Clinical Characteristics of Enterovirus A71 Neurologic Disease During an Outbreak in Children in Colorado, 2018
35 Pages Posted: 13 Jul 2019More...
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
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