Fever After Influenza, Diphtheria-Tetanus-Acellular Pertussis, and Pneumococcal Vaccinations

To determine if administration of the quadrivalent inactivated influenza vaccine (IIV4) at a separate visit from the 13-valent pneumococcal conjugate vaccine (PCV13) and diphtheria–tetanus–acellular pertussis vaccine (DTaP) would affect the occurrence of postvaccination fever.

The study included 221 children aged 12 to 16 months (median age 14.6 months) who were fully up-to-date on vaccinations as per the Advisory Committee on Immunization Practices (ACIP). 93.2% of patients were receiving either their first or only dose of influenza vaccine for the season, and 89.8% also received a nonstudy ACIP-recommended vaccine at visit 1 only.

A prospective, randomized, open label clinical trial was carried out at two sites. Subjects were assigned to either the simultaneous group and received PCV13, DTaP, and IIV4 on the same visit or the sequential group that received IIV4 two weeks following PCV13 and DTaP. Postvaccination fever was measured using a temporal artery thermometer. The fever risk window of interest included the day of and the day after (days 1–2) the 2 visits in which vaccines could potentially be administered.

The primary measured outcome was to evaluate the number of children who developed fever (≥38.0°C, or ≥100.4°F) on the first two days after visits 1 and 2 combined. The incidence of fever was similar between the simultaneous group (8.1%) and the sequential group (9.3%; RR, 0.87; 95% CI 0.36–2.10). The height and duration of fever also did not differ between groups. Although the use of antipyretics was greater in the simultaneous group versus the sequential group (37.4% vs 22.4%; P = .020), no significant difference was observed when evaluating the use of antipyretics specifically for fever.

In children aged 12–16 months, administering IIV4 two weeks after DTaP and PCV13 did not decrease the occurrence of postvaccination fever.

This study provides further evidence that vaccine delay may increase the risk of vaccine-preventable illness without additional benefit. By demonstrating that delayed administration of the quadrivalent influenza vaccine did not change the occurrence of postvaccination fever, this study may also provide some support for pediatricians with regard to counseling parents on the use of prophylactic antipyretics. Although the clinical relevance is unknown, prophylactic antipyretics have been shown to affect the immunogenicity of certain vaccines depending on the antipyretic used, the timing of its administration, and the vaccine(s) administered [Wysocki J, Center KJ, Brzostek J, et al. A randomized study of fever prophylaxis and the immunogenicity of routine pediatric vaccinations. Vaccine. 2017;35(15):1926–1935].