Narkolepsi etter Pandemrix – en samling lesestoff

Våren 2010 forsto den svenske barnenevrologen Lars Palm at noe uvanlig skjedde. I løpet av bare et par måneder hadde han diagnostisert narkolepsi hos seks barn, mot vanligvis bare ett i året. Han oppdaget at symptomene hadde startet innen et par uker etter at barna hadde fått vaksinasjon med Pandemrix mot influensa høsten og vinteren 2009-10. Han varslet det svenske Läkemedelsverket.

Slik startet oppdagingen av denne katastrofen. Undersøkelser i Sverige, Finland og Irland avdekket etterhvert at barn som fikk Pandemrix, i ukene etterpå hadde om lag ti ganger større risiko for å få narkolepsi enn barn som ikke ble vaksinert.

Narkolepsi er en kronisk nevrologisk sykdom som preges av ekstrem søvnighet på dagtid og korte anfall med tap av muskelkraft i enkelte muskelgrupper.

Her følger lenker til sentrale artikler og rapporter om sammenhengen mellom Pandemrix og narkolepsi, ordnet etter land, med de nyeste først.

Oversiktsartikler om de epidemiologiske artiklene

• Sarkanen TO og kolleger. Incidence of narcolepsy after H1N1 influenza and vaccinations: Systematic review and meta-analysis. Sleep Med Rev 2018; 38: 177-86.
• Verstraeten T og kolleger. Pandemrix™ and narcolepsy: A critical appraisal of the observational studies. Hum Vaccin Immunother. 2015 Sep 17:1-7.
• Edwards K og kolleger. Narcolepsy and pandemic influenza vaccination. Ped Infect Dis J 2019; 38: 873-6.

Finland

• Krister Melen og kolleger. No serological evidence of influenza A H1N1pdm09 virus infection as a contributing factor in childhood narcolepsy after Pandemrix vaccination campaign in Finland. PLoS ONE 2013; 8: e68402.
• Jukka Jokinen og kolleger. Pandemiarokotteen ja narkolepsian yhteys aikuisilla. Varmennettuihin rekisteritietoihin perustuva kohorttitutkimus. Helsinki: Institutet för Hälsa og Välfârd, 2013.
• Hanna Nohynek og kolleger. AS03 adjuvanted AH1N1 vaccine associated with an abrupt increase in the incidence of childhood narcolepsy in Finland. PLoS ONE 2012; 7: e33536.
• Markku Partinen og kolleger. Increased incidence and clinical picture of childhood narcolepsy following the 2009 H1N1 pandemic vaccination campaign in Finland. PLoS ONE 2012; 7: e33723.
• National Narcolepsy Task Force. Kansallisen narkolepsiatyöryhmän loppuraportti 31.8.2011. Helsinki: Institutet för Hälsa och Välfärd, 2011.
• National Narcolepsy Task Force. Interim Report 31 January 2011. Helsinki: Institutet för Hälsa och Välfärd, 2011.

Sverige

• Feltelius N og kolleger. A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden. J Intern Med 2015; 278: 335-53.
• Ingemar Persson og kolleger. Risks of neurological and immune-related diseases, including narcolepsy, after vaccination with Pandemrix: a population- and registry-based cohort study with over 2 years of follow-up. J Intern Med 2014; 275: 172-90.
• Läkemedelsverket. Registerstudie med fokus på neurologiska och immunrelaterade sjukdomar efter vaccination med Pandemrix. Uppsala: Läkemedelsverket, 2013.
• Attila Szakács og kolleger. Increased childhood incidence of narcolepsy in western Sweden after H1N1 influenza vaccination. Neurology 2013; 80:
• Anna Käll. The Pandemrix – narcolepsy tragedy: how it started and what we know today. Acta Paediatrica 2013; 102: 2-4.
• Carola Bardage og kolleger. Neurological and autoimmune disorders after vaccination against pandemic influenza A (H1N1) with a monovalent adjuvanted vaccine: population based cohort study in Stockholm, Sweden. British Medical Journal 2011; 343: d5956.
• Läkemedelsverket. Occurrence of narcolepsy with cataplexy among children and adolescents in relation to the H1N1 pandemic and Pandemrix vaccinations. Uppsala: Läkemedelsverket, 2011.
• Läkemedelsverket. A registry based comparative cohort study in four Swedish counties of the risk for narcolepsy after vaccination with Pandemrix – A first and preliminary report. Uppsala: Läkemedelsverket, 2011.

