Age: 1.0
Sex: F
Vaccine: VARCEL
Symptoms: Blood immunoglobulin M normal, CD4 lymphocytes normal, CD8 lymphocytes, CSF glucose decreased, CSF lymphocyte count increased
Clinical narrative: A small cluster of vesicles was observed over the right knee. Filmarray encephalitis/meningitis multiplex panel test on the cerebrospinal fluid was positive for varicella-zoster virus; Filmarray encephalitis/meningitis multiplex panel test on the cerebrospinal fluid was positive for varicella-zoster virus;   Information was received from the authors in a published literature article entitled as stated above. This case concerns to a 14 years-old female patient. The patient's concurrent conditions included asthma since age 3 years; the asthma attacks were induced by viral respiratory infections. The patient's historical vaccination included measles-mumps-rubella (manufacturer unknown) at ages 1 and 5 years and additionally, she received all recommended childhood immunizations (unspecified). Her concomitant medications were not reported.  On an unknown date, when the patient was 1 years-old, she was vaccinated with the first dose of varicella virus vaccine live (oka/merck)(manufacturer unknown). Then at age of 5 years-old, she was vaccinated with the second dose of varicella virus vaccine live (oka/merck)(manufacturer unknown) (lot number, expiration dates, route of administration and dose for both doses were not reported), both doses administered for prophylaxis. Other suspect therapies included included beclomethasone, 80 mg twice daily, intermittently using an oral metered-dose inhaler); and prednisone, 20 milligrams daily by oral route, administered due to asthma worsening. Prednisone was administered 4 weeks before the patient's admission, and the duration of the administration was 5 days.  It was reported that the patient had been having intermittent but less severe headaches as well as abdominal pain and back pain for 2 weeks. She had gone to a medical clinic, where a computed tomogram of the abdomen /pelvis with contras was performed 10 days before the patient's admission. That scan did not show any abnormalities. Then on an unknown date in 2019, the patient was admitted to a hospital because of increasingly severe headaches. The headaches were accompanied by dizziness, nausea, vomiting and confusion. When she first presented in the emergency department late in the evening, she was noted to be febrile. A complete blood cell count and metabolic panel were unremarkable. A head computed tomogram was performed and read as normal. Thereafter, a lumbar puncture was performed, with the following results on cerebrospinal fluid: colorless; protein 132 mg/dL, glucose 45mg/dL, red blood cells 5/mm3, and nucleated cell count 775/mm3 with 82% lymphocytes. A biofire Filmarray encephalitis/meningitis multiplex panel test on the cerebrospinal fluid was positive for varicella-zoster virus. To confirm the result of the multiplex assay, the authors tested for varicella antibody in the cerebrospinal fluid and the test was positive (Herpes zoster meningitis). The cerebrospinal fluid sample was stored frozen after aliquots were removed for the initial screening test. Subsequently, the sample was thawed for the first time in order to perform partial sequencing of the viral genome known to be present in cerebrospinal fluid after the varicella-positive screening PCR test. Within 12 hours after admission, therapy with intravenous acyclovir (30 mg/kg/d) was initiated. Later in the same day, a small cluster of vesicles was observed over her right knee (Disseminated varicella zoster vaccine virus infection). Fluid from one vesicle was tested by Focus Integrated Cycler for both herpes simplex virus and varicella virus DNA; only varicella was positive. Head magnetic resonance imaging was performed and was normal except for increased enhancement along the leptomeningeal surface, consistent with meningitis. It was reported that neither she nor her mother recalled any family member with varicella or herpes zoster rashes in the month preceding onset of meningitis. Therefore, there was no possibility of a recent transmission of varicella vaccine virus to the adolescent.   During her hospitalization, she completed a 7-day course of intravenous acyclovir, followed by 2 weeks of valacyclovir tablets (1 g thrice daily), with complete resolution of symptoms and the patient was discharged on an unknown date. Then, one month after discharge, she returned for an immunology evaluation. Serum levels of immunoglobulins IgM, IgA, and IgG were within normal limits, as were levels of the 4 IgG subclasses. Similarly, the levels of IgG antibodies to both tetanus toxoid and diphtheria toxoid were within normal ranges for a child who had previously received 4 tetanus-diphtheriapertussis vaccinations. The total serum complement level was normal. The B-cell phenotyping profile for immunodeficiency and immune competence assessment was normal. Percentages of CD3, CD4, CD8, and CD16 and CD56 lymphocytes (unknown date): were normal by flow cytometry analysis. Likewise, a CD8 immune competence assessment was normal as measured by gamma interferon level and CD107a/CD107b markers.  At the reporting time, the outcome of the events was recovered on an unknown date. The authors stated that all the adverse events were related to varicella virus vaccine live (oka/merck)(manufacturer unknown), as they reported that it was a serious and unusual complication with the vaccination. Additionally, they considered that the events were also related to the therapy with prednisone and beclomethasone as this could be a precipitating risk factor for herpes zoster infection, as systemic corticosteroid regimens have been known to precipitate herpes Zoster in children with cancer and other chronic diseases.   Upon internal review the events were considered as medically significant adverse events.  A copy of the published article is attached as further documentation of the patient's experience.