Meningitis Caused by the Live Varicella Vaccine Virus: Metagenomic Next Generation Sequencing, Immunology Exome Sequencing and Cytokine Multiplex Profiling
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
Affiliations
Prashanth S. Ramachandran
Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94110, USA
Michael R. Wilson
Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94110, USA
Gaud Catho
Division of Pediatric Infectious Diseases, Geneva University Hospitals, Faculty of Medicine, University of Geneva, 1205 Geneva, Switzerland
Geraldine Blanchard-Rohner
Pediatric Immunology and Vaccinology Unit, Division of General Pediatrics, Department of Pediatrics, Gynecology and Obstetrics, Geneva University Hospitals, University of Geneva, 1205 Geneva, Switzerland
Nicoline Schiess
Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA
Randall J. Cohrs
Department of Neurology, University of Colorado School of Medicine, Aurora, CO 80045, USA
David Boutolleau
Virology Department, National Reference Center for Herpesviruses, Pitie-Salpetriere Hospital, Sorbonne University, 75013 Paris, France
Sonia Burrel
Virology Department, National Reference Center for Herpesviruses, Pitie-Salpetriere Hospital, Sorbonne University, 75013 Paris, France
Tetsushi Yoshikawa
Department of Pediatrics, Fujita Health University School of Medicine, Aichi, Toyoake 470-1192, Japan
Anne Wapniarski
Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA 94110, USA
Ethan H. Heusel
Division of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
John E. Carpenter
Division of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Wallen Jackson
Division of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
Bradley A. Ford
Department of Pathology, University of Iowa, Iowa City, IA 52242, USA
Charles Grose
Division of Infectious Diseases/Virology, Department of Pediatrics, University of Iowa, Iowa City, IA 52242, USA
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.
