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Clinical Characteristics of Enterovirus A71 Neurologic Disease During an Outbreak in Children in Colorado, 2018

35 Pages Posted: 13 Jul 2019

See all articles by Kevin Messacar

Kevin Messacar

Children's Hospital Colorado; University of Colorado at Denver - School of Medicine

Emily Spence-Davizon

Colorado Department of Public Health and the Environment

Christina Osborne

University of Colorado at Denver - Children’s Hospital Colorado

Craig Press

Children's Hospital Colorado

Teri L. Schreiner

Children's Hospital Colorado

Jan Martin

Children's Hospital Colorado

Ricka Messer

Children's Hospital Colorado

John Maloney

Children's Hospital Colorado

Alexis Burakoff

Colorado Department of Public Health and the Environment

Meghan Barnes

Colorado Department of Public Health and the Environment

Shannon Rogers

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

Adriana S. Lopez

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

Janell Routh

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

Susan I. Gerber

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

M. Steven Oberste

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

Allan Nix

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

Mark J. Abzug

University of Colorado at Denver - Children’s Hospital Colorado

Ken Tyler

Colorado Department of Public Health and the Environment

Rachel Herlihy

Colorado Department of Public Health and the Environment

Samuel R. Dominguez

Children's Hospital Colorado

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Abstract

Background: In May 2018, Children's Hospital Colorado (CHCO) noted an outbreak of enterovirus (EV) A71-associated neurologic disease.

Methods: A case of EV-associated neurologic disease was defined as any child presenting to CHCO with meningitis, encephalitis, acute flaccid myelitis (AFM), and/or seizures between March 1 and November 30, 2018 with an EV detected from a biologic specimen. EV-A71 cases were compared to other EV cases during the same period. EV-A71-associated AFM cases were also compared to EV-D68-associated AFM cases from 2013-2018.

Findings: Of seventy-four children with EV-associated neurologic disease, forty-three (58%) were EV-A71-associated. Median age of EV-A71 cases was 22.7 months (IQR: 4-31.9 months); 34 (79%) were male. Neurologic involvement in EV-A71 cases included meningitis (93%), encephalitis (72%), and AFM (23%). All EV-A71 cases had fever; eighteen (42%) had hand, foot, or mouth (HFM) lesions. Neurologic findings distinguishing EV-A71-associated cases from other EV-associated cases (n=31) included myoclonus (60% vs. 16%, p<0.0001), ataxia (58% vs. 16%, p=0.003), weakness (30% vs. 6%, p=0.012), and autonomic instability (47% vs. 10%, p<0.0001). Amongst specimens collected from EV-A71 cases, EV-A71 was detected in 94% of rectal, 79% of oropharyngeal, 56% of nasopharyngeal, and 20% of cerebrospinal fluid specimens. Overall, 91% of children with EV-A71-associated neurologic disease fully recovered. Compared to EV-D68-associated AFM cases (n=8), EV-A71-associated AFM cases (n=10) were younger (19 vs. 100 months, p=0.034) with earlier neurologic onset after prodromal illness (median 1 vs. 5.5 days, p=0.011). HFM lesions were only present in EV-A71-associated AFM cases (60%), whereas preceding respiratory symptoms were more uniformly noted with EV-D68. EV-A71-associated AFM cases had milder weakness, more rapid improvement and were more likely to completely recover (90% vs. 13%, p=0.0029).

Interpretation: This outbreak of EV-A71 neurologic disease, the largest reported in the Western hemisphere, was characterized by fever, myoclonus, ataxia, weakness, autonomic instability, and full recovery in the majority. Testing of non-sterile site specimens was key to case and outbreak identification.

Funding Statement: KM receives funding through NIH/NIAID grant K23AI28069. RM receives funding through the Pediatric Epilepsy Research Consortium and West Pharmaceuticals, Inc. CP receives funding from C.R. Bard. TS receives private donor funding. Colorado Department of Public Health and Environment receives funding through Centers for Disease Control and Prevention grant CK14-1401.

Declaration of Interests: The authors report no conflicts of interest.

Ethics Approval Statement: Research and data collection protocols were approved by the Colorado Multiple Institutional Review Board with waiver of informed consent.

Keywords: enterovirus, encephalitis, meningitis, myelitis, neurologic disease

Suggested Citation

Messacar, Kevin and Spence-Davizon, Emily and Osborne, Christina and Press, Craig and Schreiner, Teri L. and Martin, Jan and Messer, Ricka and Maloney, John and Burakoff, Alexis and Barnes, Meghan and Rogers, Shannon and Lopez, Adriana S. and Routh, Janell and Gerber, Susan I. and Oberste, M. Steven and Nix, Allan and Abzug, Mark J. and Tyler, Ken and Herlihy, Rachel and Dominguez, Samuel R., Clinical Characteristics of Enterovirus A71 Neurologic Disease During an Outbreak in Children in Colorado, 2018 (July 8, 2019). The Lancet Infectious Diseases, VOLUME 20, ISSUE 2, P230-239, FEBRUARY 01, 2020, https://doi.org/10.1016/S1473-3099(19)30632-2, Available at SSRN: https://ssrn.com/abstract=3417873 or http://dx.doi.org/10.2139/ssrn.3417873

Kevin Messacar (Contact Author)

Children's Hospital Colorado ( email )

Aurora, CO 80045
United States

University of Colorado at Denver - School of Medicine ( email )

Building 500 - 13001 E. 17th Place, Campus Box C29
Aurora, CO 80045
United States

Emily Spence-Davizon

Colorado Department of Public Health and the Environment

CO
United States

Christina Osborne

University of Colorado at Denver - Children’s Hospital Colorado

13123 East 16th Avenue
Aurora, CO 80045
United States

Craig Press

Children's Hospital Colorado

Aurora, CO 80045
United States

Teri L. Schreiner

Children's Hospital Colorado

Aurora, CO 80045
United States

Jan Martin

Children's Hospital Colorado

Aurora, CO 80045
United States

Ricka Messer

Children's Hospital Colorado

Aurora, CO 80045
United States

John Maloney

Children's Hospital Colorado

Aurora, CO 80045
United States

Alexis Burakoff

Colorado Department of Public Health and the Environment

CO
United States

Meghan Barnes

Colorado Department of Public Health and the Environment

CO
United States

Shannon Rogers

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

1600 Clifton Rd., NE
Atlanta, GA 30333
United States

Adriana S. Lopez

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

1600 Clifton Rd., NE
Atlanta, GA 30333
United States

Janell Routh

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

1600 Clifton Rd., NE
Atlanta, GA 30333
United States

Susan I. Gerber

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

1600 Clifton Rd., NE
Atlanta, GA 30333
United States

M. Steven Oberste

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

1600 Clifton Rd., NE
Atlanta, GA 30333
United States

Allan Nix

Government of the United States of America - Centers for Disease Control and Prevention (CDC)

1600 Clifton Rd., NE
Atlanta, GA 30333
United States

Mark J. Abzug

University of Colorado at Denver - Children’s Hospital Colorado

13123 East 16th Avenue
Aurora, CO 80045
United States

Ken Tyler

Colorado Department of Public Health and the Environment

CO
United States

Rachel Herlihy

Colorado Department of Public Health and the Environment

CO
United States

Samuel R. Dominguez

Children's Hospital Colorado

Aurora, CO 80045
United States

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