A systematic post-licensure review of the varicella vaccine Varivax® (Merck) safety in the United States of America (USA) was presented in preparation for an update of the WHO position paper on varicella vaccines.3 A summary of the 2011 US Institute of Medicine (IOM) report,4 a literature review from December 2010 to October 2012, and review of key post-licensure observational studies from the US Centers for Disease Control and Prevention and Merck were included. The focus of the review was to update the safety profile of the varicella vaccine, especially for events considered significant. The IOM committee addressed 15 potential adverse events by a comprehensive review of the literature from 1950 to December 2010. Five events were assessed as having convincing evidence in support of a causal relationship with the vaccine: disseminated varicella infection (widespread chickenpox rash shortly after vaccination); disseminated varicella infection with subsequent infection resulting in pneumonia, meningitis or hepatitis; vaccine strain viral reactivation (appearance of chickenpox rash months to years after vaccination); vaccine strain viral reactivation with subsequent infection resulting in meningitis or encephalitis; and anaphylaxis. While the risks for these adverse events were not quantified in the IOM review, GACVS reviewed evidence from case series and other studies that demonstrated them to be rare events. Ten other adverse events were assessed to have insufficient evidence to support causality: encephalopathy, seizure, cerebellar ataxia, acute disseminated encephalomyelopathy, transverse myelitis, GBS, small fibre neuropathy, new onset arthropathy, stroke, and thrombocytopenia.
A review of more recent post-licensure safety studies of the combination measles, mumps, rubella (MMR) and varicella vaccine, which contains the same Oka strain as Varivax® (ProQuad®), identified a new risk of febrile seizures after vaccination among children aged 12–23 months, compared with children receiving separate MMR and varicella vaccination. In addition, Merck’s pregnancy registry for Varivax® revealed no cases of congenital varicella syndrome during 16 years of vaccine use and the data do not support a signal of an increased risk of spontaneous abortion or birth defects. Finally, a comprehensive literature review from 2010 to 2012 revealed no additional safety concerns.
GACVS raised several questions not covered by this review. These included: (1) whether varicella vaccination increases the risk of shifting varicella disease to older age groups, where disease is generally more serious, and whether this potential risk depends on the number of vaccine doses administered (i.e. would a single dose lead to greater risk than 2 doses and would additional booster doses be required?); (2) whether risks from currently available varicella vaccines remain similar to those described earlier; and (3) what the risk–benefit ratio of varicella vaccine use would be in low and middle income countries (LMICs) with a high proportion of undetected immunocompromised people, especially children with HIV, cancer and other immunodeficiencies. GACVS recommended that additional data are needed to determine the full safety profile of varicella vaccine if it is to be deployed in LMICs. GACVS recommended conducting surveillance for varicella disease to assess the effectiveness, as well as enhanced vaccine adverse event monitoring if varicella vaccine is introduced in LMICs.
Noting that substantial new safety evidence has accumulated since the last WHO report in 1998, GACVS concluded that additional data should be gathered and reviewed to complete the full benefit–risk assessment of varicella vaccine globally.
3See No. 32, 1998, pp. 241–248.
4 Stratton K et al., eds. Adverse events of vaccines: evidence and causality. Washington, DC, Institute of Medicine of the National Academies. August 2011.