Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis in developed countries and is characterized by various degrees of weakness, sensory abnormalities and autonomic dysfunction. Although the underlying aetiology and pathophysiology of GBS are not completely understood, it is broadly believed that immune stimulation plays a role in its pathogenesis. Thus, since vaccines have an effect on the immune system it is biologically plausible that immunizations may be associated with subsequent GBS.
The objective of this article is to review the current body of evidence that either supports or does not support a causal, rather than just temporal, association between various vaccines and GBS, and to provide an evidence-based review of this issue. The scope of the article includes published reports that, regardless of method of case ascertainment, appeared in peer-reviewed literature between 1950 and 2008.
Our review indicates that, with rare exceptions, associations between vaccines and GBS have been only temporal. There is little evidence to support a causal association with most vaccines. The evidence for a causal association is strongest for the swine influenza vaccine that was used in 1976–77. Studies of influenza vaccines used in subsequent years, however, have found small or no increased risk of GBS.
Older formulations of rabies vaccine cultured in mammalian brain tissues have been found to have an increased risk of GBS, but newer formulations of rabies vaccine, derived from chick embryo cells, do not appear to be associated with GBS at a greater than expected rate.
In an earlier review, the Institute of Medicine concluded that the evidence favoured a causal association between oral polio vaccine and tetanus toxoid-containing vaccines and GBS. However, recent evidence from large epidemiological studies and mass immunization campaigns in different countries found no correlation between oral polio vaccine or tetanus toxoid-containing vaccines and GBS.
Spontaneous reports to the US Vaccine Adverse Events Reporting System shortly after the introduction of quadrivalent conjugated meningococcal vaccine (MCV4) raised concerns of a possible association with GBS. Comparisons with expected rates of GBS, however, were inconclusive for an increased risk, and lack of controlled epidemiological studies makes it difficult to draw conclusions about a causal association.
For other vaccines, available data are based on isolated case reports or very small clusters temporally related to immunizations, and no conclusion about causality can be drawn.
There are certain circumstances in which immunizing individuals, particularly those with a prior history of GBS, may require caution. However, the benefit of vaccines in preventing disease and decreasing morbidity and mortality, particularly for influenza, needs to be weighed against the potential risk of GBS.
KeywordsInfluenza Influenza Vaccine Oral Polio Vaccine Rabies Vaccine Vaccine Adverse Event Reporting System
The authors would like to thank Claudia Vellozzi, Eric Weintraub and Elaine Miller for help providing useful VAERS data analysis on Meningococcal Polysaccharide Diphtheria Toxoid Conjugates Vaccine reports to VAERS, Barbara Slade and John Iskander for overall comments, Rick Colbert at CDC for his extensive help in searches and allocation of the relevant articles used for this review, and Alena Kromova from Sanofi Pasteur, for translating from French a case report on Haemophilus influenzaeType B Vaccines that is cited in this review. The preparation of this review has been funded by the US government. The authors have no conflicts of interest that are directly relevant to the content of this review.
- 2.Institute of Medicine (IOM). Adverse events associated with childhood vaccines: evidence bearing on causality. Washington, DC: National Academy Press, 1994Google Scholar
- 3.Institute of Medicine (IOM). Immunization safety review. Influenza vaccines and neurological complications. Washington, DC: National Academies Press, 2003Google Scholar
- 4.Zhou W, Pool V, Iskander JK, et al. Surveillance for safety after immunization: Vaccine Adverse Event Reporting System (VAERS) —United States, 1991–2001. MMWR Morb Mortal Wkly Rep 2003; 52(SS-1): 1–24Google Scholar
- 5.Vaccine Adverse Event Reporting System (VAERS) [online]. Available from URL: http://vaers.hhs.gov/ [Accessed 2008 Jun 16]
- 7.Hankey GJ. Guillain-Barré syndrome in Western Australia, 1980–85. Med J Aust 1987; 75: 95–100Google Scholar
