Assessment of pre-specified adverse events following varicella vaccine: A population-based self-controlled risk interval study.

Background: Clinical trials and spontaneous reporting systems have revealed rare but biologically plausible adverse events following varicella immunization. Few post-marketing controlled studies have been conducted to assess the relationship between the varicella vaccine and these outcomes.

Objectives: To evaluate the risk of pneumonia, idiopathic thrombocytopenic purpura (ITP), meningitis, encephalitis and ischemic stroke following varicella immunization.

Materials And Methods: This nationwide observational study was based on Taiwan National Health Insurance data and National Immunization Information System from 2004 through 2014. Primary analysis included children aged 12-35 months who received the single varicella vaccine on the date of administration. The self-controlled risk interval design compared the incidence of pre-specified outcomes during a risk interval of 1-42 days post-vaccination and a control interval of 43-84 days. The outcomes of interest were defined as admitted pneumonia, ITP, meningitis, encephalitis, and ischemic stroke, as well as fracture as a negative control. Conditional Poisson regression was used to assess the incidence rate ratio (aIRR) with adjustments for age and seasonal effects.

Results: Among 1,194,189 children, who receiving the varicella vaccine, there was no observed increase in the risk for ITP (aIRR 1.00; 95% CI, 0.76-1.33), meningitis (aIRR 1.21; 95% CI, 0.49-2.95), encephalitis (aIRR 1.00; 95% CI, 0.62-1.60), or ischemic stroke (aIRR 1.24; 95% CI, 0.31-4.95). A clustering feature with pneumonia occurred during days 36-42 post-vaccination (aIRR 1.10; 95% CI, 1.02-1.18). An increase in the risk for ITP was observed in children receiving the varicella and MMR vaccines concomitantly (aIRR 1.70; 95% CI, 1.19-2.43), but not among those receiving the varicella vaccine only.

Conclusions: We detected a small risk of incidental pneumonia associated with varicella vaccine in the 6th week after immunization. There was no increase in the risk of other pre-specified adverse events.