Enterovirus A71 Outbreak in Colorado Underscores Need for Better Surveillance

A 2018 outbreak of enterovirus A71 in Colorado highlights the need for better detection and treatment of the infection, which has been associated with the mysterious polio-like disease acute flaccid myelitis (AFM) and other serious diseases.

An observational cohort study, published in The Lancet Infectious Diseases, sheds light on the clinical characteristics of enterovirus (EV)-A71 during the outbreak. It included 74 children at Colorado Children’s Hospital that presented with neurological disease and enterovirus detection between March 1 and November 30, 2018, including 43 with EV-A71. Among those, 40 showed evidence of meningitis, 31 showed evidence of encephalitis and 10 met the criteria for acute flaccid myelitis.

“This is the largest reported outbreak of enterovirus A71 neurologic disease in the Americas to date,” first author Kevin Messacar, MD, assistant professor in the Department of Pediatrics, Sections of Hospital Medicine and Infectious Disease at the University of Colorado's School of Medicine, told Contagion^®. “While EV-A71 has caused large cyclic epidemics of hand-foot-mouth and neurologic disease in the Asia Pacific for years prompting vaccine development, this virus has been uncommon in the US. Enhanced enterovirus surveillance in the US is needed to determine whether this outbreak was an isolated event or foreboding of future outbreaks of neurologic disease to come.”

One of more than 100 non-polio enteroviruses, EV-A71 was first recognized in California in 1969 as a common cause of hand, foot and mouth disease. Previous outbreaks of EV-A71 were reported in Colorado in 2003 and 2005.

A study published in October in the journal Nature Medicine, noted evidence of enterovirus in the cerebrospinal fluid of children diagnosed with AFM, which has been linked to 2 strains of enterovirus—EV-D68 and EV-A71.

The Colorado study noted differences between diseases from EV-A71 and other enteroviruses, including myoclonus, ataxia, weakness, and autonomic instability.

“A subset of children with EV-A71 neurologic disease had acute flaccid myelitis, which had important differences from AFM cases associated with EV-D68,” Messacar told Contagion^®. “Children with EV-A71 AFM had a shorter prodrome, were more likely to have characteristic hand-foot-mouth lesions than respiratory disease, had milder weakness and were more likely to recover than those with EV-D68. This study demonstrates that different enteroviruses can cause AFM that have different clinical features and different outcomes.”

The study also noted limitations in testing for EV-A71 and predicted that better methods of diagnosing EV infections would reveal more previously unidentified infections.

“Clinicians should be able to recognize signs of enterovirus associated neurologic disease in children and should test comprehensively, not just cerebrospinal fluid, but also respiratory and rectal/stool samples,” Messacar told Contagion^®. “Only 20% of the children with EV-A71 neurologic disease in this study had virus in their CSF, rectal and throat swabs were much more sensitive for virus detection. The lack of non-sterile site testing for EVs in cases of neurologic disease is one of the major reasons these cases are under-recognized, under-diagnosed, and under-reported.”

The Colorado outbreak began in the spring, before the typical late-summer emergence of enterovirus infections in the state. The study noted clusters of cases among children ages 4 and younger and evidence the infection spreading in classrooms and households. Early recognition of the outbreak helped providers differentiate the infection from other syndromes with similar symptoms.

“Enteroviruses are an underappreciated and important cause of neurologic disease in children,” Messacar told Contagion^®. “Increased resources are needed for enhanced surveillance and development of therapeutic and preventative strategies.”