To the Editor: Italiano and colleagues described a 49-year-old woman with prolonged vaccine viraemia, associated with hepatitis, streptococcal toxic shock syndrome and poststreptococcal reactive arthritis following routine varicella vaccination.1 The woman, initially seronegative for varicella zoster virus (VZV), was stated to be immunocompetent, possibly because she was previously well and produced varicella IgG following vaccination. It is not clear whether other aspects of her immune status were investigated. Although VZV IgG was detected after vaccination, indicating appropriate adaptive immune activation, this does not necessarily exclude a defect in the innate immune system.

Natural killer (NK) cells, which comprise 10%–15% of total lymphocytes, are part of the innate immune system and play an important role in the suppression of VZV replication via direct cell killing and production of γ-interferon.2,3 A smaller population of lymphocytes, known as NKT cells, which express both NK cell surface markers and T-cell receptors, also appear be important in controlling VZV infection in humans.2 The role of these cells in the immune response to varicella vaccine is unclear. In children, NK cell cytotoxicity increased after wild-type VZV infection but not after vaccine administration.4 However, disseminated life-threatening VZV infection was observed after varicella vaccination in a child with NKT cell deficiency.2

Primary isolated deficiencies and functional defects in NK function have been reported in children and adolescents with severe, life-threatening wild-type VZV infection.5 Some of these patients were previously well and came to medical attention only after VZV exposure. It is not clear how many had prior varicella vaccination, but at least one patient had previously received VZV vaccine with no adverse consequences and developed disseminated disease only with the wild-type virus.

Acquired defects in NK immunity have also been reported. Severe transient depressions of NK and CD8 cell numbers and NK cell function have been documented in children at the time of severe VZV infection, with return of immune competence following convalescence.3 This phenomenon may be due to initial CD8 and NK cell exhaustion or redistribution of these cells from the circulation into inflamed peripheral tissue under the influence of chemokines.3

It has been suggested that an NK cell defect should be considered in unexplained severe herpesvirus infections.5 It would therefore be of interest to determine NK cell number and function and NKT cell number in the patient reported by Italiano and colleagues.