Drug Safety

, Volume 33, Issue 12, pp 1109–1115

Fever Following Immunization with Influenza A (H1N1) Vaccine in Children

A Survey-Based Study in the Netherlands
  • Nancy Broos
  • Eugène P. van Puijenbroek
  • Kees van Grootheest
Original Research Article


Background: In November 2009, all children in the Netherlands from 6 months up to 4 years of age were indicated to receive the Influenza A (H1N1) vaccine. Fever is a common adverse event following immunization in children. Pandemrix®, an inactivated, split-virus influenza A (H1N1) vaccine, was used for this age group. A clinical study mentioned in the Summary of Product Characteristics of Pandemrix® found an increased reactogenicity after the second dose in comparison with the first dose, particularly in the rate of fever. In the Netherlands, this adverse reaction was a point of concern for the parents or caregivers of these children.

Objective: To investigate the course and height of fever following the first and second dose of Pandemrix® in children aged from 6 months up to 4 years. The secondary aim was to evaluate the use of an online survey during a vaccination campaign.

Design: Survey-based descriptive study.

Setting: Adverse drug reaction reporting database of the Netherlands Pharmacovigilance Centre (Lareb).

Participants: Parents or caregivers (n = 839) of vaccinated children who reported fever to Lareb following the first immunization with Pandemrix®. Questionnaires were sent by email to parents or caregivers of eligible children following the first and second doses of Pandremix®.

Main Outcome Measures: Time between vaccination and the occurrence of fever, the maximum measured temperature, the occurrence of other adverse events after first and second vaccination, the decision to get the second vaccination and the social implication of the fever in terms of absence from work, nursery or school, and hospitalization.

Results: Following the first vaccination against Influenza A (H1N1), the height of the fever was between 39.0 and 40.0°C in 359/639 (56.2%) of the children. In most of these children (235/639 [36.8%]), the onset of fever was between 6 and 12 hours following vaccination. 450/639 (70.4%) children recovered within 2 days. Of the 539 responders to the second questionnaire, 380 (70.5%) received the second vaccination against Influenza A (H1N1) and 213 (56.1%) of these children experienced fever again. The height of the fever was significantly lower (t-test; p = 0.001) and the duration was significantly shorter (Pearson’s Chisquare; p = 0.002) in comparison with the first vaccination. The height of the fever after the first vaccination was associated with the decision to receive the second vaccination (t-test; p = 0.000). In the studied group, 342 (53.5%) parents or caregivers needed to stay home from work and 405 (63.4%) children stayed home from nursery or school due to fever following the first vaccination.

Conclusions: The results of this study can be used in future vaccination campaigns to be able to inform people in an evidence-based manner about the risks and benefits of the vaccine and to avoid unnecessary concern and negative media attention. This could contribute to improved immunization levels. A web-based survey is demonstrated to be a useful tool to quickly gather information about a current safety concern and consequently inform the public to support an ongoing vaccination campaign.

Supplementary material

40264_2012_33121109_MOESM1_ESM.pdf (118 kb)
Supplementary material, approximately 120 KB.


  1. 1.
    World Health Organization. Statement from WHO Global Advisory Committee on Vaccine Safety about the safety profile of pandemic influenza A (H1N1) 2009 vaccines. 18 December 2009 [online]. Available from URL: http://www.who.int/csr/resources/publications/swineflu/cp164_2009_1612_gacvs_h1n1_vaccine_safety.pdf [Accessed 2010 Feb 22]
  2. 2.
    World Health Organization. Director-General’s opening statement at virtual press conference: H1N1 in post-pandemic period. 10 August 2010 [online]. Available from URL: http://www.who.int/mediacentre/news/statements/2010/h1n1_vpc_20100810/en/index.html [Accessed 2010 Sep 12]
  3. 3.
    World Health Organization. Pandemic (H1N1) 2009 briefing note 23. WHO recommendations for the post-pandemic period. 10 August 2010 [online]. Available from URL: http://www.who.int/csr/disease/swineflu/notes/briefing_20100810/en/index.html [Accessed 2010 Sep 12]
  4. 4.
    Dutch Health Council. Vaccination against pandemic Influenza A (H1N1) 2009: target groups and prioritization (1). 17 August 2009 [online]. Available from URL: http://www.gezondheidsraad.nl/sites/default/files/200910_0.pdf [Accessed 2010 Feb 22]
  5. 5.
    Dutch Health Council. Vaccination against pandemic Influenza A (H1N1) 2009: target groups and prioritization (3). 9 November 2009 [online]. Available from URL: http://www.gezondheidsraad.nl/sites/default/files/Briefadvies%20influenza%20A_H1N1%202009%20DEEL3R%20_gewijzigd%20dd20nov2009_0.pdf [Accessed 2010 Feb 22]
  6. 6.
    Haber P, Sejvar J, Mikaeloff Y, et al. Vaccines and Guillain-Barre syndrome. Drug Saf 2009; 32(4): 309–23PubMedCrossRefGoogle Scholar
  7. 7.
    Kohl KS, Marcy SM, Blum M, et al. Fever after immunization: current concepts and improved future scientific understanding. Clin Infect Dis 2004; 39(3): 389–94PubMedCrossRefGoogle Scholar
  8. 8.
    Michael MS, Kohl KS, Dagan R, et al. Fever as an adverse event following immunization: case definition and guidelines of data collection, analysis, and presentation. Vaccine 2004; 22(5–6): 551–6CrossRefGoogle Scholar
  9. 9.
    European Medicines Agency. Pandemrix®: summary of product characteristics [online]. Available from URL: http://eudrapharm.eu/eudrapharm/showDocument?documentId=6519788735704300414 [Accessed 2010 Feb 22]
  10. 10.
    European Medicines Agency. European Medicines Agency advises of risk of fever in young children following vaccination with Pandemrix. 4 December 2009 [press release; online]. Available from URL: http://www.ema.europa.eu/pdfs/general/direct/pr/78440409en.pdf [Accessed 2010 Feb 22]
  11. 11.
    van Puijenbroek EP, Broos N, van Grootheest K. Monitoring adverse events of the vaccination campaign against influenza A (H1N1) in the Netherlands. Drug Saf 2010; 33(12): 1097–108PubMedCrossRefGoogle Scholar
  12. 12.
    SurveyMonkey [online]. Available from URL: http://www.surveymonkey.com/ [Accessed 2010 Aug 24]
  13. 13.
    Crocetti M, Moghbeli N, Serwint J. Fever phobia revisited: have parental misconceptions about fever changed in 20 years? Pediatrics 2001; 107(6): 1241–6PubMedCrossRefGoogle Scholar
  14. 14.
    Eskerud JR, Hoftvedt BO, Laerum E. Fever: knowledge, perception and attitudes: results from a Norwegian population study. Fam Pract 1991; 8(1): 32–6PubMedCrossRefGoogle Scholar
  15. 15.
    Van der Linden M. Second national study to diseases and performances in the general practitioner practice: symptoms and diseases in the population and the general practitioner practice. Utrecht/Bilthoven: NIVEL/RIVM, 2004Google Scholar
  16. 16.
    Wright PF, Thompson J, Vaughn WK, et al. Trials of influenza A/New Jersey/76 virus vaccine in normal children: an overview of age-related antigenicity and reactogenicity. J Infect Dis 1977; 136 Suppl.: S731–41PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2010

Authors and Affiliations

  • Nancy Broos
    • 1
  • Eugène P. van Puijenbroek
    • 1
  • Kees van Grootheest
    • 1
  1. 1.Netherlands Pharmacovigilance Centre Lareb’s-Hertogenboschthe Netherlands

Personalised recommendations