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Genomic and serologic characterization of enterovirus A71 brainstem encephalitis.
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, Maria; Valero-Rello, Ana; Langelier, Charles; Muñoz-Almagro, Carmen; DeRisi, Joseph L; Wilson, Michael R.
Afiliação
  • Leon KE; 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 Franc
  • Schubert RD; 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 Franc
  • Casas-Alba D; 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 Franc
  • Hawes IA; 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 Franc
  • Ramachandran PS; 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 Franc
  • Ramesh A; 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 Franc
  • Pak JE; 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 Franc
  • Wu W; 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 Franc
  • Cheung CK; 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 Franc
  • Crawford ED; 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 Franc
  • Khan LM; 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 Franc
  • Launes C; 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 Franc
  • Sample HA; 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 Franc
  • Zorn KC; 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 Franc
  • Cabrerizo M; 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 Franc
  • Valero-Rello A; 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 Franc
  • Langelier C; 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 Franc
  • Muñoz-Almagro C; 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 Franc
  • DeRisi JL; 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 Franc
  • Wilson MR; 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 Franc
Neurol Neuroimmunol Neuroinflamm ; 7(3)2020 05.
Article em En | MEDLINE | ID: mdl-32139440
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tronco Encefálico / RNA Viral / Encefalite Viral / Enterovirus Humano A / Infecções por Enterovirus / Meningite Viral Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Neurol Neuroimmunol Neuroinflamm Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tronco Encefálico / RNA Viral / Encefalite Viral / Enterovirus Humano A / Infecções por Enterovirus / Meningite Viral Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Child, preschool / Female / Humans / Infant / Male Idioma: En Revista: Neurol Neuroimmunol Neuroinflamm Ano de publicação: 2020 Tipo de documento: Article