Compared to just three cases in 2014, Europe had at least 31
cases of AFM in in 2016, all of them linked to enterovirus D68, reported Bert
Niesters, PhD, professor of medical microbiology and director of the laboratory
of clinical virology at the University Medical Center Groningen in the
Netherlands.
No prior medical or news publication has reported on
European-wide figures for AFM linked to EV-D68 until now, and such reports as
were published described only a handful of cases in widely scattered countries.
Even the 31 cases, Dr. Niesters said, is almost certainly an
under-count.
“We are missing data from Eastern Europe, and many of the
countries we do have data from are only partial,” Dr. Niesters told Neurology
Today in a telephone interview. “In Europe AFM is not mandated to be reported
everywhere, and even when it is, it is only when linked to polio. There is no
common infrastructure. We have to join together to make people more aware of
this issue.”
The presentation to the European Centre for Disease
Prevention and Control by Dr. Niesters, who is editor-in-chief of the Journal
of Clinical Virology, included 12 cases of AFM for which full clinical and
imaging data was available, another 19 based on personal communications he had
with clinicians and public health authorities across the continent, and five
more probable cases based on personal communications. The 31 cases came from 12
countries, all of them in Western Europe: Ireland (1), Scotland (5), Wales (3),
Norway (3), Sweden (3), Denmark (3), Netherlands (2), France (4), Spain (2),
Germany (2), Austria (1), and Italy (2)…
“The virus was seen in the US, but the ECDC insisted at the
time that there was no problem in Europe,” Dr. Niesters said. “We disagreed,
and during a virology conference in Prague, we asked our colleagues to test for
the virus. We tested over 17,000 samples in a few months and found that it was
present in Europe and related to the US strain. However, only three cases of
AFM were reported that year in Europe.”
Beyond the 31 cases in Europe in 2016, Dr. Niesters said
there are likely many more that have gone unreported.
“The number of cases in Germany and Italy are improbably
low, given the number of inhabitants there,” he said. “And Eastern Europe is
especially problematic. We have nothing out of those countries. They don't seem
to have the resources.”…
“I don't think we have a good handle on the numbers,” said
Carol Glaser, MD, a pediatric infectious disease specialist at Kaiser
Permanente in Oakland, CA. “When we have to depend on physicians to report
something to a public health department, it just doesn't happen well. It's
time-consuming and complicated for them.”
Manisha Patel, MD, the leader of the CDC team investigating
the outbreak, said that the CDC is working closely with the Council of State
and Territorial Epidemiologists (CSTE), as well as with clinicians and health
departments, to continue to improve surveillance and understand what is causing
AFM. Even so, she said, “It's still a very rare disease, with less than one in
a million cases. With any serious condition, especially one that affects
children, there's always concern. But it is important to know that it is rare.
In any rare condition, there's a lot of thought that goes into exactly what is
the ultimate goal in terms of identifying how common this illness is, what
might be causing it, and how to protect individuals.”…
Dr. Engel said he doubted that many cases of AFM are going
unreported. “When the outcomes are dramatic, like AFM, a lot of times the
health departments depend on the public to report these things. I don't think
there are children out there with paralyzed limbs who have gone unreported in
great numbers. Moms and dads would call the health departments directly, just
as they do when a food-borne outbreak is related to a particular restaurant.”…
Dr. Greenberg organized a meeting in Dallas on January 23 of
over two dozen neurologists, virologists, and epidemiologists who shared their
expertise and experience on AFM and EV-D68.
The take-away from the meeting, he said, was that “we're not
done with this virus. There is no anti-viral to treat it. It's got a worldwide
footprint. It's human-to-human transmissible. It's got more rhinovirus
capability rather than the classical enteroviruses. It's spread by nasal-oral transmission,
which is a bigger deal [than oral-fecal]. It's meeting all the criteria for a
major national resource investment. I'd just love to see that investment made
now, when there's been about 250 children affected, rather than waiting till it
affects 2,000.”…
John B. Bodensteiner, MD, FAAN, who served as president of
the Child Neurology Society from 2007 to 2009, and is presently a consultant in
child and adolescent neurology with the Mayo Clinic in Rochester, MN, said that
he is certain that cases of AFM are, in fact, falling through the cracks
without being reported to public health authorities.
