Genomic and serologic characterization of enterovirus A71 brainstem encephalitis.
Brain Stem
Child, Preschool
Cohort Studies
Encephalitis, Viral
/ virology
Enterovirus A, Human
/ genetics
Enterovirus Infections
/ virology
Enzyme-Linked Immunosorbent Assay
Female
High-Throughput Nucleotide Sequencing
Humans
Infant
Male
Meningitis, Viral
/ virology
Phylogeny
RNA, Viral
/ blood
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, RNA
Journal
Neurology(R) neuroimmunology & neuroinflammation
ISSN: 2332-7812
Titre abrégé: Neurol Neuroimmunol Neuroinflamm
Pays: United States
ID NLM: 101636388
Informations de publication
Date de publication:
05 2020
05 2020
Historique:
received:
18
10
2019
accepted:
06
02
2020
entrez:
7
3
2020
pubmed:
7
3
2020
medline:
3
8
2021
Statut:
epublish
Résumé
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. 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. 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) ( 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.
Identifiants
pubmed: 32139440
pii: 7/3/e703
doi: 10.1212/NXI.0000000000000703
pmc: PMC7136061
pii:
doi:
Substances chimiques
RNA, Viral
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : F31 NS113432
Pays : United States
Organisme : NINDS NIH HHS
ID : K08 NS096117
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007618
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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