Irland

• Darina O’Flanagan og kolleger. Investigation of an association between onset of narcolepsy and vaccination with pandemic influenza vaccine, Ireland April 2009-December 2010. Euro Surveill 2014; 19: pii=20789.
• National Narcolepsy Study Steering Committee. Investigation of an increase in the incidence of narcolepsy in children and adolescents in 2009 and 2010. Dublin: Department of Health, 2012.

England

• Elizabeth Miller og kolleger. Risk of narcolepsy in children and young people receiving AS03 adjuvanted pandemic A/H1N1 2009 influenza vaccine: retrospective analysis. British Medical Journal 2013; 346:
• J Stowe og kolleger. Risk of Narcolepsy after AS03 Adjuvanted Pandemic A/H1N1 2009 Influenza Vaccine in Adults: A Case-Coverage Study in England. Sleep 2016.

Frankrike

• Centre Hospitalier et Universitaire de Bordeaux, Inserm, et Universite Bordeaux Segalen. Etude NarcoFlu-VF NarcoFlu VAESCO-France. Bordeaux: Universite de Bordeaux, 2012.
• Yves Dauvilliers og kolleger. Increased risk of narcolepsy in children and adults after pandemic H1N1 vaccination in France. Brain 2013; 136: 2486-96.

Tyskland

• Oberle D og kolleger. Spontaneous reporting of suspected narcolepsy after vaccination against pandemic influenza A (H1N1) in Germany. Pharmacoepidemiol Drug Saf 2017; 26: 1321-7.

Europa

• Gadroen K og kolleger. Patterns of spontaneous reports on narcolepsy following administration of pandemic influenza vaccine; a case series of individual case safety reports in Eudravigilance. Vaccine 2016; 34: 4892-7.
• Leonoor Wijnansa og kolleger. The incidence of narcolepsy in Europe: Before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns. Vaccine 2013; 31: 1246–54.
• ECDC. Narcolepsy in association with pandemic influenza vaccination. A multi-country European epidemiological investigation. Stockholm: European Centre for Disease Prevention and Control, 2012.

Norge

• Trogstad L og kolleger. Narcolepsy and hypersomnia in Norwegian children and young adults following the influenza A(H1N1) 2009 pandemic. Vaccine; 2017:
• Heier MS, et al. Incidence of narcolepsy in Norwegian children and adolescents after vaccination against H1N1 influenza A. Sleep Med 2013;
• Helse- og omsorgsdepartementet. Beredskap mot pandemisk influensa. Meld. St. 16 (2012–2013).
• Folkehelseinstituttet. Rapport om forskning etter influensapandemien i 2009, oppdatert, 2. mars 2012. Oslo: Folkehelseinstituttet, 2012.
• Folkehelseinstituttet. Rapport om utredning av narkolepsi etter Pandemrix, 26. september 2011. Oslo: Folkehelseinstituttet, 2011.
• Folkehelseinstituttet. Foreløpig rapport om narkolepsi etter Pandemrix, 2. august 2011. Oslo: Folkehelseinstituttet, 2011.

Canada
(I Canada ble vaksinen Arepanrix benyttet. Den skal være lik Pandemrix bortsett fra at den ble produsert i Canada.)

• Harris T og kolleger. Did narcolepsy occur following administration of AS03-adjuvanted A(H1N1) pandemic vaccine in Ontario, Canada? A review of post-marketing safety surveillance data. Euro Surveill 2014; 19: pii=20900.
• Montplaisir J og kolleger. Risk of narcolepsy associated with inactivated adjuvanted (AS03) A/H1N1 (2009) pandemic influenza vccine in Quebec. PLoS ONE  2014; 9: e108489.

USA
(I USA ble andre vaksiner enn Pandemrix benyttet.)

