Investigate the association between influenza vaccination and the risk of developing encephalitis in the United States.

The Vaccine Adverse Event Reporting System database from 1990-2018 was reviewed. Cases of encephalitis, encephalomyelitis, and encephalopathy were identified, rated by the Brighton criteria, and characterized by their temporal relationship with influenza vaccination. Case-centered analysis using a logistic regression model was utilized. The initial 6 weeks after vaccination were defined as the risk period for possible cause-effect between vaccination and encephalitis.

130 cases of encephalitis (mean age 36.77 years, 60.15% male) following influenza vaccination that had a known onset time and met Brighton criteria were identified. There was an unbalanced distribution of post-vaccination encephalitis cases: 124 patients (95.38%) developed encephalitis within 6 weeks, of which 105 (84.68%) developed encephalitis within 2 weeks. 4 patients (3.08%) developed encephalitis between 6-10 weeks, and 2 (1.54%) developed encephalitis after over 10 weeks post-vaccination. 59 patients (45.38%) visited the emergency room or doctor’s office, 106 (81.54%) were hospitalized, 27 (20.77%) experienced disability, and 15 (11.54%) died. The estimated annual reporting rate of encephalitis after influenza vaccination was 0.5 cases per 10 million vaccinations given, lower than the occurrence of encephalitis in the general population. Case-centered analysis found that there is an increased risk of encephalitis in the 42 days following vaccination (relative risk: 5.682, 95% confidence interval: 4.490-7.298).

This study reveals that there is a higher risk of developing encephalitis within the first 6 weeks following influenza vaccination than outside of this period. Though the incidence of encephalitis post-vaccination is not increased as compared to the general population, the unbalanced distribution of encephalitis within the 6 weeks following influenza vaccination suggests the need for careful monitoring of recently vaccinated patients for encephalitis.