Global impact of ten-valent and 13-valent pneumococcal conjugate vaccines on invasive pneumococcal disease in all ages

Read articles Submitted by: Submitted by: Monash Children’s Hospital, Andres Noé, Matthew O’Brien and Jeremy Carr.Background: Streptococcus pneumoniae is a leading cause of morbidity and mortality globally, particularly among young children. The 10-valent (PCV10) and 13-valent (PCV13) pneumococcal conjugate vaccines became widely available around 2010 and have been implemented in 170 national infant immunisation programs worldwide. Before PCV introduction, over 70% of Invasive Pneumococcal Disease (IPD) cases were estimated to be caused by serotypes targeted by these vaccines. The PSERENADE project was commissioned by the WHO to evaluate the long-term, global impact of PCV10 and PCV13 use on IPD incidence, including all clinical presentations and specific syndromes like meningitis. The program specifically evaluated changes in vaccine-type disease incidence, non-vaccine-type (NVT) replacement, and the resulting serotype distribution in the period of mature vaccine use (at least 5 years post-introduction). Understanding serotype replacement is crucial, as the decline in vaccine-type disease is often partially counterbalanced by increases in NVT serotypes.Main Findings: - Overall IPD and Meningitis Reduction: By six years after PCV introduction, all-serotype IPD declined among children younger than 5 years (ranging from 58 to 74%), and all-serotype pneumococcal meningitis also declined substantially in this age group (ranging from 48 to 74%). - Vaccine serotype Dynamics: IPD caused by PCV10 serotypes was nearly eliminated, declining by 96 to 99% in children younger than 5 years at both PCV10 and PCV13 sites. - Serotype 19A: Serotype 19A IPD showed differences between PCV10 and PCV13 sites: it increased by ~200% at PCV10 sites among children younger than 5 years but declined by ~75% at PCV13 sites in the same age group. After vaccine introduction at PCV10 sites, serotype 19A became the leading serotype overall, accounting for 30% of IPD cases in children younger than 5 years. - Serotype 3: Serotype 3 was the only vaccine-type IPD for which no consistent trends were observed for either vaccine (PCV10 or PCV13) or age group, making it the top serotype overall at PCV13 sites (causing 9.6% of IPD in children <5 years). Simultaneously, non-PCV13-type IPD increased 2.3 to 3.3-fold in children younger than 5 years across both PCV10 and PCV13 sites, offsetting some of the vaccine benefitsStrengths and limitations: - Global Scope and standardisation: The PSERENADE project compiled the largest and most globally diverse IPD surveillance database, including data from up to 54 sites across up to 41 countries, using standardised methodology and common definitions that reduce bias compared to single-site studies and literature reviews. - Analytical methodology: The analytical methods used to estimate incidence changes and serotype distribution maximised the use of partially serotyped data and accounted for uncertainty and heterogeneity across sites. - Data Paucity: Analyses were limited by sparse data from high-burden countries, low-income settings, Asia, Africa, and countries utilising a 3+0 dosing schedule, which reduced the ability to make robust regional or schedule-specific estimates. - Pre-PCV trends and Confounding: Difficult to model the counterfactual due to small annual case counts and too few years of pre-PCV surveillance data at some sites. The studies were unable to control for many confounding factors contributing to heterogeneity, such as underlying comorbidities or adult immunisation uptake.Take home message: Long-term use of PCV10 or PCV13 substantially reduced all-serotype IPD in young children, though continuing serotype 19A increases at PCV10 sites suggested that switching to a PCV13 formulation would provide further disease reduction. Overall, infant PCV programs also reduced pneumococcal meningitis across all age groups, but replacement with non-PCV13 types was generally lower and more time-limited for meningitis compared to all IPD, suggesting that newer PCVs may make greater inroads in reducing this syndrome. Ultimately, newer, higher-valency PCVs are anticipated to extend impact by covering most remaining IPD (e.g., PCV20 targets about half of all non-PCV13-type disease), but their real-life effect warrants careful surveillance, especially since serotype 3 remains a leading cause of disease.