“I saw a child just last week who was not properly diagnosed
as having AFM for more than six months,” said Dr. Bodensteiner. “It's being
misdiagnosed in some cases as transverse myelitis or Guillain-Barré.”
http://journals.lww.com/neurotodayonline/Fulltext/2017/03020/Rise_in_Acute_Flaccid_Myelitis_Cases_Reported_in.4.aspx
See: http://childnervoussystem.blogspot.com/2016/10/acute-flaccid-myelitis.html
Alison M. Hixon, Guixia Yu, J. Smith Leser, Shigeo Yagi, Penny Clarke, Charles Y. Chiu, Kenneth L. Tyler. A mouse model of paralytic myelitis caused by enterovirus D68. PLOS Pathogens. Published: February 23, 2017http://dx.doi.org/10.1371/journal.ppat.1006199
ReplyDeleteAbstract
In 2014, the United States experienced an epidemic of acute flaccid myelitis (AFM) cases in children coincident with a nationwide outbreak of enterovirus D68 (EV-D68) respiratory disease. Up to half of the 2014 AFM patients had EV-D68 RNA detected by RT-PCR in their respiratory secretions, although EV-D68 was only detected in cerebrospinal fluid (CSF) from one 2014 AFM patient. Given previously described molecular and epidemiologic associations between EV-D68 and AFM, we sought to develop an animal model by screening seven EV-D68 strains for the ability to induce neurological disease in neonatal mice. We found that four EV-D68 strains from the 2014 outbreak (out of five tested) produced a paralytic disease in mice resembling human AFM. The remaining 2014 strain, as well as 1962 prototype EV-D68 strains Fermon and Rhyne, did not produce, or rarely produced, paralysis in mice. In-depth examination of the paralysis caused by a representative 2014 strain, MO/14-18947, revealed infectious virus, virion particles, and viral genome in the spinal cords of paralyzed mice. Paralysis was elicited in mice following intramuscular, intracerebral, intraperitoneal, and intranasal infection, in descending frequency, and was associated with infection and loss of motor neurons in the anterior horns of spinal cord segments corresponding to paralyzed limbs. Virus isolated from spinal cords of infected mice transmitted disease when injected into naïve mice, fulfilling Koch’s postulates in this model. Finally, we found that EV-D68 immune sera, but not normal mouse sera, protected mice from development of paralysis and death when administered prior to viral challenge. These studies establish an experimental model to study EV-D68-induced myelitis and to better understand disease pathogenesis and develop potential therapies.
Author summary
Reports of polio-like paralysis, referred to as acute flaccid myelitis (AFM), have recently emerged in association with infections caused by enterovirus D68 (EV-D68). In the second half of 2014, 120 cases of AFM, mostly in young children, were reported during a nationwide outbreak of EV-D68 respiratory disease. The number of AFM cases has risen again in 2016. Although epidemiological evidence between EV-D68 infection and AFM is accumulating, a causal link has not been definitely established. Here we demonstrate that strains of EV-D68 recovered during the 2014 epidemic can cause a paralytic illness in mice that resembles human AFM. Evidence that EV-D68 causes paralysis in this mouse model include: (1) loss of spinal cord motor neurons innervating paralyzed limbs, (2) detection of virus in the spinal cord and, specifically, motor neurons, (3) transmission of neurological disease when injecting virus isolated from spinal cords of paralyzed mice into naïve mice, thus fulfilling Koch’s postulates, and (4) the ability to prevent AFM by pre-administering serum containing EV-D68 antibodies from previously infected mice. This experimental mouse model can be used to better understand the pathogenesis of EV-D68-induced CNS disease and to facilitate the development of potential therapies.
Courtesy of: http://journals.lww.com/neurotodayonline/Fulltext/2017/03020/New_Mouse_Model_Developed_for_Acute_Flaccid.5.aspx