Genomic surveillance of post-immunization pneumococcal carriage in Ghana

<i>Streptococcus pneumoniae</i> remains a major cause of morbidity and mortality worldwide, especially among children under 5 years of age. The introduction of pneumococcal conjugate vaccines (PCVs) has significantly reduced invasive pneumococcal disease globally. Ghana introduced routine immunization with PCV13 in 2012; however, its impact on pneumococcal carriage at the genomic level remains largely unexplored. This is the first genomic characterization of pneumococcal carriage in Ghana post-PCV13 introduction; in the absence of a matched pre-vaccination genomic dataset, findings are interpreted in the context of the post-vaccination era rather than as a direct pre-post-comparison. We identified substantial genomic diversity among carriage isolates, including 49 Global Pneumococcal Sequence Clusters (GPSCs) and 67 sequence types (STs), of which 21 STs were novel, and 4 were international Pneumococcal Molecular Epidemiology Network clones (Spain9V-3, Greece6B-22, NorwayNT-42 and Sweden15A-25). GPSC 5 (14%) was the most prevalent cluster, followed by GPSC 20 (6%). GPSCs associated with antibiotic resistance (GPSCs 1, 6 and 10) represented 2%, 3% and 2% of isolates, respectively. Importantly, we observed a significant decline in vaccine serotypes (VTs) and a corresponding rise in non-vaccine serotypes (NVTs), notably serotypes 23B and 15BC. Additionally, VTs demonstrated higher levels of antibiotic resistance compared to NVTs (<i>P</i><0.05). This study provides the first genomic epidemiological insights into pneumococcal populations in Ghana post-PCV13 introduction and underscores the importance of continuous genomic surveillance to monitor serotype replacement and antibiotic resistance trends.