Varicella Vaccine Meningitis as a Complication of Herpes Zoster in Twice-Immunized Immunocompetent Adolescents

Abstract

Varicella-zoster virus vaccination is recommended for virtually all young children in the United States, Canada, and several other countries. Varicella vaccine is a live attenuated virus that retains some of its neurotropic properties. Herpes zoster caused by vaccine virus still occurs in immunized children, although the rate is much lower than in children who had wild-type varicella. It was commonly thought that 2 varicella vaccinations would protect children against the most serious complication of meningitis following herpes zoster; however, 2 meningitis cases have already been published. We now report a third case of varicella vaccine meningitis and define risk factors shared by all 3 immunized adolescents. The diagnosis in cerebrospinal fluid in this third case was verified by amplifying and sequencing portions of the viral genome, to document fixed alleles found only in the vaccine strain. Viral antibody was also detected in the cerebrospinal fluid by confocal microscopy. When compared with the other 2 cases, remarkably all 3 were 14 years old when meningitis occurred. All 3 were treated with intravenous acyclovir, with complete recovery. The adolescent in our case report also had recurrent asthma, which was treated with both prednisone tablets and beclomethasone inhaler before onset of meningitis. When the 3 cases were considered together, they suggested that immunity to varicella-zoster virus may be waning sufficiently in some twice-immunized adolescents to make them vulnerable to varicella vaccine virus reactivation and subsequent meningitis. This complication rarely happens in children after wild-type varicella.

Keywords: acyclovir; asthma; cerebrospinal fluid; prednisone; vaccine; varicella.

Figure 1.

Detection of antibody to varicella virus in the cerebrospinal fluid of meningitis case. The patient’s antibody that attaches to virus-infected cells is stained fluorescent green; these positive areas are designated by yellow arrows (A-D). Positive and negative controls (E, F). Nuclei within the cells are stained dark blue (For interpretation of the references to colours in this figure legend, refer to the online version of this article).

Figure 2.

Model for pathogenesis of varicella vaccine meningitis following herpes zoster in an immunized adolescent. This figure includes a photo of the herpes zoster rash on the right leg of our case of meningitis (panel C). DRG, dorsal root ganglia.