Age: 1.0
Sex: F
Vaccine: VARCEL
Symptoms: Cytopenia, Diarrhoea, Dyspnoea, Enterovirus test positive, Escherichia test positive
Clinical narrative: This literature marketed report was received from the authors in a published literature article titled as stated above, regarding a 12-month-old female patient who, on an unknown date, when she was 9 months old, she experienced viral illness with prolonged febrile illness with seizures, triggered by seasonal coronavirus HKU1 infection. Later, when she was 10 months old, she experienced severe influenza A pneumonia with very high fever and progressive respiratory failure despite treatment with oseltamivir (dose, route and frequency not reported), ceftriaxone (dose, route and frequency not reported), methylprednisolone (dose, route and frequency not reported), and oxygen delivered by high-flow nasal cannula. She required intubation and mechanical ventilation for 3 days but recovered on an unknown date.  After that, on an unknown date, when she was 12 months old she was vaccinated with varicella virus vaccine live (oka/merck)(manufacturer unknown), along with measles, mumps, and rubella (wistar ra 27-3) virus vaccine, live (manufacturer unknown), hepatitis a vaccine, inactivated (manufacturer unknown), hib conj vaccine (unspecified carrier) and pneumococcal 13v conj vaccine (crm197) (administration routes, doses and frequencies were not reported), all of them for prophylaxis. It was mentioned that, during vaccination, the patient showed nasal congestion and clear rhinorrhea.  Then, 6 days after vaccinations, the patient presented with high fever, diarrhea, new onset vomiting, nasal congestion, cough, irritability, and lethargy.  On an unknown date, the patient was hospitalized. Then, a partial septic screen yielded above 100000 colony forming units/ml of Escherichia coli from her urine and a polymerase chain reaction (PCR) for rhinovirus/enterovirus RNA from a nasopharyngeal swab sample showed positive results. The patient's high fever continued despite intravenous ceftriaxone for presumed pyelonephritis, and she was on the pediatric ward for 2 days with continuing high fever up to 41°C.  On day 3, she was transferred to the Pediatric Intensive Care Unit (PICU) because of poor bilateral lower extremity perfusion that failed to improve on multiple fluid boluses. This was accompanied by persistent tachycardia, increased work of breathing, and a diffuse erythematous rash. On the 4th day after the onset of fever, she underwent several laboratory tests, which result were reported as follows: hemoglobin 12.1 g/dL (normal range between 10.2 to 14.7 g/dL); hematocrit of 34.4 percent (normal range between 30.8 to 43.7 percent); White blood cell count 7.6 x10x9/L (normal range between 6 to 17.5 x10x9/L); Absolute neutrophil count of 4 x10x9/L (normal range between 1.5 to 8.5 x10x9/L); Absolute lymphocyte count 2.3 x10x9/L (normal range between 4 to 10.5 x10x9/L(decreased)); Absolute monocyte count 1.2 x10x9/L (normal range between 0.3 to 0.9  x10x9/L (increased)); Platelet count 242 x10x9/L (normal range between 150 to 450 x10x9/L); aspartate aminotransferase (AST) 66 U/L (normal range between 10 to 37 U/L (increased)); alanine aminotransferase (ALT) 57 U/L (normal range between 5 to 30U/L (increased)). Also, a blood culture collected on day 4 and it was sterile.  On an unknown date, on the 6th day after the onset of fever, she underwent several laboratory tests, which result were reported as follows: hemoglobin 10.4 g/dL; hematocrit of 30.1 percent (decreased); White blood cell count 3.5 x10x9/L (decreased); Absolute neutrophil count of 2.2 x10x9/L; Absolute lymphocyte count 1 x10x9/L (decreased); Absolute monocyte count 0.2 x10x9/L (decreased)); Platelet count 144 x10x9/L (decreased); aspartate aminotransferase (AST) 57 U/L (increased); alanine aminotransferase (ALT) 38 U/L (increased); C-reactive protein 76 mg/dL (normal range between 0 to 0.8 mg/dL(increased)). Also, a blood culture was collected on day 6 and it was sterile. In addition, virology investigations were consistent with human herpes virus type 6 (HHV6) reactivation, based on positive blood PCR (23,500 (log 4.4) copies/ml of HHV-6 type B), positive HHV6 IgG at 1:80 (negative if below 1:10) and negative IgM (below 1:20) on day 6. On the 7th day after the onset of fever, she underwent several laboratory tests, which result were reported as follows: hemoglobin 10.1 g/dL (decreased); hematocrit of 29.2 percent (decreased); White blood cell count 2.3 x10x9/L (decreased); Absolute neutrophil count of 1.2 x10x9/L (decreased); Absolute lymphocyte count 1 x10x9/L (decreased); Absolute monocyte count 0.1 x10x9/L (decreased)); Platelet count 127 x10x9/L (decreased). On the 8th day after the onset of fever, she underwent several laboratory tests, which result were reported as follows: hemoglobin 9.4 g/dL (decreased); hematocrit of 26.9 percent (decreased); White blood cell count 1.4 x10x9/L (decreased); Absolute neutrophil count of 0.8 x10x9/L (decreased); Absolute lymphocyte count 0.6 