Since 2014, doctors have been stymied by a medical mystery: People, mostly children, were coming down with a previously unknown, polio-like illness that causes paralysis. Now, an international team of doctors published in The Lancet believe they have managed to confirm the main culprit.
Ever since the defeat of polio in the US a half-century ago, reported cases of paralysis brought on by infection had been virtually non-existent. Mosquito-borne germs, like West Nile virus, are known to trigger a polio-like paralysis, while others can cause a rare autoimmune complication called Guillain-Barré syndrome, but neither happen with any regular frequency. Starting in 2014, though, doctors started seeing a spate of children suffering an acute and rapid weakening of their muscles and paralysis, primarily affecting the limbs, along with confirmed spinal cord damage. That year, there were 120 confirmed cases of this acute flaccid myelitis, as it's formally known, found across 34 U.S. states, while 2016 saw 149 cases across 39 states. Several deaths have also been linked to the condition.
The afflicted children had little in common, except that some seemed to have been infected by an airborne virus related to polio known as Enterovirus D68 just before falling ill. EV-D68 infection had long been thought to cause nothing more than the common cold, and there had been only 26 reported cases of it in the U.S. from 1970 to 2005, following its initial discovery in the early 1960s. But both 2014 and 2016 had large outbreaks of EV-D68 that occurred around the same time that clusters of AFM were detected, while 2015 saw almost no cases of either the virus or the condition. And there's been evidence that cases have stretched as far back as 2012.
At the same time, though, there were arguments against the EV-D68 theory. Not every person with AFM was found to have EV-D68, and it was unclear if the virus could even be found in the spinal cord and damage it in the specific way needed to cause AFM.
The team of researchers, including doctors in Colorado who treated some of the first known cases, argue that despite these inconsistencies, enough evidence has been collected over the past three years to to fulfil a checklist used to establish whether a germ causes a specific illness, known as the Bradford Hill criteria.
"What started as a mystery illness that was causing sudden paralysis in children is now much better understood," lead author Kevin Messacar, an infectious disease specialist at Children's Hospital Colorado, said in a statement.
For one, some of the co-authors of the Lancet paper have recently been able to study EV-D68 in mice, and show that samples taken from infected humans (but not past EV-D68 strains) are indeed capable of causing lesions in the spinal cord that lead to paralysis. They then took the virus out of these mice and successfully infected and paralysed other mice. And they found evidence that this specific strain resembles polio much more than other strains, suggesting a clear change in how it attacks the body. Striking, too, is people with EV-D68 alongside AFM have been now found across six continents and 14 countries.
"They are making a really compelling, meticulous argument that is being increasingly accepted among infectious disease specialists," Paul Krogstad, an infectious disease and pediatric expert and pediatrician at the UCLA School of Medicine, told Gizmodo. Krogstad, who was not involved with the new research, and his colleagues have been exploring how commonly enteroviruses like EV-D68 are causing human disease, as well as potential antiviral treatments that can stop them.
The Bradley-Hill criteria, Krogstad says, has been used to help recognise Zika infection in pregnant women as a potential source of birth defects, another rarely seen health risk that was difficult to directly prove existed. The arguments against the link between EV-D68 and AFM aren't necessarily damning either. Even in cases of paralysis clearly caused by polio, he points out, it's hard to isolate the virus in someone's spinal fluid.
While the researchers believe that more direct evidence still needs to be gathered, such as tissue samples of the spine taken from people who died from AFM, they say the time has come to acknowledge that EV-D68 is a leading cause of AFM, and work from there. The same lab mice that helped them prove EV-D68 can cause paralysis, for instance, could also help researchers figure out how to best treat and prevent cases.
That's a important priority, Krogstad says, since it's likely EV-D68 and its cousins will almost certainly emerge again to cause havoc, even if most cases do turn out to be mild. "These sorts of outbreaks demonstrate the epidemic potential of the whole family of enteroviruses," he said, "and with no currently licensed antiviral agents for these, I think it's another example of the need for federal funding for emerging public health threats out there.
Agencies such as the CDC, however, have so far shied away from officially recognising the link between EV-D68 and AFM.
"It's understandable that those in public health would want to be conservative about recognising associations between new viruses and patterns of disease... but there is a certain point where the argument is compelling," Krogstad said. "And I think we are there with EV-D68."