• Duffy J og kolleger. Narcolepsy and influenza A(H1N1) pandemic 2009 vaccination in the United States. Neurology 2014;

Generelt

• Luo G og kolleger. Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy. PNAS 2018; 115: E12323-E12332. https://www.pnas.org/content/115/52/E12323
• Sarkanen TO og kolleger. Narcolepsy Associated with Pandemrix Vaccine. Curr Neurol Neurosci Rep 2018; 18: 43. https://www.ncbi.nlm.nih.gov/pubmed/29855798
• Luo G og kolleger. Absence of anti-hypocretin receptor 2 autoantibodies in post pandemrix narcolepsy cases. PLoS One 2017; 12: e0187305.
• Lind A og kolleger. Antibody affinity against 2009 A/H1N1 influenza and Pandemrix vaccine nucleoproteins differs between childhood narcolepsy patients and controls. Viral Immunol 2017; 30: 590-600.
• Bomfim IL og kolleger. The immunogenetics of narcolepsy associated with A(H1N1)pdm09 vaccination (Pandemrix) supports a potent gene-environment interaction. Genes Immun 2017; 18: 75-81. https://www.ncbi.nlm.nih.gov/pubmed/28332559
• Bollaerts K og kolleger. Application of probabilistic multiple-bias analyses to a cohort- and a case-control study on the association between Pandemrix™and narcolepsy. PLoS ONE 2016; 11: e0149289.
• Wijnans L. Pandemic influenza vaccine & narcolepsy: simulations on the potential impact of bias. Exp Rev Vaccines 2016.
• Tesorieroa C og kolleger. H1N1 influenza virus induces narcolepsy-like sleep disruption and targets sleep–wake regulatory neurons in mice. PNAS 2016; 113: E368–E377.
• Scammell TE. Narcolepsy. N Engl J Med 2015; 373: 2654-62.
• Sturkenboom MCJM og kolleger. The  narcolepsy-pandemic  influenza  story: Can  the  truth  ever  be unraveled? Vaccine 2015; 33S: B6-B13.
• van der Heide A og kolleger. Immunohistochemical screening for antibodies in recent onset type 1 narcolepsy and after H1N1 vaccination.  J Neuroimmunol 2015; 283: 58-62.
• Thebault S og kolleger. Neuronal antibodies in children with or without narcolepsy following H1N1-AS03 vaccination. PLoS ONE 2015; 10: e0129555.
• Vaarala O og kolleger. Antigenic differences between AS03 adjuvanted influenza A (H1N1) pandemic vaccines: implications for Pandemrix-associated narcolepsy risk. PLoS ONE  2014; 9: e114361.
• Partinen M og kolleger. Narcolepsy as an autoimmune disease: the role of H1N1 infection and vaccination. Lancet Neurol 2014; 13: 600-13.
• Mignot EJM. History of narcolepsy at Stanford University. Immunol Res 2014; xxxx.
• Ahmed SS og kolleger. Narcolepsy, 2009 A(H1N1) pandemic influenza, and pandemic influenza vaccinations: What is known and unknown about the neurological disorder, the role for autoimmunity, and vaccine adjuvants. J Autoimmun 2014; xxxx.
• L Fugger og L Steinman. A scientific sequel to Stieg Larsson: relationship between Pandemrix – pandemic influenza vaccine – and the subsequent development of narcolepsy. J Intern Med 2014; 275: 195-7.
• GACVS. Global Advisory Committee on Vaccine Safety, December 2012. Wkly Epidemiol Rec 2013; 88: 65-71.
• Kelly Morris og kolleger. Implications of narcolepsy link with swine-influenza vaccine. Lancet Infect Dis 2013; 13: 396-6.
• Thebault S og kolleger. Narcolepsy and H1N1 vaccination: a link? Curr Opin Pumo Med 2013; 19: 587–93.
• Barker CIS, Snape MD. Pandemic influenza A H1N1 vaccines and narcolepsy: vaccine safety surveillance in action. Lancet Infect Dis 2013; 19 December.
• De la Herrán-Arita AK og kolleger. CD4+ T cell autoimmunity to hypocretin/orexin and cross-reactivity to a 2009 H1N1 influenza A epitope in narcolepsy. Science Transl Med 2013; 5: 216ra176. [FORFATTERNE HAR TRUKKET TILBAKE DENNE ARTIKKELEN]
• Sarah C Gilbert. Influenza vaccines and immunopathology. Expert Rev Vaccines 2012; 11: 873–5.

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