Three-dimensional image of enterovirus D68 (center) reconstructed from cryo-electron micrographs.
Courtesy of Yue Liu and Michael Rossmann, Purdue University.

Genetic sequencing of a virus found in respiratory secretions of children in California and Colorado who suffered from paralysis or muscle weakness last fall reveals that they were infected with a mutated strain of enterovirus D68 that is closer to polio than other strains common in previous years.

The study, published Monday in Lancet Infectious Diseases, sheds new light on one of the most troubling medical mysteries of recent years. Amid a nationwide outbreak of severe respiratory illness, doctors at hospitals nationwide began to report that they were seeing an alarming number of children with unexplained weakness in an arm or a leg to complete paralysis that required them to be put on ventilators. Treating physicians noted that many of the children appeared to be infected with enterovirus D68, but researchers were cautious about drawing a causal link because virus had been bouncing around the world since the 1960s and had typically only caused breathing issues such as coughing and wheezing.

While the research does not provide a definitive link -- that would only be established if the virus were  found in the spinal fluid and it was not -- it provides the strongest evidence to date of the link between enterovirus D68 and paralysis. The researchers theorize that the reason the virus was not found in the spinal fluid could be because the samples were taken too late. Scientists also tested the children for the presence of other pathogens capable of causing the symptoms but didn't find other viruses, bacteria, fungi or parasites.

The new research reveals that the children had a novel strain of the virus, called B1, which emerged about four years ago. That strain has only five to six coding differences from previous strains that were commonly found in the United States but each of those are mutated in the direction of polio or another nerve-damaging virus known as EV-D70.

"These are changes that may have made the virus more polio-like," said Charles Chiu, an associate professor at the University of California-San Francisco who worked on the study.

While the study identified D68 as a possible trigger of the paralysis, it was not able to shed any light on another key question: Why have some children been affected so severely while others have been fine?

[Mystery paralysis in children is perplexing parents — and researchers]

The study included a pair of siblings with a 100 percent genetically identical strain of the virus. One experienced muscle weakness and paralysis while the other only experienced upper respiratory symptoms.

Chiu said the study suggests that there are individual differences in patients' biology that may determine how the virus affects them. A group of researchers at Johns Hopkins and at Children's Hospital Colorado is gathering DNA from patients around the country to try to explain the different outcomes.

Kevin Messacar, an infectious diseases specialist at Children's Hospital Colorado, where the first large cluster was identified, said the hospital has established a new clinic to treat and study the children who have been affected. He said the researchers will be looking at genetic and immune response in children that may make them more susceptible to paralysis.

"If you think about viruses like polio back in the day hundreds of people were infected whereas only a handful would end up with paralysis. Other illnesses like influenza--many will get fever and achy joints and some will get severe respiratory disease. So I think everybody reacts to infectious diseases differently and it’s not unusual to see different diseases in different people," Messacar explained.

The question is critically important as the vast majority of children affected have not fully recovered. Last fall, many doctors had said they were hopeful the muscle weakness and paralysis were temporary but that has not turned out to be the case. In the Lancet study, none of the children had fully recovered by day 30. Chiu said that the researchers now have 60 day data and 70 percent of the children had minimal to no improvement.

"This is starting to look more like polio unfortunately where the paralysis appears to be permanent or semi-permanent. This is why there is such an urgency for more research to investigate this," Chiu said.

[Polio becomes ‘public health emergency’ in Pakistan as number of cases soars]

The Lancet study's authors -- which included researchers at hospital centers in Aurora, Colo., San Francisco, Palo Alto, and Los Angeles -- emphasized the need for ongoing surveillance for D68 and the need for more resources to develop an effective treatment or vaccine.

With the start of enterovirus season starting in a few months -- it tends to peak in late summer and early fall -- researchers say they cannot predict whether the B1 strain of enterovirus D68 will make a come back. At any given time there are typically more than 100 different enteroviruses and rhinoviruses floating around that cause the common cold and in any given year doctors may only see a few of those strains circulating.

"Even if we don’t see it again this year, which would be the best case scenario, it doesn't mean we should stop doing research. The fact is if you have a virus associated with the common cold that is linked to paralysis it is concerning," Chiu said.

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