Complicated pneumococcal pneumonia in the era of higher-valent pneumococcal conjugate vaccines: a systematic literature review and meta-analysis, 2001–2022

PURPOSE: To estimate pneumococcal conjugate vaccine (PCV) national program impact on pneumococcal complicated pneumonia (PnCP) based on changes in PnCP population-based incidence, PnCP proportion of all-cause complicated pneumonia (or invasive pneumococcal disease), and PnCP serotype distribution. METHODS: MEDLINE, EMBASE, and Global Index Medicus articles (2001-March 2022) reporting laboratory-confirmed PnCP studies were stratified by age group, outcome measure, PCV program period(s) (pre-PCV, transition, and post-PCV), serotype distribution (based on serotyping methodology used), and PCV serotype formulation. Random effect meta-analysis of the total number of serotyped isolates within each study was used to calculate pooled serotype-specific percentages. RESULTS: Of 1360 publications screened, the 134 studies included from 30 countries differed widely by methodological approaches. Pediatric PnCP incidence tended to decline from pre-PCV to post-PCV periods, as did PnCP as a proportion of all-cause complicated pneumonia from transition to post-PCV periods. Studies describing changes in serotype distribution by PCV program period applied detection methods that varied from pre-PCV period microbiological culture with Quellung serotyping to in the transition and post-PCV periods molecular methods like PCR. Meta-analysis revealed near elimination of pediatric PCV7-serotype PnCP between pre- and post-PCV, while the PCV13nonPCV7 percentage increased from 51.1% pre-PCV period to 76.5% in the transition period, remaining stable post-PCV period. Non-PCV13 serotypes increased slightly from low baseline numbers. Adult data were lacking or inconsistent. CONCLUSIONS: Although studies were heterogeneous, pediatric PnCP incidence and proportion tended to decline from pre-PCV to post-PCV periods, and PCV13nonPCV7 serotype distribution percentage remained unchanged from transition to post-PCV period. Standardization of PnCP surveillance methods, definitions, and reporting is needed to evaluate accurately PCV program impact.