New Evidence Strengthens Link Between Enterovirus and Acute Flaccid Myelitis

NEW YORK (Reuters Health) – Patients with acute flaccid myelitis (AFM) commonly have antibodies to enterovirus (EV) peptides in their cerebrospinal fluid (CSF), further supporting a link between EV and AFM, researchers report.

“The implication of an infectious agent is an important step in targeting efforts for intervention,” Dr. W. Ian Lipkin of Columbia University Mailman School of Public Health, in New York City, told Reuters Health by email. “Our findings support the use of specific culture-based and animal models for testing the effects of antivirals and drugs that may mitigate damage. A vaccine for all enteroviruses isn’t feasible. However, a vaccine to prevent infection with a specific enterovirus (such EV-D68) is achievable.”

Although the cause of AFM has eluded researchers so far, previous studies have identified evidence supporting the presence of EV in respiratory or fecal samples in patients with AFM.

Dr. Lipkin and colleagues used viral-capture high-throughput sequencing and peptide microarray approaches to examine the role of EV in AFM, using specimens from 14 confirmed AFM patients, six patients with non-AFM CNS diseases (NAC), 10 patients with Kawasaki disease (KDC), and 11 adult controls (AC).

Virologic testing identified EV-A71 in CSF and feces of one of 14 AFM cases; echovirus 25 in CSF, respiratory, and fecal samples of one of five non-AFM cases; and EV in respiratory and/or fecal specimens from seven of 14 AFM cases and two of 6 non-AFM cases.

Approximately 11,000 copies of EV RNA per mL of CSF were present in one AFM patient, compared with 270 copies per mL of CSF in one non-AFM patient, the researchers report in mBio, online August 13.

CSF samples from 11 of 14 AFM patients were immunoreactive to a peptide region corresponding to capsid proteins of EV, whereas this was true of samples from only one of five NAC patients, none of 10 KDC children, and two of 11 AC patients.

The researchers also identified a peptide sequence in the carboxyl terminus of the EV-D68 VP1 protein that was immunoreactive with six of 14 CSF samples and eight of 11 serum samples of AFM patients, but not with CSF or serum samples from five NAC, 10 KDC, or 11 AC patients.

“New tools for microbial diagnostics and discovery are revolutionizing medicine,” Dr. Lipkin said. “Serology has the potential to reveal links to disease that may not be found with other methods.”

Dr. Kevin Messacar of the University of Colorado/Children’s Hospital Colorado, in Aurora, who recently reviewed the features and outcomes of AFM among 28 children diagnosed between 2011 and 2016, told Reuters Health by email, “This is now the second lab independently confirming the presence of enterovirus antibodies in the spinal fluid of children with acute flaccid myelitis, which provides further evidence that these viruses, and in particular enterovirus D68, are driving the recent increase in cases of this disease in the U.S.”

“Though viruses are rarely detectable in spinal fluid of children by the time they are paralyzed, the detection of enterovirus antibodies in spinal fluid supports that they are a cause of acute flaccid myelitis and may become a primary method to diagnose an enterovirus-related case,” he said. “Early recognition and diagnosis of acute flaccid myelitis with prompt collection of appropriate specimens and reporting to public health authorities is needed to continue to improve our understanding of this condition.”

Dr. Jelte Helffereich and Dr. Hubert G. Niesters of University Medical Center Groningen, in the Netherlands, who have reviewed the role of enterovirus D68 in AFM, told Reuters Health by email, “While both the index group and the control group are small, the most interesting result of this study is the identification of immunoreactivity to enterovirus (and in particular EV-D68) in CSF of AFM patients. This provides more proof that this virus is causing AFM. It also shows that the detection of this virus by RNA amplification is not that common and that, similar to poliovirus or rabies virus, are not easily, if at all, detected in CSF. Probably the virus is present just for a very short period of time early in the infection, in CSF.”

“The increasing incidence of AFM, not in only in the USA but also in Europe, warrants clinicians and microbiologists to be aware of AFM and its association with different enteroviruses, to perform adequate diagnostics in a suspected case, and to cooperate in the identification of treatment and preventive options,” they said. “The use of proper diagnostics for enteroviruses by diagnostic laboratories, using RNA detection in, for instance, respiratory material for enterovirus D68, is essential.”


mBio 2019.

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