Prophylactic Acetaminophen/Immunogenicity

[TiredMom]

This study will appear in the medical journal "Lancet" tomorrow.

 

Prophylactic Acetaminophen Reduces Immunogenicity of Childhood Vaccines

 

Children given acetaminophen with vaccinations have lower rates of fever in response, but the vaccinations produce a lower immunogenicity, reports a Lancet study.

 

Researchers, including some from the sponsoring vaccine manufacturer, followed over 400 infants receiving primary and booster immunizations. Half received acetaminophen via suppository in three doses over the first 24 hours after vaccination, and half received no prophylaxis.

 

The percentage of children with a temperature of 38 degrees C or higher was significantly lower in the acetaminophen group by some 40% to 50% both at primary and booster immunizations. However, vaccine immunogenicity was lower in the acetaminophen group — significantly so for some antigens, e.g., all 10 pneumococcal serotypes after the primary immunization. The authors hypothesize that the effect could result from acetaminophen' s preventing inflammation.

 

Over 95% of all children had seroprotective antibody levels, but researchers argue that antipyretics "should ... no longer be routinely recommended" with vaccination. Editorialists agree, calling the case "compelling. "

 

Articles

The Lancet, Volume 374, Issue 9698, Pages 1339 - 1350, 17 October 2009 <Previous Article|Next Article>doi: 10.1016/S0140- 6736(09)61208- 3Cite or Link Using DOIEffect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: two open-label, randomised controlled trials

Original Text

Prof Roman Prymula MD a , Prof Claire-Anne Siegrist MD b, Roman Chlibek MD a, Helena Zemlickova MD c, Marie Vackova MD a, Jan Smetana MD a, Patricia Lommel BScb d, Eva Kaliskova MD e, Dorota Borys MD d, Lode Schuerman MD d

Summary

Background

Although fever is part of the normal inflammatory process after immunisation, prophylactic antipyretic drugs are sometimes recommended to allay concerns of high fever and febrile convulsion. We assessed the effect of prophylactic administration of paracetamol at vaccination on infant febrile reaction rates and vaccine responses.

Methods

In two consecutive (primary and booster) randomised, controlled, open-label vaccination studies, 459 healthy infants were enrolled from ten centres in the Czech Republic. Infants were randomly assigned with a computer-generated randomisation list to receive three prophylactic paracetamol doses every 6—8 h in the first 24 h (n=226) or no prophylactic paracetamol (n=233) after each vaccination with a ten-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) co-administered with the hexavalent diphtheria-tetanus- 3-component acellular pertussis-hepatitis B-inactivated poliovirus types 1, 2, and 3-H influenzae type b (DTPa-HBV-IPV/ Hib) and oral human rotavirus vaccines. The primary objective in both studies was the reduction in febrile reactions of 38·0°C or greater in the total vaccinated cohort. The second objective was assessment of immunogenicity in the according-to- protocol cohort. These studies are registered

with ClinicalTrials. gov, numbers NCT00370318 and NCT00496015.

Findings

Fever greater than 39·5°C was uncommon in both groups (after primary: one of 226 participants [<1%] in prophylactic paracetamol group vs three of 233 [1%] in no prophylactic paracetamol group; after booster: three of 178 [2%] vs two of 172 [1%]). The percentage of children with temperature of 38°C or greater after at least one dose was significantly lower in the prophylactic paracetamol group (94/226 [42%] after primary vaccination and 64/178 [36%] after booster vaccination) than in the no prophylactic paracetamol group (154/233 [66%] after primary vaccination and 100/172 [58%] after booster vaccination) . Antibody geometric mean concentrations (GMCs) were significantly lower in the prophylactic paracetamol group than in the no prophylactic paracetamol group after primary vaccination for all ten pneumococcal vaccine serotypes, protein D, antipolyribosyl- ribitol phosphate, antidiphtheria, antitetanus, and antipertactin. After boosting, lower antibody

GMCs persisted in the prophylactic paracetamol group for antitetanus, protein D, and all pneumococcal serotypes apart from 19F.

Interpretation

Although febrile reactions significantly decreased, prophylactic administration of antipyretic drugs at the time of vaccination should not be routinely recommended since antibody responses to several vaccine antigens were reduced.

Funding

GlaxoSmithKline Biologicals (Belgium).

 

Take care.