1887

Abstract

Serotype 3 pneumococci remains a significant cause of disease despite its inclusion in PCV13. Whilst clonal complex 180 (CC180) represents the major clone, recent studies have refined the population structure into three clades: Iα, Iβ and II, with the last being a recent divergent and more antibiotic-resistant. We present a genomic analysis of serotype 3 isolates from paediatric carriage and all-age invasive disease, collected between 2005 and 2017 in Southampton, UK. Forty-one isolates were available for analysis. Eighteen were isolated during the annual cross-sectional surveillance of paediatric pneumococcal carriage. The remaining 23 were isolated from blood/cerebrospinal fluid specimens at the University Hospital Southampton NHS Foundation Trust laboratory. All carriage isolates were CC180 GPSC12. Greater diversity was seen with invasive pneumococcal disease (IPD) with three GPSC83 (ST1377: =2, ST260: =1) and one GPSC3 (ST1716). For both carriage and IPD, Clade Iα was dominant (94.4 and 73.9 % respectively). Two isolates were Clade II with one from carriage (a 34-month-old, October 2017) and one invasive isolate (49-year-old, August 2015). Four IPD isolates were outside the CC180 clade. All isolates were genotypically susceptible to penicillin, erythromycin, tetracycline, co-trimoxazole and chloramphenicol. Two isolates (one each from carriage and IPD; both CC180 GPSC12) were phenotypically resistant to erythromycin and tetracycline; the IPD isolate was also resistant to oxacillin.In the Southampton area, carriage and invasive disease associated with serotype 3 is predominantly caused by Clade Iα CC180 GPSC12.

Funding
This study was supported by the:
  • Pfizer UK
    • Principle Award Recipient: StuartC. Clarke
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-03-03
2024-05-04
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References

  1. Wasserman M, Chapman R, Lapidot R, Sutton K, Dillon-Murphy D et al. Twenty-year public health impact of 7- and 13-Valent pneumococcal conjugate vaccines in US Children. Emerg Infect Dis 2021; 27:1627–1636 [View Article]
    [Google Scholar]
  2. Mackenzie GA, Hill PC, Sahito SM, Jeffries DJ, Hossain I et al. Impact of the introduction of pneumococcal conjugate vaccination on pneumonia in The Gambia: population-based surveillance and case-control studies. Lancet Infect Dis 2017; 17:965–973 [View Article]
    [Google Scholar]
  3. Galanis I, Lindstrand A, Darenberg J, Browall S, Nannapaneni P et al. Effects of PCV7 and PCV13 on invasive pneumococcal disease and carriage in Stockholm, Sweden. Eur Respir J 2016; 47:1208–1218 [View Article] [PubMed]
    [Google Scholar]
  4. Waight PA, Andrews NJ, Ladhani SN, Sheppard CL, Slack MPE et al. Effect of the 13-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in England and Wales 4 years after its introduction: an observational cohort study. Lancet Infect Dis 2015; 15:535–543 [View Article] [PubMed]
    [Google Scholar]
  5. Moore MR, Link-Gelles R, Schaffner W, Lynfield R, Lexau C et al. Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: analysis of multisite, population-based surveillance. Lancet Infect Dis 2015; 15:301–309 [View Article] [PubMed]
    [Google Scholar]
  6. Løchen A, Croucher NJ, Anderson RM. Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency. Sci Rep 2020; 10:18977 [View Article] [PubMed]
    [Google Scholar]
  7. Kandasamy R, Voysey M, Collins S, Berbers G, Robinson H et al. Persistent circulation of vaccine serotypes and serotype replacement After 5 years of infant immunization With 13-valent pneumococcal conjugate vaccine in the United Kingdom. J Infect Dis 2020; 221:1361–1370 [View Article]
    [Google Scholar]
  8. Gladstone RA, Devine V, Jones J, Cleary D, Jefferies JM et al. Pre-vaccine serotype composition within a lineage signposts its serotype replacement - a carriage study over 7 years following pneumococcal conjugate vaccine use in the UK. Microb Genom 2017; 3:e000119 [View Article] [PubMed]
