The AS03-adjuvanted 2009 pandemic H1N1 influenza vaccine (trade name: PandemrixTM) was associated with an increased risk of narcolepsy in several northern European countries. In other countries where there is a lower prevalence of genetic factors associated with narcolepsy, studies did not find an increase in risk with this vaccine or other influenza vaccines. The vaccine in question (PandemrixTM) was not licensed in the United States, and vaccines in routine use in the United States* have not been shown to cause narcolepsy.
Why This is an Issue
A sharp increase in the number of narcolepsy diagnoses in children was noticed shortly after immunization campaigns for the pandemic 2009 H1N1 vaccines in Finland and Sweden. Subsequent analysis confirmed an association between the European AS03-adjuvanted pandemic 2009 H1N1 vaccine (PandemrixTM) and narcolepsy onset in several northern European countries. Immunization with this vaccine is thus no longer recommended in children [1-3]. This vaccine was not used in the United States, and no increase in narcolepsy has been found with any vaccine routinely used in the United States.
Multiple studies have consistently documented an increased risk of narcolepsy associated with AS03-adjuvanted influenza vaccines, primarily in the childhood populations of northern European countries [1-14]. The estimated rate was 1 case per 16,000 persons vaccinated between 4 and 19 years of age in Finland . The strength of this association varied depending on the country studied, with an intermediate association in the rest of Europe and a possible association in Canada [8, 15]. This could be explained by differences in population genetics . Studies have not shown any association between narcolepsy and other influenza vaccines, either MF59-adjuvanted or without an adjuvant [17-21]. A cohort study of almost one million adolescent girls in Denmark and Sweden found no association between quadrivalent HPV vaccine and narcolepsy . A 2018 meta-analysis found that during the first year after vaccination with PandemrixTM the relative risk of narcolepsy increased 5 to 14-fold in children and adolescents and 2 to 7-fold in adults, and the vaccine attributable risk in children and adolescents was approximately 1 per 18,400 doses of vaccine .
Proposed Biological Mechanism
The 1918 pandemic of influenza infection was associated with an illness consistent with narcolepsy. The 2009-10 pandemic influenza may have been associated with an increase in narcolepsy in China, but no increase was observed in many other countries . Almost all patients with narcolepsy have HLA DQB1*0602, a genetic marker for predisposition to the disorder [25, 26]. Recent studies have provided further evidence that infections may serve as a potential trigger for the pathogenesis of narcolepsy . A number of mechanisms have been postulated to explain the association with the ASO3-adjuvanted vaccine in several European countries, but many of these hypotheses have been found to be lacking. One recent hypothesis includes the possibility that a combination of infection with the 2009 pandemic H1N1 influenza virus followed by the ASO3-adjuvanted vaccine could have resulted in narcolepsy in genetically predisposed individuals .
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