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Abstract

The implementation of pneumococcal conjugate vaccines (PCVs) has led to a decline in vaccine-type disease. However, there is evidence that the epidemiology of non-typeable Haemophilus influenzae (NTHi) carriage and disease can be altered as a consequence of PCV introduction. We explored the epidemiological shifts in NTHi carriage using whole genome sequencing over a 5-year period that included PCV13 replacement of PCV7 in the UK’s National Immunization Programme in 2010. Between 2008/09 and 2012/13 (October to March), nasopharyngeal swabs were taken from children <5 years of age. Significantly increased carriage post-PCV13 was observed and lineage-specific associations with Streptococcus pneumoniae were seen before but not after PCV13 introduction. NTHi were characterized into 11 discrete, temporally stable lineages, congruent with current knowledge regarding the clonality of NTHi. The increased carriage could not be linked to the expansion of a particular clone and different co-carriage dynamics were seen before PCV13 implementation when NTHi co-carried with vaccine serotype pneumococci. In summary, PCV13 introduction has been shown to have an indirect effect on NTHi epidemiology and there exists both negative and positive, distinct associations between pneumococci and NTHi. This should be considered when evaluating the impacts of pneumococcal vaccine design and policy.

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2018-08-06
2019-10-20
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References

  1. de Chiara M, Hood D, Muzzi A, Pickard DJ, Perkins T et al. Genome sequencing of disease and carriage isolates of nontypeable Haemophilus influenzae identifies discrete population structure. Proc Natl Acad Sci USA 2014;111:5439–5444 [CrossRef][PubMed]
    [Google Scholar]
  2. Peltola H. Worldwide Haemophilus influenzae type b disease at the beginning of the 21st century: global analysis of the disease burden 25 years after the use of the polysaccharide vaccine and a decade after the advent of conjugates. Clin Microbiol Rev 2000;13:302–317 [CrossRef][PubMed]
    [Google Scholar]
  3. Ladhani S, Slack MP, Heath PT, von Gottberg A, Chandra M et al. Invasive Haemophilus influenzae disease, Europe, 1996–2006. Emerg Infect Dis 2010;16:455–463 [CrossRef][PubMed]
    [Google Scholar]
  4. Rovers MM, Schilder AGM, Zielhuis GA, Rosenfeld RM. Otitis media. The Lancet 2004;363:465–473 [CrossRef]
    [Google Scholar]
  5. Lyczak JB, Cannon CL, Pier GB. Lung infections associated with cystic fibrosis. Clin Microbiol Rev 2002;15:194–222 [CrossRef][PubMed]
    [Google Scholar]
  6. Rayner RJ, Hiller EJ, Ispahani P, Baker M. Haemophilus infection in cystic fibrosis. Arch Dis Child 1990;65:255–258 [CrossRef][PubMed]
    [Google Scholar]
  7. Eldika N, Sethi S. Role of nontypeable Haemophilus influenzae in exacerbations and progression of chronic obstructive pulmonary disease. Curr Opin Pulm Med 2006;12:118–124 [CrossRef][PubMed]
    [Google Scholar]
  8. Whittaker R, Economopoulou A, Dias JG, Bancroft E, Ramliden M et al. Epidemiology of invasive Haemophilus influenzae disease, Europe, 2007–2014. Emerg Infect Dis 2017;23:396–404 [CrossRef][PubMed]
    [Google Scholar]
  9. Wiertsema SP, Kirkham LA, Corscadden KJ, Mowe EN, Bowman JM et al. Predominance of nontypeable Haemophilus influenzae in children with otitis media following introduction of a 3+0 pneumococcal conjugate vaccine schedule. Vaccine 2011;29:5163–5170 [CrossRef][PubMed]
    [Google Scholar]
  10. Revai K, Mccormick DP, Patel J, Grady JJ, Saeed K et al. Effect of pneumococcal conjugate vaccine on nasopharyngeal bacterial colonization during acute otitis media. Pediatrics 2006;117:1823–1829 [CrossRef][PubMed]
    [Google Scholar]
  11. Xu Q, Almudervar A, Casey JR, Pichichero ME. Nasopharyngeal bacterial interactions in children. Emerg Infect Dis 2012;18:1738–1745 [CrossRef][PubMed]
    [Google Scholar]
  12. Camilli R, Vescio MF, Giufrè M, Daprai L, Garlaschi ML et al. Carriage of Haemophilus influenzae is associated with pneumococcal vaccination in Italian children. Vaccine 2015;33:4559–4564 [CrossRef][PubMed]
    [Google Scholar]
  13. Spijkerman J, Prevaes SM, van Gils EJ, Veenhoven RH, Bruin JP et al. Long-term effects of pneumococcal conjugate vaccine on nasopharyngeal carriage of S. pneumoniae, S. aureus, H. influenzae and M. catarrhalis. PLoS One 2012;7:e39730 [CrossRef][PubMed]
    [Google Scholar]
  14. Lewnard JA, Givon-Lavi N, Huppert A, Pettigrew MM, Regev-Yochay G et al. Epidemiological markers for interactions among Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus in upper respiratory tract carriage. J Infect Dis 2016;213:1596–1605 [CrossRef][PubMed]
    [Google Scholar]
  15. Shiri T, Nunes MC, Adrian PV, van Niekerk N, Klugman KP et al. Interrelationship of Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus colonization within and between pneumococcal-vaccine naïve mother-child dyads. BMC Infect Dis 2013;13:483 [CrossRef][PubMed]
