Fever is part of the body's normal inflammatory process after receiving immunisations. Paracetamol is sometimes administered prophylactically to allay parental fears of high fever or febrile convulsions in children after routine infant vaccinations. But while prophylactic paracetamol does reduce post-vaccination fever, it also reduces the child's response to some of the vaccine antigens. Thus use of prophylactic paracetamol can no longer be routinely recommended in this setting. This is the conclusion of an Article in this week's edition of The Lancet, written by Professor Roman Prymula, University of Defence, Hradec Kralove, Czech Republic, and colleagues.
The authors did two randomised controlled trials in the study—one at the time of initial childhood vaccinations, and the other at the time of booster injections. The vaccinations were the routine vaccinations offered to children in developed nations, to offer protection against pneumococcal disease, Haemophilus influenzae type b, diphtheria, tetanus, whooping cough, hepatitis B, polio, and rotavirus. Infants from 10 centres in the Czech Republic were randomly assigned to receive three prophylactic paracetamol doses every 6—8 hours in the first 24 hours after vaccination (226 infants), or no paracetamol (233). The primary aim of the study was the reduction in fever of 38oC or higher, while the secondary aim was to analyse immunogenicity of the administered vaccines.
The researchers found that, after initial vaccinations, a lower proportion of infants in the paracetamol group had temperatures above 38oC compared to the control group (42 % vs 66% respectively). Similar results were observed after booster vaccinations (36% in prophylactic paracetamol group vs 58% in control). Geometric mean concentrations (GMCs)* were significantly lower in the paracetamol group than in the control group, for antibodies against the pneumococcal serotypes contained in the vaccine, Haemophilus influenzae type b, diphtheria and tetanus toxoids, and for one of the whooping cough antibodies. After booster vaccinations, lower antibody GMCs persisted in the paracetamol group for tetanus toxoid and most pneumococcal serotypes.
The authors say: "To our knowledge, such an effect of prophylactic paracetamol on postimmunisation immune responses has not been documented before... the interference of paracetamol on antibody responses could result from the prevention of inflammation."
The authors postulate that prophylactic paracetamol could reduce immune responses because it interferes with the early phase of post-vaccination immune reactions that require interaction between different cells of the immune system (dendritic cells, T cells, and B cells). But for this hypothesis to be correct, paracetamol should interfere with responses only if administered at the time of or early after immunisation. Their analysis of the data confirmed this. They also analysed 10 previous studies, and their findings supported the hypothesis that paracetamol maximally interferes with vaccine responses if administered early, whereas if used therapeutically once fever and the corresponding inflammatory signals have already been established, its effect (if any) can be expected to be smaller.
The authors conclude: "The clinical relevance of these immunological findings is unknown and needs further assessment. Prophylactic administration of antipyretic** drugs at the time of vaccination should nevertheless no longer be routinely recommended without careful weighing of the expected benefits and risks."
In an accompanying Comment, Dr Robert T Chen, Centers for Disease Control and Prevention, Atlanta, GA, USA, and colleagues say: "In today's study, the high proportion of vaccine recipients reaching seroprotective antibody levels suggests that the effect of paracetamol for any given individual might be small; further assessment at the individual level, such as whether or not paracetamol increases the proportion of vaccine non-responders, is warranted. However, a larger question is the extent to which paracetamol might reduce population protection. This point has implications, especially for Haemophilus influenzae and pneumococcus, for which higher and sustained antibody concentrations are needed to interrupt the carrier state and reduce transmission within the population, and for pertussis, the bacterial vaccine-preventable disease that is the least well controlled."
Professor Roman Prymula, University of Defence, Hradec Kralove, Czech Republic. T) +420 602 488 620 E) prymula@pmfhk.cz
Dr Robert T Chen, Centers for Disease Control and Prevention, Atlanta, GA, USA. T) +1 404 639 3755 E) rtc1@cdc.gov
For full Article and Comment, see: http://press.thelancet.com/paracetkids.pdf
Note to editors: * Antibody geometric mean concentration is a measure of the immune system's response to a vaccine.
**antipyretic drug=a drug which reduces body temperature in response to situations such as fever. Paracetamol is an antipyretic.
Journal
The Lancet