Encephalitis after influenza and vaccination: a nationwide population-based registry study from Norway

Background: Influenza is known to be associated with various neurological complications, including encephalitis. We conducted a registry-based study to assess the risk of encephalitis after influenza and A(H1N1)pdm09 vaccine. Methods: Data from Norwegian national health registries during 2008-14 were linked using the unique personal identifiers given to all Norwegian residents (N = 5 210 519). Cox proportional-hazard models with time-varying variables were fitted to estimate hazard ratios (HRs) of encephalitis after influenza and A(H1N1)pdm09 vaccine, using the risk windows 0-7, 0-14, 0-30, 0-60, 0-90 and 0-180 days. Results: In Norway, 684 172 individuals received an influenza diagnosis and 2793 patients were hospitalized with encephalitis during 2008-14. The risk of encephalitis increased after influenza: HR, 7-day risk window: 47.8 (95% confidence interval (CI): 35.8-63.8), and the HR decreased for longer risk windows; HR, 180-day risk window: 3.8 (95% CI: 3.1-4.7). HR of encephalitis after influenza during the 2009 main pandemic wave using a 7-day risk window was 30.0 (95% CI: 10.8-83.2). We found no differences in the risk of encephalitis after the seasonal influenza compared with influenza during the 2009 main pandemic wave; HR, 7-day risk window: 1.3 (95% CI: 0.4-4.3). A(H1N1)pdm09 vaccine was not associated with the risk of encephalitis: HR, 14-day risk window: 0.6 (95% CI: 0.2-2.1). Conclusions: There was an increased risk of encephalitis following influenza but not after A(H1N1)pdm09 vaccine. The risk of encephalitis was highest in the first few weeks after influenza.