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Abstract

Globally, India has a high burden of pneumococcal disease, and pneumococcal conjugate vaccine (PCV) has been rolled out in different phases across the country since May 2017 in the national infant immunization programme (NIP). To provide a baseline for assessing the impact of the vaccine on circulating pneumococci in India, genetic characterization of pneumococcal isolates detected prior to introduction of PCV would be helpful. Here we present a population genomic study of 480 isolates collected across India and from all age groups before vaccine introduction (2009–2017), including 294 isolates from pneumococcal disease and 186 collected through nasopharyngeal surveys. Population genetic structure, serotype and antimicrobial susceptibility profile were characterized and predicted from whole-genome sequencing data. Our findings revealed high levels of genetic diversity represented by 110 Global Pneumococcal Sequence Clusters (GPSCs) and 54 serotypes. Serotype 19F and GPSC1 (CC320) was the most common serotype and pneumococcal lineage, respectively. Coverage of PCV13 (Pfizer) and 10-valent Pneumosil (Serum Institute of India) serotypes in age groups of ≤2 and 3–5 years were 63–75 % and 60–69 %, respectively. Coverage of PPV23 (Merck) serotypes in age groups of ≥50 years was 62 % (98/158). Among the top five lineages causing disease, GPSC10 (CC230), which ranked second, is the only lineage that expressed both PCV13 (serotypes 3, 6A, 14, 19A and 19F) and non-PCV13 (7B, 13, 10A, 11A, 13, 15B/C, 22F, 24F) serotypes. It exhibited multidrug resistance and was the largest contributor (17 %, 18/103) of NVTs in the disease-causing population. Overall, 42 % (202/480) of isolates were penicillin-resistant (minimum inhibitory concentration ≥0.12 µg ml) and 45 % (217/480) were multidrug-resistant. Nine GPSCs (GPSC1, 6, 9, 10, 13, 16, 43, 91, 376) were penicillin-resistant and among them six were multidrug-resistant. Pneumococci expressing PCV13 serotypes had a higher prevalence of antibiotic resistance. Sequencing of pneumococcal genomes has significantly improved our understanding of the biology of these bacteria. This study, describing the pneumococcal disease and carriage epidemiology pre-PCV introduction, demonstrates that 60–75 % of pneumococcal serotypes in children ≤5 years are covered by PCV13 and Pneumosil. Vaccination against pneumococci is very likely to reduce antibiotic resistance. A multidrug-resistant pneumococcal lineage, GPSC10 (CC230), is a high-risk clone that could mediate serotype replacement.

Funding
This study was supported by the:
  • Centers for Disease Control and Prevention
    • Principle Award Recipient: LesleyMcGee
  • 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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2021-09-08
2021-09-16
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References

  1. 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]
  2. Wahl B, O’Brien KL, Greenbaum A, Majumder A, Liu L. 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]
  3. Suri S. Reducing infectious diseases in children: Tracking india’s progress and outlining the challenges; 2019 https://www.orfonline.org/wp-content/uploads/2019/04/ORF_Special_Report_86_Infectious_Diseases.pdf
  4. Lahariya C. Vaccine epidemiology: A review. J Family Med Prim Care 2016; 5:7–15 [View Article] [PubMed]
    [Google Scholar]
  5. Sharma-Kuinkel BK, Rude TH, Fowler VG. Pulse field Gel electrophoresis. Methods Mol Biol 2016; 1373:117–130 [View Article] [PubMed]
    [Google Scholar]
  6. Sabat AJ, Budimir A, Nashev D, Sá-Leão R, van Dijl J m et al. Overview of molecular typing methods for outbreak detection and epidemiological surveillance. Euro Surveill 2013; 18:20380 [View Article] [PubMed]
