Age: 31.0
Sex: M
Vaccine: VARCEL
Symptoms: CSF virus identified, CSF white blood cell count increased, Cryptococcus test, Cytomegalovirus test negative, Epstein-Barr virus test negative
Clinical narrative: This literature marketed report has been received from the authors of the literature article, and refers to a 31 year old male patient who, in 2015, was found to be non-immune to varicella based on low varicella zoster virus (VZV) antibody levels. It was reported that the patient did not have varicella infection during childhood and denied any active signs or symptoms suggestive of varicella. On an unknown date in 2015, the patient was evaluated by occupational health services (OHS). The patient denied any medical history or current illness, and received his first dose of varicella virus vaccine live (Oka/Merck) (manufacturer unknown) on 07-DEC-2015. In January 2016, approximately one month after vaccination, the patient presented with a generalized vesicular rash. He denied any fever or other constitutional symptoms. He was evaluated by OHS and given a provisional diagnosis of chickenpox. Laboratory studies showed leukopenia. Samples from vesicular lesions collected for polymerase chain reaction (PCR) testing were positive for VZV. Positive VZV samples were sent to the Centers for Disease Control and Prevention (CDC) to distinguish the vaccine strain (Oka virus) from wild-type VZV. CDC molecular testing was indicative of vaccine-strain VZV. The patient was then diagnosed with a vaccine-strain disseminated varicella rash. He was treated with a 10-day course of oral acyclovir. In 2016, within four weeks of diagnosis of the vaccine-induced disseminated varicella rash, the patient presented to the emergency department with a main complaint of blurred vision in both eyes. Five days earlier, he woke up with sudden-onset painful red eyes and blurring of vision. He denied any fever, chills, eye discharge, headaches, rash or similar vision complaints in the past. Review of systems was negative. He had failed to follow-up with his primary care physician for an immunological check-up. His social history was positive for high-risk sexual behaviour with male partners. On physical examination, he was a thin male in moderate distress with multiple umbilicated nodules on the face. Eye examination revealed equal and reactive pupils with no conjunctival injection. Bilateral visual acuity was limited to hand movements alone. Retinal examination showed outer retinitis with haemorrhage in the right eye and multi-focal outer retinitis in the left eye. Fluorescein angiography showed vasculitis with outer retinitis in both eyes. Initial laboratory studies showed a white blood cell count of 2400/mm3 (without differential) and a platelet count of 169,000/mm3. Lumbar puncture showed cerebrospinal fluid (CSF) glucose of 46 mg/dL, protein of 69 mg/dL, nucleated cells of 9/mm3 (97% lymphocytes, 3% monocytes) and red blood cells 20/mm3. CSF culture showed no growth. CSF viral studies were negative except for VZV PCR. CSF testing for syphilis, cryptococcal antigen and fungal cultures were negative. Serum HIV antigen/antibody combination testing was positive with an HIV viral load of 266,370 copies/mL and CD4 of 6%. Posterior and anterior chamber taps were performed, and vitreal and aqueous humour fluid were sent for analysis. No growth occurred in bacterial and fungal culture of eye fluid from both eyes. Viral studies were positive for VZV PCR in both eyes. Eye fluid testing was negative for other infections such as Epstein-Barr virus PCR, cytomegalovirus PCR, toxoplasma PCR and Mycobacterium tuberculosis PCR. Further VZV PCR typing at CDC for both eye fluid samples tested positive for vaccine-strain VZV. The patient was diagnosed with advanced HIV infection with vaccine-strain-varicella-associated progressive outer retinal necrosis and meningitis. The patient was hospitalized on an unknown date. During hospitalization, he underwent four bilateral intravitreal injections of foscarnet and ganciclovir. Intravenous acyclovir 15 mg/kg, q8 followed by intravenous ganciclovir 900 mg BID with intravenous foscarnet 90 mg bid was continued for treatment of progressive outer retinal necrosis. Due to lack of vision change from this antiviral treatment, he was initiated on antiretroviral therapy containing tenofovir (+) emtricitabine (manufacturer unknown) and dolutegravir regimen on day 3 of retinitis treatment. He was hospitalized for two weeks, and showed mild improvement in retinitis in the right eye on discharge. Visual acuity in his right eye was restricted to 20/400, and vision in his left eye was restricted to finger counting. The patient was transitioned to long-term oral valacyclovir treatment on discharge, with plans for infectious diseases (ID) and ophthalmology follow-up. However, he was non-compliant with outpatient ID follow-up. Ophthalmology outpatient records reported no improvement in retinitis in his left eye and retinal detachment in his right eye requiring vitrectomy. The last record on visual acuity showed vision restricted to finger counting in both eyes. The outcome of the meningitis was unknown. Upon internal review, the necrotising retinitis and the meningitis were determined to be medically significant.