The Impact of Post-Vaccination Fever and Antipyretic Use Upon Quadrivalent Influenza Vaccine Immunogenicity in Children

Abstract

Background

Annual vaccination is the most effective method for preventing serious illness from influenza, however the impact of fever and antipyretic use in the post-vaccination period on immunogenicity in children receiving quadrivalent influenza vaccination (QIV) is limited.

Methods

Individual-level data from eight paediatric clinical trials of QIV were obtained. Estimates of the effect of fever, antipyretic use and the combination of both on post-vaccination haemagglutination inhibition (HI) titres were calculated utilising a linear mixed effects regression model.

Results

The 4 935 included participants had a mean age of 4.1 years, 47% were female and 36% considered ‘primed’. Fever was reported by 8.8% in the first 6 days post-vaccination, and antipyretic use was 15.6%, with rates of both highest in younger cohorts.

For the combined all-ages analysis, fever and antipyretic use had a statistically significant effect upon HI titres across all four influenza strains at days 0-6 (p<0.005). Fever without antipyretic use was associated with a 26% increase in geometric mean HI titres for the A/H3N2 strain. Antipyretic use without fever was associated with a decrease in post-vaccination HI titres for the A/H1N1, A/H3N2 and B/Yamagata strains (GMT ratios 0.80-0.82). The combination of both fever and antipyretic use was associated with an increase in post-vaccination HI titres for the A/H3N2 and B/Victoria strains (GMT ratios 1.26 – 1.80).

Conclusions

This thesis demonstrates important associations between fever, antipyretic use and post-influenza-vaccination serological measures of immunogenicity in paediatric patients, however clinical implications require further prospective research.