Enterovirus D68 (EV-D68) stands accused of playing a key role in a paralytic illness that’s struck down hundreds across the US in recent years. Unfortunately, evidence of its presence has so far been at best circumstantial, until now.
At long last, researchers have uncovered signs of the virus’s fingerprints right where it matters: in the spinal fluid of patients affected by the polio-like disease. It still doesn’t tell us how the condition arises, but having such solid evidence of the suspected cause is a significant step in the right direction.
Two recent complementary studies identified the presence of antibodies specific to the enterovirus in fluid surrounding the central nervous system of patients diagnosed with acute flaccid myelitis, or AFM.
One study published back in August found scant signs of the virus’s RNA in samples of patient serum and spinal fluid, but identified enterovirus antibodies in nearly 80 percent of AFM cases, compared with only 20 percent of healthy patients.
The results were certainly suggestive, but the small size of the study counted against it; an unmatched sample of just 14 patients affected by the condition, and five healthy controls, still leaves a little too much room for scepticism.
Now, a more recent investigation conducted by researchers from the University of California, San Francisco has found similar results among 42 children diagnosed with AFM.
Exposing the fluid samples to a library of just under half a million virus proteins, the researchers went on the hunt for antibodies in the patients’ spinal fluid that might recognise the enterovirus.
These samples were compared with specimens taken from 58 children who were either healthy or had other assorted neurological conditions.
Similar to the previous study, there was little sign of the virus itself. But in over two-thirds of the samples from patients with AFM, antibodies matching proteins belonging to EV-D68’s virus family and genus were found. By comparison, just 7 percent of the controls presented with similar antibodies in their spinal fluid.
Further testing using a separate, more sensitive test confirmed it – antibodies for the virus were far more likely to be present in the nervous systems of patients with the paralysing condition.
The results fall just short of catching the virus red-handed, but still provide the strongest evidence to date that a relatively common pathogen is behind an epidemic that has for years baffled health authorities.
Cases of AFS have spiked every two years since it was first recognised in 2012, with hundreds of children across the US suffering the disease’s debilitating effects.
Symptoms typically begin much like a cold, but can steadily progress into severe neurological damage that weakens muscles and reduces reflex movements.
Similarities to the paralysing effects of polio initially drew comparisons between the illnesses, but with no sign of the poliovirus found in anybody diagnosed with AFS, epidemiologists have had to look elsewhere.
Focus soon turned to EV-D68 – a relatively common pathogen once associated with mild respiratory problems.
The agent wasn’t exactly unknown to health experts, having been first identified back in the 1960s, but nor was it considered a cause for alarm, with only 26 cases of EV-D68 infection having been reported in the US between 1970 and 2005.
That changed in 2014, with reports of record outbreaks of severe respiratory infections caused by EV-D68 across the US.
An overlap in outbreak locations between AFS and EV-D68, not to mention the fact that many of those diagnosed with AFS have reported experiencing cold-like symptoms and muscle fatigue, and it seemed all too likely the two were related.
In 2017, researchers demonstrated the virus was capable of causing paralysis in mice. It seemed like an open-and-shut case.
But nobody could find convincing signs of the actual virus in people with AFS. Without any way to put the virus at the scene of each and every case of the disease, there was always going to be doubt.
“People were hung up on the fact that enteroviruses were rarely detected in the cerebrospinal fluid of AFM patients,” says UCSF neurologist Michael Wilson.
“They wanted to know how someone could get neurologic symptoms with no virus detectable in their central nervous system.”
With matching fingerprints in the form of antibodies, though, researchers can now double down on efforts to understand the underlying pathology of this once uncommon virus, and maybe even explain how it turned so nasty.
There’s currently no specific way to prevent AFS. Fortunately, it’s thought that less than one in a hundred children who become infected by EV-D68 succumb to the paralysing effects of AFM. Learning why that is is another mystery, and one that future research can hopefully solve.
This research was published in Nature Medicine.