Sex: M
Vaccine: VARCEL
Symptoms: CSF protein normal, CSF red blood cell count positive, CSF white blood cell count increased, Central venous catheterisation, Gram stain
Clinical narrative: meningitis; herpes zoster; vaccine strain VZV reactivation leading to meningitis in a previously vaccinated child;   It was reported in a published article, title as stated above that following primary infection, varicella zoster virus (VZV) establishes latency in cranial nerve and dorsal root ganglia and can subsequently reactivate to produce disease in infected individuals Although wild-type VZV has been isolated from previously immunized children with herpes zoster, recent studies also indicate that vaccine strain VZV is a potential cause of herpes zoster in immunocompetent and immunocompromised children. Data from post-licensure surveillance indicate that clinical severity is milder in vaccinated children compared with children who have had the wild-type VZV infections. The central nervous system involvement in VZV reactivation is believed to be a rare complication. In this report, we describe herpes zoster and meningitis in an immunocompetent child with the vaccine strain of VZV.   A previously healthy 7 year old boy was vaccinated with varicella virus vaccine live (Oka/Merck) at 12 months of  age. On an unspecified date the patient presented with a 4-day history of right arm pain; a 2-day history of right arm rash; and a 1-day history of fever, headache, photophobia, and vomiting. The rash started on his right elbow and spread to the rest of his upper right arm and shoulder over 2 days. There was no history of sick contact. On admission, his temperature was 37.1°C, pulse 96/min, respiratory rate 16/min, and blood pressure was 101/56. The physical examination was notable for multiple erythematous, maculopapular lesions without clear vesicles over the lateral side of his right arm. There was no nuchal rigidity, and there was no evidence of neurologic deficit or altered mental status. Laboratory studies revealed a peripheral white blood cell count of 7000 cells/mm with 77% neutrophils. 13% lymphocytes, and 10% monocytes. His serum electrolytes, liver transaminases, hemoglobin, and platelet counts were within normal limits. Cerebrospinal fluid (CSF) revealed 16 white blood  cells with 71% lymphocytes and 3 red blood cells/mm. The protein was 29 mg/dL, and the glucose was 57 mg/dL. The CSF Gram stain and culture were negative for bacterial pathogens. A swab from a skin lesion, and CSF were positive for VZV by polymerase chain reaction. VZV from both sites was identified as vaccine strain according to genotyping performed. Subsequent immune evaluation showed normal numbers, percentages, and ratios of peripheral T and B cell subsets and a negative serology for human immunodeficiency virus. The patient was treated with intravenous acyclovir (10 mg/kg every 8 hours). His symptoms improved, and he was discharged home on hospital day 3 with a peripherally inserted central catheter to complete a 21-day course of acyclovir. He was asymptomatic with a normal physical examination at 2 weeks after discharge.   The authors discussed that the implementation of routine varicella vaccination has dramatically shifted the clinical epidemiology of primary VZV infection  for children. The risk of herpes zoster has also been described as being decreased in vaccinated children. Data from post-licensure surveillance indicated that 7 cases of herpes zoster due to wild-type VZV and 10 from vaccine strain VZV in patients hospitalized with herpes zoster have been identified. This data suggest that vaccine strain VZV is currently an important cause of herpes zoster among immunized children.  The incidence of neurologic complications in herpes zoster is not well defined in the medical literature, but they are believed to be rare complications. Although children with defects in cell-mediated immunity are expected to be more susceptible to neurologic complications, meningitis and meningoencephalitis resulting from reactivation of wild-type VZV have been reported in both immunocompetent and immunocompromised children. Notably, recent reports also identified meningitis as a complication in reactivation of vaccine strain VZV in immunocompetent  and immunocompromised children. In this regard, our report rep-resents the fifth laboratory confirmed case of vaccine strain VZV reactivation leading to meningitis in a previously vaccinated child(vaccination failure).  The etiologic agent in our case, as in other reported cases, was established by the VZV genotyping at the Centers for Disease Control and Prevention. Given the routine childhood immunization with varicella vaccine, we speculate that the incidence of meningitis caused by the reactivation of vaccine strain VZV may be on the increase. Appropriate testing to identify the VZV strain in future cases of patients presenting with herpes zoster meningitis will be important to establish the incidence and risk of this rare vaccine complication.     Additional information has been received from literature article tittle as stated above.  Varicella vaccine has been shown to be extremely safe. In contrast to 100 varicella deaths annually from wild type (WT) disease in the pre-vaccine era, there is only one varicella death from the Oka strain on record in the world literature, in an child with underlying leukemia, in the past 15 years. The most frequently reported adverse reaction to vaccination was a mild rash that appears several weeks later in about 5 percent of healthy children, particularly after a first vaccine dose. Extensive rashes, with occasional pneumonia or neurologic symptoms have been reported rarely in immunocompromised children who were inadvertently vaccinated, such as those with undiagnosed AIDS, natural killer (NK) cell deficiency, and other immunodeficiency diseases. They have been treated successfully with antiviral therapy. There is a potential for transmission of the vaccine virus if vaccines develop rash from the Oka strain, but transmission is extremely rare from healthy individuals; fewer than 10 instances of transmission have been reported since 1995, during which time as many as 60 million children were vaccinated (Centers-for Disease-Control). A few notable neurologic events were related to varicella vaccine. There are 9 reports of herpes zoster (HZ) due to the Oka strain with accompanying meningitis, in which varicella zoster virus (VZV) DNA was found in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR). The patients were a mixture of healthy and immunocompromised children; most received antiviral therapy and all recovered. This form of meningitis has also been reported as being caused by WT VZV. It is therefore unclear whether or not these 9 Oka meningitis patients should be classified as having a vaccine-associated adverse event. There was no known denominator for meningitis caused by WT or Oka VZV; therefore the incidence of these complications is not known, but this illness in vaccines appears to be rare. Transient cerebellar ataxia has been reported following vaccination, but its connection to VZV, if any, has not been proven.  Additional information has been requested.  A copy of the published articles are attached as further documentation of the patient's experience.  Follow up information was received on 15-MAY-2020.  It has been determined that case# US-009507513-2005USA003016 is a duplicate of case # US-009507513-1103USA02203. Therefore, case # US-009507513-2005USA003016 is being deleted from our files and the cases are consolidated into case #US-009507513-1103USA02203.; Sender's Comments:  US-009507513-1212USA008259: US-009507513-0803USA04453: US-009507513-0802USA02752: US-009507513-0803USA03578: US-009507513-0803USA04484: US-009507513-0805USA06017: US-009507513-0812USA03301: GR-009507513-0712USA01081: US-009507513-0906USA05714: