Role of EV-D68 in polio-like illnesses still unclear

As the nationwide outbreak of enterovirus D68 (EV-D68) infections grew again today, federal and state health officials said they still have no idea whether the virus is contributing to a number of prolonged polio-like illnesses that have cropped up in a few states, especially California and Colorado.

The count of EVD-68 cases, almost all of them in children, climbed to 538, up 24 from yesterday, the Centers for Disease Control and Prevention (CDC) announced today. The number of affected states stayed level at 43.

Colorado officials reported recently that 4 children out of 9 at Children's Hospital Colorado in Denver who had neurologic illness involving limb weakness and cranial nerve dysfunction tested positive for EV-D68. Today, California health officials reported that a patient in Los Angeles County with a similar illness tested positive for the virus in August.

As reported earlier, the virus was also found in two other California patients with neurologic symptoms in 2012.

Mere coincidence?

But during a teleconference for clinicians today, CDC officials said they don't know if the polio-like conditions are related to EV-D68 or just coincidental. They also said that, lacking any good baseline data on the neurologic illnesses, they're not even sure how unusual the numbers are.

"Are these neurologic cases related to EV-D68? I don't think we can say that they are at this point. We're really not sure what's causing this cluster," said Daniel Feikin, MD, chief of the Epidemiology Branch, Division of Viral Diseases, in the CDC's National Center for Immunization and Respiratory Diseases

"It's possible that [EV-D68] is a coincidental finding in these patients and may not be related to their neurologic illness," he said. "That's why we need to continue investigating."

During the teleconference, doctors from New York state, Boston, and Michigan reported having patients with neurologic problems like those described in Colorado and California, but they did not indicate that any of them have tested positive for EV-D68 so far.

When a participant asked CDC officials if they have an idea how many cases of the mysterious neuorologic illness have surfaced so far, Feikin said the agency recently started evaluating reports from around the country and has no definitive numbers yet.

"We know enteroviruses circulate at this time of year and can result in neurologic disease, but we don't have a good baseline to compare it to," Feikin said. "Normally we just don't see that many of this presentation; in a normal year we don't even see a case of this, or maybe one case. There's an impression out there that there's an increase, at least in certain areas. But without a good baseline it's hard to say."

Reports detail California, Colorado cases

The CDC and officials from California and Colorado published separate articles today in Morbidity and Mortality Weekly Report (MMWR) on the neurologic illness clusters in the two states.

The California report describes 23 cases of acute flaccid paralysis (AFP) with anterior myelitis that occurred from June 2012 through June 2014. The patients' median age was 10 years, with a range of 1 to 73 years, and they were scattered around the state. Just two of the patients tested positive for EV-D68.

More cases have surfaced in California since the MMWR report was written: At a news briefing and in a statement today, California health officials said that as of Oct 1, they have identified 35 patients with AFP and spinal cord involvement since 2012. They include three patients infected with EV-D68, two in 2012 and the recent one in Los Angeles County.

"Because EV-D68 was found in respiratory specimens from these patients, it is not known whether EV-D68 was a cause of paralysis or a coincidental finding," said the statement from the California Department of Public Health (CDPH). In the Colorado cases, likewise, the virus was found in respiratory samples but not in the cerebrospinal fluid.

The CDPH also reported that 14 EV-D68 cases have been identified in California this year, 13 of them involving respiratory illness and one involving AFP.

Illnesses are prolonged

During the CDC teleconference, officials said the neurologic symptoms have been prolonged.

Carol Glaser, DVM, MPVM, MD, interim chief of the CDPH's Immunization Branch, said, "We've done fairly extensive follow-up and they are having prolonged paresis and paralysis. . . . But some had a remarkably good recovery as much as a year later. It's not consistent, but it's very prolonged in all cases, at least 6 months."

A Colorado official said most of the patients there have shown "minimal improvement" so far. All of them fell ill in August or September.

There is no specific treatment for EV-D68, CDC officials noted. They said three antivirals, all with the same mechanism of action, have been tested against the virus, but none of them worked.

James Sejvar, MD, a CDC neuroepidemiologist, said the agency is working on management guidelines for EV-D68 and hopes to make them available within a week or so. He warned against the use of steroids, saying that in some enterovirus infections, steroid treatment has been shown to lead to a poorer outcome.

"Experience with other forms of infectious flaccid paralysis or anterior myelitis essentially demonstrates the same thing," he added.

Faster test under development

Testing for EV-D68 is complex and slow, but the CDC is working on a new test that will be faster, officials said today.

"We're in the process of developing a specific real-time assay," said Steve Oberste, PhD, chief of the CDC's Polio and Picornavirus Laboratory Branch. "It's being validated now, and we hope to have it available very soon."

CDC officials also said they have completed genome sequencing for seven EV-D68 isolates representing all the circulating strains and that the sequences would be deposited in GenBank today.

A physician from Ann Arbor, Mich., commented during the conference that her center has seven pediatric patients who recently presented with neurologic symptoms. "Two or three children don't have acute paralysis right away, but have a pain syndrome," she said. "They walk slowly but don't have obvious paralyzed or weak limbs."

In response, a Colorado physician on the call said several patients in the cluster there had low back pain or calf pain before the onset of neurologic deficit, "but it seems to have gone away as they proceeded in their course."

Glaser, of the CDPH, commented, "This is absolutely consistent with what we've seen, too."

The AFP cases in California included one death, in an older adult. Glaser said there was no autopsy, and the cause of death wasn't clear.

She noted that about half of the California AFP patients required mechanical ventilation at some point, and five were still on a ventilator when they were discharged to rehabilitation facilities.

See also:

CDC EV-D68 page

Oct 3 MMWR report on Colorado cases

Oct 3 MMWR report on California cases

Oct 3 CDPH press release

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