The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
Genomic and serologic characterization of enterovirus A71 brainstem encephalitis
Open accessAbstract
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.
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“Another study used mNGS, VirScan, and serology and found a high rate of enterovirus detection (up to 92%) relative to routine qRT-PCR and mNGS (36).”
From Viruses Causing Aseptic Meningitis: A Tertiary Medical Center Experience With a Multiplex PCR Assay (2020) · cites this paper as [36]
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Clinical Metagenomic Sequencing for Diagnosis of Meningitis and Encephalitis
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“The subjects 1–10 were negative by the BioFire FilmArray Meningitis/Encephalitis panel.(2) All EVpositive subjects (by clinical PCR) were genotyped at the Enterovirus Unit of the Spanish National Centre for Microbiology according to a previously described procedure.”
BackgroundMethodMiller, S. A., Naccache, S. N., Samayoa, E., Messacar, K., Arevalo, S., Federman, S., Stryke, D., Pham, E., Fung, B., Bolosky, W. J., et al. (2019) · Genome Research · doi:10.1101/gr.238170.118 · Cited by 593
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Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71
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Virus genomes reveal factors that spread and sustained the Ebola epidemic
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Metagenomics for neurological infections — expanding our imagination
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Viruses Causing Aseptic Meningitis: A Tertiary Medical Center Experience With a Multiplex PCR Assay
Aldriweesh, M. A., Shafaay, E. A., Alwatban, S. M., Alkethami, O. M., Aljuraisi, F. N., Bosaeed, M., & Alharbi, N. K. (2020) · Frontiers in Neurology · doi:10.3389/fneur.2020.602267 · Cited by 30
“Another study used mNGS, VirScan, and serology and found a high rate of enterovirus detection (up to 92%) relative to routine qRT-PCR and mNGS (36).”
Result
Metadata
- Authors
- Leon, K. E., Schubert, R. D., Casas-Alba, D., Hawes, I. A., Ramachandran, P. S., Ramesh, A., Pak, J. E., Wu, W., Cheung, C. K., Crawford, E. D., Khan, L. M., Launes, C., Sample, H. A., Zorn, K. C., Cabrerizo, M., Valero-Rello, A., Langelier, C., Muñoz-Almagro, C., DeRisi, J. L., & Wilson, M. R.
- Affiliations
- University of California, San Francisco (US)
- From the Medical Scientist Training Program (K.E.L.), University of California, San Francisco; Biomedical Sciences Graduate Program (K.E.L., I.A.H.), University of California, San Francisco; Weill Institute for Neurosciences (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Department of Neurology (R.D.S., I.A.H., P.S.R., A.R., M.R.W.), University of California, San Francisco; Institut de Recerca Pediàtrica Hospital Sant Joan de Déu (D.C.-A., C.L., A.V.-R., C.M.-A.),...
- Corresponding author
- Wilson, Michael R.
- ORCID
- Venue
- Neurology Neuroimmunology & Neuroinflammation
- Published
- 2020-05
- Volume
- 7
- Issue
- 3
- ISSN
- 2332-7812 (ISSN-L)
- PMC
- PMC7136061
- OpenAlex
- W3010465504
- Cited by
- 32
- References
- 39
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 5 · 2023: 6 · 2022: 4 · 2021: 6 · 2020: 4
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Update notices
- correction (2025-10-06)
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Neurology Neuroimmunology & Neuroinflammation (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Hispana (publishedVersion, cc-by-nc-nd)
- Repository of Digital Objects for Teaching Research and Culture (University of Valencia) (submittedVersion, cc-by-nc)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by-nc-nd)
- Funders
- Multiple Sclerosis Society
- National Institutes of Health
- University of California, San Francisco
- European Regional Development Fund
- National Institute of General Medical Sciences (T32GM007618)
- National Institute of Neurological Disorders and Stroke (F31NS113432, K08NS096117)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Immunology Research
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Keywords
- enterovirus 71, brainstem encephalitis, cerebrospinal fluid viral detection, metagenomic next-generation sequencing
- MeSH terms
- Brain Stem, Child, Preschool, Enterovirus Infections, Enzyme-Linked Immunosorbent Assay, Female, Humans, Infant, Male, Meningitis, Viral, Phylogeny, RNA, Viral, Cohort Studies, Sequence Analysis, RNA, Encephalitis, Viral, Reverse Transcriptase Polymerase Chain Reaction, Enterovirus A, Human, High-Throughput Nucleotide Sequencing
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