Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis

Abstract

Setting Sleep centres and paediatric neurology centres in England.Participants Children and young people aged 4-18 with onset of narcolepsy from January 2008. Main outcome measuresThe odds of vaccination in those with narcolepsy compared with the age matched English population after adjustment for clinical conditions that were indications for vaccination. The incidence of narcolepsy within six months of vaccination compared with the incidence outside this period measured with the self controlled cases series method.Results Case notes for 245 children and young people were reviewed; 75 had narcolepsy (56 with cataplexy) and onset after 1 January 2008. Eleven had been vaccinated before onset; seven within six months. In those with a diagnosis by July 2011 the odds ratio was 14.4 (95% confidence interval 4.3 to 48.5) for vaccination at any time before onset and 16.2 (3.1 to 84.5) for vaccination within six months before onset. The relative incidence from the self controlled cases series analysis in those with a diagnosis by July 2011 with onset from October 2008 to December 2010 was 9.9 (2.1 to 47.9). The attributable risk was estimated as between 1 in 57 500 and 1 in 52 000 doses. ConclusionThe increased risk of narcolepsy after vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine indicates a causal association, consistent with findings from Finland. Because of variable delay in diagnosis, however, the risk might be overestimated by more rapid referral of vaccinated children. IntroductionNarcolepsy is a chronic disorder presenting with excessive daytime sleepiness, often accompanied by a transient loss of muscle tone triggered by strong emotion (cataplexy). Diagnosis is based on clinical criteria and can be confirmed by polysomnography followed by a multiple sleep latency test. 1 Estimates of prevalence generally range between 25 and 50 per 100 000, though might be less in some populations, possibly because of differences in genetic susceptibility or exposure to aetiological risk factors.2 Information on incidence is more limited. Onset can occur at any age 2 but is commonest in those aged 10-19, in whom an incidence of 3.84 per 100 000 person years has been reported. 3 The interval between onset and diagnosis can be long, with a median of 10.5 years in one study. 4 Diagnostic delay is less in those with cataplexy and in younger patients. 5 There is a strong association with human leucocyte antigen (HLA) DQB1*0602 and reported associations with environmental factors such as streptococcal infection, 6 seasonal influenza, 7 and more recently pandemic A/H1N1 2009 influenza. 8 In England, a monovalent pandemic strain vaccine containing the oil-in-water adjuvant AS03 (Pandemrix) was introduced in October 2009 during the second wave of infection, initially for people with high risk clinical conditions 9 10 and then in healthy 12 A second pandemic vaccine was used (Celvepan) but accounted for less than 1% of the total.In August 2010 concerns were raised in Finland and Sweden about a possible associat...

A systematic review of cognitive function and psychosocial well-being in school-age children with narcolepsy

“…Supporting the association, Miller et al [10] found a significantly increased risk of narcolepsy in children who received the vaccine in England, consistent with the findings of the cohort study conducted in Finland. It has been estimated that globally more than 1000 children have developed narcolepsy following the vaccination [12].…”

“…Following these concerns, a cohort study was conducted in Finland and the results showed that there was a 13-fold increased risk of narcolepsy in children aged 4-19 years old who received the vaccination compared to unvaccinated children [9]. These concerns led to further investigations about the incidence of narcolepsy in Europe before, during and after the swine flu pandemic and vaccination campaigns [4,10,11].…”

Rapid changes in serum cytokines and chemokines in response to inactivated influenza vaccination

“…Ongoing efforts to develop more effective influenza vaccines have had limited success. In addition, the unexpected association of an adjuvanted 2009 H1N1 vaccine in Europe with increased risk of narcolepsy in children25, 26, 27 highlights the need to better understand the biologic mechanisms mediating vaccine responses.…”

The manufacturing process should remain the focus for severe febrile reactions in children administered an Australian inactivated influenza vaccine during 2010

“…CSL have fulfilled this role as the major supplier of influenza vaccine in Australia for more than 50 years. However, episodic vaccine safety concerns have the potential to suddenly interrupt vaccine supply from a particular manufacturer and highlight the importance of having multiple vaccine manufacturers in the market 1, 2…”