Genomic and serologic characterization ofenterovirus A71 brainstem encephalitis
Author
Leon, Kristoffer E.
Schubert, Ryan D.
Casas-Alba, Didac
Hawes, Isobel A.
Ramachandran, Prashanth S.
Ramesh, Akshaya
Pak, John E.
Wu, Wesley
Cheung, Carly K.
Crawford, Emily D.
Khan, Lillian M.
Launes, Cristian
Sample, Hannah A.
Zorn, Kelsey C.
Cabrerizo, María
Valero-Rello, Ana
Langelier, Charles
Muñoz-Almagro, Carmen
DeRisi, Joseph L.
Wilson, Michael R.
Publication date
2020ISSN
2332-7812
Abstract
Objective: In 2016, Catalonia experienced a pediatric brainstem encephalitis outbreak caused by enterovirus A71 (EV-A71). Conventional testing identified EV in the periphery but rarely in CSF. Metagenomic next-generation sequencing (mNGS) and CSF pan-viral serology (VirScan) were deployed to enhance viral detection and characterization.Methods: RNA was extracted from the CSF (n = 20), plasma (n = 9), stool (n = 15), and nasopharyngeal samples (n = 16) from 10 children with brainstem encephalitis and 10 children with meningitis or encephalitis. Pathogens were identified using mNGS. Available CSF from cases (n = 12) and pediatric other neurologic disease controls (n = 54) were analyzed with VirScan with a subset (n = 9 and n = 50) validated by ELISA. Results: mNGS detected EV in all samples positive by quantitative reverse transcription polymerase chain reaction (qRT-PCR) (n = 25). In qRT-PCR-negative samples (n = 35), mNGS found virus in 23% (n = 8, 3 CSF samples). Overall, mNGS enhanced EV detection from 42% (25/60) to 57% (33/60) (p-value = 0.013). VirScan and ELISA increased detection to 92% (11/12) compared with 46% (4/12) for CSF mNGS and qRT-PCR (p-value = 0.023). Phylogenetic analysis confirmed the EV-A71 strain clustered with a neurovirulent German EV-A71. A single amino acid substitution (S241P) in the EVA71 VP1 protein was exclusive to the CNS in one subject. Conclusion: mNGS with VirScan significantly increased the CNS detection of EVs relative to qRT-PCR, and the latter generated an antigenic profile of the acute EV-A71 immune response. Genomic analysis confirmed the close relation of the outbreak EV-A71 and neuroinvasive German EV-A71. A S241P substitution in VP1 was found exclusively in the CSF.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medical sciences
Keywords
Genomes
Encefalitis
Meningitis
Infants -- Salud i Higiene
Tronc de l'encèfal
Serologia
Genomas
Encefalitis
Meningitis
Niños -- Salud e higiene
Cerebro
Serología
Genomes
Encephalitis
Meningitis
Children -- Health and hygiene
Brainstem
Serology
Pages
11
Publisher
Wolters Kluwer
Collection
7;3
Is part of
Neurology: Neuroimmunology & Neuroinflammation
Citation
Leon, Kristoffer E.; Schubert, Ryan D.; Casas-Alba, Didac [et al.]. Genomic and serologic characterization ofenterovirus A71 brainstem encephalitis. Neurology: Neuroimmunology & Neuroinflammation, 2020, 7(3), p. 1-10. Disponible en: <https://nn.neurology.org/content/7/3/e703>. Fecha de acceso: 16 feb. 2021. DOI: 10.1212/NXI.0000000000000703
This item appears in the following Collection(s)
- Ciències de la Salut [725]
Rights
© 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloadingand sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/