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Abstract

Due to the emergence of non-vaccine serotypes in vaccinated populations, remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA). To characterize lineages and antimicrobial resistance in 16F isolates obtained from South Africa and place the local findings in a global context, we analysed 10 923 . carriage isolates obtained from infants recruited as part of a broader SA birth cohort. We inferred serotype, resistance profile for penicillin, chloramphenicol, cotrimoxazole, erythromycin and tetracycline, and global pneumococcal sequence clusters (GPSCs) from genomic data. To ensure global representation, we also included carriage and disease isolates from the Global Pneumococcal Sequencing (GPS) project database (=19 607, collected from 49 countries across 5 continents, 1995–2018, accessed 17 March 2022). Nine per cent (934/10923) of isolates obtained from infants in the Drakenstein community in SA and 2 %(419/19607) of genomes in the GPS dataset were serotype 16F. Serotype 16F isolates were from 28 different lineages of with GPSC33 and GPSC46 having the highest proportion of serotype 16F isolates at 26 % (346/1353) and 53 % (716/1353), respectively. Serotype 16F isolates were identified globally, but most isolates were collected from Africa. GPSC33 was associated with carriage [OR (95 % CI) 0.24 (0.09–0.66); =0.003], while GPSC46 was associated with disease [OR (95 % CI) 19.9 (2.56–906.50); =0.0004]. Ten per cent (37/346) and 15 % (53/346) of isolates within GPSC33 had genes associated with resistance to penicillin and co-trimoxazole, respectively, and 18 % (128/716) of isolates within GPSC46 had genes associated with resistance to co-trimoxazole. Resistant isolates formed genetic clusters, which may suggest emerging resistant lineages. Serotype 16F lineages were common in southern Africa. Some of these lineages were associated with disease and resistance to penicillin and cotrimoxazole. We recommend continuous genomic surveillance to determine the long-term impact of serotype 16F lineages on vaccine efficacy and antimicrobial therapy globally. Investing in vaccine strategies that offer protection over a wide range of serotypes/lineages remains essential. This paper contains data hosted by Microreact.

Funding
This study was supported by the:
  • National Research Foundation of South Africa Grants (Award SRUG2204224295 & SNSF22071239126)
    • Principle Award Recipient: FelixDube
  • Wellcome Trust (Award 098051 and 206194)
    • Principle Award Recipient: StephenD Bentley
  • Bill and Melinda Gates Foundation (Award OPP1034556)
    • Principle Award Recipient: StephenD Bentley
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2023-11-02
2024-06-13
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References

