by H. Cody Meissner, M.D., FAAP
Enterovirus D68 (EV-D68) was first identified
in California in 1962. Initially, it was classified as
a rhinovirus but now is classified as one of more
than 100 non-polio enteroviruses. For several decades after the initial description, EV-D68 was rarely
recovered from patients. Between 2008 and 2014,
the virus was isolated occasionally from clusters of
children younger than 5 years of age with severe respiratory illness.
Which of the following statements are false?
a) Most enterovirus infections are asymptomatic.
b) Infants and children are at increased risk for
infection by EV-D68 relative to adults because
they are less likely to have developed immunity
from a previous infection.
c) Enterovirus infections are most common in the
summer and fall in the U.S.
d) EV-D68 is reliably inactivated with alco-
hol-based hand rub.
e) EV-D68 is a documented cause of acute flaccid
In the summer and fall of 2014, a nationwide
outbreak of EV-D68 occurred and was associated
with severe respiratory tract disease. In September
2014, the Centers for Disease Control and Prevention (CDC) began to receive reports of AFM, and
a possible association with EV-D68 was considered.
During this enterovirus season, the CDC confirmed
more than 1,100 infections, largely among children,
many of whom had a history of asthma. Many more
people likely experienced a mild EV-D68 infection
for which medical treatment was not sought or from
whom cultures were not obtained.
During the 2015 enterovirus season, the CDC
received about 700 specimens for enterovirus testing,
and none were positive for EV-D68. During most of
2016, sporadic EV-D68 detections occurred in the
U.S., but evidence of unusual activity was not apparent. (See AAP News article “CDC: 108 cases of acute
flaccid myelitis this year,” http://bit.ly/2h YZ9k7.)
EV-D68 should be considered especially during
the summer and fall as a cause of unexplained, severe
acute respiratory illness in children especially during
clusters of disease. Nasopharyngeal or oropharyngeal
specimens that test positive for enterovirus or rhinovirus should be considered for molecular testing
using real-time polymerase chain reaction (PCR) or
nested PCR. Virus may be detected in stool or rectal swabs for a longer period than from respiratory
Infection-control precautions for suspected cases
should include standard, contact and droplet precau-
tions. Non-enveloped viruses such as EV-D68 may
be less susceptible to alcohol inactivation than en-
veloped viruses. Hand hygiene with soap and water
upon removal and prior to donning of gloves may
be preferred to alcohol-based hand rub.
Between 2012 and 2015, an increasing number of
reports of a distinct syndrome of acute flaccid paralysis with anterior myelitis was noted. Symptoms were
similar to those caused by polio viruses and to avoid
confusion, the term acute flaccid myelitis (AFM) was
proposed. AFM is defined as a case of acute flaccid
weakness with either spinal cord gray matter lesions
detected on imaging or evidence of spinal cord motor neuron injury on electrodiagnostic testing.
A typical case of AFM is preceded by a median
of five days with rhinorrhea, cough or pharyngitis.
Gastrointestinal symptoms (vomiting, diarrhea)
are reported in about two-thirds of patients. Most
patients report improvement of symptoms prior
to return of fever and onset of muscle sti;ness or
pain around the time of neurologic deficit onset.
Over a period of a few hours to a few days, there is
progression from full strength to neurologic deficit.
Weakness is flaccid with decreased or absent reflexes
in one to four extremities and generally is asymmetric. Limb weakness may be accompanied by
cranial nerve dysfunction resulting in hypophonia
(soft speech), dysarthria, dysphagia, facial weakness
Optimal management of a patient with AFM
is not clear. Immunomodulatory agents, antiviral
agents, intravenous immune globulin, high-dose
corticosteroids and plasmapheresis have not been
evaluated in a controlled fashion, and no significant
improvement or deterioration has been described
with these interventions.
;ree antiviral drugs in clinical
trials for treatment of other enterovirus infections (pleconaril, poca-pavir, vapendavir) do not demonstrate activity against EV-D68 in
vitro. Fluoxetine (Prozac), a selective serotonin reuptake inhibitor,
interferes with EV-D68 replication
in vitro, but its role as a therapeutic
agent has not been evaluated.
Causes of AFM include polio
virus and non-polio enteroviruses (such as enteroviruses A71 and
D70), West Nile virus, Japanese
encephalitis virus, St. Louis encephalitis virus and adenoviruses.
Non-infectious causes include environmental toxins, genetic disorders, Guillain-Barré syndrome and
acute disseminated encephalomyelitis.
Although a mild to moderate
pleocytosis in the cerebrospinal
fluid (CSF) generally is present,
;e proposed association between EV-D68 infection and AFM is based on epidemiologic evidence.
;e increase in AFM and EV-D68 infections both
temporally and geographically suggests an association. ;e biologic plausibility of an association is
substantiated by evidence supporting other non-polio enteroviruses as a cause of paralysis.
Dr. Meissner is professor of pediatrics
at Floating Hospital for Children, Tufts
Medical Center. He also is an ex o;cio
member of the AAP Committee on Infectious Diseases and associate editor of
the AAP Visual Red Book.
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Image courtesy of the Centers for Disease Control and Prevention
Electron micrograph of a thin section of EV-D68-infected cell showing
numerous spherical viral particles in the cytoplasm.
Is EV-D68 infection a cause of acute flaccid myelitis in children?
A ns w er: d a n d e are n ot c orre ct