24 Jun Risk of Narcolepsy after ASO3 adjuvanated pandemic A/H1N1 2009 influenza vaccine in English adults.
The study in question aimed to determine if there was an increased risk of narcolepsy in English adults after the 2009 A/H1N1 Pandermrix vaccine was found to increase narcolepsy risk rates in children.
Information was collected from 6 sleep centres located in England during a time frame between November 2012 and February 2014, and information about patient’s vaccination & clinical histories was obtained. Any patients with suspected cases of narcolepsy were further reviewed to determine relevant information. Out of the total 2554 potential patients, after cross referencing and de duplicating the list, 1446 remained. Of these patients 926 had symptom onset before the vaccine, and 441 clearly did not have narcolepsy after further review. Out of all patients reviewed 40 were diagnosed with narcolepsy (28 with cataplexy). Of the 40 narcoleptic patients, 5 had received the Pandermrix vaccine and the same 5 had narcolepsy with cataplexy. In total these are statically significant values as the odds ratio for vaccination cases compared to the population was 4.24 (95% confidence interval 1.45–12.38) using all cases and 9.06 (1.90–43.17) using cases with a diagnosis by November 2011, giving an attributable risk of 0.59 cases per 100,000 doses, which finds that there was a statically higher risk of narcolepsy development following the Panderix vaccination in England. This risk however is lower in adults in comparison to children, as seen in a different study of similar design.
Discussion: Whilst the values and overall study design appears valid, with authors and researchers blinded to vaccination status, the study was completed on quite a small sample size and doesn’t take into account of all possible cases of narcolepsy (diagnosed in a difference sleep centre or non-diagnosed cases)
The other problem with this study is that the mechanism by which narcolepsy with cataplexy is associated with Pandemrix is currently not known. This is relevant as all cases with the vaccine/ narcolepsy crossover, presented with cataplexy. It has been found that HLA DQB1*06:02 is present in 95% of patients with narcolepsy with cataplexy (type 1). The two patients tested for this gene were positive for HLA DQB1*06:02. Following Knudsons 2 hit hypothesis, it is possible that Pandemrix provides a second hit in those patients with a genetic vulnerability to the development of narcolepsy with cataplexy. Alternatively Pandemrix may result in the development or augmentation of autoantibodies to hypocretin-producing cells and the destruction of these cells results in the development of narcolepsy with cataplexy. This is too relevant as other studies have speculated on autoimmunity as a mechanism to explain the link between narcolepsy and Pandemrix.