2026-04-29T22:57:41Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/92792025-05-14T10:30:02Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19609

00925njm 22002777a 4500 dc 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 author 2020-05 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. 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 Genomic and serologic characterization of enterovirus A71 brainstem encephalitis