A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden

N. Feltelius, I. Persson, J. Ahlqvist-Rastad, M. Andersson, L. Arnheim-Dahlström, P. Bergman, F. Granath, C. Ádori, T. Hökfelt, S. Kühlmann-Berenzon, P. Liljeström, M. Maeurer, T. Olsson, Örtqvist, M. Partinen, T. Salmonson, B. Zethelius

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination-related adverse events.

Original languageEnglish
Pages (from-to)335-353
Number of pages19
JournalJournal of Internal Medicine
Volume278
Issue number4
DOIs
Publication statusPublished - Oct 1 2015

Fingerprint

Narcolepsy
Sweden
Vaccination
Incidence
Human Influenza
Research
Mass Vaccination
Patient Advocacy
Molecular Models
Hemagglutinins
Neuraminidase
Genetic Association Studies
Pandemics
Advisory Committees
Streptococcus
Autoimmune Diseases
Interferon-gamma
Epidemiologic Studies
Epitopes
Theoretical Models

Keywords

  • Adverse events
  • Influenza
  • Narcolepsy
  • Sweden
  • Vaccination

ASJC Scopus subject areas

  • Internal Medicine

Cite this

A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden. / Feltelius, N.; Persson, I.; Ahlqvist-Rastad, J.; Andersson, M.; Arnheim-Dahlström, L.; Bergman, P.; Granath, F.; Ádori, C.; Hökfelt, T.; Kühlmann-Berenzon, S.; Liljeström, P.; Maeurer, M.; Olsson, T.; Örtqvist; Partinen, M.; Salmonson, T.; Zethelius, B.

In: Journal of Internal Medicine, Vol. 278, No. 4, 01.10.2015, p. 335-353.

Research output: Contribution to journalArticle

Feltelius, N, Persson, I, Ahlqvist-Rastad, J, Andersson, M, Arnheim-Dahlström, L, Bergman, P, Granath, F, Ádori, C, Hökfelt, T, Kühlmann-Berenzon, S, Liljeström, P, Maeurer, M, Olsson, T, Örtqvist, Partinen, M, Salmonson, T & Zethelius, B 2015, 'A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden', Journal of Internal Medicine, vol. 278, no. 4, pp. 335-353. https://doi.org/10.1111/joim.12391
Feltelius, N. ; Persson, I. ; Ahlqvist-Rastad, J. ; Andersson, M. ; Arnheim-Dahlström, L. ; Bergman, P. ; Granath, F. ; Ádori, C. ; Hökfelt, T. ; Kühlmann-Berenzon, S. ; Liljeström, P. ; Maeurer, M. ; Olsson, T. ; Örtqvist ; Partinen, M. ; Salmonson, T. ; Zethelius, B. / A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden. In: Journal of Internal Medicine. 2015 ; Vol. 278, No. 4. pp. 335-353.
@article{90290302a9a24f489b4d40e2e92bf27e,
title = "A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden",
abstract = "In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination-related adverse events.",
keywords = "Adverse events, Influenza, Narcolepsy, Sweden, Vaccination",
author = "N. Feltelius and I. Persson and J. Ahlqvist-Rastad and M. Andersson and L. Arnheim-Dahlstr{\"o}m and P. Bergman and F. Granath and C. {\'A}dori and T. H{\"o}kfelt and S. K{\"u}hlmann-Berenzon and P. Liljestr{\"o}m and M. Maeurer and T. Olsson and {\"O}rtqvist and M. Partinen and T. Salmonson and B. Zethelius",
year = "2015",
month = "10",
day = "1",
doi = "10.1111/joim.12391",
language = "English",
volume = "278",
pages = "335--353",
journal = "Journal of Internal Medicine",
issn = "0954-6820",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - A coordinated cross-disciplinary research initiative to address an increased incidence of narcolepsy following the 2009-2010 Pandemrix vaccination programme in Sweden

AU - Feltelius, N.

AU - Persson, I.

AU - Ahlqvist-Rastad, J.

AU - Andersson, M.

AU - Arnheim-Dahlström, L.

AU - Bergman, P.

AU - Granath, F.

AU - Ádori, C.

AU - Hökfelt, T.

AU - Kühlmann-Berenzon, S.

AU - Liljeström, P.

AU - Maeurer, M.

AU - Olsson, T.

AU - Örtqvist,

AU - Partinen, M.

AU - Salmonson, T.

AU - Zethelius, B.

PY - 2015/10/1

Y1 - 2015/10/1

N2 - In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination-related adverse events.

AB - In response to the 2009-2010 influenza A(H1N1)pdm09 pandemic, a mass vaccination programme with the AS03-adjuvanted influenza A(H1N1) vaccine Pandemrix was initiated in Sweden. Unexpectedly, there were a number of narcolepsy cases amongst vaccinated children and adolescents reported. In this review, we summarize the results of a joint cross-disciplinary national research effort to investigate the adverse reaction signal from the spontaneous reporting system and to better understand possible causative mechanisms. A three- to fourfold increased risk of narcolepsy in vaccinated children and adolescents was verified by epidemiological studies. Of importance, no risk increase was observed for the other neurological and autoimmune diseases studied. Genetic studies confirmed the association with the allele HLA-DQB1*06:02, which is known to be related to sporadic narcolepsy. Furthermore, a number of studies using cellular and molecular experimental models investigated possible links between influenza vaccination and narcolepsy. Serum analysis, using a peptide microarray platform, showed that individuals who received Pandemrix exhibited a different epitope reactivity pattern to neuraminidase and haemagglutinin, as compared to individuals who were infected with H1N1. Patients with narcolepsy were also found to have increased levels of interferon-gamma production in response to streptococcus-associated antigens. The chain of patient-related events and the study results emerging over time were subjected to intense nationwide media attention. The importance of transparent communication and collaboration with patient representatives to maintain public trust in vaccination programmes is also discussed in the review. Organizational challenges due to this unexpected event delayed the initiation of some of the research projects, still the main objectives of this joint, cross-disciplinary research effort were reached, and important insights were acquired for future, similar situations in which a fast and effective task force may be required to evaluate vaccination-related adverse events.

KW - Adverse events

KW - Influenza

KW - Narcolepsy

KW - Sweden

KW - Vaccination

UR - http://www.scopus.com/inward/record.url?scp=84941025668&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84941025668&partnerID=8YFLogxK

U2 - 10.1111/joim.12391

DO - 10.1111/joim.12391

M3 - Article

C2 - 26123389

AN - SCOPUS:84941025668

VL - 278

SP - 335

EP - 353

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 0954-6820

IS - 4

ER -