High-resolution genomics identifies pneumococcal diversity and persistence of vaccine types in children with community-acquired pneumonia in the UK and Ireland

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2024年4月27日

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Juan Pablo Rodriguez-Ruiz,
Basil Britto Xavier,
Wolfgang Stöhr,
Liesbet van Heirstraeten,
Christine Lammens,
Adam Finn,
Herman Goossens,
Julia Anna Bielicki,
Michael Sharland,
Surbhi Malhotra-Kumar,
Diana M. Gibb,
Mark D. Lyttle,
Sam Barratt,
David Dunn,
Michelle Clements,
Kate Sturgeon,
Elizabeth Molyneux,
Chris C. Butler,
Alan Smyth,
Catherine Prichard,
Tim E. A. Peto,
Simon Cousens,
Stuart Logan,
Alasdair Bamford,
Anna Turkova,
Anna L. Goodman,
Felicity Fitzgerald,
Saul N. Faust,
Colin Powell,
Paul S. Little,
Julie Robotham,
Mandy Wan,
Nigel Klein,
Louise Rogers,
Elia Vitale,
Daniel B. Hawcutt,
Mathew Rotheram,
Stuart Hartshorn,
Deepthi Jyothish,
James G. Ross,
Poonam Patel,
Stefania Vergnano,
Jeff Morgan,
Godfrey Nyamugunduru,
John C. Furness,
Susannah J. Holt,
John Gibbs,
Anastasia E. Alcock,
Dani Hall,
Ronny Cheung,
Arshid Murad,
K. M. Jerman,
Chris Bird,
Tanya K. Z. Baron,
Fleur Cantle,
Niall Mullen,
Rhona McCrone,
Gisela Robinson,
Lizzie Starkey,
Sean O’Riordan,
Damian Roland,
Srini Bandi,
Chris Gough,
Sharryn Gardner,
M. J. Barrett,
Emily K. Walton,
Akshat Kapur,
Steven J. Foster,
R. M. Bland,
Ben Bloom,
Ami Parikh,
Katherine Potier,
Judith Gilchrist,
Noreen West,
Paul T. Heath,
Yasser Iqbal,
Ian K. Maconochie,
Maggie Nyirenda,
Sophie Keers,
Katrina Cathie,
Jane Bayreuther,
Elizabeth-Jayne L. Herrieven,
Willian Townend

摘要

Background

Streptococcus pneumoniae is a global cause of community-acquired pneumonia (CAP) and invasive disease in children. The CAP-IT trial (grant No. 13/88/11; https://www.capitstudy.org.uk/) collected nasopharyngeal swabs from children discharged from hospitals with clinically diagnosed CAP, and found no differences in pneumococci susceptibility between higher and lower antibiotic doses and shorter and longer durations of oral amoxicillin treatment. Here, we studied in-depth the genomic epidemiology of pneumococcal (vaccine) serotypes and their antibiotic resistance profiles.

Methods

Three-hundred and ninety pneumococci cultured from 1132 nasopharyngeal swabs from 718 children were whole-genome sequenced (Illumina) and tested for susceptibility to penicillin and amoxicillin. Genome heterogeneity analysis was performed using long-read sequenced isolates (PacBio, n = 10) and publicly available sequences.

Results

Among 390 unique pneumococcal isolates, serotypes 15B/C, 11 A, 15 A and 23B1 were most prevalent (n = 145, 37.2%). PCV13 serotypes 3, 19A, and 19F were also identified (n = 25, 6.4%). STs associated with 19A and 19F demonstrated high genome variability, in contrast to serotype 3 (n = 13, 3.3%) that remained highly stable over a 20-year period. Non-susceptibility to penicillin (n = 61, 15.6%) and amoxicillin (n = 10, 2.6%) was low among the pneumococci analysed here and was independent of treatment dosage and duration. However, all 23B1 isolates (n = 27, 6.9%) were penicillin non-susceptible. This serotype was also identified in ST177, which is historically associated with the PCV13 serotype 19F and penicillin susceptibility, indicating a potential capsule-switch event.

Conclusions

Our data suggest that amoxicillin use does not drive pneumococcal serotype prevalence among children in the UK, and prompts consideration of PCVs with additional serotype coverage that are likely to further decrease CAP in this target population. Genotype 23B1 represents the convergence of a non-vaccine genotype with penicillin non-susceptibility and might provide a persistence strategy for ST types historically associated with vaccine serotypes. This highlights the need for continued genomic surveillance.