Signs of enterovirus in children paralyzed with polio-like illness, study reports

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In a study published in Nature Medicine, a team from the University of California San Francisco (CA, USA) detected the immunological remnants of enterovirus (EV) in the spinal fluid of patients diagnosed with acute flaccid myelitis (AFM) – an illness similar to polio that causes permanent and sometimes life-threatening paralysis in young children.

AFM was first documented in 2012. Since then, outbreaks have followed every other year with over 500 confirmed cases reported so far. However, identifying the cause of AFM has been a challenge for the medical community.

EVs usually only cause cold-like symptoms or the rash producing hand, foot and mouth disease. However, emerging evidence suggests that EVs could also be the cause of AFM, specifically the strains D68 and A71, which have been reported to causes paralysis in mice.

Furthermore, scientists noticed that EV outbreaks coincided with spikes in AFM cases and respiratory samples from children diagnosed with AFM tested positive for the virus.

Despite this, many experts remained sceptical due to the virus not being traced in 98% of AFM patients who had their spinal fluid tested.

“If we could detect something specific to a virus in in the spinal fluid of AFM patients, we would feel more secure claiming that the neurologic symptoms of the disease are virally mediated,” commented senior author, Michael Wilson (University of California San Francisco).

Following the failed use of advanced deep sequencing technology, the team of researchers used an enhanced version of a virus-hunting tool called VirScan to search for the virus directly in the spinal fluid of patients.

“When there’s an infection in the spinal cord, antibody-making immune cells travel there and make more antibodies. We think finding antibodies against enterovirus in the spinal fluid of AFM patients means the virus really does go to the spinal cord. This helps us lay the blame on these viruses,” explained lead author, Ryan Schubert (University of California San Francisco).

Antibodies against enterovirus were found in the spinal fluid of almost 70% of AFM patients compared with only 7% of non-AFM controls. Furthermore, the samples from the AFM patients did not contain antibodies for any other virus, eliminating others as possible causes.

AFM-causing strains of enterovirus were identified decades ago, however, have only recently been linked to causing paralysis, suggesting that there are changes that occur causing the virus to act more neurovirulent.

Further, EVs have only been demonstrated to causes paralysis in children, Schubert added: “We don’t know for sure why children get paralysis and adults don’t. The thinking is that young children have low immunity to the virus that increases as they get older, so we see the most severe effects in children around the age of two. But more work needs to be done to understand AFM.”

Currently, there is no way to treat or prevent AFM and as the virus is very common is it difficult to avoid. Further investigation on the role EVs have in causing AFM could help towards creating a vaccine to prevent the disease.

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Sources: Schubert RD, Hawes IA, Ramachandran PS et al. Pan-viral serology implicates enteroviruses in acute flaccid myelitis. Nat. Med. doi:10.1038/s41591-019-0613-1 (2019); www.ucsf.edu/news/2019/10/415696/missing-virus-detected-dozens-children-paralyzed-polio-illness


What is acute flaccid myelitis (AFM)?

Acute flaccid myelitis (AFM) is a rare but serious condition affecting the nervous system, specifically the spinal cord. Symptoms include sudden weakness in the arms or legs, along with loss of muscle tone and decreased or absent reflexes. AFM is often referred to as a ‘polio-like’ condition, although samples from AFM patients have been tested negative for polio, the symptoms bear a resemblance.

Why are cases of AFM increasing?

The CDC reports an increase in AFM cases every 2 years since 2014v, primarily in young children. In the UK, increases have been temporally associated with an upsurge in enterovirus D68 activity, however, as the cause is yet to be confirmed, the reason for increase is also unknown,

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