Guillain–Barré syndrome following influenza vaccination: A 15-year nationwide population-based case–control study

Abstract

Background and purpose: Influenza vaccination may increase the risk of developing Guillain–Barré syndrome (GBS) due to an elicited immune response, but the exact magnitude and duration of risk is unclear and hence the aim of this study. Methods: We conducted a retrospective nationwide population-based case–control study of prospectively collected data on all patients with first-time hospital-diagnosed GBS in Denmark between 2002 and 2016 and 10 age-, sex- and index date-matched population controls per case. The primary exposure was incident influenza vaccination 1 month prior to admission with GBS. We used medical registries to ascertain a complete hospital contact history of pre-existing morbidities. To examine duration of GBS risk, we repeated the analysis for five consecutive 1-month risk periods following vaccination. Results: Of the 1295 GBS cases and 12,814 controls, 20 cases (1.5%) and 119 controls (0.9%) had received an influenza vaccination within the last month, yielding a comorbidity-adjusted odds ratio of 1.9 (95% confidence interval 1.1–3.2) for GBS. Stratified analyses by calendar time, gender and age showed similar results. The increased risk of GBS was largely confined to 1 month following influenza vaccination. The population-attributable fraction of GBS from influenza vaccination in Denmark was 0.4%. Conclusions: Influenza vaccination was associated with a slightly elevated risk of GBS occurrence within 1 month after vaccination. However, only 1.5% of GBS cases in Denmark are associated with recent influenza vaccination. Thus, the benefit of influenza vaccines in preventing influenza infections and associated morbidity and mortality needs to be weighed against the small absolute risk of GBS.