Influenza vaccine and Guillain Barrè syndrome

The hypothesis

The hypothesis that influenza vaccination may be associated with Guillain Barrè Syndrome emerged for the first time between 1976 and 1977 in the USA1-6. In the 6-8 weeks after the anti-influenza vaccination campaign against an A(H1N1) strain, a statistically significant increase in cases of Guillain Barrè Syndrome (GBS) in vaccinated adults compared to unvaccinated adults was reported in New Jersey 1,7. Subsequent studies showed an increase in the incidence of GBS in the first two weeks after vaccination; the data, however, were not sufficiently uniform to confirm the diagnosis and a number of events besides vaccination could be associated with GBS, including other viral infections, immune deficiencies and Campylobacter jejuni infections, as such a clear causal relationship could not be established 8-15.

Scientific elements that refute a causal relationship between the influenza vaccine and Guillain Barrè syndrome

Following the observation of this increase in cases, numerous studies were carried out over the years to confirm or refute this association. A 2003 review by the Institute of Medicine concluded that the available evidence was in favour of a causal link between the vaccine used in 1976-77 and Guillain Barré syndrome in adults 16.

However, this relationship was called into question in the subsequent flu seasons during which no association was found.

Another study was conducted in the United States to evaluate reports of post-vaccination GBS from 1990 to 2009 and to provide further information on the characteristics and temporal profile of these trends 17. The study analysed the data collected by the adverse event reporting system VAERS (Vaccine Adverse Event Reporting System), coordinated by the Center for Disease Control (CDC) in Atlanta. The risk-benefit analysis was in favour of influenza vaccination, even though the data suggest a possible trigger effect of the vaccine on the onset of some cases of GBS 17.

In 2012, following the review of 21 studies, the Institute of Medicine concluded that the available epidemiological evidence points to the absence of a causal relationship between vaccination and event, but that, however, such evidence is insufficient to unconditionally accept or reject an association, and as such a link cannot be categorically excluded 18.

A second study carried out in Canada showed a modest association between the influenza A (H1N1) vaccination carried out in 2009 and the onset of Guillain Barré syndrome 19. The analysis considered all cases of Guillain Barré syndrome within the flu season and showed that the four childhood cases reported during surveillance of children between the ages of 6 months and 9 years occurred in children who had not been vaccinated or had received the vaccine more than 8 weeks after the onset of the disease 19.

Also in 2009, an Australian study showed that there is no statistically significant difference in the increased risk of GBS following vaccination with the A/H1N1 vaccine. However, the authors state that it is not possible to exclude a small increase in relative incidence, as has also been suggested by other research conducted on larger populations with a high vaccination coverage 20.


From the set of available studies, it seems clear that the association between the anti-influenza vaccine and Guillain Barré syndrome in the season between 1976-77 was substantial but that in successive seasons, this risk was not demonstrated. Furthermore, with the vaccines currently on the market, a possible risk could perhaps result in the observation of an of additional disease case for every million doses administered, limited to people over 50 years of age 21.

It is important to note that GBS commonly follows a gastrointestinal infection or an acute respiratory infection including influenza 22-23, thus flu vaccination may effectively reduce the overall risk of GBS by preventing influenza. Therefore, in light of the available evidence, annual immunisation with the flu vaccine is an important public health practice that must be continued and encouraged in order to prevent morbidity and mortality from this serious disease 24.

