More research is needed into acute flaccid myelitis (AFM), the polio-like condition in children caused by unknown illnesses, although non-polio enteroviruses remain among the chief suspects, researchers at the National Institute of Allergy and Infectious Diseases (NIAID) argued.
While there have been temporal associations with epidemics of AFM and the non-polio enterovirus, enterovirus (EV)-D68, there has still been no definitive cause found for these spikes in AFM cases, reported David Morens, MD, and Anthony Fauci, MD, both of NIAID in Bethesda, Maryland, and colleagues, writing in mBio, an open-access journal of the American Society for Microbiology.
AFM made national news in 2018, with a total of 228 confirmed cases in 41 U.S. states, and four confirmed cases in 2019. The spike in reported cases in 2018 was so dramatic that in October, the CDC announced they would start tracking AFM cases.
Acute flaccid myelitis was characterized by Morens and colleagues as a “newly coined term” for a subset of cases of the “long-recognized syndrome of acute flaccid paralysis … in which cord myelitis is documented.” It was described as a “seemingly novel condition” in 2010, with the first large outbreak reported in 2014.
Researchers also discussed the epidemiology of non-polio enteroviruses (NPEVs), which are more commonly transmitted by the respiratory route, and can cause a wide variety of “disease syndromes,” such as respiratory infections, conjunctivitis, myositis, and occasionally, sporadic AFM. They noted that the first non-polio enterovirus was isolated from a child with AFM.
Then they cited the strange seasonal pattern of AFM and non-polio enterovirus, enterovirus (EV)-D68, where “AFM epidemics in the United States have recurred in 2-year cycles of increasing magnitude, usually during seasonal EV-D68 circulation.” Indeed, just as AFM cases spiked in 2018, the CDC recently reported a large spike in cases of EV-D68-associated respiratory illness (from two cases in 2017 to 358 cases in 2018).
However, EV-D68 is not the smoking gun for all AFM cases. In October, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the CDC, said in a press briefing that in some AFM cases, researchers found enterovirus, but in some cases, they found rhinovirus.
Still, Morens and colleagues offered up some hypotheses for the association between AFM and EV-D68, characterizing the link between the two as “circumstantial, but nonetheless strong.”
“A precipitating EV-D68 infection, often with low-level viral replication, may well have run its course by the time of onset and diagnosis of AFM, several days to a week or more later,” they wrote. “Early transient viremia during the respiratory prodrome might also have resolved by the time of AFM onset.”
The authors then cited several sobering “plot twists” — namely that AFM was associated with both EV-D68 and enterovirus A71, “a well-known cause of both hand-foot-and-mouth disease and AFM that has been problematic in other regions of the world, but historically less so in the United States.”
“Could we be entering some kind of new epidemic era, in which fundamental but unappreciated determinants of enterovirus evolution and spread are changing?” Morens and colleagues said, adding that another explanation could be that epidemic AFM may result from “rapid viral evolution via mutation and recombination that leads to increased viral pathogenicity.”
Clinically, researchers noted that AFM is difficult to treat, with therapies such as “intravenous immunoglobulin, glucocorticoids, plasma exchange, and antiviral drugs such as pleconaril” being largely unsuccessful. There is mounting evidence, they said, for early intensive physical therapy, similar to that for polio.
Future directions for research include non-polio enterovirus specific diagnostics and virus-specific serologic tests to support epidemiologic studies, as well as experimental animal models, which could identify gene markers and potentially drug therapies.
“Until such time as the causes of the AFM epidemic are better understood, development of preventive vaccines will remain challenging,” Morens and colleagues concluded.
Fauci is the director of NIAID.
Morens and co-authors disclosed no relevant relationships with industry.
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