Clinical features and outcomes of pediatric breakthrough invasive pneumococcal disease (IPD) in vaccinated children in Calgary, Alberta, Canada, 2003–2024

Background Since the introduction of pneumococcal conjugate vaccines (PCV7 in 2002 and PCV13 in 2010) in Alberta, the overall burden of invasive pneumococcal disease (IPD) in children has declined. However, vaccine-type invasive pneumococcal disease (VT-IPD) continues to occur, including in vaccinated children. Methods The Calgary Area Streptococcus pneumoniae Epidemiology Research (CASPER) study is a prospective, population-based surveillance program capturing all IPD cases in the Calgary area. We compared clinical features and outcomes of 227 vaccinated children (<18 years, ≥2 PCV doses) with IPD between 2003 and 2024. Among these, 44 (19.4%) had breakthrough infection and 183 (80.6%) had non-vaccine-type IPD (NVT-IPD). Results In multivariable analysis, pneumonia/empyema (OR: 5.9, 95% CI: 2.3–14.6) and IPD between 2018 and 2024 (OR: 4.0, 95% CI: 1.2–13.5) were associated with breakthrough infections, whereas comorbidities were not. Serotypes 3 (included in PCV13) and 19F (included in PCV7 and PCV13) accounted for most breakthrough infections. During the late PCV13 era, over 25% of IPD cases were breakthrough infections. Immunologic evaluation of a subset of children with breakthrough disease was largely unremarkable. Conclusions Although PCVs remain highly effective overall, serotypes 3 and 19F continue to account for a disproportionate number of breakthrough IPD infections. Breakthrough disease became more common during the later PCV13 era and was associated with pneumonia/empyema but not underlying comorbidities, suggesting serotype specific factors may play a greater role than host susceptibility. Continued surveillance is needed to monitor breakthrough disease and the impact of evolving pneumococcal vaccine programs.