Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis. BMJ 346:f794

Immunisation, Hepatitis and Blood Safety Department, Health Protection Agency, Colindale, London NW9 5EQ, UK.
BMJ (online) (Impact Factor: 17.45). 02/2013; 346(feb26 2):f794. DOI: 10.1136/bmj.f794
Source: PubMed


To evaluate the risk of narcolepsy in children and adolescents in England targeted for vaccination with ASO3 adjuvanted pandemic A/H1N1 2009 vaccine (Pandemrix) from October 2009.
Retrospective analysis. Clinical information and results of sleep tests were extracted from hospital notes between August 2011 and February 2012 and reviewed by an expert panel to confirm the diagnosis. Vaccination and clinical histories were obtained from general practitioners.
Sleep centres and paediatric neurology centres in England.
Children and young people aged 4-18 with onset of narcolepsy from January 2008.
The 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.
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.
The 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.

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    • "Surveillance of adverse reactions is needed for an appraisal of the balance between benefit and risk, and to ensure both appropriate use of vaccines and public confidence in vaccine safety. After 2009, narcolepsy and Guillain–Barré syndrome have been linked to H1N1 vaccines, although the final verdicts concerning causality have not yet been made [1] [2] [3] [4] [5] [6]. The two diseases are considered to be autoimmune, possibly triggered by infection or immunization [7] [8] [9] [10]. "
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    ABSTRACT: Background: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is associated to infections and it has been suggested that vaccination can trigger the disease. However, little is known about the specific association between clinically manifest influenza/influenza vaccine and CFS/ME. As part of a registry surveillance of adverse effects after mass vaccination in Norway during the 2009 influenza A (H1N1) pandemic, we had the opportunity to estimate and contrast the risk of CFS/ME after infection and vaccination. Methods: Using the unique personal identification number assigned to everybody who is registered as resident in Norway, we followed the complete Norwegian population as of October 1, 2009, through national registries of vaccination, communicable diseases, primary health, and specialist health care until December 31, 2012. Hazard ratios (HRs) of CFS/ME, as diagnosed in the specialist health care services (diagnostic code G93.3 in the International Classification of Diseases, Version 10), after influenza infection and/or vaccination were estimated using Cox proportional-hazards regression. Results: The incidence rate of CFS/ME was 2.08 per 100,000 person-months at risk. The adjusted HR of CFS/ME after pandemic vaccination was 0.97 (95% confidence interval [CI]: 0.91-1.04), while it was 2.04 (95% CI: 1.78-2.33) after being diagnosed with influenza infection during the peak pandemic period. Conclusions: Pandemic influenza A (H1N1) infection was associated with a more than two-fold increased risk of CFS/ME. We found no indication of increased risk of CFS/ME after vaccination. Our findings are consistent with a model whereby symptomatic infection, rather than antigenic stimulation may trigger CFS/ME.
    No preview · Article · Oct 2015 · Vaccine
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    • "The SCCS methodology is now routinely used to evaluate vaccine safety. For instance, following H1N1 vaccination, it has recently been used to evaluate the risks of Guillain–Barré syndrome [14], narcolepsy [15], epileptic seizures [16], convulsions [17], and multiple sclerosis [18]. Its efficiency compared to the cohort design has been established, which is a desirable feature when studying rare events such as intussusception [19]. "
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    ABSTRACT: The increased risk of intussusception after vaccination with the rhesus-human reassortant rotavirus vaccine Rotashield led to its withdrawal in 2005. We assess the risk of intussusception following the pentavalent rotavirus vaccine (RV5) on the basis of worldwide reports to the manufacturer up to May 2014, using a self-controlled case series. The method had to be modified to account for the under-reporting, a specific feature of pharmacovigilance spontaneous reports. The risk of intussusception occurring in either of the 0- to 2-day, 3- to 7-day or 8- to 14-day risk periods, was compared to the risk in the 15- to 30-day period. A total of 502 cases occurring 0-30 days after a vaccine dose were studied, including 188 cases after the first dose, 190 cases after the second dose, and 124 cases after the third dose. The incidence risk ratio relative to the control period was highest for the 3- to 7-day period and equal to 3.45 (95% CI 1.84-6.55), 1.63 (0.86-3.13) and 1.73 (0.86-3.51) after the first, second and third dose, respectively. Rotavirus vaccination with RV5 increases the risk of intussusception 3-7 days following vaccination, mainly after the first dose and marginally after the second and third doses. The risk is small and restricted to a short time window. It does not outweigh the benefit of the vaccination, but parents of vaccinated infants should be informed in order to react appropriately to the first symptoms. With appropriate assumptions about the reporting rate, spontaneous reports of adverse events after vaccination can be studied to evaluate vaccine safety. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Jan 2015 · Vaccine
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    • "Animal narcolepsy models and optogenetic device studies have shown that hypocretin maintains wakefulness, increases arousal, and suppresses REM and non-REM sleep [8] [9]. The observed association of narcolepsy with streptococcal [10] and H1N1 [11] infections and with H1N1 vaccination [12] [13] [14] [15] further supports the concept that narcolepsy is an immune-mediated disease. "
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    ABSTRACT: Despite published treatment recommendations and the availability of approved and off-label pharmacologic therapies for narcolepsy, clinical management of this incurable, chronic neurologic disorder remains challenging. While treatment is generally symptomatically driven, decisions regarding which drug(s) to use need to take into account a variety of factors that may affect adherence, efficacy, and tolerability. Type 1 narcolepsy (predominantly excessive daytime sleepiness with cataplexy) or type 2 narcolepsy (excessive daytime sleepiness without cataplexy) may drive treatment decisions, with consideration given either to a single drug that targets multiple symptoms or multiple drugs that each treat a specific symptom. Other drug-related characteristics that affect drug choice are dosing regimens, tolerability, and potential drug-drug interactions. Additionally, the patient should be an active participant in treatment decisions, and the main symptomatic complaints, treatment goals, psychosocial setting, and use of lifestyle substances (i.e., alcohol, nicotine, caffeine, cannabis) need to be discussed with respect to treatment decisions. Although there is a lack of narcolepsy-specific instruments for monitoring therapeutic effects, clinically relevant subjective and objective measures of daytime sleepiness (e.g., Epworth Sleepiness Scale, Maintenance of Wakefulness Test) can be used to provide guidance on whether treatment goals are being met. These considerations are discussed with the objective of providing clinically relevant recommendations for making treatment decisions that can enhance effective management of patients with narcolepsy.
    Full-text · Article · Oct 2014 · Sleep Medicine
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