Objective: to assess the effect of the administration of paracetamol (prophylactic [PP] or therapeutic [TP]) on the immune response to the pentavalent vaccine (diphtheria, tetanus, cellular pertussis, hepatitis B, Haemophilus influenzae) (PV) in infants.
Design: cohort study performed by means of a post hoc analysis of the data of a multicentre (11 study sites) randomised single-blind controlled clinical trial designed to compare two pentavalent vaccines (the vaccine manufactured by Sanofi Pasteur versus a locally-licensed vaccine manufactured in India).
Study population: 1085 infants aged 6 to 8 weeks. Exclusion criteria: born at less than 37 weeks’ gestation, chronic disease, receipt of any other vaccine except oral polio, birth dose of hepatitis B or the bacillus Calmette-Guérin (BCG) vaccines.
Intervention: the authors analysed the immune response that followed administration of three doses of two different formulations of PV (at 6-8 weeks, 10-12 weeks, 14-16 weeks) and its correlation to the administration of paracetamol (PP or TP) or lack thereof.
Outcome measurement: levels of antibodies (seroprotection) against diphtheria (≥ 0.01 IU/ml), tetanus (≥ 0.01 IU/ml) and Haemophilus influenzae (≥ 0.15 μg/ml) and two types of seroresponse for antibodies against pertussis (if initially seropositive: increase from pre-vaccination titre; if seronegative: 4-fold titre rise) and hepatitis B (≥ 10 IU/ml before and after administration of PV).
Main results: the analysis included 928 patients (85%). It found differences in the immune response of patients with paracetamol (both PP and TP) and without paracetamol in the analysis of the two vaccines (pooled and separate) against pertussis, Haemophilus influenzae and hepatitis B. It found a lower level of antibodies against tetanus (pooled results) in patients with PP versus patients without paracetamol, although there were no differences between the PP group and any of the other two groups. The levels of antibodies against diphtheria in infants with PP that received the locally-licensed vaccine were lower than those of children without paracetamol in the same group, there were no differences between the PP and the other two groups in this vaccine group or in the pooled analysis for both vaccines. The seroresponse to the vaccine against pertussis was similar in every group (without paracetamol: 63.6%; 95% confidence interval [95 CI]: 58.8 to 68.3]; PP: 69% [95 CI: 56.9 to 79.5]; TP: 66% [95 CI: 61.4 to 70.4]).
Conclusion: the data suggested that paracetamol given for either prophylaxis or treatment of vaccine reactions after administration of the PV does not impact the immune response to the vaccine. The observed differences were minimal and seemed to be of no clinical relevance.
Conflicts of interest: ten of the 21 authors, including those listed first and last, were employees of the manufacturer or the investigational vaccine (Sanofi Pasteur). The rest of the authors received research grants from the Sanofi Pasteur laboratories.