Age: 1.3
Sex: F
Vaccine: HIBV, MMR, PPV, VARCEL
Symptoms: Cell-mediated immune deficiency, Chest X-ray abnormal, Complement factor normal, Condition aggravated, Culture urine positive
Clinical narrative: This spontaneous report as received from an other health professional describing in a draft of the manuscript referring a case of fatal varicella due to vaccine-strain VZV following vaccination with VARIVAX (Merck). A 15-month old child who developed a varicella-like rash 20 days after VARIVAX (Merck) that lasted for 2 months despite continued acyclovir treatment. The rash was confirmed to be due to VARIVAX (Merck). The patient developed severe respiratory complications that worsened with each new crop of varicella lesions; vaccine-strain VZV was detected in the bronchial lavage specimen. Sepsis and multi-organ failure led to death. The patient did not have any diagnosed immuno-compromising conditions for which varicella vaccination would have been contraindicated, but did have a number of underlying conditions that were severe enough to have required several hospitalizations in the past and might have been indicative of underlying immuno-compromising. The possibility of acyclovir resistance and a change in antiviral therapy to foscarnet should be considered if lesions do not improve after 10 days of treatment. VARIVAX (Merck) was introduced in 1995. It contains live attenuated varicella-zoster virus (VZV). The routine childhood varicella vaccination program in the country has led to substantial declines in varicella related morbidity and mortality. Serious adverse events reported to the Vaccine Adverse Event Reporting System were rare; those confirmed to be due to the vaccine-strain VZV include pneumonia, hepatitis, herpes zoster with meningitis, and severe rash. The patient received her first dose of VARIVAX (Merck) on 12-AUG-2009, along with vaccinations against MMR, HIB, and pneumococcal disease at age 1-year. She was born healthy, weighing 6.9 pounds; mother had no pregnancy complications. She did not have any recognized immuno-compromising conditions. Her newborn blood spot was negative for severe combined immunodeficiency. The patient had a milk protein allergy, anemia and chromosomal abnormality. She had a history of global developmental delay, failure to thrive (weight 14 pounds at age 15 months), type 2 muscular dystrophy, profound hypotonia, gastroesophageal reflux disease, otitis media and varicella. She had a gastrostomy tube placed at age 9-months due to poor feeding. She had episodes of bronchiolitis, pneumonia due to respiratory syncytial virus infection (RSV), and aspiration pneumonia (recurrent) that resulted in 5 hospitalizations before her first birthday, two of which required mechanical ventilation. Her only routine medication at the time of vaccination was lansoprazole. Quantitative serum immuno-globulin levels measured at 10 months were normal, except for elevated IgE levels at 424 (normal range: 0.8-4.3 IV/ml^17). On week after vaccination (19-AUG-2009), the patient was hospitalized for severe respiratory distress and was treated with albuterol, budesonide and amoxicillin clavulanate. On the hospital day 10 (16 days post-vaccination) (29-AUG-2009), she was started on methylprednisolone IV, 3.5 mg q 12 for 3 days (equivalent to 8.8 mg/day of prednisone) followed by prednisolone via g-tube 3.5 mg q12 for 2 days (equivalent to 7.0 mg/day of prednisone). Her respiratory distress resolved and she was discharged on hospital day 14 (01-SEP-2009). On the day of hospital discharge (01-SEP-2009), her mother noticed a rash on one of her hands that disseminated into a generalized maculopapular vesicular rash by the next day (02-SEP-2009), at which point, she was seen by her primary care physician and started on oral acyclovir. A skin lesion specimen collected on the next day (20 days post-vaccination) (02-SEP-2009) was positive for vaccine-strain VZV by polymerase chain reaction. Four days after rash onset (05-SEP-2009), the patient developed another episode of respiratory distress and was hospitalized. On admission, she had diffuse vesicular and crusted lesions and was febrile to 104 F. Chest x-ray showed increased opacity in the left lung. She was switched to IV acyclovir and was started on broad-spectrum antibiotics. Starting on hospital day 4 (09-SEP-2009), she received IV methylprednisolone (12 mg 1 dose for 1 day then 6 mg qd for 2 days), followed by 2 doses of prednisolone for one day. On hospital day 11 (16-SEP-2009), the patient had an episode of acute respiratory failure and was intubated. She required high-frequency oscillatory ventilation until her death 7 weeks later (02-NOV-2009).  