Effect of prophylactic paracetamol administration at time of vaccination on febrile reactions and antibody responses in children: Two open-label, randomized controlled trials

Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic.
The Lancet (Impact Factor: 45.22). 10/2009; 374(9698):1339-50. DOI: 10.1016/S0140-6736(09)61208-3
Source: PubMed

ABSTRACT 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.
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 degrees 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, numbers NCT00370318 and NCT00496015.
Fever greater than 39.5 degrees 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 degrees 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.
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.
GlaxoSmithKline Biologicals (Belgium).

Download full-text


Available from: Roman Prymula, Aug 27, 2015
1 Follower
  • Source
    • "This could explain why the global success of mass immunization contrasts with the largely recognized failure of strategies targeting individuals at higher risk of complications, whether from underlying health condition or treatment [15]. For example, the impact of anti-inflammatory drugs on the immune system is unknown; the inhibitory effect on the immune response of prophylactic acetaminophen at time of vaccination came as a surprise [134]. Whether all this considerably limits the rational design of best possible immunisation approaches, it also raises several questions about the safety, efficacy and effectiveness of novel highdose and/or adjuvanted formulation specifically designed for all aged individuals regardless of the functionality of their immune system [25]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vaccines are powerful public health tools that have been of tremendous benefit in protecting vulnerable populations worldwide from many pathogens. However, vaccine- preventable diseases still remain a considerable burden and this is particularly true among aging and aged populations in industrialized countries. The predicted demographic shift in the population landscape towards an ever-increasing aging population and the evidence suggesting that older individuals mount less-than optimal immune response to vaccination have raised the question of improving vaccine responses in older individuals. This review presents recent progress in the understanding at the cellular and molecular levels of age related immune decline and strategies to translate current knowledge into the development of immunization strategies to promote healthy aging, keeping older members of society autonomous and independent.
    Current topics in medicinal chemistry 09/2013; 13. DOI:10.2174/15680266113136660181 · 3.45 Impact Factor
  • Source
    • "The study population consisted of healthy children, aged 31–44 months, previously primed with PHiD-CV at 3, 4 and 5 months of age and boosted at 12–15 months of age and of a non-randomised age-matched PCV-naïve control group enrolled at the time of booster vaccination (Fig. 1) [15]. PHiD-CV primed groups were randomised (1:1) in the primary vaccination study (Fig. 1) into the PP group who received paracetamol prophylactically at the time of vaccination and every 6–8 h within the first 24 h after each vaccine dose, or the NPP group who received no prophylactic antipyretics [15]. PHiD-CV primed groups received a single (fifth) PHiD-CV dose at 40–48 months of age (Fig. 1). "
    [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: Prophylactic paracetamol (PP) was previously shown to reduce primary and booster antibody responses against the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV). This study further evaluated the effect of PP on antibody persistence, immunological memory and nasopharyngeal carriage (NPC). METHODS: Two hundred and twenty children previously primed (3 doses, NCT00370318) and boosted (NCT00496015) with PHiD-CV with (PP group) or without (NPP group) prophylactic paracetamol administration received one PHiD-CV dose in their fourth year of life to assess the induction of immunological memory following previous immunisations. A control group of age-matched unprimed children enrolled in study NCT00496015 received an investigational tetravalent Neisseria meningitidis serogroups A, C, W-135, Y tetanus toxoid-conjugate vaccine, and thus remained unprimed for pneumococcal vaccination. Of these, 223 unprimed children received in the present study at least one PHiD-CV dose of a 2-dose catch-up regimen, which was relevant as control for assessment of immunological memory in PHiD-CV primed children. RESULTS: Induction of immunological memory was shown irrespective of PP administration at primary and booster vaccination. Antibody geometric mean concentrations were lower in the PP group for serotypes 1, 4, 7F and 9V. Opsonophagocytic titres did not differ significantly between PP and NPP groups. Previous use of PP seemed to have only a minor impact on kinetics of antibody persistence. Reduced NPC of vaccine pneumococcal serotypes and trends towards increased NPC of non-vaccine and non-cross-reactive serotypes were seen in primed groups versus the control group, with no obvious differences between PP and NPP groups. CONCLUSION: Regardless of whether previous PHiD-CV vaccination was given with or without PP, induction of immunological memory and persistence of PHiD-CV's impact on carriage was seen until at least 28 months post-booster vaccination. Our study results therefore suggest that the lower immune responses after primary and booster vaccination with PP are of transient nature.
    Vaccine 02/2013; 31(16). DOI:10.1016/j.vaccine.2013.01.044 · 3.49 Impact Factor
  • The Lancet 10/2009; 374(9698):1305-6. DOI:10.1016/S0140-6736(09)61802-X · 45.22 Impact Factor
Show more