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Reduction of adverse events following immunization (AEFI) could improve vaccine uptake. Evidence suggests sex and age affect AEFI rates but, with limited understanding of their interaction, groups at higher risk for adverse reaction cannot be identified. Using deidentified data (n = 308,481) from Australians receiving influenza vaccinations in the 2020 calendar year, we analyzed the effects of independent predictors (i.e. age and sex), on experiencing an AEFI using logistic regression generalized additive modeling to capture any nonlinear relationships and adjusting for vaccine brand and concomitant vaccination. The overall reaction rate was 5.5%. Modeling revealed significant effects of age (p &lt; 0.001), sex (p &lt; 0.001), and age × sex (p &lt; 0.001). Females were more likely than males to experience AEFIs between 7.5 and 87.5 years of age and exhibited peak odds at about 53 years, while peak odds for males occurred in infancy. The results suggest there is a need for targeting AEFI reduction in females, particularly in 30–70-year-olds, to improve the vaccination experience. The results further suggest that reducing concomitant vaccination and choosing less reactogenic vaccine brands could reduce risk of AEFI, however, retaining concomitant vaccination may optimize vaccine uptake.

Adverse events following influenza immunization: understanding the role of age and sex interactions