2026-04-29T22:57:42Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/92792025-05-14T10:30:02Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609
Repisalud
author
Leon, Kristoffer E
author
Schubert, Ryan D
author
Casas-Alba, Didac
author
Hawes, Isobel A
author
Ramachandran, Prashanth S
author
Ramesh, Akshaya
author
Pak, John E
author
Wu, Wesley
author
Cheung, Carly K
author
Crawford, Emily D
author
Khan, Lillian M
author
Launes, Cristian
author
Sample, Hannah A
author
Zorn, Kelsey C
author
Cabrerizo, Maria
author
Valero-Rello, Ana
author
Langelier, Charles
author
Muñoz-Almagro, Carmen
author
DeRisi, Joseph L
author
Wilson, Michael R
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Instituto de Salud Carlos III
2020-03-18T11:59:06Z
2020-03-18T11:59:06Z
2020-05
Neurol Neuroimmunol Neuroinflamm. 2020 Mar 5;7(3). pii: e703.
10.1212/NXI.0000000000000703
2332-7812
2332-7812
Neurology(R) neuroimmunology & neuroinflammation
32139440
http://hdl.handle.net/20.500.12105/9279
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.
eng
Genomic and serologic characterization of enterovirus A71 brainstem encephalitis
research article
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GenomicAndSerologicCharacterization_2020.pdf
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GenomicAndSerologicCharacterization_2020.pdf.txt