    [Google Scholar]
  9. Devine VT, Cleary DW, Jefferies JMC, Anderson R, Morris DE et al. The rise and fall of pneumococcal serotypes carried in the PCV era. Vaccine 2017; 35:1293–1298 [View Article] [PubMed]
    [Google Scholar]
  10. Ladhani SN, Collins S, Djennad A, Sheppard CL, Borrow R et al. Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000-17: a prospective national observational cohort study. Lancet Infect Dis 2018; 18:441–451 [View Article] [PubMed]
    [Google Scholar]
  11. Sings HL, De Wals P, Gessner BD, Isturiz R, Laferriere C et al. Effectiveness of 13-valent pneumococcal conjugate vaccine against invasive disease caused by serotype 3 in children: a systematic review and meta-analysis of observational studies. Clin Infect Dis 2019; 68:2135–2143 [View Article]
    [Google Scholar]
  12. Southern J, Andrews N, Sandu P, Sheppard CL, Waight PA et al. Pneumococcal carriage in children and their household contacts six years after introduction of the 13-valent pneumococcal conjugate vaccine in England. PLoS One 2018; 13:e0195799 [View Article] [PubMed]
    [Google Scholar]
  13. Pick H, Daniel P, Rodrigo C, Bewick T, Ashton D et al. Pneumococcal serotype trends, surveillance and risk factors in UK adult pneumonia, 2013-18. Thorax 2020; 75:38–49 [View Article] [PubMed]
    [Google Scholar]
  14. Choi EH, Zhang F, Lu Y-J, Malley R. Capsular polysaccharide (CPS) release by serotype 3 pneumococcal strains reduces the protective effect of anti-type 3 CPS antibodies. Clin Vaccine Immunol 2016; 23:162–167 [View Article]
    [Google Scholar]
  15. Azarian T, Mitchell PK, Georgieva M, Thompson CM, Ghouila A et al. Global emergence and population dynamics of divergent serotype 3 CC180 pneumococci. PLoS Pathog 2018; 14:e1007438 [View Article] [PubMed]
    [Google Scholar]
  16. Groves N, Sheppard CL, Litt D, Rose S, Silva A et al. Evolution of Streptococcus pneumoniae serotype 3 in England and Wales: a major vaccine evader. Genes (Basel) 2019; 10:845 [View Article]
    [Google Scholar]
  17. Gladstone RA, Lo SW, Lees JA, Croucher NJ, van Tonder AJ et al. International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact. EBioMedicine 2019; 43:338–346 [View Article] [PubMed]
    [Google Scholar]
  18. Epping L, van Tonder AJ, Gladstone RA, Bentley SD et al. SeroBA: rapid high-throughput serotyping of Streptococcus pneumoniae from whole genome sequence data. Microb Genom 2018; 4:e000186 [View Article]
    [Google Scholar]
  19. J. Page A, Taylor B, A. Keane J. Multilocus sequence typing by blast from de novo assemblies against PubMLST. JOSS 2016; 1:118 [View Article]
    [Google Scholar]
  20. Lees JA, Harris SR, Tonkin-Hill G, Gladstone RA, Lo SW et al. Fast and flexible bacterial genomic epidemiology with PopPUNK. Genome Res 2019; 29:304–316 [View Article] [PubMed]
    [Google Scholar]
  21. Metcalf BJ, Gertz RE, Gladstone RA, Walker H, Sherwood LK et al. Strain features and distributions in pneumococci from children with invasive disease before and after 13-valent conjugate vaccine implementation in the USA. Clin Microbiol Infect 2016; 22:60 [View Article]
    [Google Scholar]
  22. Li Y, Metcalf BJ, Chochua S, Li Z, Gertz RE Jr et al. Validation of β-lactam minimum inhibitory concentration predictions for pneumococcal isolates with newly encountered penicillin binding protein (PBP) sequences. BMC Genomics 2017; 18:621 [View Article] [PubMed]
    [Google Scholar]
  23. Li Y, Metcalf BJ, Chochua S, Li Z, Gertz RE et al. Penicillin-binding protein transpeptidase signatures for tracking and predicting β-lactam resistance levels in Streptococcus pneumoniae. mBio 2016; 7:e00756-16 [View Article]
    [Google Scholar]
  24. Ewels PA, Peltzer A, Fillinger S, Patel H, Alneberg J et al. The nf-core framework for community-curated bioinformatics pipelines. Nat Biotechnol 2020; 38:276–278 [View Article] [PubMed]
    [Google Scholar]
  25. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25:1754–1760 [View Article] [PubMed]
    [Google Scholar]
  26. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J et al. The sequence alignment/map format and SAMtools. Bioinformatics 2009; 25:2078–2079 [View Article]
    [Google Scholar]
  27. Li H. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics 2011; 27:2987–2993 [View Article] [PubMed]
    [Google Scholar]
  28. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015; 43:e15 [View Article] [PubMed]
    [Google Scholar]
  29. Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom 2016; 2:e000056 [View Article] [PubMed]
    [Google Scholar]
  30. Kozlov AM, Darriba D, Flouri T, Morel B, Stamatakis A. RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference. Bioinformatics 2019; 35:4453–4455 [View Article] [PubMed]
    [Google Scholar]
  31. Hadfield J, Croucher NJ, Goater RJ, Abudahab K, Aanensen DM et al. Phandango: an interactive viewer for bacterial population genomics. Bioinformatics 2017; 34292–293 [View Article]
    [Google Scholar]
  32. Didelot X, Croucher NJ, Bentley SD, Harris SR, Wilson DJ. Bayesian inference of ancestral dates on bacterial phylogenetic trees. Nucleic Acids Res 2018; 46:22 [View Article] [PubMed]
    [Google Scholar]
  33. Seemann T. Abricate Github. n.d https://github.com/tseemann/abricate
  34. Inouye M, Dashnow H, Raven L-A, Schultz MB, Pope BJ et al. SRST2: Rapid genomic surveillance for public health and hospital microbiology labs. Genome Med 2014; 6:90 [View Article] [PubMed]
    [Google Scholar]
  35. Connor TR, Loman NJ, Thompson S, Smith A, Southgate J et al. CLIMB (the Cloud Infrastructure for Microbial Bioinformatics): an online resource for the medical microbiology community. Microb Genom 2016; 2:e000086 [View Article] [PubMed]
    [Google Scholar]
  36. R Core R: A language and environment for statistical computing. n.d https://www.R-project.org/
  37. Wickham H. ggplot2. In Elegant Graphics for Data Analysis Cham: Springer-Verlag New York; 2016 [View Article]
    [Google Scholar]
  38. Yu G. Using ggtree to visualize data on tree-like structures. Curr Protoc Bioinformatics 2020; 69:e96 [View Article]
    [Google Scholar]
  39. Coughtrie AL, Jefferies JM, Cleary DW, Doncaster CP, Faust SN et al. Microbial epidemiology and carriage studies for the evaluation of vaccines. J Med Microbiol 2019; 68:1408–1418 [View Article] [PubMed]
    [Google Scholar]
  40. Cleary DW, Jones J, Gladstone RA, Osman KL, Devine VT et al. Changes in serotype prevalence of Streptococcus pneumoniae in Southampton, UK between 2006 and 2018. Sci Rep 2022; 12:13332 [View Article]
    [Google Scholar]
  41. Weinberger DM, Grant LR, Weatherholtz RC, Warren JL, O’Brien KL et al. Relating pneumococcal carriage among children to disease rates among adults before and after the introduction of conjugate vaccines. Am J Epidemiol 2016; 183:1055–1062 [View Article]
    [Google Scholar]
  42. Lo SW, Gladstone RA, van Tonder AJ, Lees JA, du Plessis M et al. Pneumococcal lineages associated with serotype replacement and antibiotic resistance in childhood invasive pneumococcal disease in the post-PCV13 era: an international whole-genome sequencing study. Lancet Infect Dis 2019; 19:759–769 [View Article] [PubMed]
    [Google Scholar]
  43. Jolley KA, Bray JE, Maiden MCJ. Open-access bacterial population genomics: BIGSdb software, the PubMLST.org website and their applications. Wellcome Open Res 2018; 3:124 [View Article] [PubMed]
    [Google Scholar]
  44. Mitchell PK, Azarian T, Croucher NJ, Callendrello A, Thompson CM et al. Population genomics of pneumococcal carriage in Massachusetts children following introduction of PCV-13. Microb Genom 2019; 5:e000252 [View Article] [PubMed]
    [Google Scholar]
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