Guillain-Barré Syndrome and Vaccinations

Questions have been raised about Guillain-Barré syndrome (GBS) after vaccinations since the 1976 Swine flu vaccine was associated with a 7to 8-fold increased risk for GBS in the 6 weeks after vaccination, resulting in about 1 excess case of GBS per 100 000 vaccinees. There is evidence to support several possible biological mechanisms for the development of GBS, but no one has been able to determine the mechanism responsible for the association with the 1976 Swine influenza vaccine [1, 2]. The only other vaccine that has been associated with an increased risk of GBS is the mouse brain– produced rabies vaccine [3]. Several infections, including Campylobacter jejuni [4, 5], cytomegalovirus [6], and influenzalike illnesses [7–9], have been associated with an increased risk of GBS. Influenza vaccines since 1976 have not been associated with the level of risk seen in 1976; however, it is not clear if post1976 influenza vaccines had any increased risk of GBS. Most epidemiologic studies since 1976 found no associations between GBS and influenza vaccines, and some studies found a statistically significant but very small risk of about 1 excess case of GBS per million vaccinated persons. In 2011, the Institute of Medicine (IOM) reviewed data through the 2008–2009 influenza seasons and concluded that “the evidence is inadequate to accept or reject a causal relationship between influenza vaccine and GBS” [10]. The IOM report further stated that “[w]hile the weight of epidemiological evidence does not support a causal link between influenza vaccinations evaluated over the last 30 years, an association cannot be confidently ruled out, particularly for future vaccine strains” [10]. The 2009–2010 H1N1 vaccine program included the most comprehensive safety monitoring program for any vaccine ever used, including 6 active surveillance systemsmonitoring for GBS among about 23 million persons in the United States [11]. An increased risk for GBS was seen in each of these 6 surveillance systems in the 6 weeks after vaccination; however, some systems and not others had results that were statistically significant. A metaanalysis of GBS cases across these 6 systems found a significantly increased risk of about 2.35, translating into about 1–2 excess cases per million persons vaccinated. This risk ratio was consistent across age groups, although the attributable risk was higher among persons >65 years of age because of a higher background of GBS in this age group. Risk did not vary among persons who did or did not receive seasonal influenza vaccine or reported influenza-like symptoms. A multinational European case-control study of 2009 H1N1 vaccine found an increased risk of GBS after adjuvanted vaccines in an unadjusted analysis; however, the risk no longer existed after adjusting for influenza-like illness or upper respiratory tract infection and seasonal influenza vaccination [12]. There have been case reports of GBS after other vaccinations [13], but the IOM concluded in 2011 that there was inadequate evidence to draw conclusions for measles, mumps, rubella, varicella, hepatitis A or B, human papillomavirus, and diphtheria toxoid, tetanus toxoid, or acellular pertussis–containing vaccines [10]. Concerns were raised when 17 suspected cases of GBS were reported to the Vaccine Adverse Event Reporting System, a passive reporting system, within 6 weeks of a meningococcal vaccine (Menactra) among adolescents 11–19 years of age; however, an epidemiologic study including 18 million person-years and 1.4 million Menactra vaccines identified no cases within 6 weeks of vaccination, excluding a risk of ≥1.5 cases per million vaccines [14]. In this issue of Clinical Infectious Diseases, Baxter and colleagues [15] examined the risk of GBS after administration Received 25 March 2012; accepted 31 March 2013; electronically published 11 April 2013. Correspondence: Neal A. Halsey, MD, Institute for Vaccine Safety, Johns Hopkins Bloomberg School of Public Health, 615 N Wolfe St, Rm W5041, Baltimore, MD 21205 (nhalsey@ jhsph.edu). Clinical Infectious Diseases 2013;57(2):205–7 © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/cit218