tetano
Editor, Senior Moderator
The incidence of narcolepsy in Europe: Before, during, and after the influenza A(H1N1)pdm09 pandemic and vaccination campaigns
Leonoor Wijnansa, b,
Coralie Lecomtea,
Corinne de Vriesc,
Daniel Weibela, d, Corresponding author contact information, E-mail the corresponding author,
Cormac Sammonc,
Anders Hviide,
Henrik Svanstr?me,
Ditte M?lgaard-Nielsene,
Harald Heijbelf,
Lisen Arnheim Dahlstr?mg,
Jonas Hallgreng,
Par Spareng,
Poul Jennumh,
Mees Mossevelda,
Martijn Schuemiea,
Nicoline van der Maasi,
Markku Partinenj,
Silvana Romioa,
Francesco Trottak,
Carmela Santucciok,
Angelo Mennal,
Giuseppe Plazzim,
Keivan Kaveh Moghadamm,
Salvatore Ferron,
Gert Jan Lammerso,
Sebastiaan Overeemp,
Kari Johansenq,
Piotr Kramarzq,
Jan Bonhoefferd, r, E-mail the corresponding author,
Miriam C.J.M. Sturkenbooma
a Erasmus University Medical Center, Rotterdam, The Netherlands
b Medicines Evaluation Board, The Netherlands
c University of Bath, Bath, United Kingdom
d Brighton Collaboration Foundation, Basel, Switzerland
e Statens Serum Institut, Copenhagen, Denmark
f Swedish Institute for Infectious Disease Control, Lund, Sweden
g The Karolinska Institute, Stockholm, Sweden
h Danish Center for Sleep Medicine, Copenhagen, Denmark
i National Institute of Public Health, Bilthoven, The Netherlands
j Helsingin Uniklinikka, Helsinki, Finland
k Italian Medicines Agency, Rome, Italy
l Regional Health Authority, Tuscany, Italy
m Department of Neurological Sciences, University of Bologna, Bologna, Italy
n Regional Health Authority, Emilia Romagna, Italy
o Leiden University Medical Center, Leiden, The Netherlands
p Department of Neurology, Donders Institute for Neuroscience, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
q European Centre for Disease Prevention and Control, Stockholm, Sweden
r University Children's Hospital, Basel, Switzerland
http://dx.doi.org/10.1016/j.vaccine.2012.12.015
Background
In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification.
Methods
We used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000?2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom.
Results
Overall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90?0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women > men) and around 60 years of age. In the age group 5?19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1?3.1) in Denmark, 6.4 (95% CI: 4.2?9.7) in Finland and 7.5 (95% CI: 5.2?10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time.
Conclusions
The results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.
Highlights
► We identified 2608 narcolepsy cases in 6 EU countries between 2000 and 2010. ► After pandemic vaccination, incidence rates increased in Finland, Sweden and Denmark. ► In Denmark, the increase did not follow high pandemic vaccination coverage. ► In Italy, the Netherlands and the United Kingdom no increased rates were seen.
http://www.sciencedirect.com/science/article/pii/S0264410X12017823
Leonoor Wijnansa, b,
Coralie Lecomtea,
Corinne de Vriesc,
Daniel Weibela, d, Corresponding author contact information, E-mail the corresponding author,
Cormac Sammonc,
Anders Hviide,
Henrik Svanstr?me,
Ditte M?lgaard-Nielsene,
Harald Heijbelf,
Lisen Arnheim Dahlstr?mg,
Jonas Hallgreng,
Par Spareng,
Poul Jennumh,
Mees Mossevelda,
Martijn Schuemiea,
Nicoline van der Maasi,
Markku Partinenj,
Silvana Romioa,
Francesco Trottak,
Carmela Santucciok,
Angelo Mennal,
Giuseppe Plazzim,
Keivan Kaveh Moghadamm,
Salvatore Ferron,
Gert Jan Lammerso,
Sebastiaan Overeemp,
Kari Johansenq,
Piotr Kramarzq,
Jan Bonhoefferd, r, E-mail the corresponding author,
Miriam C.J.M. Sturkenbooma
a Erasmus University Medical Center, Rotterdam, The Netherlands
b Medicines Evaluation Board, The Netherlands
c University of Bath, Bath, United Kingdom
d Brighton Collaboration Foundation, Basel, Switzerland
e Statens Serum Institut, Copenhagen, Denmark
f Swedish Institute for Infectious Disease Control, Lund, Sweden
g The Karolinska Institute, Stockholm, Sweden
h Danish Center for Sleep Medicine, Copenhagen, Denmark
i National Institute of Public Health, Bilthoven, The Netherlands
j Helsingin Uniklinikka, Helsinki, Finland
k Italian Medicines Agency, Rome, Italy
l Regional Health Authority, Tuscany, Italy
m Department of Neurological Sciences, University of Bologna, Bologna, Italy
n Regional Health Authority, Emilia Romagna, Italy
o Leiden University Medical Center, Leiden, The Netherlands
p Department of Neurology, Donders Institute for Neuroscience, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands
q European Centre for Disease Prevention and Control, Stockholm, Sweden
r University Children's Hospital, Basel, Switzerland
http://dx.doi.org/10.1016/j.vaccine.2012.12.015
Background
In August 2010 reports of a possible association between exposure to AS03 adjuvanted pandemic A(H1N1)pdm09 vaccine and occurrence of narcolepsy in children and adolescents emerged in Sweden and Finland. In response to this signal, the background rates of narcolepsy in Europe were assessed to rapidly provide information for signal verification.
Methods
We used a dynamic retrospective cohort study to assess the narcolepsy diagnosis rates during the period 2000?2010 using large linked automated health care databases in six countries: Denmark, Finland, Italy, the Netherlands, Sweden and the United Kingdom.
Results
Overall, 2608 narcolepsy cases were identified in almost 280 million person years (PY) of follow up. The pooled incidence rate was 0.93 (95% CI: 0. 90?0.97) per 100,000 PY. There were peaks between 15 and 30 year of age (women > men) and around 60 years of age. In the age group 5?19 years olds rates were increased after the start of pandemic vaccination compared to the period before the start of campaigns, with rate ratios (RR) of 1.9 (95% CI: 1.1?3.1) in Denmark, 6.4 (95% CI: 4.2?9.7) in Finland and 7.5 (95% CI: 5.2?10.7) in Sweden. Cases verification in the Netherlands had a significant effect on the pattern of incidence over time.
Conclusions
The results of this incidence study provided useful information for signal verification on a population level. The safety signal of increased narcolepsy diagnoses following the start of the pandemic vaccination campaign as observed in Sweden and Finland could be observed with this approach. An increase in narcolepsy diagnoses was not observed in other countries, where vaccination coverage was low in the affected age group, or did not follow influenza A(H1N1)pdm09 vaccination. Patient level analyses in these countries are being conducted to verify the signal in more detail.
Highlights
► We identified 2608 narcolepsy cases in 6 EU countries between 2000 and 2010. ► After pandemic vaccination, incidence rates increased in Finland, Sweden and Denmark. ► In Denmark, the increase did not follow high pandemic vaccination coverage. ► In Italy, the Netherlands and the United Kingdom no increased rates were seen.
http://www.sciencedirect.com/science/article/pii/S0264410X12017823