Twelve Children with Varicella Vaccine Meningitis: Neuropathogenesis of Reactivated Live Attenuated Varicella Vaccine Virus

Abstract

Varicella vaccine is a live attenuated varicella-zoster virus (VZV). Like its parental strain called VZV pOka, the vaccine virus vOka retains some neurotropic properties. To better understand vOka neuropathogenesis, we reassessed 12 published cases of vOka meningitis that occurred in once-immunized and twice-immunized children, all of whom had bouts of herpes zoster preceding the central nervous system infection. Eight of the 12 meningitis cases occurred in children who had received only one immunization. There was no pattern to the time interval between varicella vaccination and the onset of herpes zoster with meningitis. Four of the meningitis cases occurred in children who had received two immunizations. Since all four children were 14 years old when meningitis was diagnosed, there was a strong pattern to the interval between the first vaccination at age 1 year and onset of meningitis, namely, 13 years. Knowledge of pathogenesis requires knowledge of the location of herpes zoster; the majority of dermatomal rashes occurred at sites of primary immunization on the arm or thigh, while herpes zoster ophthalmicus was uncommon. Based on this literature review, currently there is no consensus as to the cause of varicella vaccine meningitis in twice-immunized children.

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

“…Nevertheless, eight cases of varicella vaccine meningitis, a consequence of herpes zoster, have been reported in children who have received one varicella vaccination [3,4]. Even more recently, four cases of varicella vaccine meningitis in twice-immunized children have been reported [5]. We now report two new cases of varicella vaccine meningitis that occurred in twice-immunized, previously healthy boys.…”

“…Furthermore, we performed additional testing on an archived sample from an earlier varicella meningitis patient and we reviewed the histories of all published cases to define risk factors. In order to distinguish each patient separately, we have chosen to continue the nomenclature that was used in an earlier review that summarized data from 12 patients with varicella vaccine meningitis [5]. Therefore, the two new cases will be called case 13 and case 14.…”

Corticosteroids Contribute to Serious Adverse Events Following Live Attenuated Varicella Vaccination and Live Attenuated Zoster Vaccination

“…Although this case is cited in some reviews of adverse events of varicella vaccination, this case is different in that the complication occurred 5 years after vaccination. This case more closely resembles the eight cases of varicella vaccine meningitis that occurred years after a single varicella vaccination [ 26 ]. However, his case is the first in this meningitis group known to be associated with recent corticosteroids.…”

Herpes Zoster in an Immunocompetent Child without a History of Varicella

“…Thus, HZ in children may also arise from subclinical infection of VZV [ 7 , 9 , 11 ]. Additionally, despite clustered vesicular lesions in dermatomal distribution being the most common symptom of HZ in children, previous reports also include cases of central nervous system (CNS) infection, in which either wild type or vaccine strain was found in the virology screening for the cerebrospinal fluid (CSF) and further led to meningitis or encephalitis [ 13 , 16 , 18 , 19 , 34 ]. It is suggested that both wild type and vaccine strain VZV reactivation, can result in severe complications, especially CNS involvement.…”