International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact

Tutkimustuotos: Lehtiartikkelivertaisarvioitu


  • Global Pneumococcal Sequencing


  • Wellcome Sanger Inst, Wellcome Trust Sanger Institute, Parasites & Microbes
  • NYU, New York University, Sch Med
  • Imperial Coll London, Imperial College London, Public Health England, Fac Med, Sch Publ Hlth
  • Univ Oslo, University of Oslo, Dept Biostat
  • Univ Peruana Cayetano Heredia, Universidad Peruana Cayetano Heredia, Inst Med Trop
  • Univ Hong Kong, University of Hong Kong, Dept Microbiol, Carol Yu Ctr Infect, Queen Mary Hosp
  • Natl Inst Communicable Dis, Ctr Resp Dis & Meningitis
  • Malawi Liverpool Wellcome Trust Clin Res Programm, University of Malawi
  • London Sch Hyg & Trop Med, University of London, London School of Hygiene & Tropical Medicine, WHO Collaborating Ctr New Vaccines Surveillance, Med Res Council Unit Gambia
  • Ben Gurion Univ Negev, Ben Gurion University, Fac Hlth Sci
  • Univ Witwatersrand, National Research Foundation - South Africa, University of Witwatersrand, Dept Sci & Technol, Natl Res Fdn Vaccine Preventable Dis
  • Emory Univ, Emory University, Rollins School Public Health, Rollins Sch Publ Hlth
  • Univ Edinburgh, University of Edinburgh, Queens Res Inst
  • Univ Warwick, University of Warwick, Div Microbiol & Immun, Warwick Med Sch
  • Ctr Dis Control & Prevent, Centers for Disease Control & Prevention - USA
  • Emory Global Hlth Inst


Background: Pneumococcal conjugate vaccines have reduced the incidence of invasive pneumococcal disease, caused by vaccine serotypes, but non-vaccine-serotypes remain a concern. We used whole genome sequencing to study pneumococcal serotype, antibiotic resistance and invasiveness, in the context of genetic background.

Methods: Our dataset of 13,454 genomes, combined with four published genomic datasets, represented Africa (40%), Asia (25%). Europe (19%), North America (12%), and South America (5%).These 20,027 pneumococcal genomes were clustered into lineages using PopPUNK, and named Global Pneumococcal Sequence Clusters (GPSCs). From our dataset, we additionally derived serotype and sequence type, and predicted antibiotic sensitivity. We then measured invasiveness using odds ratios that relating prevalence in invasive pneumococcal disease to carriage.

Findings: The combined collections (n = 20,027) were clustered into 621 GPSCs. Thirty-five GPSCs observed in our dataset were represented by >100 isolates, and subsequently classed as dominant-GPSCs. In 22/35 (63%) of dominant-GPSCs both non-vaccine serotypes and vaccine serotypes were observed in the years up until, and including, the first year of pneumococcal conjugate vaccine introduction.

Penicillin and multidrug resistance were higher (p <.05) in a subset dominant-GPSCs (14/35, 9/35 respectively), and resistance to an increasing number of antibiotic classes was associated with increased recombination (R-2 = 0.27 p <.0001). In 28/35 dominant-GPSCs, the country of isolation was a significant predictor (p <.05) of its antibiogram (mean misdassification error 0.28, SD +/- 0.13).

We detected increased invasiveness of six genetic backgrounds, when compared to other genetic backgrounds expressing the same serotype. Up to 1.6-fold changes in invasiveness odds ratio were observed.

Interpretation: We define GPSCs that can be assigned to any pneumococcal genomic dataset, to aid international comparisons. Existing non-vaccine-serotypes in most GPSCs preclude the removal of these lineages by pneumococcal conjugate vaccines; leaving potential for serotype replacement. A subset of GPSCs have increased resistance, and/or serotype-independent invasiveness.


TilaJulkaistu - toukokuuta 2019
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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