0940 Effect of paracetamol on immunogenicity of childhood vaccines

Prior to the advent of acellular pertussis vaccines and to reduce postimmunisation fever, the US Advisory Committee on Immunisation Practice recommended that it would be reasonable to administer antipyretics at the time of immunization to children at higher risk for seizures. Apart from the fact that there was a poor correlation between degree of fever and convulsions in children who experienced post-immunisation seizures, the post-vaccination administration of antipyretics became fairly routine. This prompted bodies such as the Canadian National Advisory Committee on Immunisation to advise against routine use of antipyretics. This admonition has been reinforced by a recent Czech study in which 459 young children undergoing routine vaccination were randomized into paracetamol and control groups, the former receiving 3 prophylactic doses every 6-8 hours within the first 24 hours. Subjects received primary and booster immunizations against pneumococcus, H. influenzae, DTP (acellular), hepatitis B, polio, and rotavirus. Fever of >39.5 degrees was uncommon in both groups (1/226 vs 3/233 after primary immunization and 3/178 vs 2/172 after boosting), however temperature of ≥38 was lower in the study group (42% and 36% after primary and booster immunisations vs 66% and 58%). On measuring antibody responses 1 month post primary and booster immunization there were significant reductions in concentrations to most of the antigens in the paracetamol group. The pre-booster concentrations were also lower in the paracetamol group. The proposed mechanism for the effect is independent of the subjects’ temperature (because immune responses in subjects with and without fever were similar), implicating interference with early interactions of dendritic, T and B cells on the primary immune response through a reduction of inflammatory signals at the injection site. Clinical significance of this finding is not clear, but there is concern that there are implications for population immunity (i.e. susceptibility to H influenzae and pneumococcal infections.

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Lancet 2009; 374: 1305-6 and 1339-50
Eur J Pediatr 2008; 167: 17-27
Arch Dis Child 2004; 89: 751-56