Summary: Study connects enterovirus A71, which causes Hand, Foot, and Mouth Disease, to a large outbreak of neurological illness in the U.S in 2018. Symptoms of the virus include myoclonus, ataxia, weakness, and autonomic instability.

Source: Children’s Hospital Colorado

The Lancet Infectious Diseases recently published the results of an observational study led by researchers on Children’s Hospital Colorado Infectious Disease and Neurology teams, along with counterparts at the Centers for Disease Control and Colorado Department of Public Health and Environment. The study was conducted from March 1 to November 30, 2018, and led to a discovery of the largest outbreak of enterovirus A71 (EV-A71) in the United States.

Since the 1990s, every 1 to 3 years, EV-A71 has caused large-scale, and sometimes deadly epidemics in the Asia-Pacific region, which has prompted the development of EV-A71 vaccines. In the United States, detections of this virus have been small-scale and sporadic. However, the unique symptoms, unusually high number of cases, and the geographic clustering of children who were observed during this study, indicated an outbreak.

“We need to watch this very closely,” said Kevin Messacar, MD, pediatric infectious disease physician and researcher at Children’s Hospital Colorado and University of Colorado Anschutz Medical Campus . “Enhanced surveillance is needed in order to determine whether this outbreak was an isolated event, or a warning of impending cyclic outbreaks of EV-A71 neurological disease in the U.S.”

In addition to highlighting the need to improve enterovirus surveillance, the observational study also helped identify what other medical providers should be looking for. Children with EV-A71 disease were best differentiated from children with other enteroviruses by the neurological findings of myoclonus (quick, involuntary muscle jerks), ataxia (dizziness), weakness and autonomic instability (dysregulation of heart rate, blood pressure and perfusion). Often times these symptoms can be misunderstood or misattributed to other diagnoses – especially among young children.

Finally, it’s important to note that these viruses tend to appear in seasonal waves. If through additional surveillance efforts, the United States continues to see enteroviruses circulating that cause neurological illness, the development of antivirals and vaccines may need to become a priority.

“Were it not for Children’s Hospital Colorado’s ongoing interest and commitment to the study of enteroviruses, this outbreak would probably not have been detected,” noted Drs. Carol Glaser and Mike Wilson in a commentary published alongside the Lancet study. “The USA has yet to have large-scale epidemics of enteroviruses as are seen in Asia and other countries, but it should take steps to become better prepared.”

About this neuroscience research article

Source:

Children’s Hospital Colorado

Media Contacts:

Allison Miller – Children’s Hospital Colorado

Image Source:

The image is in the public domain.

Original Research: Closed access

“Clinical characteristics of enterovirus A71 neurological disease during an outbreak in children in Colorado, USA, in 2018: an observational cohort study”. Kevin Messacar et al.

The Lancet: Infectious Diseases doi:10.1016/S1473-3099(19)30632-2.

Abstract

Clinical characteristics of enterovirus A71 neurological disease during an outbreak in children in Colorado, USA, in 2018: an observational cohort study

Background

In May, 2018, Children’s Hospital Colorado noted an outbreak of enterovirus A71 (EV-A71) neurological disease. We aimed to characterise the clinical features of EV-A71 neurological disease during this outbreak.

Methods

In this retrospective observational cohort study, children (younger than 18 years) who presented to Children’s Hospital Colorado (Aurora, CO, USA) between March 1 and November 30, 2018, with neurological disease (defined by non-mutually exclusive criteria, including meningitis, encephalitis, acute flaccid myelitis, and seizures) and enterovirus detected from any biological specimen were eligible for study inclusion. The clinical characteristics of children with neurological disease associated with EV-A71 were compared with those of children with neurological disease associated with other enteroviruses during the same period. To explore the differences in clinical presentation of acute flaccid myelitis, we also used a subgroup analysis to compare clinical findings in children with EV-A71-associated acute flaccid myelitis during the study period with these findings in those with enterovirus D68 (EV-D68)-associated acute flaccid myelitis at the same hospital between 2013 and 2018.

Findings

Between March 10 and Nov 10, 2018, 74 children presenting to Children’s Hospital Colorado were found to have enterovirus neurological disease; EV-A71 was identified in 43 (58%) of these children. The median age of the children with EV-A71 neurological disease was 22·7 months (IQR 4·0–31·9), and most of these children were male (34 [79%] children). 40 (93%) children with EV-A71 neurological disease had findings suggestive of meningitis, 31 (72%) children showed evidence of encephalitis, and ten (23%) children met our case definition of acute flaccid myelitis. All children with EV-A71 disease had fever and 18 (42%) children had hand, foot, or mouth lesions at or before neurological onset. Children with EV-A71 disease were best differentiated from those with other enteroviruses (n=31) by the neurological findings of myoclonus, ataxia, weakness, and autonomic instability. Of the specimens collected from children with EV-A71, this enterovirus was detected in 94% of rectal, 79% of oropharyngeal, 56% of nasopharyngeal, and 20% of cerebrospinal fluid specimens. 39 (93%) of 42 children with EV-A71 neurological disease who could be followed up showed complete recovery by 1–2 months. Compared with children with EV-D68-associated acute flaccid myelitis, children with EV-A71-associated acute flaccid myelitis were younger, showed neurological onset earlier after prodromal symptom onset, had milder weakness, showed more rapid improvement, and were more likely to completely recover.

Interpretation

This outbreak of EV-A71 neurological disease, the largest reported in the Americas, was characterised by fever, myoclonus, ataxia, weakness, autonomic instability, and full recovery in most patients. Because EV-A71 epidemiology outside of Asia remains difficult to predict, identification of future outbreaks will be aided by prompt recognition of these distinct clinical findings, testing of non-sterile and sterile site specimens, and enhanced enterovirus surveillance.

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