x10x9/L (decreased); Absolute monocyte count 9.1 x10x9/L (increased)); Platelet count 107 x10x9/L (decreased). On the 9th day after the onset of fever, she underwent several laboratory tests, which result were reported as follows: hemoglobin 9.7 g/dL (decreased); hematocrit of 27 percent (decreased); White blood cell count 1.5 x10x9/L (decreased); Absolute neutrophil count of 0.8 x10x9/L (decreased); Absolute lymphocyte count 0.7 x10x9/L (decreased); Absolute monocyte count  0 x10x9/L (decreased)); Platelet count 85 x10x9/L (decreased); AST 221 U/L (increased); ALT 100 U/L (increased); Ferritin 1980 ng/dL (normal range between 12 to 207 ng/dL(increased)); Lactate dehydrogenase1043 U/L  (normal range between 190 to 420 U/L (increased)); Triglycerides 289 mg/dL (normal range between 30 to 120 mg/dL (increased)). An attempt at bone marrow aspiration on day 9 of admission was aborted due to apnea and profound desaturation. She was quickly resuscitated and returned to baseline within a few hours while hematologic parameters began spontaneously improving by day 10.  Also on 10th day after the onset of fever, she underwent several laboratory tests, which result were reported as follows: hemoglobin 9.8 g/dL (decreased); hematocrit of 26.3 percent (decreased); White blood cell count 2.7 x10x9/L (decreased); Absolute neutrophil count of 1.1 x10x9/L (decreased); Absolute lymphocyte count 1.3 x10x9/L (decreased); Absolute monocyte count  0.2 x10x9/L (decreased)); Platelet count 85 x10x9/L (decreased); AST 125 U/L (increased); ALT 94 U/L (increased); D-dimer above 9999 ng/ml (normal range between 0 to 499 (increased)); fibrinogen 71 mg/dL (normal range between 175 to 375 mg/dL (decreased)); Soluble interleukin-2 receptor 14740 pg/mL (normal range lower than 1034 (increased). Persistent high fever was accompanied by worsening cytopenia's, elevated triglycerides, elevated ferritin to equal or higher than 500 ng/ml, and elevated soluble interleukin-2 receptor level. These results met 5 of 8 criteria for the diagnosis of hemophagocytic lymph histiocytosis (HLH). Treatment with corticosteroids and other unspecified immunomodulators was planned after the bone marrow aspiration, but not administered because of clinical and laboratory evidence suggestive of spontaneous HLH resolution on day 10.  On the 11th day after the onset of fever, she underwent several laboratory tests, which result were reported as follows: hemoglobin 8.9 g/dL (decreased); hematocrit of 25.7 percent (decreased); White blood cell count 3.5 x10x9/L (decreased); Absolute neutrophil count of 1.4 x10x9/L (decreased); Absolute lymphocyte count 1.7 x10x9/L (decreased); Absolute monocyte count  0.3 x10x9/L; Platelet count 101 x10x9/L (decreased); AST 104 U/L (increased); ALT 85 U/L (increased); fibrinogen 65 mg/dL (decreased). On the 12th day after the onset of fever, she underwent several laboratory tests, which result were reported as follows: hemoglobin 8.1 g/dL (decreased); hematocrit of 24.5 percent (decreased); White blood cell count 5.6 x10x9/L (decreased); Absolute neutrophil count of 2.4 x10x9/L; Absolute lymphocyte count 2.6 x10x9/L (decreased); Absolute monocyte count  0.4 x10x9/L; Platelet count 135 x10x9/L (decreased); AST 82 U/L (increased); ALT 78 U/L (increased). On the 15th day after the onset of fever, she underwent several laboratory tests, which result were reported as follows: hemoglobin 8.9 g/dL (decreased); hematocrit of 27.3 percent (decreased); White blood cell count 9.1 x10x9/L; Absolute neutrophil count of 3.1 x10x9/L; Absolute lymphocyte count 24.6 x10x9/L; Absolute monocyte count 0.7 x10x9/L; Platelet count 534 x10x9/L (increased); AST 73 U/L (increased); ALT 55 U/L (increased). All the laboratory results were assessing as unremarkable. On an unknown date, the patient underwent ultrasonography, repeated plain x-radiography, contrast computerized tomogram (CT) and echocardiography which results showed no evidence of an infective focus in the renal tract, chest, abdomen/pelvis, or heart, respectively. The diagnosis was considered to be transient HLH triggered by HHV6 infection. Fever abated after 15 days and the child was discharged on no antibiotics.  On an unknown date, 20 days after vaccinations and immediately after hospital discharge, she developed a diffuse vesicular rash from which varicella-zoster virus (VZV) DNA was detected by PCR. The patient received treatment with acyclovir 20 mg/kg every 6 h, for 5 days, without complication.  The outcome of disseminated varicella zoster vaccine virus infection was reported as recovered. The reporter considered disseminated varicella zoster vaccine virus infection to be related to varicella virus vaccine live (Oka/Merck) (VARIVAX) as they considered tht it was more consistent with vaccine-strain varicella, than a wild type varicella.  Upon internal review, the event Disseminated varicella zoster vaccine virus infection was considered to be medically significant.  A copy of the published article is attached as further documentation of the patient's experience.