterovirus and rhinovirus
(19%), the authors reported.
Also, in non-CDC laboratories, 61 of 151 children who had respiratory
specimens tested were positive for enterovirus and rhinovirus (46%) and
22 of 78 patients with stool samples were positive for enterovirus and
rhinovirus (52%), they added.
The number of cases to be reported in the study period across the
U.S. could be underestimated as AFM is not a nationally notifiable
condition, and has a range of clinical severity, the authors reported.
Also, enterovirus surveillance is limited by geographic variability and
an inability to determine type-specific trends by year, they added.
“Enhanced AFM surveillance with focused analysis of distinct signals
from outbreak periods is essential to targeting the development of
specific therapeutics and preventive vaccines to combat this potentially
devastating neurologic condition,” according to Dominguez and
colleagues.
Ayers and co-authors disclosed no relevant relationships with industry.
Dominguez disclosed no relevant relationships with industry. A
co-author disclosed support from the National Institute of Allergy and
Infectious Diseases.
