Investigating two decades of Streptococcus pneumoniae bacteraemia in the Gelderland area, the Netherlands, using whole-genome sequencing

Ana D. Sanches Ferreira; Alannah C. King; Femke Wolters; Heiman F.L. Wertheim; Bert Mulder; Caroline M.A. Swanink; Christa E. van der Gaast-De Jongh; Daan W. Arends; Nina M. van Sorge; Carel Schaars; Harry C.H. Hung; Paulina A. Hawkins; Lesley McGee; Stephen D. Bentley; Jan Willem Veening; Marien I. de Jonge; Stephanie W. Lo; Amelieke J.H. Cremers

doi:10.1099/mgen.0.001377

Investigating two decades of Streptococcus pneumoniae bacteraemia in the Gelderland area, the Netherlands, using whole-genome sequencing

Ana D. Sanches Ferreira, Alannah C. King, Femke Wolters, Heiman F.L. Wertheim, Bert Mulder, Caroline M.A. Swanink, Christa E. van der Gaast-De Jongh, Daan W. Arends, Nina M. van Sorge, Carel Schaars, Harry C.H. Hung, Paulina A. Hawkins, Lesley McGee, Stephen D. Bentley, Jan Willem Veening, Marien I. de Jonge, Stephanie W. Lo, Amelieke J.H. Cremers

Research output: Contribution to journal › Article › peer-review

Abstract

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 pneu-mococcal 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 (n=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; P<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 (P>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 Streptococcus pneumoniae in the Gelderland area, the Netherlands, while maintaining a low prevalence of AMR in the pneumococcal population.

Original language	English
Article number	001377
Journal	Microbial Genomics
Volume	11
Issue number	3
Early online date	18 Mar 2025
DOIs	https://doi.org/10.1099/mgen.0.001377
Publication status	Published - 31 Mar 2025

Acknowledgements

The authors would like to thank all members of The Global Pneumococcal Sequencing Consortium for their collaborative spirit and determination during the task of sampling, extracting and sequencing this dataset; Jacques F. Meis, Gerben Ferwerda, Aldert L. Zomer and Peter W. Hermans as original co-founders of the study framework; Michael Rogers, Marc Eleveld and Fred van Opzeeland for their valuable help submitting, extracting and sequencing specimens; the Pathogen Informatics Team at the Wellcome Sanger Institute for technical support of bioinformatic analyses; and Dr Adam Cohen at the CDC for his review of this study and feedback on this manuscript.

Funding

This work was supported by Wellcome under grant reference 206194 and by the Bill and Melinda Gates Foundation under Investment ID OPP1189062, as part of the Global Pneumococcal Sequencing project. AC was supported by a Fellowship from the Swiss National Science Foundation, grant no. 209768. The funding sources had no role in the analysis or data interpretation. For the purposes of Open Access, the author has applied a CC BY public copyright licence to any Author Accept Manuscript version arising from this submission. The corresponding author had full access to the data and is responsible for the final decision to submit.

Keywords

antimicrobial resistance
invasive pneumococcal disease (IPD)
pneumococcal conjugate vaccine (PCV)
pneumococcal lineage
serotype
the Netherlands

ASJC Scopus subject areas

Epidemiology
Microbiology
Molecular Biology
Genetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Cite this

Sanches Ferreira, A. D., King, A. C., Wolters, F., Wertheim, H. F. L., Mulder, B., Swanink, C. M. A., van der Gaast-De Jongh, C. E., Arends, D. W., van Sorge, N. M., Schaars, C., Hung, H. C. H., Hawkins, P. A., McGee, L., Bentley, S. D., Veening, J. W., de Jonge, M. I., Lo, S. W., & Cremers, A. J. H. (2025). Investigating two decades of Streptococcus pneumoniae bacteraemia in the Gelderland area, the Netherlands, using whole-genome sequencing. Microbial Genomics, 11(3), Article 001377. https://doi.org/10.1099/mgen.0.001377

Sanches Ferreira, AD, King, AC, Wolters, F, Wertheim, HFL, Mulder, B, Swanink, CMA, van der Gaast-De Jongh, CE, Arends, DW, van Sorge, NM, Schaars, C, Hung, HCH, Hawkins, PA, McGee, L, Bentley, SD, Veening, JW, de Jonge, MI, Lo, SW & Cremers, AJH 2025, 'Investigating two decades of Streptococcus pneumoniae bacteraemia in the Gelderland area, the Netherlands, using whole-genome sequencing', Microbial Genomics, vol. 11, no. 3, 001377. https://doi.org/10.1099/mgen.0.001377

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Investigating two decades of Streptococcus pneumoniae bacteraemia in the Gelderland area, the Netherlands, using whole-genome sequencing

Abstract

Acknowledgements

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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