    [Google Scholar]
  16. Murphy TF. Vaccines for nontypeable Haemophilus influenzae: the future is now. Clin Vaccine Immunol 2015;22:459–466 [CrossRef][PubMed]
    [Google Scholar]
  17. Devine VT, Cleary DW, Jefferies JM, Anderson R, Morris DE et al. The rise and fall of pneumococcal serotypes carried in the PCV era. Vaccine 2017;35:1293–1298 [CrossRef][PubMed]
    [Google Scholar]
  18. 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 [CrossRef][PubMed]
    [Google Scholar]
  19. Gladstone RA, Jefferies JM, Tocheva AS, Beard KR, Garley D et al. Five winters of pneumococcal serotype replacement in UK carriage following PCV introduction. Vaccine 2015;33:2015–2021 [CrossRef][PubMed]
    [Google Scholar]
  20. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014;30:2114–2120 [CrossRef][PubMed]
    [Google Scholar]
  21. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012;19:455–477 [CrossRef][PubMed]
    [Google Scholar]
  22. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014;30:2068–2069 [CrossRef][PubMed]
    [Google Scholar]
  23. Inouye M, Dashnow H, Raven LA, Schultz MB, Pope BJ et al. SRST2: Rapid genomic surveillance for public health and hospital microbiology labs. Genome Med 2014;6:90 [CrossRef][PubMed]
    [Google Scholar]
  24. Davis GS, Sandstedt SA, Patel M, Marrs CF, Gilsdorf JR. Use of bexB to detect the capsule locus in Haemophilus influenzae. J Clin Microbiol 2011;49:2594–2601 [CrossRef][PubMed]
    [Google Scholar]
  25. Hunt M, Mather AE, Sánchez-Busó L, Page AJ, Parkhill J et al. ARIBA: rapid antimicrobial resistance genotyping directly from sequencing reads. Microb Genom 2017;3:e000131 [CrossRef][PubMed]
    [Google Scholar]
  26. Jia B, Raphenya AR, Alcock B, Waglechner N, Guo P et al. CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database. Nucleic Acids Res 2017;45:D566–D573 [CrossRef][PubMed]
    [Google Scholar]
  27. Skaare D, Allum AG, Anthonisen IL, Jenkins A, Lia A et al. Mutant ftsI genes in the emergence of penicillin-binding protein-mediated β-lactam resistance in Haemophilus influenzae in Norway. Clin Microbiol Infect 2010;16:1117–1124 [CrossRef][PubMed]
    [Google Scholar]
  28. Slater GS, Birney E. Automated generation of heuristics for biological sequence comparison. BMC Bioinformatics 2005;6:31 [CrossRef][PubMed]
    [Google Scholar]
  29. Atkinson CT, Kunde DA, Tristram SG. Acquired macrolide resistance genes in Haemophilus influenzae?. J Antimicrob Chemother 2015;70:2234–2236 [CrossRef][PubMed]
    [Google Scholar]
  30. Peric M, Bozdogan B, Jacobs MR, Appelbaum PC. Effects of an efflux mechanism and ribosomal mutations on macrolide susceptibility of Haemophilus influenzae clinical isolates. Antimicrob Agents Chemother 2003;47:1017–1022 [CrossRef][PubMed]
    [Google Scholar]
  31. Tait-Kamradt A, Davies T, Cronan M, Jacobs MR, Appelbaum PC et al. Mutations in 23S rRNA and ribosomal protein L4 account for resistance in pneumococcal strains selected in vitro by macrolide passage. Antimicrob Agents Chemother 2000;44:2118–2125 [CrossRef][PubMed]
    [Google Scholar]
  32. Hadfield J, Croucher NJ, Goater RJ, Abudahab K, Aanensen DM et al. Phandango: an interactive viewer for bacterial population genomics. Bioinformatics 2017;btx610-btx [CrossRef][PubMed]
    [Google Scholar]
  33. Treangen TJ, Ondov BD, Koren S, Phillippy AM. The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol 2014;15:524 [CrossRef][PubMed]
    [Google Scholar]
  34. Castresana J. Selection of conserved blocks from multiple alignments for their use in phylogenetic analysis. Mol Biol Evol 2000;17:540–552 [CrossRef][PubMed]
    [Google Scholar]
  35. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 2014;30:1312–1313 [CrossRef]
    [Google Scholar]
  36. Miller MA, Pfeiffer W, Schwartz T. Creating the CIPRES Science Gateway for inference of large phylogenetic trees. 2010 Gateway Computing Environments Workshop (GCE); 2010 14-14 Nov 2010
    [Google Scholar]
  37. Cheng L, Connor TR, Sirén J, Aanensen DM, Corander J. Hierarchical and spatially explicit clustering of DNA sequences with BAPS software. Mol Biol Evol 2013;30:1224–1228 [CrossRef][PubMed]
    [Google Scholar]
  38. Argimón S, Abudahab K, Goater RJ, Fedosejev A, Bhai J et al. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microb Genom 2016;2:e000093 [CrossRef][PubMed]
    [Google Scholar]
  39. Didelot X, Lawson D, Darling A, Falush D. Inference of homologous recombination in bacteria using whole-genome sequences. Genetics 2010;186:1435–1449 [CrossRef][PubMed]
    [Google Scholar]
  40. Oksanen J, Blanchet F, Kindt R, Legendre P, O’Hara R. Vegan: Community ecology package. R Packag. 2.3-3. 2016
  41. Lin AV, Stewart V. Functional roles for the GerE-family carboxyl-terminal domains of nitrate response regulators NarL and NarP of Escherichia coli K-12. Microbiology 2010;156:2933–2943 [CrossRef]
    [Google Scholar]
  42. Dabernat H, Delmas C, Seguy M, Pelissier R, