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Acetaminophen After Vaccination Reduces Antibody Response

Prophylactic doses of acetaminophen given after vaccination reduce fever but blunt antibody response to multiple antigens.

Fever is common after vaccination, leading some to recommend prophylactic antipyretics. But do such agents affect vaccine immune response? In an industry-supported study, investigators randomized healthy infants in the Czech Republic to receive vaccines alone or followed by three doses of acetaminophen (suppositories) over 24 hours. They assessed febrile response and antibody response to vaccine antigens after primary and booster doses.

The infants received 10-valent pneumococcal nontypeable Haemophilus influenzae conjugate vaccine coadministered with diphtheria–tetanus–acellular pertussis, hepatitis B, H. influenzae type B, oral rotavirus, and inactivated poliovirus types 1, 2, and 3 vaccines. Primary vaccine doses were administered at ages 3–5 months; booster doses at ages 12–15 months. Infants remained in the same group for primary and booster doses; however, based on initial results, the study was amended before completion, and not all acetaminophen-group infants received acetaminophen after booster immunization.

Fever >39.5°C was uncommon after primary vaccination in both groups (3/233 [1%] with no acetaminophen; 1/226 [<1%] with prophylactic acetaminophen). However, fever 38°C was significantly more common in the no-acetaminophen group than in the acetaminophen group (66% vs. 42%). Acetaminophen recipients showed significantly reduced antibody response to 10 pneumococcal conjugate vaccine serotypes and multiple other antigens. Children with and without fever in the acetaminophen group showed similar diminution of antibody response.

Comment: The authors conclude that acetaminophen should not be given prophylactically as a routine practice with vaccination. Whether the same effect would occur with other commonly used agents, such as ibuprofen, is unknown but should be studied. The authors postulate that acetaminophen may interfere with interactions among dendritic, B, and T cells by reducing the local inflammatory response. Editorialists note the need to also assess whether antipyretics increase the proportion of vaccine nonresponders and reduce population protection.

— Mary E. Wilson, MD

Published in Journal Watch Infectious Diseases November 4, 2009

Citation(s):

Prymula R et al. Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: Two open-label, randomised controlled trials. Lancet 2009 Oct 17; 374:1339.

• Medline abstract (Free)

Chen RT et al. The yin and yang of paracetamol and paediatric immunisations. Lancet 2009 Oct 17; 374:1305.

• Medline abstract (Free)