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    The risk of Guillain-Barré syndrome after influenza vaccination

    Guillain-Barré syndrome (GBS) is an immune-mediated flaccid paralysis that can range from muscle weakness and tingling to respiratory paralysis requiring prolonged respiratory support and ventilation.  Overall, GBS is a rare disease, with annual incidence averaging 1 to 2 cases per 100,000 individuals.1

    Origins

    The cause of this autoimmune disease is thought to be the result of molecular mimicry between gangliosides (a type of glycolipid found in cell membranes with high concentrations in nervous system tissues) and lipopolysaccharides of bacteria and viruses.1 Essentially, antibodies formed against an antigenic component of a pathogen also have affinity for a component of the host’s cell membrane, such as a glycolipid. 

    Approximately one-third of all GBS cases are preceded by Campylobacter jejuni infections, a common cause of gastrointestinal illness.1 The risk of GBS is estimated to be over 38 times greater for those who have been recently infected by C jejuni and over 18 times greater for those with influenza and influenza-like illnesses.2

    An increased rate of GBS was observed during the 1976 swine flu vaccination campaign, with approximately one additional case of GBS per 100,000 individuals vaccinated above background rates (532 cases in 45 million vaccinees).3

    Studies

    Since 1976, the rate of GBS attributed to influenza vaccination has been approximately one additional case per one million vaccinees. Numerous studies have been conducted over single and multiple influenza seasons and their corresponding vaccines. A thorough review of the topic can be found in a 2012 publication from the Institute of Medicine, which concluded that there was sufficient evidence to reject an association between influenza vaccination and GBS.5

    A recent study by Baxter, et.al. (2013) further supported a lack of association between GBS and several vaccines, including influenza. This study spanned 13 years and included almost 33 million patient-years. The background incidence of GBS was 1.27 per 100,000 individuals, matching typically reported rates. When patients with a preceding gastrointestinal or respiratory illness were controlled for, only 5 cases of GBS were noted in almost 7 million influenza vaccine recipients. Over 8.5 million doses of other vaccines (including oral polio, measles-mumps-rubella, conjugated pneumococcal, live attenuated influenza, diphtheria-tetanus-acellular pertussis, varicella, and Haemophilus B) were administered to children, with no cases of GBS reported following vaccination.6

    Perspective

    This and other recent studies (e.g., Kwong, JC, et.al. 2013)7 have cast a great deal of doubt on the possibility of a causal relationship between influenza vaccination and GBS. Furthermore, the increased risk of GBS following influenza infection lends additional support to use of influenza vaccination to reduce the likelihood of acquiring GBS via immunity to influenza.

    Patients or providers concerned about GBS should keep this rare disease in perspective.  Influenza infects up to 20% of the population and contributes to an average of 36,000 deaths annually, with highest rates of mortality in infants, the elderly, and individuals with chronic diseases.1 With vaccine effectiveness for 2012-2013 estimated at 56%8, it is clear that the reduction in influenza infection and death outweighs an unsupported one-in-a-million theoretical risk from vaccination.

    References

    1. Institute of Medicine. Immunization safety review: influenza vaccines and neurological complications. Washington (DC): National Academy Press; 2004.

    2. 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. doi:10.1371/journal.pone.0000344.

    3. 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.

    4. Nachamkin I, Shadomy SV, Moran AP, et al. Anti-ganglioside antibody induction by swine (A/NJ/1976/H1N1) and other influenza vaccines: Insights into vaccine-associated Guillain-Barre syndrome. J Infect Dis 2008;198:226–233.

    5. Institute of Medicine (U.S.). Adverse effects of vaccines: Evidence and causality. Washington (DC): National Academy Press; 2012.

    6. Baxter R, Bakshi N, Fireman B, et al. Lack of association of Guillain-Barre syndrome with vaccinations. Clin Infect Dis 2013; 57(2):197–204.

    7. Kwong JC, Vasa PP, Campitelli MA, et al. Risk of Guillain-Barre syndrome after seasonal influenza vaccination and influenza health-care encounters: A self-controlled study. Lancet Inf Dis 28 June 2013; DOI: 10.1016/S1473-3099(13)70104-X.

    8. CDC. Interim adjusted estimates of influenza vaccine effectiveness — United States, February 2013. MMWR 2013;62(7):119–123.

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