Risk of narcolepsy associated with inactivated adjuvanted (AS03) A/H1N1 (2009) pandemic influenza vaccine in Quebec.

Jacques Montplaisir,Manale Ouakki,Marie-Josée Quinn,Geneviève Deceuninck,Alex Desautels,Philippe De Wals,Emmanuel Mignot,Dominique Petit,Suryaprakash Sambhara

doi:10.1371/journal.pone.0108489

Abstract

ContextAn association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe.ObjectiveTo assess narcolepsy risk following administration of a similar vaccine in Quebec.DesignRetrospective population-based study.SettingNeurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre.PopulationPatients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry.Main Outcome MeasuresConfirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1st, 2009, and December 31st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method.ResultsA total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009–2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50–11.12). RR was 2.07 (0.70–6.17) in the SCCS, and 1.48 (0.37–7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases.ConclusionsResults are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.

Highlights

Narcolepsy is characterized by the occurrence of excessive daytime sleepiness (EDS), which is usually the most disabling feature of the disease [1,2,3]
Identification of narcolepsy cases A retrospective review of medical charts of all patients who consulted for somnolence at the sleep clinic of the Hopital du Sacre-Coeur de Montreal’ (HSCM) between January 1st, 2009 and July 21, 2011 was performed
588 cases were excluded because they received another diagnosis or because onset of first symptoms was prior to January 1st, 2009 or later than December 31st, 2010

Summary

Introduction

Narcolepsy is characterized by the occurrence of excessive daytime sleepiness (EDS), which is usually the most disabling feature of the disease [1,2,3]. The other major manifestation of narcolepsy is cataplexy, consisting of sudden drops of muscle tone triggered by emotions such as laughter, anger or surprise. The manifestations of the disease can be alleviated by medical treatment and their consequences mitigated through adaptation but there is no cure. Narcolepsy is caused by a selective loss of hypocretinproducing cells in the hypothalamus, presumably the consequence of an autoimmune disorder, with a genetic predisposition [4,5]. Environmental factors that could trigger the occurrence of narcolepsy include head trauma, stressful life events or infections [6,7,8]

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