Division of Infection Control, Norwegian Institute of Public Health, Lovisenberggata 6, 0456, Oslo, Norway.
Centre for Antimicrobial Resistance, Norwegian Institute of Public Health, Oslo, Norway.
Genome Med. 2024 Oct 25;16(1):123. doi: 10.1186/s13073-024-01396-3.
Streptococcus pneumoniae is a major cause of mortality globally. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced the incidence of the targeted serotypes significantly, but expansion of non-targeted serotypes, serotype replacement, and incomplete vaccine-targeting contribute to pneumococcal disease in the vaccine era. Here, we characterize the changing population genetic landscape of S. pneumoniae in Norway over a 41-year period (1982-2022).
Since 2018, all cases of invasive pneumococcal disease have undergone whole-genome sequencing (WGS) at the Norwegian Institute of Public Health. In order to characterize the changing population over time, historical isolates were re-cultured and sequenced, resulting in a historical WGS dataset. Isolates were assigned to global pneumococcal sequence clusters (GPSCs) using PathogenWatch and assigned to serotypes using in silico (SeroBA) and in vitro methods (Quellung reaction). Temporal phylogenetic analyses were performed on GPSCs of particular interest.
The availability of WGS data allowed us to study capsular variation at the level of individual lineages. We detect highly divergent fates for different GPSCs following the introduction of PCVs. For two out of eight major GPSCs, we identified multiple instances of serotype switching from vaccine types to non-vaccine types. Dating analyses suggest that most instances of serotype switching predated the introduction of PCVs, but expansion occurred after their introduction. Furthermore, selection for penicillin non-susceptibility was not a driving force for the changing serotype distribution within the GPSCs over time.
PCVs have been major shapers of the Norwegian disease-causing pneumococcal population, both at the level of serotype distributions and the underlying lineage dynamics. Overall, the introduction of PCVs has reduced the incidence of invasive disease. However, some GPSCs initially dominated by vaccine types escaped the effect of vaccination through expansion of non-vaccine serotypes. Close monitoring of circulating lineages and serotypes will be key for ensuring optimal vaccination coverage going forward.
肺炎链球菌是全球范围内导致死亡的主要原因。肺炎球菌结合疫苗（PCV）的引入显著降低了目标血清型的发病率，但非目标血清型的扩展、血清型替换和不完全疫苗靶向作用导致了疫苗时代的肺炎球菌疾病。在这里，我们描述了在 41 年期间（1982-2022 年）挪威肺炎链球菌人群遗传景观的变化。
自 2018 年以来，挪威公共卫生研究所对所有侵袭性肺炎球菌病病例进行了全基因组测序（WGS）。为了描述随时间变化的人群变化，我们重新培养和测序了历史分离株，从而产生了一个历史 WGS 数据集。使用 PathogenWatch 将分离株分配到全球肺炎链球菌序列簇（GPSC）中，并使用计算机模拟（SeroBA）和体外方法（Quellung 反应）将其分配到血清型。对特定 GPSC 进行了时间系统发育分析。
WGS 数据的可用性使我们能够在个体谱系水平上研究荚膜变异。我们发现，在 PCV 引入后，不同 GPSC 有高度不同的命运。对于八个主要 GPSC 中的两个，我们发现了从疫苗类型到非疫苗类型的多次血清型转换。约会分析表明，大多数血清型转换发生在 PCV 引入之前，但在引入之后发生了扩展。此外，青霉素不敏感性的选择并不是 GPSC 中血清型分布随时间变化的驱动力。
PCV 是导致挪威致病肺炎球菌人群的主要因素，无论是在血清型分布还是潜在的谱系动态方面。总体而言，PCV 的引入降低了侵袭性疾病的发病率。然而，一些最初由疫苗类型主导的 GPSC 通过非疫苗血清型的扩展逃脱了疫苗接种的影响。密切监测循环谱系和血清型将是确保未来最佳疫苗接种覆盖率的关键。
