Genomic characterization of invasive disease-causing Streptococcus pneumoniae in Lebanon, 2003–2025

Background. Streptococcus pneumoniae is a major human pathogen responsible for invasive pneumococcal diseases (IPDs). We utilized whole-genome sequencing to assess the impact of pneumococcal conjugate vaccines (PCVs) on the pneumococcal population causing IPD in Lebanon. Methods. S. pneumoniae isolates collected between 2003 and 2025 (n=273) were sequenced and included in the study, which was divided into three periods. Private-PCV7 (2003–2009) and Private-PCV13 (2010–2015) correspond to the periods when the PCV7 and PCV13 vaccines were available only in the private healthcare sector, respectively. EPI-PCV13 (2016–2025) represents the period following PCV13 incorporation into the Expanded Program on Immunization (EPI). The Global Pneumococcal Sequencing (GPS) genome analysis pipeline was used to infer serotypes, genetic lineages, pilus locus and antimicrobial resistance (AMR) for 19 antibiotics. Phylogeny was constructed based on SNPs across the pneumococcal genome. Results. A total of 58 GPS clusters (GPSCs) expressing 40 serotypes were identified. Overall, serotypes 3, 14 and 19F were the most prevalent serotypes, while GPSC6, GPSC12 and GPSC1 were the most predominant pneumococcal lineages. We detected a significant increase in non-vaccine types (NVTs) after PCV7 and PCV13 introduction. In contrast, PCV7 serotypes declined significantly over the three study periods. Collectively, PCV7 serotypes were associated with significantly higher mortality (31.1%) compared to NVT (15.9%). Moreover, IPD-associated mortality was significantly higher among older adult patients (33.3%) compared to children aged ≤5 years (12.1%). Non-susceptibility to penicillin was the most prevalent resistance (62.1%), and multidrug resistance (MDR; non-susceptibility to at least three antibiotics) was identified in 36.4% of the isolates. MDR was primarily driven by GPSC1, GPSC9, GPSC6 and GPSC10. A significant decline in MDR and AMR against seven antibiotics was observed in the EPI-PCV13 period compared to previous study periods. Conclusions. Genomic surveillance is robust for tracking current NVT and identifying lineages that may influence future IPD trends in Lebanon. Given the high mortality rate detected in older adult IPD patients, implementing a routine immunization programme in this population may be beneficial.