Acute flaccid myelitis – blame an enterovirus, not the polio vaccine

In 2014, I reported on an outbreak of a mysterious viral disease that exhibited polio-like symptoms. At the time, around 23 children and young adults were afflicted with this polio-like syndrome, known as acute flaccid myelitis. Since then, a total of around 350 individuals have been stricken by the acute flaccid myelitis from 2014 through 2018.

Recent reports of another outbreak of acute flaccid myelitis in Minnesota has brought out zombie memes pushed by the anti-vaccine religion, they blame acute flaccid myelitis on the polio vaccine. Of course, these bogus claims aren’t based on any scientific evidence, but that’s never stopped the anti-vaccine zealots.

These outbreaks have caused the public health sleuths to search for the actual causes of this polio-like syndrome. And there just isn’t any robust or valid evidence that the polio vaccine is any way related to acute flaccid myelitis.

As we know, polio can be a crippling and potentially deadly infectious disease caused by the poliovirus, a human enterovirus, that spreads from person to person invading the brain and spinal cord and causing paralysis. Because polio has no cure, the polio vaccine is the best way to protect ourselves from the crippling disease.

The United States last experienced a polio epidemic in the 1950sprior to the introduction of the polio vaccine 60 years ago. Today, polio has been eradicated from most of the planet, as the number of worldwide polio cases has fallen from an estimated 350,000 in 1988 to 113 in 2017 – a decline of more than 99% in reported cases.

Because real scientists wanted to know what caused this acute flaccid myelitis outbreak, they tried to hunt down the actual cause. And that’s when they landed on enterovirus 68, a once-rare virus. As we always do, we’ll look at the facts behind this virus and it’s relationship to polio (or polio vaccines).

Enteroviruses

Enteroviruses are a genus of several RNA viruses that are associated with numerous human and mammalian diseases. As of today, researchers have identified 71 different serotypes of human enteroviruses, although there is some variability in antigens within each of the different serotypes.

Early in the research on these viruses, they were given separate names, such as poliovirusesCoxsackie A virusesCoxsackie B viruses, and echoviruses. Today, the viruses, as they are identified, are given names in a system of consecutive numbers. Enterovirus 68 (known as EV68, EV-D68, or HEV68) is the 68th in the list of these viruses.

Although many people claim that enteroviruses are only transmitted from the stool of an infected person (hence the “entero” portion of the name of the virus), it also can be found in respiratory secretions. Probably, the most famous enterovirus is the poliovirus which is responsible for poliomyelitis.

Poliovirus is an enterovirus, but not all enteroviruses cause polio. There are 64 non-polio enteroviruses that can cause disease in humans – 23 Coxsackie A viruses, 6 Coxsackie B viruses, 28 echoviruses, and 5 other enteroviruses. Several of these viruses, such as poliovirus, are transmitted through the oral-fecal route, but others can be transmitted through oral-oral routes like simple sneezing.

According to the CDC, there have been many non-polio enterovirus outbreaks across the world recently:

  • Coxsackievirus A16 is the most common cause of hand, foot, and mouth disease (HFMD) in the United States.
  • Coxsackievirus A6 was the most commonly reported type of enterovirus in this country from 2009 to 2013, mostly due to a large outbreak in 2012 of severe hand, foot, and mouth disease. Some of the infected people developed symptoms that were more severe than usual.
  • Coxsackievirus A24 and enterovirus 70 have been associated with outbreaks of conjunctivitis.
  • Echoviruses 13, 18, and 30 have caused outbreaks of viral meningitis in the United States.
  • Enterovirus 71 has caused large outbreaks of HFMD worldwide, especially in children in Asia. Some infections from this virus have been associated with severe neurologic disease, such as brainstem encephalitis.
  • Enterovirus 68 caused a nationwide outbreak in 2014 of severe respiratory illness in the United States.

So, enteroviruses are quite common and have been associated with numerous outbreaks across the world.

Enterovirus 68

I first became aware of EV68 when I read a 2014 report from the CDC which described results from testing of 23 children in California who had presented with the polio-like syndrome or acute flaccid myelitis. The syndrome is a muscle weakness or paralysis along with an infection of the grey matter of the spinal cord. In general, these are symptoms of paralytic polio, though many other viruses can present with the same symptoms (See note 1).

EV68 almost always causes various respiratory illnesses, which can vary from mild to severe. However, the symptoms can range from nothing to flu-like to polio-like. Generally, the initial symptoms are like the common cold, which include a runny nose, sore throat, cough, and fever. As the infection progresses, more serious symptoms may arise up to and including flaccid paralysis.

The majority of people who are exposed to EV68 may not realize that they’ve contracted the disease. In healthy adults, the disease is mostly asymptomatic, and they may not even know that they had contracted the virus. However, EV68 is disproportionately debilitating to very young children. It is in this group that we need to focus. 

Outbreak of polio-like syndrome

As I mentioned previously, the CDC examined the early data on 23 patients who had contracted AFM. They determined that none of the patients had any form of the poliovirus. They also couldn’t find any evidence of a recent infection with any other infectious agent that could possibly be linked to AFM. In addition, they found that apparently only two of the patients had an EV68 infection.

In another study, published in Lancet Infectious Diseases, the researchers closely examined samples from 14 patients with AFM with an EV68 infection – they could not find any other infectious disease, other than EV68. The authors concluded that:

These findings strengthen the putative association between enterovirus D68< and acute flaccidmyelitis and the contention that acute flaccid myelitis is a rare yet severe clinical manifestation of enterovirus D68 infection in susceptible hosts.

By 2014, there was a wider outbreak of enterovirus 68 in the USA. The CDC reported that,

In summer and fall 2014, the United States experienced a nationwide outbreak of EV-D68 associated with severe respiratory illness. From mid-August 2014 to January 15, 2015, CDC or state public health laboratories confirmed a total of 1,153 people in 49 states and the District of Columbia with respiratory illness caused by EV-D68. Almost all of the confirmed cases were among children, many whom had asthma or a history of wheezing. Additionally, there were likely many thousands of mild EV-D68 infections for which people did not seek medical treatment and/or get tested.

CDC received about 2,600 specimens for enterovirus testing during 2014, which was substantially more than usual. About 36% of those tested positive for EV-D68. About 33% tested positive for an enterovirus or rhinovirus other than EV-D68.

EV-D68 was detected in specimens from 14 patients who died in the U.S. in 2014. State and local officials have the authority to determine and release information about the cause of these deaths.

After all of this data and evidence, what can we conclude?

First of all, acute flaccid myelitis is extraordinarily rare, so rare that we might only see 1.4 cases per 100,000 population. Because it is rare, it is extraordinarily difficult to establish causality between a virus, like EV68, and the outbreak of AFM. But like good scientists everywhere, researchers provided evidence that helped us link the AFM outbreak to EV68.

Second, polio was ruled out. This was not polio. These diseases are unrelated to polio. And the polio vaccine had nothing to do with it (given that 2 out of 23 people were unvaccinated, making the risk of AFM technically higher for unvaccinated individuals than vaccinated ones based on this limited sample).

What we know about the acute flaccid myelitis cases

Dr. Vincent Ianelli, writing at Vaxopedia, reviewed the nearly 350 cases of the acute flaccid myelitis, or the subtype of polio like syndrome, that we have been seeing since 2014. Dr.

  • most cases occur in children
  • they have a magnetic resonance image (MRI) showing spinal cord lesion largely restricted to gray matter and spanning one or more vertebral segments
  • AFM can be caused by viruses, environmental toxins, and genetic disorders, although no common etiology has been found in recent cases
  • cases are occurring sporadically – after 120 cases in 34 states in 2014, there were only 24 cases in 17 states in 2015, but then 149 cases in 39 states in 2016 and 33 cases in 16 states in 2017. And there have been about 38 cases in 16 states in 2018.
  • most cases occur in the late summer and early fall
  • most had symptoms of a preceding viral illness, including respiratory symptoms or diarrhea
  • some were unvaccinated
  • the ages of affected children has ranged from 5 months to 20 years
  • some, but not all, were positive for enterovirus D68

Causality in acute flaccid myelitis outbreak

In a recent study published in the respected journal Eurosurveillance, a journal that specifically focuses on infectious diseases and epidemiology, Australian researchers focused on this 2014 outbreak of acute flaccid myelitis. EV68 is a rare virus, and initially, it was never considered to cause the polio-like syndrome.

However, using the Bradford Hill criteria, a method that includes a checklist of nine points that can be used to provide epidemiologic evidence of a causal relationship between a presumed cause and an observed effect, the researchers examined all of the data that related to this outbreak of AFM to determine if EV68 was the causal factor.

They drew on 20 published studies that had focused on the polio-like syndrome outbreak and EV68. Using the Bradford Hill criteria, the researchers quantitatively analyzed each of the points that establish causality, the authors concluded that:

In summary, the application of the Bradford Hill criteria suggests that EV-D68 causes AFM. AFM has not previously been associated with EV-D68, and a mouse model shows that the original Fermon strain does not cause AFM, whereas the 2014 outbreak strain does. It appears that the incidence of this infection and the clade-specific epidemiology have changed. Phylogeographic epidemiology will further our understanding of the temporal and spatial spread of increasingly neurovirulent clades and improve risk analysis. Further investigation into this relationship is important because of the severity of AFM, ongoing outbreaks of AFM and because there is currently no treatment for AFM related to EV-D68, and no vaccine to prevent infection.

That’s a lot of solid evidence that EV68 probably was the infectious agent that caused the outbreak of polio-like syndrome, acute flaccid myelitis. And we have pretty solid evidence that it was not polio or a vaccine-derived poliovirus (VDPV) a very rare virus caused by the mutation or recombination of the attenuated viruses used in the oral polio vaccine (OPV).

VDPV is extremely rare, and generally, it is only a concern in populations that have low levels of vaccination against polio. In populations with high levels of polio vaccination, people would be immune to the VDPV, since its antigens are the same as wild-type poliovirus.

It is important to note that the AFM outbreak occurred mostly in countries, like the USA and Canada, where the typical vaccine used is the injectable polio vaccine (IPV) which uses inactivated poliovirus and cannot replicate or mutate.  In other words, if you’re trying to blame the polio-like syndrome outbreak on the polio vaccine, at least in most of the world which uses IPV, those claims are implausible if not impossible.

Summary

Some of the anti-vaccine pseudoscience crowd claim that the polio vaccine created EV68, which led to the acute flaccid myelitis outbreak. As I wrote above, EV68 is related, generally, to polioviruses – they are in the same genus, Enterovirus. But, saying that EV68 is the same as poliovirus is scientifically incorrect.

It is nearly impossible to determine when the common ancestor of the poliovirus and EV68 diverged during the evolution of enteroviruses, but they are so different that EV68 RNA cannot recombine with poliovirus RNA. They have completely different protein coats that means when EV68 meets up with poliovirus, they’re as different as a dog and cat – they’re both furry and all, but they would rather not have much to do with each other.

We know that the polio vaccine is unrelated to acute flaccid myelitis. It would take special pleading or magic to create some biologically implausible link between the vaccine and any polio-like syndrome.

Enterovirus 68 seems to be linked to some of the outbreaks of polio-like flaccid myelitis, an extremely rare disease. If it becomes less rare, we’d probably develop a vaccine for it.

The polio vaccine is demonstrably safe, but who among you think that this claim will go away?

Notes

  1. There appear to be several interchangeable medical terms for the same disease. For the purposes of this article, I will stick with either polio-like syndrome (some people call it polio-like illness) or acute flaccid myelitis, even though they aren’t completely interchangeable. In addition, acute flaccid paralysis with anterior myelitis has been used to describe the polio-like syndrome, although acute flaccid myelitis is now the most common term.
  2. This article was first written in January 2018. I’ve updated it because of the recent outbreak, and because the anti-vaccine crowd is screaming about the polio vaccine.

Key citations:



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The Original Skeptical Raptor
Chief Executive Officer at SkepticalRaptor
Lifetime lover of science, especially biomedical research. Spent years in academics, business development, research, and traveling the world shilling for Big Pharma. I love sports, mostly college basketball and football, hockey, and baseball. I enjoy great food and intelligent conversation. And a delicious morning coffee!