    [Google Scholar]
  7. Dhar R, Ghoshal A, Guleria R, Sharma S, Kulkarni T et al. Clinical practice guidelines 2019: Indian consensus-based recommendations on pneumococcal vaccination for adults. Lung India 2020; 37:19 [View Article]
    [Google Scholar]
  8. Deng X, Memari N, Teatero S, Athey T, Isabel M. Whole-genome sequencing for surveillance of invasive pneumococcal diseases in Ontario, Canada: rapid prediction of genotype, antibiotic resistance and characterization of emerging serotype 22F. Front Microbiol 2016; 7:2099 [View Article] [PubMed]
    [Google Scholar]
  9. Donkor ES. Molecular typing of the pneumococcus and its application in epidemiology in sub-Saharan Africa. Front Cell Infect Microbiol 2013; 3:12 [View Article] [PubMed]
    [Google Scholar]
  10. 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]
  11. Shah AS, Nisarga R, Ravi Kumar KL, Hubler R, Herrera G. Establishment of population-based surveillance for invasive pneumococcal disease in Bangalore, India. Indian J Med Sci 2009; 63:498–507 [View Article] [PubMed]
    [Google Scholar]
  12. Vandana G, Feroze AG, Geetha N, Avid H, Ravi Kumar KL. Pan India distribution of pneumococcal serotypes (PIDOPS) causing invasive pneumococcal disease and pneumonia in children between 6 weeks and 5 years and their antimicrobial resistance – Phase I. Pediatric Infectious Disease 2016; 8:47–51 [View Article]
    [Google Scholar]
  13. Epping L, van Tonder AJ, Gladstone RA. The Global Pneumococcal Sequencing Consortium Bentley SD et al. Seroba: Rapid high-throughput serotyping of Streptococcus pneumoniae from whole genome sequence data. Microb Genom 2018; 4: [PubMed]
    [Google Scholar]
  14. 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]
  15. 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; 22:60e9–60 [View Article] [PubMed]
    [Google Scholar]
  16. Li Y, Metcalf BJ, Chochua S, Li Z, Gertz RE. 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]
  17. Metcalf BJ, Chochua S, Gertz RE Jr, Li Z, Walker H et al. Using whole genome sequencing to identify resistance determinants and predict antimicrobial resistance phenotypes for year 2015 invasive pneumococcal disease isolates recovered in the United States. Clin Microbiol Infect 2016; 22:1002e1-1002.e8 [View Article] [PubMed]
    [Google Scholar]
  18. Li Y, Metcalf BJ, Chochua S, Li Z, Gertz RE et al. Penicillin-binding protein transpeptidase signatures for tracking and prbinding protein transpeptidase signatures for tracking and predicting β-lactam resistance levels in Streptococcus pneumoniae. mbio 2016; 7: [View Article]
    [Google Scholar]
  19. Hausdorff WP, Feikin DR, Klugman KP. Epidemiological differences among pneumococcal serotypes. Lancet Infect Dis 2005; 5:83–93 [View Article] [PubMed]
    [Google Scholar]
  20. Price MN, Dehal PS, Arkin AP. FastTree 2 – approximately maximum-likelihood trees for large alignments. PLoS One 2010; 5:e9490 [View Article] [PubMed]
    [Google Scholar]
  21. Smalt A mapper for DNA sequencing reads; 2021 https://sourceforge.net/projects/smalt
  22. Gladstone RA, SW L, Goater R, Yeats C, Taylor B. Visualizing variation within Global Pneumococcal Sequence Clusters (GPSCs) and country population snapshots to contextualize pneumococcal isolates. Microb Genom 2020; 6: [View Article] [PubMed]
    [Google Scholar]
  23. 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]
    [Google Scholar]
  24. Balsells E, Dagan R, Yildirim I, Gounder PP, Steens A. The relative invasive disease potential of Streptococcus pneumoniae among children after PCV introduction: a systematic review and meta-analysis. J Infect 2018; 77:368–378 [View Article] [PubMed]