IV acyclovir was discontinued on hospital day 12 (17-SEP-2009), restarted on low-dose prolonged steroid therapy protocol for acute respiratory distress syndrome (IV methyl prednisolone for 32 days, starting with 13 mg for 1 dose and tapered to 0.4 mg bid). Despite ongoing acyclovir treatment, she continued to develop recurrent crops of maculopapular vesicular skin lesions every 7-8 days throughout her hospitalization. Her respiratory status deteriorated with each new crop of lesions and the chest x-ray showed bilateral interstitial infiltrates consistent with viral pneumonia that became increasingly confluent, with worsening interstitial edema and opacification. The patient subsequently developed bilateral pneumothoraces. On the day of her death, she had 50-100 skin lesions. A bronchial lavage specimen collected on hospital day 19 (24-SEP-2009) was positive for VZV DNA and later confirmed to vaccine-strain VZV; an additional bronchial lavage specimen collected on hospital day 34 (09-OCT-2009) was also VZV-positive but not genotyped. Blood, respiratory, and tracheal aspirate specimens collected between days 12-19 (17-SEP-2009 to 24-SEP-2009) of hospitalization were positive of Pseudomonas aeruginosa by culture and several urine specimens collected between days 20-44 (25-SEP-2009 to 19-OCT-2009) of hospitalization were positive for Candida albicans by culture. Blood collected on day 11 (16-SEP-2009) of hospitalization showed normal humoral immunity and complement levels. A T-cell deficiency was considered as the patient's T-cell counts on hospital days 11 (16-SEP-2009) and 17 (25-SEP-2009) were lower than normal: absolute T-cell counts were 223 and 864 (respectively (normal range: 1600-6700); CD-8 counts were 46 and 180 (normal range: 400-2100); and CD-4 counts were 169 and 656 (normal range: 1000-4600). It is unknown why the patient described in this report had a prolonged rash that was unresponsive to acyclovir therapy. The patient may have had depressed T-cell function. This case-patient's symptoms may have been exacerbated by treatment with steroids 2 weeks after vaccination. Although the steroid dosage used to treat this case would not be classified as high-dose, it still may have been immuno-suppressive. The benefits of varicella vaccination outweigh the very low risk of serious adverse events occurring. Providers should carefully monitor for any signs of adverse reactions after vaccination among all persons, especially among persons with medical histories that may be indicative of an immuno-suppressive condition. If these persons develop a rash after vaccination, they should be immediately treated with acyclovir. Death certificate received Date of death 02-NOV-2009, cause of death: multisystem organ failure, acute respiratory distress syndrome, varicella pneumonitis. Discharge summary received for date 27-AUG-2009: DX: respiratory difficulty, bronchospasms, hypotonia. Chief c/o respiratory distress, IRI*1 day, fever, tachypnea, retractions. Caretaker reports patient having difficulty breathing, fever, irritable. Assessment, (+)fever, grunting, retractions, hypotonia, O2 sat 91% on 3LNC. Speech and swallow eval: oropharyngeal dysphagia. Patient improved over 3 days, stable at discharge. ER/hospital 05-SEP-2009 to 29-OCT-2009. DX: muscular weakness disorder, viral pneumonitis, varicella. Respiratory distress, fever. Parent stated varicella vaccine on 12-AUG-2009. Varicella skin rash formed 31-AUG-2009. EMS presented patient to ER. Assessment: stridor, rash, fever, mild distress. Patient admitted and following day respiratory distress increased, grunting, increase in fever 103 F, patient found to be irritable, O2 sats 92% with O2 therapy. TYLENOL was given, within 30 min temperature of 104.5F. One hour later patient heart rate 220-240 bpm. Patient later was stabilized but prognosis was guarded. Additional information had been requested.