Risk of Guillain-Barre syndrome after seasonal influenza vaccination and influenza health-care encounters: a self-controlled study

Background The possible risk of Guillain-Barre syndrome from influenza vaccines remains a potential obstacle to achieving high vaccination coverage. However, influenza infection might also be associated with Guillain-Barre syndrome. We aimed to assess the risk of Guillain-Barre syndrome after seasonal influenza vaccination and after influenza-coded health-care encounters. Methods We used the self-controlled risk interval design and linked universal health-care system databases from Ontario, Canada, with data obtained between 1993 and 2011. We used physician billing claims for influenza vaccination and influenza-coded health-care encounters to ascertain exposures. Using fixed-effects conditional Poisson regression, we estimated the relative incidence of hospitalisation for primary-coded Guillain-Barre syndrome during the risk interval compared with the control interval. Findings We identified 2831 incident admissions for Guillain-Barre syndrome; 330 received an influenza vaccine and 109 had an influenza-coded health-care encounter within 42 weeks before hospitalisation. The risk of Guillain-Barre syndrome within 6 weeks of vaccination was 52% higher than in the control interval of 9-42 weeks (relative incidence 1.52; 95% CI 1.17-1.99), with the greatest risk during weeks 2-4 after vaccination. The risk of Guillain-Barre syndrome within 6 weeks of an influenza-coded health-care encounter was greater than for vaccination (15.81; 10.28-24.32). The attributable risks were 1.03 Guillain-Barre syndrome admissions per million vaccinations, compared with 17.2 Guillain-Barre syndrome admissions per million influenza-coded health-care encounters. Interpretation The relative and attributable risks of Guillain-Barre syndrome after seasonal influenza vaccination are lower than those after influenza illness. Patients considering immunisation should be fully informed of the risks of Guillain-Barre syndrome from both influenza vaccines and influenza illness.