Do recommended high-risk adults benefit from a first influenza vaccination?

It is unknown whether a first influenza vaccination protects high-risk adults from severe morbidity and mortality during influenza epidemics. As part of the PRISMA nested case–control study, we aimed to evaluate the effectiveness of first-time and repeat influenza vaccinations in adult persons recommended for vaccination aged between 18 and 64 years during the 1999–2000 influenza A epidemic. After adjustments, 69% of hospitalizations for acute respiratory or cardiovascular disease or death were prevented in first-time vaccinees (95% percent confidence interval [95% CI]: 8–90%). The corresponding figure in persons who were vaccinated before was 85% (95% CI: 36–96%). Adult persons with high-risk medical conditions can substantially benefit from a first and repeat influenza vaccination prior to an epidemic.