Children's 'polio-like' illness may return in August. But a possible vaccine will cost millions to test

©The Philadelphia Inquirer

PHILADELPHIA — A few weeks after his 4th birthday, Fenton McEvoy came down with what seemed like an ordinary cold, except that his neck and right hand started to feel weak. Within 24 hours, he could not move his arms or legs.

That was 2018, when the Georgia boy and more than 200 other children in the United States were diagnosed with acute flaccid myelitis, a debilitating disease that seems to surge every two years in late summer and fall. In 2016, 153 such cases were confirmed by the U.S. Centers for Disease Control and Prevention. Two years before that, the number was 120.

If the pattern holds, dozens of preschool-age children will be afflicted this year, starting in August.

Like COVID-19, the condition is blamed on a virus — in this case, one related to the virus that causes polio. Unlike COVID, which rarely causes severe symptoms in the young, this one hits children almost exclusively.

“It’s the same effect of someone that suffered a traumatic spinal injury,” said Fenton’s father, Brian, an attorney in Atlanta. “Except in his case there was no trauma. He caught a cold, and the next day he ended up in the ICU.”

If there is a hint of hope this year, physicians say the social-distancing restrictions aimed at limiting the coronavirus also could limit EV-D68, the virus linked to acute flaccid myelitis. And on Friday, researchers at Vanderbilt University Medical Center said they had taken a big step toward a possible treatment for AFM.

Mice were protected from the disease after being injected with antibodies that had been isolated from human patients, the researchers reported in Science Immunology. When given antibodies before being exposed to the virus, the mice developed no muscle weakness or other symptoms. Even when treated up to three days after being exposed, animals experienced fewer symptoms than those that were not treated.

What happens next, as with so much else in science, depends on money.

With the coronavirus, research has proceeded at unprecedented speed, with billions pledged to the cause so far by the U.S. and other governments. Several vaccines are being tested in humans just months after the microbe’s genetic code was deciphered, though how well they will work remains uncertain.

For AFM, which strikes a small fraction of the number infected with COVID, $10 to $15 million would be needed to test the antibody in human patients and scale up production for clinical use, said James E. Crowe Jr., director of the Vanderbilt Vaccine Center and senior author of the new study. That is a pittance compared to the spending on COVID, yet the funds remain elusive.

“We cannot seem to put together everything we need,” he said.

The antibody study was conducted in mice, and such results often do not translate to humans. Still, the results are “really encouraging,” said Sarah E. Hopkins, a neurologist at Children’s Hospital of Philadelphia who was not involved in the research.

“Even when they gave it to mice after they had the infection for a day or two, they still seem to have benefited,” she said.

One hurdle in administering such a treatment would be identifying which children have the disease.

In the first few years after AFM was identified, the CDC was slow to label the virus EV-D68 as the cause, in part because it is not detected in some patients. But the microbe — a type of virus called an enterovirus — is now generally considered the prime culprit, Hopkins and Crowe agreed. (Some milder cases may be caused by another enterovirus called A71.)

Still, children can go days before being diagnosed if physicians are not on the lookout for the condition. Levels of the virus are highest during the first day of infection and may be hard to detect later, Hopkins said.

That’s what happened with Fenton McEvoy, who is now 6. He never tested positive for the virus, but was diagnosed with the disease based on clinical findings. He has regained some function in both legs, but uses a motorized chair and relies on a breathing machine, his father said.

In 2019, the boy underwent a surgery called nerve transfer at Shriners Hospital for Children in Philadelphia. Physicians attempted to reactivate his paralyzed diaphragm, the muscle used in breathing, by rerouting a healthy nerve from elsewhere in the body, but it was not successful. Other patients at Shriners and CHOP have benefited from such procedures, however.

As many as one-third of AFM patients need mechanical breathing support, said Hopkins, the neurologist. Most have paralysis or weakness in just the upper extremities, sometimes in just one arm, she said. The weakness may affect the shoulder more than the hands.

“Often these kids can hold onto your hand, but they can’t lift their hand up above their heads to give you a high-five,” she said.

Though the virus is respiratory, it somehow leads to weakness or paralysis by inducing the formation of lesions on the spinal cord. Yet a big mystery remains: the virus strikes nearly everyone at some point, but in most cases it results in nothing more than a cold. Genetic studies are underway to find out why.

In addition to surgery, treatments for the paralysis can include steroids and other drugs to minimize inflammation. For the antibody treatment studied at Vanderbilt, several scenarios are possible, said Crowe, who collaborated with researchers at the University of Wisconsin-Madison and Purdue University.

One option is to treat any child with a cold who tests positive for the virus. But since the vast majority of children do not develop paralysis, that would mean giving a drug that is likely to be pricey to many who do not need it. Alternatively, doctors could wait and give the drug to those who start to develop muscle weakness — except that might be too late.

Another option: if one child in a preschool class develops the disease, the antibody could be given to others in the class that were exposed. Again, most would not need it, though that would be a more targeted approach, Crowe said.

In the event of a big outbreak in a community, Crowe envisions that the drug could be given on a more widespread, preventive basis, almost like a vaccine. That seems unlikely for now, as the disease is rare. But Crowe worries the number of cases could keep growing, as it did with polio.

“It’s pretty tricky to figure out what we need to do,” he said.

The virus’s two-year cycle also remains something of a mystery, though such multi-year cycles are not unheard of in infectious disease. In simplest terms, viruses spread when enough people are susceptible. So last year and in other odd-numbered years, most preschool-age children may already have been infected.

This fall, a new population of susceptible children will start preschool, though pediatricians are hopeful that reduced hours and other forms of COVID-related social distancing may hamper the spread of the enterovirus.

But Hopkins, the CHOP neurologist, worries that it might simply come back stronger next year. If that is the case, Crowe and his colleagues studying the antibody plan to be ready — if they can get enough support.

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©2020 The Philadelphia Inquirer