  1. Wahl B, O’Brien KL, Greenbaum A, Majumder A, Liu L et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15. Lancet Glob Health 2018; 6:e744–e757 [View Article] [PubMed]
    [Google Scholar]
  2. Balsells E, Guillot L, Nair H, Kyaw MH. Serotype distribution of Streptococcus pneumoniae causing invasive disease in children in the post-PCV era: a systematic review and meta-analysis. PLoS One 2017; 12:e0177113 [View Article] [PubMed]
    [Google Scholar]
  3. Hanage WP. Serotype replacement in invasive pneumococcal disease: where do we go from here?. J Infect Dis 2007; 196:1282–1284 [View Article] [PubMed]
    [Google Scholar]
  4. 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]
  5. Brooks LRK, Mias GI. Streptococcus pneumoniae’s virulence and host immunity: aging, diagnostics, and prevention. Front Immunol 2018; 9:1366 [View Article] [PubMed]
    [Google Scholar]
  6. Bentley SD, Aanensen DM, Mavroidi A, Saunders D, Rabbinowitsch E et al. Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes. PLoS Genet 2006; 2:e31 [View Article] [PubMed]
    [Google Scholar]
  7. 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]
  8. Maiden MC, Bygraves JA, Feil E, Morelli G, Russell JE et al. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 1998; 95:3140–3145 [View Article] [PubMed]
    [Google Scholar]
  9. GPS:: Global Pneumococcal Sequencing Project. n.d https://www.pneumogen.net/gps/project_outline.html accessed 6 June 2022
  10. Dube FS, Ramjith J, Gardner-Lubbe S, Nduru P, Robberts FJL et al. Longitudinal characterization of nasopharyngeal colonization with Streptococcus pneumoniae in a South African birth cohort post 13-valent pneumococcal conjugate vaccine implementation. Sci Rep 2018; 8:1–9 [View Article] [PubMed]
    [Google Scholar]
  11. Bar-Zeev N, Swarthout TD, Everett DB, Alaerts M, Msefula J et al. Impact and effectiveness of 13-valent pneumococcal conjugate vaccine on population incidence of vaccine and non-vaccine serotype invasive pneumococcal disease in Blantyre, Malawi, 2006-18: prospective observational time-series and case-control studies. Lancet Glob Health 2021; 9:e989–e998 [View Article] [PubMed]
    [Google Scholar]
  12. Savulescu C, Krizova P, Lepoutre A, Mereckiene J, Vestrheim DF et al. Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study. Lancet Respir Med 2017; 5:648–656 [View Article] [PubMed]
    [Google Scholar]
  13. Mackenzie GA, Hill PC, Jeffries DJ, Hossain I, Uchendu U et al. Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study. Lancet Infect Dis 2016; 16:703–711 [View Article] [PubMed]
    [Google Scholar]
  14. 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]
  15. Ben-Shimol S, Givon-Lavi N, Grisaru-Soen G, Megged O, Greenberg D et al. Comparative incidence dynamics and serotypes of meningitis, bacteremic pneumonia and other-IPD in young children in the PCV era: insights from Israeli surveillance studies. Vaccine 2018; 36:5477–5484 [View Article] [PubMed]
    [Google Scholar]
  16. Bentley SD, Lo SW. Global genomic pathogen surveillance to inform vaccine strategies: a decade-long expedition in pneumococcal genomics. Genome Med 2021; 13:84 [View Article] [PubMed]
    [Google Scholar]
  17. Javaid N, Olwagen C, Nzenze S, Hawkins P, Gladstone R et al. Population genomics of pneumococcal carriage in South Africa following the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) immunization. Microb Genom 2022; 8:mgen000831 [View Article] [PubMed]
    [Google Scholar]
  18. Dayie N, Tettey EY, Newman MJ, Bannerman E, Donkor ES et al. Pneumococcal carriage among children under five in Accra, Ghana, five years after the introduction of pneumococcal conjugate vaccine. BMC Pediatr 2019; 19:316 [View Article] [PubMed]
    [Google Scholar]
  19. Phillips MT, Warren JL, Givon-Lavi N, Tothpal A, Regev-Yochay G et al. Evaluating post-vaccine expansion patterns of pneumococcal serotypes. Vaccine 2020; 38:7756–7763 [View Article] [PubMed]
    [Google Scholar]
  20. Chaguza C, Senghore M, Bojang E, Gladstone RA, Lo SW et al. Within-host microevolution of Streptococcus pneumoniae is rapid and adaptive during natural colonisation. Nat Commun 2020; 11:3442 [View Article] [PubMed]
    [Google Scholar]
  21. Daniels B, Kuhn L, Spooner E, Mulol H, Goga A et al. Cotrimoxazole guidelines for infants who are HIV-exposed but uninfected: a call for a public health and ethics approach to the evidence. Lancet Glob Health 2022; 10:e1198–e1203 [View Article] [PubMed]
    [Google Scholar]
  22. Vidal JE, Ghanem EB, Wu X, Wu K, Bai G et al. Transmission, colonization, and molecular pathogenesis of pneumococcus. Frontiers Media SA 2022231 [View Article]
    [Google Scholar]
  23. Kalizang’oma A, Chaguza C, Gori A, Davison C, Beleza S et al. Streptococcus pneumoniae serotypes that frequently colonise the human nasopharynx are common recipients of penicillin-binding protein gene fragments from Streptococcus mitis. Microb Genom 2021; 7:000622 [View Article] [PubMed]
    [Google Scholar]
  24. Dewé TCM, D’Aeth JC, Croucher NJ. Genomic epidemiology of penicillin-non-susceptible Streptococcus pneumoniae. Microb Genom 2019; 5:e000305 [View Article] [PubMed]
    [Google Scholar]
  25. Müller A, Kleynhans J, de Gouveia L, Meiring S, Cohen C et al. Streptococcus pneumoniae serotypes associated with death, South Africa, 2012-2018. Emerg Infect Dis 2022; 28:166–179 [View Article] [PubMed]
    [Google Scholar]
  26. Rosenthal J-L, Wong RB. Before and Beyond Divergence: The Politics of Economic Change in China and Europe Harvard University Press; 2011 p 291 [View Article]
    [Google Scholar]
  27. Weinberger DM, Warren JL, Dalby T, Shapiro ED, Valentiner-Branth P et al. Differences in the impact of pneumococcal serotype replacement in individuals with and without underlying medical conditions. Clin Infect Dis 2019; 69:100–106 [View Article] [PubMed]
    [Google Scholar]
  28. Grabenstein JD, Musey LK. Differences in serious clinical outcomes of infection caused by specific pneumococcal serotypes among adults. Vaccine 2014; 32:2399–2405 [View Article] [PubMed]
    [Google Scholar]
  29. Donkor ES, Annan JA, Badoe EV, Dayie N, Labi A-K et al. Pneumococcal carriage among HIV infected children in Accra, Ghana. BMC Infect Dis 2017; 17:133 [View Article] [PubMed]
    [Google Scholar]
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