JAMA   
July 11, 2012, Vol 308, No. 2
http://jama.ama-assn.org/current.dtl

Original Contribution | July 11, 2012
Risk of Guillain-Barré Syndrome Following H1N1 Influenza Vaccination in Quebec
Philippe De Wals, PhD; Geneviève Deceuninck, MD; Eveline Toth, MSc; Nicole Boulianne, MSc; Denis Brunet, MD; Renée-Myriam Boucher, MD; Monique Landry, MD; Gaston De Serres, PhD

Abstract
Context  In fall 2009 in Quebec, Canada, an immunization campaign was launched against the 2009 influenza A(H1N1) pandemic strain, mostly using an AS03 adjuvant vaccine. By the end of the year, 57% of the 7.8 million residents had been vaccinated.

Objective  To assess the risk of Guillain-Barré syndrome (GBS) following pandemic influenza vaccine administration.

Design  Population-based cohort study with follow-up over the 6-month period October 2009 through March 2010. The investigation was ordered by the chief medical officer of health in accordance with the Quebec Public Health Act.

Setting  All acute care hospitals and neurology clinics in Quebec.

Population  Suspected and confirmed GBS cases reported by physicians, mostly neurologists, during active surveillance or identified in the provincial hospital summary discharge database. Medical records were reviewed and cases classified according to Brighton Collaboration definitions (categorized as level 1, 2, or 3, corresponding to criteria of decreasing certainty in diagnosis). Immunization status was verified and denominators were estimated from the provincial immunization registry (4.4 million vaccinated) and census data (total target population aged ≥6 months, 7.8 million), with a total of 3 623 046 person-years of observation.

Main Outcome Measures  Relative and attributable risks were calculated using a Poisson model and the self-controlled case-series method.

Results  Over a 6-month period, 83 confirmed GBS cases were identified, including 71 Brighton level 1 through 3 cases. Twenty-five confirmed cases had been vaccinated against 2009 influenza A(H1N1) 8 or fewer weeks before disease onset, with most (19/25) vaccinated 4 or fewer weeks before onset. In the Poisson model, the age- and sex-adjusted relative risk was 1.80 (95% CI, 1.12-2.87) for all confirmed cases during the 8-week postvaccination period and was 2.75 (95% CI, 1.63-4.62) during the 4-week postvaccination period. Using the self-controlled case-series method, relative risk estimates during the 4-week postvaccination period were 3.02 (95% CI, 1.64-5.56) for all confirmed cases (n = 42) and 2.33 (95% CI, 1.19-4.57) for Brighton level 1 through 3 cases (n = 36). The number of GBS cases attributable to vaccination was approximately 2 per 1 million doses. There was no indication of an excess risk in persons younger than 50 years.

Conclusions  In Quebec, the 2009 influenza A(H1N1) vaccine was associated with a small but significant risk of GBS. It is likely that the benefits of immunization outweigh the risks.

Guillain-Barré syndrome (GBS) is a peripheral neuropathy with acute onset and is characterized, in its typical presentation, by rapidly developing motor weakness and areflexia.1 – 2 The disease is thought to be autoimmune and triggered by a stimulus of external origin.1 – 2 In 1976-1977, an unusually high rate of GBS was identified in the United States following the administration of inactivated “swine” influenza A(H1N1) vaccines.3 In 2003, the Institute of Medicine (IOM) concluded that the evidence favored acceptance of a causal relationship between the 1976 swine influenza vaccines and GBS in adults.4 Studies of seasonal influenza vaccines administered in subsequent years have found small or no increased risk.5 In mice, different influenza vaccines can induce antiganglioside antibodies that are associated with the development of GBS in humans.6 Extrapolation of results of animal studies to humans, however, is difficult. In a more recent assessment of epidemiologic studies on seasonal influenza vaccines, experimental studies in animals, and case reports in humans, the IOM Committee to Review Adverse Effects of Vaccines concluded that the evidence was inadequate to accept or reject a causal relationship.7

In the province of Quebec, Canada, a mass immunization campaign was launched in the fall of 2009 to control a pandemic caused by a new influenza A(H1N1) virus.8 – 9 Herein we report results of a population-based epidemiologic investigation ordered by the chief medical officer of health, based on GBS cases notified to public health authorities and others found in the MEDECHO provincial hospitalization database.