Does a virus that usually causes mild cold symptoms sometimes paralyze children? That’s the question facing scientists again this fall, after dozens of previously healthy kids across the United States suddenly lost muscle control in their arms or legs, a condition called acute flaccid myelitis (AFM) that eerily resembles polio.
Sixty-two AFM cases in 22 states have been confirmed in recent weeks, scientists at the Centers for Disease Control and Prevention (CDC) in Atlanta said at a news conference today; 65 more are under investigation.
Similar waves occurred in 2014 and 2016, and scientists have fingered a relative of the poliovirus, called enterovirus D68 (EV-D68), as a possible culprit. But the evidence isn’t conclusive yet, and it’s unclear why the virus would only paralyze a small minority of children it infects. Solving these mysteries is urgent because the paralysis can be severe and irreversible. AFM is “pretty rare, but it’s pretty devastating,” says Priya Duggal, a genetic epidemiologist at Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland, who’s studying whether some patients may have a genetic vulnerability to the virus. “And it appears that it’s cyclical. It’s not going away.”
EV-D68, which spreads through saliva and mucus, usually causes symptoms such as coughing, sneezing, and mild fever. It isn’t routinely diagnosed, so no one knows how common it is. But a U.S. outbreak in late summer 2014 was more serious than usual: Hundreds of children hospitalized for severe breathing problems were diagnosed with the virus. Around the same time, more than a dozen children in the Kansas City, Missouri, area and in Denver, which both had large EV-D68 outbreaks, came down with sudden loss of muscle control. Many had mild fever or cough in the days before their symptoms developed, but were otherwise healthy. By December 2014, 120 children in 34 U.S. states had been diagnosed with AFM—“something that hadn’t been reported since the days polio was circulating,” says CDC virologist Mark Pallansch.
Scientists suspected a link between the cases of paralysis and the EV-D68 outbreak, but only one patient had evidence of the virus in their cerebrospinal fluid, the usual place to look for pathogens infecting the central nervous system, and fewer than half tested positive in stool or respiratory samples. That may be because samples were taken too late to detect the virus, researchers say; AFM typically appears more than a week after initial cough or fever symptoms.
The fall of 2016 saw another wave of the puzzling cases: 149 of them in 39 U.S. states. That year, 29 patients with AFM in 12 European countries tested positive for EV-D68 as well.
At today's press conference, CDC officials did not say whether any of the recent patients have tested positive for enteroviruses, but “the pattern looks very familiar,” says Carlos Pardo-Villamizar, a neurologist at Johns Hopkins University School of Medicine, including the timing: Autumn is known as enterovirus season.
Lab research has strengthened the case that EV-D68 could be involved. Last year, Kenneth Tyler of the University of Colorado (CU) School of Medicine in Aurora and his colleagues reported that several strains of EV-D68 could cause paralysis in mice. The virus seemed to target nerve cells involved in muscle control, which makes the link much more plausible, says Kevin Messacar, a pediatric infectious disease specialist also at CU who was not involved in the study. The study also suggests the virus is attacking nerve cells directly, he says, not just triggering an immune response that damages nerves. Others have demonstrated that the virus can infect neuronal cells in the lab. Meanwhile, scientists have found that EV-D68 can be detected much more reliably in respiratory fluids than in cerebrospinal fluid or stool samples, where the poliovirus shows up, which makes identifying infections easier.
If EV-D68 is causing paralysis, it’s not clear why it does so in very few cases. But the same is true for the poliovirus, which causes only mild symptoms, or none at all, in more than 99% of those infected. One theory is that the virus can infect nerves in rare cases when it slips into an injured muscle. Another is that genetic factors play a role; Duggal and her colleagues have enrolled nearly 60 families in their study to test that theory.
Experts warn that as the 30-year campaign to eradicate polio winds down, attention will shift to other viruses that can paralyze children. (One known example is enterovirus 71; it produces blisters on children’s mouths, hands, and feet, but also occasionally causes AFM.) “We are seeing more cases of this in the U.S. than we are seeing in polio in the whole world,” Tyler says. “You don’t need an awful lot of paralyzed children to make this an important problem.”
There is no vaccine against EV-D68. A candidate vaccine developed in China has shown promising results in mice, but at the moment, the rate of serious complications from the virus is probably too low to make widespread vaccination worthwhile, says Heli Harvala, a virologist at University College London. Still, “It might be something we need to consider” in the future, she says. “It’s good to be ready.”
Rather than pinning hopes on a vaccine, doctors should be aware of the symptoms of AFM and know how to test for enteroviruses that might be involved, says Thea Kølsen Fischer, a viral epidemiologist at Nordsjællands Hospital in Hillerød, Denmark. “I would rather see investments in surveillance and diagnostics,” which could help front-line clinicians to be ready when the next cluster emerges.