NIH Scientists Call for More Research into Cause of Acute Flaccid Myelitis Outbreaks

Ever since cases of acute flaccid myelitis (AFM) — a rare condition which can affect the nervous system of young children – started rising in the United States in 2014, parents have been alarmed by the mysterious illness and state and local health agencies have worked to pinpoint the cause. Now a new paper is calling for increased research into the condition’s natural history and pathogenesis.

In 2014, an outbreak of AFM led to 120 confirmed cases of polio-like illness in 34 states, and according the US Centers for Disease Control and Prevention (CDC) since then the US has seen spikes in AFM cases every 2 years, rising to 228 confirmed cases in 2018. While the illness is not new, such big outbreaks are, and health investigators have ruled out poliovirus as the cause of these recent cases. A new paper written by experts from the National Institutes of Health’s (NIH) National Institute of Allergy and Infectious Diseases (NIAID) and published in the online journal mBio says we need an acceleration into research on this mysterious emerging viral disease.

Patients who became ill in the recent AFM outbreaks in the US typically have had illness onset between August and October, with symptoms including weakness in the arms and legs as well as sudden lost of muscle tone and reflexes. In severe cases the muscles that control breathing can weaken and cause respiratory failure. The new paper notes that the recent outbreaks of AFM have all occurred at the same time and locations as outbreaks of 2 non-polio enteroviruses typically associated with hand, foot, and mouth disease — EV-D68 and EV-A71 – suggesting a link, although the CDC has detected these viruses as well as coxsackievirus A16 in the spinal fluid of only 4 of the 558 confirmed cases of AFM.

“Unfortunately, there is very little that parents can do to prevent their children from getting AFM,” said the paper’s co-author and NIAID director Anthony S. Fauci, MD, in an interview with Contagion^®. “It is important to point out that it is a very rare disease occurring in 1 in 1,000,000. We do not know for sure what causes it and even if it is caused by the likely suspect, enterovirus D-68, the overwhelming majority of children who get infected with EV-D68 do not get AFM.”

The reemergence of EV-D68 has itself been unprecedented, notes the new paper, and establishing the link to AFM has been difficult, as EV-D68 infection can run its course more than a week before the onset of AFM symptoms. With an association also between AFM and EV-A71, the authors posit that the recent AFM outbreaks may be a sign of a new ne epidemic era, in which fundamental but unappreciated determinants of enterovirus evolution and spread are changing. As such, the paper calls for increased research to determine if epidemic AFM is occurring as a result of rapid viral evolution via mutation and recombination leading to increased viral pathogenicity.

Studying AFM will continue to be a challenge due to the fact that AFM is an uncommon and sporadically occurring complication of a common infection, and Fauci calls for better and more sensitive assays to help doctors diagnose these cases with viral specificity.

“Awareness of the disease is critical so that children do not go for an inordinate amount of time before the disease is recognized,” said Fauci, who in the paper calls for more education on AFM for the public and the community of pediatricians so that they immediately recognize cases. “We need to have pediatricians and other physicians be on the alert for this disease such that we can study and care for these children during the acute stage of disease.”