Impact of 13-valent pneumococcal conjugate vaccination in invasive pneumococcal disease incidence and mortality.

BACKGROUND The impact of the 13-valent pneumococcal conjugate vaccine (PCV13) at the population level is unclear. We explored PCV13's effect in reducing invasive pneumococcal disease (IPD)-related morbidity and mortality, and whether serotype-specific changes were attributable to vaccination or expected as a part of natural, cyclical variations. METHODS This was a Danish nationwide population-based cohort study based on the linkage of laboratory surveillance data and the Danish Civil Registration System. Changes in IPD incidence and mortality during baseline (2000-2007), 7-valent pneumococcal conjugate vaccine (PCV7) (2008-2010), and PCV13 (2011-2013) periods were estimated. Predicted incidences of serotypes were estimated controlling for cyclical trends from historical patterns observed during the past 20 years. RESULTS We observed a 21% reduction (95% confidence interval [CI], 17%-25%) in IPD incidence in the total population after PCV13's introduction, and a 71% reduction (95% CI, 62%-79%) in children aged <2 years, considered as the vaccine effectiveness. We estimated a 28% reduction (95% CI, 18%-37%) in IPD-related 30-day mortality, from 3.4 deaths (95% CI, 3.2-3.6) per 100 000 population in the pre-PCV period to 2.4 (95% CI, 2.2-2.7) in the PCV13 period. The decline in mortality was observed across all age groups but was mainly related to mortality reductions in the nonvaccinated population. For serotypes 1 and 3, there were no significant changes in incidence beyond what would be expected from natural cyclical patterns. Serotype 19A significantly increased following PCV7's introduction, but the incidence declined toward baseline in 2012. CONCLUSIONS PCV13 has brought greater benefits than we had expected in our setting. We observed a further decline on IPD incidence shortly after the shift from PCV7 to PCV13 in the national immunization program. This decline was accompanied by a substantial population-level decline in pneumococcal-related mortality of nearly 30% among nonvaccinated persons.