No association found between pandemic influenza vaccination and Guillain-Barre Syndrome in EuropeArchived
Due to an association that was observed in the United States between a swine-flu based human influenza vaccine developed in 1976 and the disease acute polyneuropathy Guillain-Barré syndrome (GBS) (1,2), GBS was one of the adverse events that was monitored in Europe and North America (3) following the 2009 influenza pandemic vaccination campaigns.
Dieleman J, Romio, S, Johansen K, Weibel D, Bonhoeffer J, Sturkenboom M.
Due to an association that was observed in the United States between a swine-flu based human influenza vaccine developed in 1976 and the disease acute polyneuropathy Guillain-Barré syndrome (GBS) (1,2), GBS was one of the adverse events that was monitored in Europe and North America (3) following the 2009 influenza pandemic vaccination campaigns. A scientific investigation has been conducted by ECDC and VAESCO (coordinated by the Brighton Collaboration, Switzerland and data analysis performed by the Erasmus University, The Netherlands), comprising Public Health authorities and academic research groups in five European countries (Denmark, France, the Netherlands, Sweden and the UK) is described here. Cases of GBS (and its variant Miller-Fisher syndrome) were identified through medical electronic databases or neurologist networks in respective countries and a common study protocol for the case-control study was used. For confirmation of cases, a case definition developed by the Brighton Collaboration was used.(4)
Based on a source population of around 50 million individuals, the investigators identified 104 validated GBS cases, which could be matched to one or more controls with a date of first symptoms between November 2009 and the end of March 2010. Each case was matched with up to 25 controls and for age, sex, date of onset and country. Data were collected for a series of potential risk factors, including influenza like illness and other respiratory symptoms, gastrointestinal infection and previous GBS, all described to be associated with a new onset of GBS. Most cases were men aged 46-61 years and were classified according to the Brighton case classification level 1 to 3. Acute infections in the six weeks leading up to the index date were more common in cases than in controls, most commonly influenza-like illness and upper respiratory tract infections.
Exposure to pandemic influenza vaccination was confirmed by primary care records in a period from one day to six weeks before the date of onset of symptoms. Various different vaccines were used, but predominantly adjuvanted vaccines in line with those included in the national pandemic vaccination campaigns.
An unadjusted pooled risk estimate was statistically significant at an odds ratio of 2.8 (95% confidence interval of 1.3 to 6.0). However after controlling for risk factors such as influenza-like illness and upper respiratry tract infections, as well as seasonal influenza vaccination, no increased risk was observed and the odds ratio declined to 1.0 (0.3 to 2.7).
ECDC Comment (July 13th 2011)
ECDC and its collaborators have already estimated background GBS incidence rates to be used in observed versus expected analyses in the safety monitoring of the 2009 pandemic vaccination campaigns. Other adverse events included in the monitoring were anaphylaxsis, convulsions and idiopathic thrombocytopaenic purpura (ITP).
The findings of the current European study are welcome and not unexpected. An earlier study in the UK found no association of the pre-pandemic seasonal vaccine and GBS; in fact the vaccine was almost protective against GBS.(4,5) Another previous study by the American CDC found the same lack of any statistical association for the non-adjuvanted pandemic vaccines used in the United States with GBS. (3) That the study was undertaken even more expeditiously in the United States is to be expected given their prior experience from 1976, where one additional case of GBS occurred for every 105 swine-origin influenza vaccinations.(1,2) GBS was considered to be a possible adverse event based on previous experience with swine-flu containing influenza vaccines. For this reason, Europe and the United States prepared to look for it.
ECDC and its collaborators (the European Medicines Agency (EMA), VAESCO and national authorities) are also investigating a possible association between one of the adjuvanted 2009 pandemic vaccines and narcolepsy-cataplexy in children and adolescents.(5,8) These investigations will take more time because of the lack of basic epidemiological data, however they will certainly be tackled with the same independence and scientific rigour as for GBS.(7)
- Schonberger LB, Bregman DJ, Sullivan-Bolyai JZ, Keenlyside RA, Ziegler DW, Retailliau HF, et al. Guillain-Barré syndrome following vaccination in the National Influenza Immunization Program, United States, 1976-1977. Am J Epidemiol 1979;110:105-23.
- Neustadt RE, Fineberg HV. The swine flu affair: decision making on a slippery disease. Washington: US Department of Health, Education and Welfare 1978.
- Centers for Disease Control and Prevention. Preliminary results: surveillance for Guillain-Barré syndrome after receipt of influenza A (H1N1) 2009 monovalent vaccine—United States, 2009-2010. MMWR Morb Mortal Wkly Rep 2010;59:657-61.
- Sejvar JJ, Kohl KS, Gidudu J, Amato A, Bakshi N, Baxter R, Burwen DR, Cornblath DR, Cleerbout J, Edwards KM, Heininger U, Hughes R, Khuri-Bulos N, Korinthenberg R, Law BJ, Munro U, Maltezou HC, Nell P, Oleske J, Sparks R, Velentgas P, Vermeer P, Wiznitzer M; Brighton Collaboration GBS Working Group Guillain-Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011 Jan 10;29(3):599-612.
- Destefano F, Vellozzi C, Schonberger LB, Chen RT. Safety of adjuvanted influenza A (H1N1) 2009 vaccines. BMJ 2011.
- Stowe J, Andrews N, Wise L, Miller E. Investigation of the temporal association of Guillain-Barré syndrome with influenza vaccine and influenza-like illness using the United Kingdom General Practice Research Database. Am J Epidemiol 2009;169:382-8.
- Dieleman J, Romio, S, Johansen K, Weibel D, Bonhoeffer J, Sturkenboom M. Guillain-Barre syndrome and adjuvanted pandemic influenza A(H1N1) 2009 vaccine: multinational case-control study in Europe BMJ 2011.
- ECDC Reports of cases of narcolepsy and cataplexy in children and adolescents in Finland, Iceland, and Sweden ECDC 02 Mar 2011