- 11.Geleijns K, Laman JD, van Rijs W, et al. Fas polymorphisms are associated the presence of anti-ganglioside antibodies in Guillain-Barré syndrome. J Neuroimmunol 2005 Apr; 161(1–2): 1893–9Google Scholar
- 13.Li H, Yuan J, Hao H, et al. HLA alleles in patients with Guillain-Barré syndrome. Chin Med J (Engl) 2000 May; 113(5): 429–32Google Scholar
- 16.Langmuir AD, Bregman DJ, Kurland LT, et al. An epidemiologic and clinical evaluation of Guillain-Barré syndrome reported in association with the administration of swine influenza vaccine. Am J Epidemiol 1984; 119: 842–79Google Scholar
- 18.Kurland LT, Wiederholt WC, Beghe E, et al. Guillain-Barré syndrome following (A/New Jersey/76) influenza (swine flu) vaccine: epidemic or artifact? Berlin: Springer-Verlag, 1986Google Scholar
- 24.Chen RT, Kent J, Rhodes P, et al. Investigation of a possible association between influenza vaccination and Guillain-Barré syndrome in the United States, 1990–91 [abstract]. Post Markt Surveill 1992; 6: 5–6Google Scholar
- 28.Preliminary FoodNet data on the incidence of infection with pathogens transmitted commonly through food: 10 states, 2007. MMWR Morb Mortal Wkly Rep 2008 Apr; 57 (14): 366–70Google Scholar
- 33.Lopez A, Held JR. Guillain-Barré syndrome associated with immunization against rabies: epidemiological aspects. Res Publ Assoc Res Nerv Ment Dis 1971; 49: 178–86Google Scholar
- 49.Bilukha OO, Rosenstein N. National Center for Infectious Diseases, Centers for Disease Control and Prevention. Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2005; 54(RR-7): 1–21Google Scholar
- 50.Centers for Disease Control and Prevention (CDC). Guillain-Barré syndrome among recipients of Menactra meningococcal conjugate vaccine —United States, June–July 2005. MMWR Morb Mortal Wkly Rep 2005; 54(40): 1023–5Google Scholar
- 51.Centers for Disease Control and Prevention (CDC). Update: Guillain-Barré syndrome among recipients of Menactra meningococcal conjugate vaccine —United States, October 2005–February 2006. MMWR Morb Mortal Wkly Rep 2009; 55(13): 364–6Google Scholar
- 52.Centers for Disease Control and Prevention (CDC). Update: Guillain-Barré syndrome among recipients of Menactra meningococcal conjugate vaccine —United States, June 2005–September 2006. MMWR Morb Mortal Wkly Rep 2006; 55(41): 1120–4Google Scholar
- 53.Health Care Cost & Utilization Project (HCUP) [online]. Available from URL: http://www.ahrq.gov/data/hcup/ [Accessed 2008 Apr 21]
- 60.Recommendations of the Advisory Committee on Immunization Practice (ACIP). Measles, mumps, and rubella vaccine use and strategies for elimination of measles, rubella, and congenital rubella syndrome and control of mumps. MMWR Morb Mortal Wkly Rep 1998; 47(RR-8): 27–30Google Scholar
- 64.Centers for Disease Control and Prevention. The safety of hepatitis B virus vaccine. MMWR Morb Mortal Wkly Rep 1983; 32: 134–6Google Scholar
- 65.Hepatitis B virus: a comprehensive strategy for eliminating transmission in the United States through universal childhood vaccination: recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Morb Mortal Wkly Rep 1991 Nov; 40(RR-13): 1–19Google Scholar
- 70.Prevention of hepatitis A through active or passive immunization: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR Morb Mortal Wkly Rep 1999; 48(RR-12): 1–37Google Scholar
- 72.D’Cruz OF, Shapiro ED, Spiegelman KN, et al. Acute inflammatory demyelinating polyradiculoneuropathy (Guillain-Barré syndrome) after immunization with Haemophilus influenzae type b conjugate vaccine. Am Pediatr 1989; 115: 743–6Google Scholar
- 81.Centers for Disease Control and Prevention. Inactivated Japanese encephalitis virus vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 1993; 42 (RR-01)Google Scholar
- 82.Glanders R. Kasuistischer Beitrag zur Polyradiculoneuritis (Guillain-Barre) im Kleinkindesalter, davon ein Fall nach Pockenschutzimpfung. Arch F Kinderh 1950; 139: 144–54Google Scholar
- 83.Drouet PL, Faivre G, Lamy P, et al. Syndromes de Guillain-Barre apparus après une vaccination antivariolique. Rev Med De Nancy 1956; 81: 22–6Google Scholar
- 86.Centers for Disease Control and Prevention (CDC). Prevention and control of influenza: recommendation of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2006; 55(RR 10): 1–42Google Scholar
- 87.Centers for Disease Control and Prevention. Prevention and control of influenza, recommendations of the Advisory Committee on Immunization Practice (ACIP). MMWR Morb Mortal Wkly Rep 2007; 56(RR06): 1–54Google Scholar
- 91.Brighton Collaboration standardized case definition [online]. Available from URL: http://www.brightoncollaboration.org/internet/en/index.html [Accessed 2008 Apr]