Introduction Pneumococcal disease, which presents a substantial health and economic burden, is prevented through pneumococcal vaccination programs. We assessed the impact of switching from a 13-valent-based (PCV13) to lower 10-valent-based (PCV10-GlaxoSmithKline [GSK] or PCV10-Serum Institute of India [SII]) or higher-valent (PCV15 or PCV20) vaccination programs in South Africa. Methods A previously published decision-analytic model was adapted to a South African setting. Historical invasive pneumococcal disease (IPD) incidence data were used to project IPD incidence over time for each vaccination program on the basis of serotype coverage. Historical incidence (IPD, pneumonia, otitis media), mortality, costs, and utilities were obtained from the published literature. Cases of disease, direct medical costs (i.e., vaccination, IPD, pneumonia, and otitis media costs) (in 2022 South African rands), life-years, quality-adjusted life-years (QALY), and incremental cost per QALY were estimated over a 5- and 10-year horizon for PCV13 and the PCV10 vaccines. Additionally, a public health impact analysis was conducted comparing PCV13, PCV15, and PCV20. Results Continuing use of PCV13 would substantially reduce disease incidence over time compared with switching to either of the PCV10 lower-valent vaccines. Cases of IPD were reduced by 4.22% and 34.70% when PCV13 was compared to PCV10-GSK and PCV10-SII, respectively. PCV13 was also found to be cost saving over 5- and 10-year time horizons compared with PCV10-SII and to be cost-effective over a 5-year time horizon and cost-saving over a 10-year time horizon compared with PCV10-GSK. PCV20 was consistently estimated to prevent more cases than the PCV10 vaccines, PCV13, or PCV15. Conclusions Switching from a higher-valent to a lower-valent vaccine may lead to disease incidence re-emergence caused by previously covered serotypes. Maintaining PCV13 was estimated to improve public health further by averting additional pneumococcal disease cases and saving more lives and also to reduce total costs in most scenarios. Higher-valent PCVs can achieve the greatest public health impact in the pediatric vaccination program in South Africa. Supplementary Information The online version contains supplementary material available at 10.1007/s40121-023-00767-4.

In June 2010, Greece introduced the 13-valent pneumococcal conjugate vaccine (PCV13) for pediatric vaccination and has since observed a large decrease in pneumococcal disease caused by these vaccine serotypes, yet the disease prevalence of non-vaccine serotypes has increased. Two higher-valent conjugate vaccines, a 15-valent (PCV15) and a 20-valent (PCV20), were developed to improve serotype coverage and combat serotype replacement. A decision-analytic model was adapted to the Greek setting using historical pneumococcal disease trends from PCV13 to forecast future clinical and economic outcomes of higher-valent PCVs over a 10-year period (2023–2033). The model estimated outcomes related to invasive pneumococcal disease (IPD), hospitalized and non-hospitalized pneumonia, and otitis media (OM) resulting from a switch in vaccination programs to PCV15 in 2023 or switching to PCV20 in 2024. Cost-effectiveness was evaluated from the third-party payer’s perspective in the Greek healthcare system. Compared to implementing PCV15 one year earlier, switching from PCV13 to PCV20 in 2024 was estimated to be a cost-saving strategy by saving the Greek health system over EUR 50 million in direct medical costs and averting over 250 IPD cases, 54,800 OM cases, 8450 pneumonia cases, and 255 deaths across all ages over a 10-year period.

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