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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Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/13/11/2286
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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
collection DOAJ
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.
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spelling doaj.art-2e9acd197dfb4512959c5818668614e02023-11-23T01:58:11ZengMDPI AGViruses1999-49152021-11-011311228610.3390/v13112286Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex ProfilingPrashanth S. Ramachandran0Michael R. Wilson1Gaud Catho2Geraldine Blanchard-Rohner3Nicoline Schiess4Randall J. Cohrs5David Boutolleau6Sonia Burrel7Tetsushi Yoshikawa8Anne Wapniarski9Ethan H. Heusel10John E. Carpenter11Wallen Jackson12Bradley A. Ford13Charles Grose14Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94110, USADepartment of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94110, USADivision of Pediatric Infectious Diseases, Geneva University Hospitals, Faculty of Medicine, University of Geneva, 1205 Geneva, SwitzerlandPediatric Immunology and Vaccinology Unit, Division of General Pediatrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, University of Geneva, 1205 Geneva, SwitzerlandDepartment of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USADepartment of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USAVirology Department, National Reference Center for Herpesviruses, Pitie-Salpetriere Hospital, Sorbonne University, 75013 Paris, FranceVirology Department, National Reference Center for Herpesviruses, Pitie-Salpetriere Hospital, Sorbonne University, 75013 Paris, FranceDepartment of Pediatrics, Fujita Health University School of Medicine, Aichi, Toyoake 470-1192, JapanDepartment of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94110, USADivision of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USADivision of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USADivision of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USADepartment of Pathology, University of Iowa, Iowa City, IA 52242, USADivision of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USAVaricella 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.https://www.mdpi.com/1999-4915/13/11/2286varicella-zoster virusOka strainhuman herpesvirus 6human herpesvirus 7corticosteroidsserious adverse event
spellingShingle 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
Viruses
varicella-zoster virus
Oka strain
human herpesvirus 6
human herpesvirus 7
corticosteroids
serious adverse event
title 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_short 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
topic varicella-zoster virus
Oka strain
human herpesvirus 6
human herpesvirus 7
corticosteroids
serious adverse event
url https://www.mdpi.com/1999-4915/13/11/2286
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