Sources / Bibliography
  1. Schonberger LB, Bregman DJ, Sullivan-Bolyai JZ, et al. Guillain-Barre syndrome following vaccination in the National Influenza Immunization Program, United States, 1976–1977. Am J Epidemiol. 1979; 110:105–123
  2. Breman JG, Hayner NS. Guillain-Barre syndrome and its relationship to swine influenza vaccination in Michigan, 1976-1977. Am J Epidemiol. 1984;119: 880–889
  3. Marks JS, Halpin TJ. Guillain-Barre syndrome in recipients of A/New Jersey influenza vaccine. JAMA. 1980;243:2490–2494
  4. Safranek TJ, Lawrence DN, Kurland LT, et al. Reassessment of the association between Guillain- Barre syndrome and receipt of swine influenza vaccine in 1976-1977: results of a two-state study. Expert Neurology Group. Am J Epidemiol. 1991;133:940–951
  5. Langmuir AD, Bregman DJ, Kurland LT, et al. An epidemiologic and clinical evaluation of Guillain- Barre syndrome reported in association with the administration of swine influenza vaccines. Am J Epidemiol. 1984;119:841–879
  6. Langmuir AD. Guillain-Barre syndrome: the swine influenza virus vaccine incident in the United States of America, 1976-77: preliminary communication. J R Soc Med. 1979;72:660–669
  7. Langmuir AD, Bregman DJ, Kurland LT, Nathanson N, Victor M. An epidemiologic and clinical evaluation of Guillain-Barre´ syndrome reported in association with the administration of swine influenza vaccines Am J Epidemiol. 1984;119:841-879
  8. Lasky T, Terracciano GJ, Magder L, et al. The Guillain-Barre syndrome and the 1992-1993 and 1993-1994 influenza vaccines. N Engl J Med. 1998; 339:1797–1802
  9. Hurwitz ES, Schonberger LB, Nelson DB, et al. Guillain-Barre syndrome and the 1978-1979 influenza vaccine. N Engl J Med. 1981;304:1557–1561
  10. Schonberger LB, Hurwitz ES, Katona P, et al. Guillain- Barre syndrome: its epidemiology and associations with influenza vaccination. Ann Neurol. 1981; 9(Suppl):31–38
  11. Kaplan JE, Katona P, Hurwitz ES, et al. Guillain-Barre syndrome in the United States, 1979-1980 and 1980- 1981. Lack of an association with influenza vaccination. JAMA. 1982;248:698–700
  12. Roscelli JD, Bass JW, Pang L. Guillain-Barre syndrome and influenza vaccination in the US Army,1980-1988. Am J Epidemiol. 1991;133:952–955
  13. Juurlink DN, Stukel TA, Kwong J, et al. Guillain-Barre syndrome after influenza vaccination in adults: a population-based study. Arch Intern Med. 2006; 166:2217–2221.
  14. Haber P, DeStefano F, Angulo FJ, et al. Guillain-Barre syndrome following influenza vaccination. JAMA. 2004;292:2478–2481.
  15. Geier MR, Geier DA, Zahalsky AC. Influenza vaccination and Guillain Barre syndrome small star, filled. Clin Immunol. 2003;107:116–121.
  16. Institute of Medicine. Immunization Safety Review: Influenza Vaccines and Neurological Complications. Washington, DC: National Academies Press; 2003.
  17. Souayah N, Yacoub HA, Khan HM, Farhad K, Mehyar LS, Maybodi L, Menkes DL, Qureshi AI. Guillain-Barré syndrome after influenza vaccination in the United States, a report from the CDC/FDA vaccine adverse event reporting system (1990-2009). J Clin Neuromuscul Dis. 2012 Dec;14(2):66-71
  18. Stratton K, Ford A, Rusch E, Wright Clayton E, eds; Institute of Medicine Committee to Review Adverse Effects of Vaccines. Adverse Effects of Vaccines: Evidence and Causality. Washington, DC: National Academies Press; 2012. Disponibile su:
  19. De Wals P, Deceuninck G, Toth E, Boulianne N, Brunet D, Boucher RM, Landry M, De Serres G. Risk of Guillain-Barré syndrome following H1N1 influenza vaccination in Quebec. JAMA. 2012 Jul 11;308(2):175-81.
  20. Crawford NW, Cheng A, Andrews N, Charles PG, Clothier HJ, Day B, Day T, Gates P, Macdonnell R, Roberts L, Rodriguez-Casero V, Wijeratne T, Kiers L. Guillain-Barré syndrome following pandemic (H1N1) 2009 influenza A immunisation in Victoria: a self-controlled case series. Med J Aust. 2012 Nov 19;197(10):574-8.
  21. Nelson KE. Invited commentary: Influenza vaccine and Guillain-Barre syndrome--is there a risk? Am J Epidemiol. 2012 Jun 1;175(11):1129-32.
  22. Lehmann HC, Hartung HP, Kieseier BC, et al. Guillain-Barre´ syndrome after exposure to influenza virus. Lancet Infect Dis. 2010;10(9):643–653
  23. Tam CC, O’Brien SJ, Petersen I, et al. Guillain-Barre´ syndrome and preceding infection with Campylobacter, influenza and Epstein-Barr virus in the General Practice Research Database. PLoS One. 2007;2(4):e344.
  24. Osterholm MT, Kelley NS, Sommer A, et al. Efficacy and effectiveness of influenza vaccines: a systematic review and meta-analysis. Lancet Infect Dis. 2012;12(1):36–44.
Was this content useful? Thanks for giving an opinion for this content.
Share this page: