Clonal expansion of global pneumococcal sequence cluster 3 within serotype 8 after 13-valent pneumococcal conjugate vaccine introduction, South Africa.

Background. Serotype 8 has emerged as a common non-vaccine serotype causing invasive pneumococcal disease (IPD) in children and adults globally after the introduction of pneumococcal conjugate vaccines (PCV). We aimed to determine serotype 8 incidence and genomic epidemiology in South Africa.Methods. From national, laboratory-based surveillance for IPD in South Africa, we calculated the incidence of serotype 8 and global pneumococcal sequence cluster 3 (GPSC3) before and after PCV introduction. We performed phylodynamic analysis of genomes from clonal complex (CC) 53 and described South African isolates in the context of a global collection of serotype 8 and GPSC3 genomes.Results. Compared to the pre-PCV period, serotype 8 incidence increased in the late-PCV13 period among children <5 years [incidence rate ratio (IRR) 2.3, 95% confidence interval (CI) 1.3-4.1] and adults >64 years (2.8, 1.1-8.3). Similarly, GPSC3 rates increased among children <5 years (IRR 2.4, 95% CI 1.4-4.3) and individuals of all ages (1.7, 1.3-2.1). Serotype 8 CC53 population dynamics predicted at least five clonal expansions since the most recent common ancestor in 1929 (credible interval 1919-1937), with future predictions showing increases in the effective population size despite remaining largely susceptible to first-line treatment. Serotype 8 CC53 isolates from South Africa had a clonal structure when contextualized within a global collection of serotype 8 and GPSC3 genomes.Conclusion. Serotype 8 invasive disease incidence increased in South Africa after PCV introduction. Predictions showed sustained increases over time. Since South Africa switched to a lower-valency PCV10 (Pneumosil, Serum Institute of India) that does not include serotype 8 in 2024, continued surveillance will be crucial to inform PCV policy-making.