Persistent vaccine-type invasive pneumococcal disease in children despite high PCV13 coverage: the role of serotype 3.
BACKGROUND Despite widespread implementation of pneumococcal conjugate vaccines (PCVs), invasive pneumococcal disease (IPD) caused by vaccine serotypes continues to occur. Evidence on vaccine failure and breakthrough infections in settings with sustained high PCV13 coverage remains limited. METHODS We conducted a retrospective observational study including children aged <18 years with IPD admitted to three paediatric referral hospitals in Catalonia, Spain, from 2018 to 2023, a period of high PCV13 coverage (>96%). Cases meeting the epidemiological definitions of vaccine failure and breakthrough infections due to PCV13 serotypes were identified and compared with cases from the pre-universal PCV13 period (2012-2016). Clinical, vaccination-related, epidemiological, microbiological and molecular variables were analysed. Univariable and multivariable logistic regression models were performed. RESULTS Among 206 PCV13-vaccinated children with IPD, 85 (48.0%) of 177 fully vaccinated were vaccine failure and 2 (6.9%) of 29 incompletely vaccinated children for breakthrough infections. Serotype 3 accounted for 84.7% of vaccine failure and all breakthrough infections and was strongly associated with complicated pneumonia. Most cases occurred in children without underlying conditions and were diagnosed exclusively by real-time PCR (81.2%). In multivariable analysis, vaccine failure was independently associated with male sex, complicated pneumonia, PCR-based diagnosis, and the 2 + 1 schedule. Multilocus sequence typing identified ST180 as the predominant lineage among serotype 3 isolates. Compared with the pre-PCV13 period, the proportion of vaccine failure remained high, although the vaccination protection period was longer during the PCV13 era. Excluding serotype 3 reduced the proportion of vaccine failure from 48.0% to 12.4%. CONCLUSIONS In a setting with sustained high PCV13 coverage, cases meeting the epidemiological definition of vaccine failure represented a substantial proportion of paediatric PCV13-type IPD and were largely driven by serotype 3. These findings underscore the importance of molecular diagnostics, continued surveillance, and the development of vaccines with improved protection against serotype 3.