TY - JOUR
T1 - Meningitis caused by the live varicella vaccine virus
T2 - Metagenomic next generation sequencing, immunology exome sequencing and cytokine multiplex profiling
AU - Ramachandran, Prashanth S.
AU - Wilson, Michael R.
AU - Catho, Gaud
AU - Blanchard-Rohner, Geraldine
AU - Schiess, Nicoline
AU - Cohrs, Randall J.
AU - Boutolleau, David
AU - Burrel, Sonia
AU - Yoshikawa, Tetsushi
AU - Wapniarski, Anne
AU - Heusel, Ethan H.
AU - Carpenter, John E.
AU - Jackson, Wallen
AU - Ford, Bradley A.
AU - Grose, Charles
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - Corticosteroids
KW - Herpes zoster
KW - Human herpesvirus 6
KW - Human herpesvirus 7
KW - IL-10
KW - IL-6
KW - Innate immunity
KW - Oka strain
KW - Serious adverse event
KW - Varicella-zoster virus
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U2 - 10.3390/v13112286
DO - 10.3390/v13112286
M3 - Article
C2 - 34835092
AN - SCOPUS:85119976674
SN - 1999-4915
VL - 13
JO - Viruses
JF - Viruses
IS - 11
M1 - 2286
ER -