Narcolepsy and adjuvanted pandemic influenza A (H1N1) 2009 vaccines - Multi-country assessment

Daniel Weibel, Miriam Sturkenboom, Steven Black, Maria de Ridder, Caitlin Dodd, Jan Bonhoeffer, Ann Vanrolleghem, Nicoline van der Maas, Gert Jan Lammers, Sebastiaan Overeem, Angela Gentile, Norberto Giglio, Vanesa Castellano, Jeffrey C. Kwong, Brian J. Murray, Karen Cauch-Dudek, Diana Juhasz, Michael Campitelli, Alexandre N. Datta, Ulf KallweitWan-Ting Huang, Yu-Shu Huang, Chung-Yao Hsu, Hsi-Chung Chen, Maria Giner-Soriano, Rosa Morros, Carles Gaig, Ester Tió, Silvia Perez-Vilar, Javier Diez-Domingo, Francisco Javier Puertas, Lawrence W. Svenson, Salaheddin M. Mahmud, Bruce Carleton, Monika Naus, Lisen Arnheim-Dahlström, Lars Pedersen, Frank DeStefano, Tom T Shimabukuro

Research output: Contribution to journalArticleAcademicpeer-review

49 Citations (Scopus)
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BACKGROUND: In 2010, a safety signal was detected for narcolepsy following vaccination with Pandemrix, an AS03-adjuvanted monovalent pandemic H1N1 influenza (pH1N1) vaccine. To further assess a possible association and inform policy on future use of adjuvants, we conducted a multi-country study of narcolepsy and adjuvanted pH1N1 vaccines.

METHODS: We used electronic health databases to conduct a dynamic retrospective cohort study to assess narcolepsy incidence rates (IR) before and during pH1N1 virus circulation, and after pH1N1 vaccination campaigns in Canada, Denmark, Spain, Sweden, Taiwan, the Netherlands, and the United Kingdom. Using a case-control study design, we evaluated the risk of narcolepsy following AS03- and MF59-adjuvanted pH1N1 vaccines in Argentina, Canada, Spain, Switzerland, Taiwan, and the Netherlands. In the Netherlands, we also conducted a case-coverage study in children born between 2004 and 2009.

RESULTS: No changes in narcolepsy IRs were observed in any periods in single study sites except Sweden and Taiwan; in Taiwan incidence increased after wild-type pH1N1 virus circulation and in Sweden (a previously identified signaling country), incidence increased after the start of pH1N1 vaccination. No association was observed for Arepanrix-AS03 or Focetria-MF59 adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the case-control study nor for children born between 2004 and 2009 in the Netherlands case-coverage study for Pandemrix-AS03.

CONCLUSIONS: Other than elevated narcolepsy IRs in the period after vaccination campaigns in Sweden, we did not find an association between AS03- or MF59-adjuvanted pH1N1 vaccines and narcolepsy in children or adults in the sites studied, although power to evaluate the AS03-adjuvanted Pandemrix brand vaccine was limited in our study.

Original languageEnglish
Pages (from-to)6202-6211
Number of pages10
Issue number41
Early online date16 Aug 2018
Publication statusPublished - 1 Oct 2018


  • AS03
  • Adjuvant
  • MF59
  • Narcolepsy
  • Pandemic H1N1 influenza
  • Influenza Vaccines/therapeutic use
  • Humans
  • Vaccination
  • Influenza, Human/immunology
  • Case-Control Studies
  • Narcolepsy/immunology
  • Influenza A Virus, H1N1 Subtype/immunology
  • Adjuvants, Immunologic/therapeutic use
  • Retrospective Studies


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