Scientists have found the strongest evidence that a virus is responsible for a mysterious disease that can start as a fungus but quickly paralyzes children.
The polyolike syndrome, called acute flaccid myelitis or AFM, is very rare. Since the first reports from California in 2012, the US has experienced an increasing outbreak every two years from late summer to fall.
Doctors have a prime suspect, but the evidence that this is the guilty germ has been frustratingly elusive.
So the researchers tried a new trick: they checked patients' spinal fluid for signs that the immune system had fought off an invading virus. Sure enough, children who got sick harbored antibodies that targeted enterovirus, the viral family that experts believe is to blame.
"This is circumstantial evidence that this is happening, but it is powerful circumstantial evidence," he said. Dr. Michael Wilson from UC San Francisco, who helped lead the research. His team reported the results Monday in Nature Medicine.
Preaching a suspect is key to a better diagnosis and eventually finding a way to prevent or treat the disease, said the study's co-author. Dr. Riley Bove, a university neurologist whose son developed AFM at age 4.
"If you don't have a cause, you can't get a vaccine," noted Bove. Wilson developed "a microscope good enough, in a sense, to find things they suspected were there."
About 590 cases of the disease have been confirmed in the US since the Centers for Disease Control and Prevention began to count in 2014. Cases have increased that year and in 2016 and last year, with only a few in subsequent years. So far, there have been 22 this year.
Bove's son Luca Waugh illustrates the pattern. His whole family caught a cold in the summer of 2014 – and a few days later Luca woke up with a weakness in his neck that ran over his shoulder. Despite rapid hospitalization, within days he had paralysis throughout his body and difficulty breathing. He recovered gradually and today still has some paralysis in the neck, shoulder and arm.
The reaction of a germ or body to a germ damages the spinal cord nerves of patients like Luca. The CDC noted that AFM peaks coincided with the seasons when certain enterovirus strains – called EV-D68 and EV-A71 – were causing widespread respiratory disease.
The problem: Doctors rarely found these viruses in patients' spinal fluid, leaving doubts about the link.
Antibodies programmed to track specific germs end up in the spinal fluid only if they fight infection there. This is what Wilson's team set out to find.
Researchers have customized a tool developed by Harvard to look for evidence of hundreds of viruses simultaneously – including herpes, measles, chickenpox, zika, and an entire list of enteroviruses. Add a little spinal fluid, and any antibody present sticks to the target that can be identified.
In spinal fluid tests of 42 AFM patients and 58 children with unrelated neurological disorders, only enterovirus-directed antibodies emerged as the possible culprit. Almost three quarters of the patients housed them, compared with less than 10% of the other children. Additional work is underway to reduce specific strains.
"Before developing potential antivirals or vaccines, you really want to prove that viruses are causing disease," he said. Dr. John V. Williams, head of infectious diseases at Pittsburgh Children's Hospital, who did not participate in the new study. "It's quite convincing" evidence.
Mysteries remain. Enteroviruses are immensely common, and doctors don't know why only a small fraction of those infected develop the disease, Williams said.
And as 2020 approaches, experts are looking for another possible peak next summer. "There's a lot of fear," said Bove.