Letter to the Editor: Fatal varicella due to the vaccine-strain varicella-zoster virus

To the Editor

Leung et al.¹ present a case report of a fatal varicella due to vaccine-strain virus. In an earlier US case, vaccine-strain varicella zoster virus (VZV) may have contributed to death after routine immunization with live varicella vaccine.

In 2006, the US Vaccine Adverse Event Reporting System (VAERS) received the following information. Within 4 weeks after vaccination with live varicella vaccine and live measles, mumps, and rubella vaccine, a 13-month-old female was hospitalized with disseminated varicella, septic shock, and multi-organ failure. During her hospitalization, she was diagnosed with severe combined immunodeficiency (SCID) due to adenosine deaminase deficiency (ADA). She had clinical varicella and a progressive severe pulmonary syndrome with isolation of all 4 vaccine viruses from the respiratory tract. In addition, she had a generalized rash that a dermatologist described as consistent with active varicella infection, and viral culture demonstrated varicella (strain not specified). Treatment included acyclovir, foscarnet, cefotaxime, ribavirin, clindamycin, trimethoprim-sulfamethoxazole, and fluconazole. Her hospital course was notable for respiratory failure requiring high-frequency oscillatory ventilation and extracorporeal membrane oxygenation; cardiovascular compromise and shock necessitating hemodynamic and inotropic support; neurological deterioration; and deep venous thrombosis. Sputum culture and polymerase chain reaction identified vaccine-strain varicella, measles, mumps, and rubella. Hypotension and irreversible respiratory failure persisted, despite extensive inotropic support and attempts at mechanical ventilation, and the child died approximately 10 weeks after vaccination. According to the autopsy report, the cause of death was catastrophic left intracerebral hemorrhage with uncal and cerebellar tonsillar herniation complicating SCID related to ADA, with multiple vaccine-derived viral infections and in-hospital development of non-vaccine-related adenovirus pneumonia. Postmortem evaluation revealed the vaccine strains of varicella, measles, mumps, and rubella in the lungs, and multiple healed, scabbed lesions consistent with varicella were noted on the skin. Retrospective medical chart review revealed a long history of recurrent pulmonary infections, persistent oral candidiasis, failure to thrive, and possible pulmonary fibrosis—evidence that might have prompted a work-up for congenital immunodeficiency. Although it is difficult to assess the relative contribution of each of the vaccine viruses, particularly in the context of adenovirus pneumonia, the isolation of vaccine-strain viruses in biologic specimens suggests a causal or contributory role in the death of this severely immunocompromised child.

Vaccination has substantially reduced the burden of wild-type disease from varicella² as well as measles,³ but live viral vaccines carry a small risk of serious complications in very rare circumstances. These 2 fatalities emphasize the importance of obtaining a careful history to identify individuals in whom an evaluation for immunodeficiency may be warranted. For those whose medical histories suggest immunodeficiency disorders (e.g., individuals with frequent or persistent infections), evaluation before vaccination should be considered to determine whether these patients are immunocompetent and to determine the risks and benefits of vaccination.