Enterovirus Antibodies Found in Spinal Fluid of Dozens of AFM Patients

Evidence is mounting that the mysterious polio-like disease known as acute flaccid myelitis (AFM) is caused by an enterovirus (EV). Most recently, new research at the University of California San Francisco that found EV antibodies in dozens of patients diagnosed with AFM.

The study, published October 21^st in the journal Nature Medicine, examined cerebrospinal fluid of 42 children diagnosed with AFM using VirScan, a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses.

“Although, like others, we did not find much evidence for viral RNA in the cerebrospinal fluid of children with AFM, we did find antibodies to enteroviruses in the cerebrospinal fluid of most of these children at levels significantly above the baseline seen in children with other neurologic diseases,” senior author Michael Wilson, MD, associate professor of neurology, member of the UCSF Weill Institute for Neurosciences, told Contagion^®. “In addition, with the pan-viral antibody tool we used, we did not find increased anti-viral antibodies against any of the other many viruses we looked at. This specific increase in enteroviral antibodies and not other types of viruses adds another strong piece of evidence implicating enteroviruses in AFM.”

EV peptides were found in 29 of 42 children (69%) diagnosed with AFM, compared with 4 of 58 (6.9%) of the control group. The VirScan tool also enabled investigators to eliminate other possible viruses as a cause of AFM. Metagenomic next-generation sequencing also was used.

“Given the broad ability of the pan-viral serology tool (VirScan) to detect antibodies to thousands of viruses, it was surprising how only enterovirus antibodies were enriched in AFM children,” Wilson told Contagion^®. “In addition, the degree of enrichment for these antibodies did not differ based on whether children had had enteroviruses detected in peripheral tissues (stool, respiratory fluids or blood) by PCR or not.”

AFM has been linked to 2 strains of enterovirus — EV-D68 and EV-A71. More research is needed to understand how these common viruses seem to have recently begun to cause paralysis in about 1% of infected children and why children are affected in this way and not adults.

“While not every single case of AFM is likely due to an enterovirus, this study suggests that a large majority of AFM cases are and that enteroviral antibody testing in the cerebrospinal fluid may be a productive way to identify these children,” Wilson told Contagion^®.

The illness occurs primarily in the late summer and early fall from August to October. Spikes in the disease have occurred every other year since 2014, when 120 confirmed cases were reported, according to the US Centers for Disease Control and Prevention (CDC). In 2018, the number of confirmed cases rose to 236. There have been 22 confirmed cases in 2019.

The UCSF study builds on previous research that has identified enterovirus as a prime suspect in the cause of AFM. An earlier study found antibodies to enteroviruses in 11 out of 14 patients diagnosed with AFM.

“These data will hopefully build consensus around the primary causes of AFM to hopefully accelerate anti-viral therapies and/or vaccine development should the number of AFM cases continue to increase,” Wilson told Contagion^®.

The study was conducted in collaboration with the Chan Zuckerberg Biohub, the CDC, the California Department of Public Health, the University of Colorado, Boston Children's Hospital and the University of Ottawa.

AFM is of key interest to health professionals. The National Institute of Health’s National Institute of Allergy and Infectious Diseases has awarded $10 million over 5 years for a natural history study on AFM. That work will be assisted by the AFM Task Force established last year by the CDC, which has urged rapid reporting by practitioners. The disease commonly starts as a mild respiratory illness or fever less than a week before patients developed arm or leg weakness. Other research has focused on developing new approaches to more rapidly and accurately diagnose the disease.