Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling

Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform furt...

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Autores principales: Prashanth S. Ramachandran, Michael R. Wilson, Gaud Catho, Geraldine Blanchard-Rohner, Nicoline Schiess, Randall J. Cohrs, David Boutolleau, Sonia Burrel, Tetsushi Yoshikawa, Anne Wapniarski, Ethan H. Heusel, John E. Carpenter, Wallen Jackson, Bradley A. Ford, Charles Grose
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:2e9acd197dfb4512959c5818668614e02021-11-25T19:14:11ZMeningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling10.3390/v131122861999-4915https://doaj.org/article/2e9acd197dfb4512959c5818668614e02021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2286https://doaj.org/toc/1999-4915Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3–4 weeks before onset of vaccine meningitis may be a risk factor in some cases.Prashanth S. RamachandranMichael R. WilsonGaud CathoGeraldine Blanchard-RohnerNicoline SchiessRandall J. CohrsDavid BoutolleauSonia BurrelTetsushi YoshikawaAnne WapniarskiEthan H. HeuselJohn E. CarpenterWallen JacksonBradley A. FordCharles GroseMDPI AGarticlevaricella-zoster virusOka strainhuman herpesvirus 6human herpesvirus 7corticosteroidsserious adverse eventMicrobiologyQR1-502ENViruses, Vol 13, Iss 2286, p 2286 (2021)
institution DOAJ
collection DOAJ
language EN
topic varicella-zoster virus
Oka strain
human herpesvirus 6
human herpesvirus 7
corticosteroids
serious adverse event
Microbiology
QR1-502
spellingShingle varicella-zoster virus
Oka strain
human herpesvirus 6
human herpesvirus 7
corticosteroids
serious adverse event
Microbiology
QR1-502
Prashanth S. Ramachandran
Michael R. Wilson
Gaud Catho
Geraldine Blanchard-Rohner
Nicoline Schiess
Randall J. Cohrs
David Boutolleau
Sonia Burrel
Tetsushi Yoshikawa
Anne Wapniarski
Ethan H. Heusel
John E. Carpenter
Wallen Jackson
Bradley A. Ford
Charles Grose
Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling
description Varicella vaccine meningitis is an uncommon delayed adverse event of vaccination. Varicella vaccine meningitis has been diagnosed in 12 children, of whom 3 were immunocompromised. We now report two additional cases of vaccine meningitis in twice-immunized immunocompetent children and we perform further testing on a prior third case. We used three methods to diagnose or investigate cases of varicella vaccine meningitis, none of which have been used previously on this disease. These include metagenomic next-generation sequencing and cytokine multiplex profiling of cerebrospinal fluid and immunology exome analysis of white blood cells. In one new case, the diagnosis was confirmed by metagenomic next-generation sequencing of cerebrospinal fluid. Both varicella vaccine virus and human herpesvirus 7 DNA were detected. We performed cytokine multiplex profiling on the cerebrospinal fluid of two cases and found ten elevated biomarkers: interferon gamma, interleukins IL-1RA, IL-6, IL-8, IL-10, IL-17F, chemokines CXCL-9, CXCL-10, CCL-2, and G-CSF. In a second new case, we performed immunology exome sequencing on a panel of 356 genes, but no errors were found. After a review of all 14 cases, we concluded that (i) there is no common explanation for this adverse event, but (ii) ingestion of an oral corticosteroid burst 3–4 weeks before onset of vaccine meningitis may be a risk factor in some cases.
format article
author Prashanth S. Ramachandran
Michael R. Wilson
Gaud Catho
Geraldine Blanchard-Rohner
Nicoline Schiess
Randall J. Cohrs
David Boutolleau
Sonia Burrel
Tetsushi Yoshikawa
Anne Wapniarski
Ethan H. Heusel
John E. Carpenter
Wallen Jackson
Bradley A. Ford
Charles Grose
author_facet Prashanth S. Ramachandran
Michael R. Wilson
Gaud Catho
Geraldine Blanchard-Rohner
Nicoline Schiess
Randall J. Cohrs
David Boutolleau
Sonia Burrel
Tetsushi Yoshikawa
Anne Wapniarski
Ethan H. Heusel
John E. Carpenter
Wallen Jackson
Bradley A. Ford
Charles Grose
author_sort Prashanth S. Ramachandran
title Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling
title_short Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling
title_full Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling
title_fullStr Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling
title_full_unstemmed Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling
title_sort meningitis caused by the live varicella vaccine virus: metagenomic next generation sequencing, immunology exome sequencing and cytokine multiplex profiling
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/2e9acd197dfb4512959c5818668614e0
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