    [Google Scholar]
  25. Salter SJ, Hinds J, Gould KA, Lambertsen L, Hanage WP. Variation at the capsule locus, cps, of mistyped and non-typable Streptococcus pneumoniae isolates. Microbiology (Reading) 2012; 158:1560–1569 [View Article] [PubMed]
    [Google Scholar]
  26. Balaji V, Jayaraman R, Verghese VP, Baliga PR, Kurien T. Pneumococcal serotypes associated with invasive disease in under five children in India & implications for vaccine policy. Indian J Med Res 2015; 142:286–292 [View Article] [PubMed]
    [Google Scholar]
  27. John J, Varghese R, Lionell J, Neeravi A, Veeraraghavan B. Non-vaccine pneumococcal serotypes among children with invasive pneumococcal disease. Indian Pediatr 2018; 55:874–876 [View Article] [PubMed]
    [Google Scholar]
  28. Ouldali N, Levy C, Varon E, Bonacorsi S, Béchet S. Incidence of paediatric pneumococcal meningitis and emergence of new serotypes: a time-series analysis of a 16-year French national survey. Lancet Infect Dis 2018; 18:983–991 [View Article] [PubMed]
    [Google Scholar]
  29. Klugman KP, Rodgers GL. Time for a third-generation pneumococcal conjugate vaccine. Lancet Infect Dis 2021; 21:14–16 [View Article] [PubMed]
    [Google Scholar]
  30. Cecil RL, Plummer N. Pneumococcus Type II Pneumonia: A clinical and bacteriologic study of one thousand cases, with special reference to serum therapy. JAMA 1932; 98:779–786
    [Google Scholar]
  31. Saha SK, Al Emran HM, Hossain B, Darmstadt GL, Saha S et al. Streptococcus pneumoniae serotype-2 childhood meningitis in Bangladesh: a newly recognized pneumococcal infection threat. PLoS One 2012; 7:e32134 [View Article] [PubMed]
    [Google Scholar]
  32. Dagan R, Ben-Shimol S, Benisty R, Regev-Yochay G, Lo SW et al. A nationwide outbreak of invasive pneumococcal disease in Israel caused by Streptococcus pneumoniae serotype 2. Clin Infect Dis 2020 [View Article]
    [Google Scholar]
  33. PubMLST Streptococcus pneumoniae isolates database; 2020 https://pubmlst.org/bigsdb?db=pubmlst_spneumoniae_isolates
  34. Collard J-M, Sanda A-K, Jusot J-F. Determination of Pneumococcal serotypes in meningitis cases in Niger, 2003–2011. PLoS ONE 2013; 8:e60432
    [Google Scholar]
  35. Saha SK, Hossain B, Islam M, Hasanuzzaman M, Saha S et al. Epidemiology of invasive pneumococcal disease in bangladeshi children before introduction of pneumococcal conjugate vaccine. Pediatr Infect Dis J 2016; 35:655–661 [View Article] [PubMed]
    [Google Scholar]
  36. Antonio M, Dada-Adegbola H, Biney E, Awine T, O’Callaghan J. Molecular epidemiology of pneumococci obtained from Gambian children aged 2–29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine. BMC Infect Dis 2008; 8:81 [View Article] [PubMed]
    [Google Scholar]
  37. Johnson HL, Deloria-Knoll M, Levine OS, Stoszek SK, Freimanis Hance L. Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: the pneumococcal global serotype project. PLoS Med 2010; 7: [View Article] [PubMed]
    [Google Scholar]
  38. Ludwig G, Garcia-Garcia S, Lanaspa M, Ciruela P, Esteva C. Serotype and clonal distribution dynamics of invasive pneumococcal strains after PCV13 introduction (2011-2016): Surveillance data from 23 sites in Catalonia, Spain. PLoS One 2020; 15:e0228612 [View Article] [PubMed]
    [Google Scholar]
  39. Klugman KP, Black S. Impact of existing vaccines in reducing antibiotic resistance: Primary and secondary effects. Proc Natl Acad Sci U S A 2018; 115:12896–12901 [View Article] [PubMed]
    [Google Scholar]
  40. Doherty TM, Hausdorff WP, Kristinsson KG. Effect of vaccination on the use of antimicrobial agents: a systematic literature review. Ann Med 2020; 52:283–299 [View Article] [PubMed]
    [Google Scholar]
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