Thirteen-year-old Billy Sticklen of Joplin, Mo., developed polio-like paralysis during the summer of 2014 during the outbreak of the respiratory virus EV-D68. At Children’s Mercy Hospital in Kansas City, Mo., on Wednesday, Jan. 28, 2015, occupational therapist Kelly Grabendike works with Billy in the therapy pool. Jill Toyoshiba/Kansas City Star/TNS/Getty Images
Last year, hundreds of children across the country got sick with what looked like a common cold. Nothing to worry about: body aches, runny nose, coughing and sneezing. But then, mysteriously, a handful of those kids became paralyzed—first, just in an arm or a leg, and then spreading so far that some children needed a ventilator to breathe. The CDC reports that since August 2014, at least 115 children in 34 states have developed unexplained muscle weakness or paralysis, which they’re now calling acute flaccid myelitis. Doctors have urgently been hunting down the origin of this strange illness for over half a year, and now they think they’ve finally identified the culprit: enterovirus D68.
Enterovirus D68 has been around for decades—it was first identified in California in 1962, and it’s one of many viral strains to blame for the common cold. It also belongs to the same genus as poliovirus, an infectious, nerve-damaging pathogen that can cause paralysis. But up until 2012, EV-D68 had never been associated with anything beyond respiratory illness. That’s when some children with baffling cases of muscle weakness and paralysis also tested positive for EV-D68. At the time, there were so few cases that doctors couldn’t definitively blame the enterovirus for the frightening symptoms. Epidemiologists also suspected EV-D86 in last fall’s outbreak, but tests of spinal fluid showed no signs of the virus, so the cause of the paralysis remained a mystery.
Now a study in the Lancet Infectious Diseases confirms doctors’ suspicions, finally linking EV-D68 to the strange neurological effects. A team led by University of California, San Francisco scientists analyzed samples of blood, spinal fluid, stool, and respiratory secretions of 48 pediatric patients from two hospitals in California and Colorado, where the largest cluster of paralysis cases occurred. The researchers used genetic tests to look for all potential sources of the disease, from viruses to bacteria to fungi.
While they found a variety of pathogens among the patients, only one viral strain—EV-D68—showed up consistently in nasal swabs. “We found no evidence of other agents,” says Charles Chiu, an associate professor of laboratory medicine and infectious diseases at UCSF. “These negative results indicate that this is the virus that’s involved in the disease.”
For the first time, they also found EV-D68 in one child’s blood, which may be a sign that the virus can infiltrate the nervous system and cause paralysis. “Blood is the gateway by which these viruses get to the brain and spinal cord,” explains Chiu. “That’s how polio works.” As with earlier testing, the team didn’t find the virus in spinal fluid, but Chiu thinks doctors may have taken samples too late after the initial infection, after the virus had cleared. It’s also possible that, like polio, this virus is just difficult to detect in spinal fluid.
Their results also suggest how this previously benign virus developed the ability to paralyze. The researchers sequenced EV-D68 samples from each paralysis patient and discovered that all of them belonged to the same strain: one that emerged in 2010, with five to six unique mutations. It’s those small changes that could explain why EV-D68 can paralyze, rather than just cause respiratory symptoms. “The virus has mutated in a direction that makes it more genetically similar to polio and other enteroviruses that cause neurological disease,” says Chiu.
Although EV-D68 genetics now more closely resemble poliovirus, it’s not clear that the virus directly causes muscle weakness and paralysis (as polio does). “I’m confident we have the culprit,” says Chiu, “but we don’t know how it’s involved in the disease.” If the virus does actually invade the nervous system, scientists still need to figure out how it invades. It’s possible that the virus might not directly attack the nervous system, but instead turn the body against itself. Chiu says EV-D68 could trigger an abnormal autoimmune response where the body produces antibodies that then invade the brain and spinal cord.
While this study shows a link to EV-D68, there’s still a small chance the virus doesn’t cause paralysis. “They’ve done a really good job showing an association,” says Avindra Nath, clinical director at the National Institute of Neurological Disorders and Stroke. “But all they have is an association—not causation—so this isn’t a smoking gun.”
In spite of all the unknowns, one thing is for sure: If this virus is the culprit, it’s only a part of the picture. Like polio and West Nile Virus, only a small fraction of children infected with EV-D68 develop neurological symptoms. The researchers saw this in their study—two siblings tested positive for the enterovirus, but one developed muscle weakness while the other only had respiratory symptoms. Genetic sequencing showed that the same viral strain infected both of them. “These findings suggest that the virus isn’t acting alone,” says Priya Duggal, a genetic epidemiologist at Johns Hopkins Bloomberg School of Public Health. “It’s acting with something else—whether it’s an individual’s genetics or immunogenetics or something from the environment.” The researchers plan to test the siblings for genetic differences that may change an individual’s reaction to the virus.
Now that scientists have linked EV-D68 to the cases of childhood paralysis, they’re racing to figure out how the virus works and whether it directly causes this disease. Those questions are critical to developing therapies and vaccines, and they’ll give doctors clues about the outcome of children already afflicted. Seventy percent of the children with muscle weakness or paralysis in Chiu’s study show little or no improvement, and not a single child has fully recovered. “There’s a possibility that this could be permanent,” says Chiu. Researchers have already tested two experimental drugs on the virus, but neither of them appears effective. “We know much less about this virus than we know about polio,” he says. “Unfortunately, we’re just at the very beginning of understanding it.”