Sanches Ferreira Ana D, King Alannah C, Wolters Femke, Wertheim Heiman F L, Mulder Bert, Swanink Caroline M A, van der Gaast-de Jongh Christa E, Arends Daan W, van Sorge Nina M, Schaars Carel, Hung Harry C H, Hawkins Paulina A, McGee Lesley, Bentley Stephen D, Veening Jan-Willem, de Jonge Marien I, Lo Stephanie W, Cremers Amelieke J H
Parasites and Microbes, Wellcome Sanger Institute, Hinxton, UK.
Department of Medical Microbiology, Radboudumc Center for Infectious Diseases, Nijmegen, The Netherlands.
Microb Genom. 2025 Mar;11(3). doi: 10.1099/mgen.0.001377.
In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV) was introduced to the childhood immunization programme in 2006 and replaced by the 10-valent PCV (PCV10, GSK) in 2011. To describe invasive pneumococcal disease in the era of childhood PCV vaccination on pneumococcal bacteraemia across all ages, we collected and sequenced 979 pneumococcal blood isolates from consecutive patients with pneumococcal bacteraemia in the Gelderland area, the Netherlands, between 2000 and 2020. In total, 58% of the bacteraemia cases (=563/979) occurred in the elderly population. Compared to the pre-PCV period (2000-2005), the odds ratio for non-PCV10 bacteraemia was 17.5 (CI 9.9-31.6; <0.001) in the late-PCV10 period, showing an overall increase in the proportion of bacteraemia cases being caused by non-vaccine serotype pneumococci (2016-2020). The increase in non-PCV10 serotypes is mainly driven by an expansion of lineage global pneumococcal sequencing cluster 3 (GPSC3) expressing serotype 8, alongside the emergence of serotype 12F that was mediated by multiple lineages (GPSC32/GPSC26/GPSC55). Both serotypes 8 and 12F were included in the latest PCV20 formulation that is licensed to be used in children and adults in Europe. Over 20 years, we observed a low prevalence of antimicrobial resistance (AMR) as predicted by genome data. There were no significant changes in AMR prevalence after vaccine introduction (>0.05 for all comparisons). We saw a stably low prevalence of reduced penicillin susceptibility, which was observed in multiple pneumococcal lineages, with GPSC10 being the most common in the Gelderland collection, whilst GPSC1 and GPSC6 were common among the penicillin-resistant pneumococcal blood culture isolates provided by the Netherlands Reference Laboratory for Bacterial Meningitis. Comparison to global collections of GPSC10, GPSC1 and GPSC6 isolates favored the likelihood of separate introductions of penicillin-resistant isolates rather than cloncal expansion. Genomic surveillance of pneumococcal bacteraemia in this unbiased population sample in the Netherlands supports the use of higher valency PCVs, such as PCV20, especially in adults, to prevent future bacteraemia cases caused by in the Gelderland area, the Netherlands, while maintaining a low prevalence of AMR in the pneumococcal population.
在荷兰，7价肺炎球菌结合疫苗（PCV）于2006年被纳入儿童免疫规划，并于2011年被10价PCV（PCV10，葛兰素史克公司生产）取代。为了描述儿童接种PCV疫苗时代所有年龄段人群肺炎球菌菌血症相关的侵袭性肺炎球菌疾病情况，我们收集并对2000年至2020年间荷兰海尔德兰地区连续的肺炎球菌菌血症患者的979株肺炎球菌血液分离株进行了测序。总体而言，58%的菌血症病例（=563/979）发生在老年人群中。与PCV疫苗接种前时期（2000 - 2005年）相比，在PCV10疫苗接种后期（2016 - 2020年），非PCV10菌血症的比值比为17.5（95%置信区间9.9 - 31.6；<0.001），这表明由非疫苗血清型肺炎球菌引起的菌血症病例比例总体有所增加。非PCV10血清型的增加主要由表达血清型8的全球肺炎球菌测序簇3（GPSC3）的扩展推动，同时还有由多个谱系（GPSC32/GPSC26/GPSC55）介导的血清型12F的出现。血清型8和12F均包含在最新的PCV20配方中，该配方已获许可在欧洲用于儿童和成人。在20多年的时间里，正如基因组数据所预测的，我们观察到抗菌药物耐药性（AMR）的患病率较低。疫苗引入后AMR患病率没有显著变化（所有比较的P值均>0.05）。我们观察到青霉素敏感性降低的患病率一直较低，在多个肺炎球菌谱系中均有出现，其中GPSC10在海尔德兰地区的样本中最为常见，而GPSC1和GPSC6在荷兰细菌性脑膜炎参考实验室提供的耐青霉素肺炎球菌血培养分离株中较为常见。与全球GPSC10、GPSC1和GPSC6分离株的集合进行比较，更倾向于认为耐青霉素分离株是分别引入而非克隆性扩增的可能性。在荷兰这个无偏倚人群样本中对肺炎球菌菌血症进行基因组监测支持使用更高价的PCV，如PCV20，特别是在成人中，以预防荷兰海尔德兰地区未来由肺炎球菌引起的菌血症病例，同时保持肺炎球菌群体中较低的AMR患病率。
