Evaluation the impact of pneumococcal conjugate vaccines on the genomic population structure of the pneumococcus. Pneumococcal genomic population structure

Ongoing invasive pneumococcal disease (IPD) due to non-vaccine serotypes after the introduction of pneumococcal conjugate vaccines (PCVs) remains a global concern. Using genomics, we aimed to evaluate changes in IPD lineages in the post-PCV era among South African children. From national, laboratory-based IPD surveillance, we included genomes (N=3104) of IPD isolates from individuals aged <18 years (2005–20). We defined PCV periods as: pre-PCV (2005-08), PCV7 (2009-10), early-PCV13 (2011-14), and late-PCV13 (2015-20). We determined pneumococcal serotypes, global pneumococcal sequence cluster lineages, and antimicrobial resistance determinants in silico. Incidence rate was used to determine changes in predominant lineages pre- and post-PCV introduction. Serotype and lineage diversity trends were determined using Simpson’s diversity index (SDI). We observed significant incidence declines in vaccine-type lineages in the late-PCV13 period. IPD persistence was driven by both vaccine-type and non-vaccine-type lineages post PCV. Significant increases in lineage diversity were observed in the early-PCV13 period, between 2011 and 2013 (0.948, 95% CI 0.937-0.960 vs 0.971, 95% CI 0.963-0.979). Among non-vaccine serotypes, increases in the prevalence of resistance to penicillin (pre-PCV n=17 [12%] of 143 vs late-PCV13 140 [22%] of 631; p=0.0066), erythromycin (pre-PCV 1 [1%] of 143 vs late-PCV13 37 [6%] of 631; p=0.032) and multidrug resistance (pre-PCV 6 [4%] of 143 vs late-PCV13 73 [12%] of 631; p=0.012) were observed. Although PCVs have substantially reduced IPD, lineages that expressed both vaccine and non-vaccine serotypes in the pre-PCV period have the potential to persist post vaccination due to the expansion of non-vaccine serotype constituents, along with antimicrobial resistance features. Continued genomic surveillance is necessary to monitor vaccine escape serotypes and predominant lineages in the post-PCV era to support policy-making and future vaccine design.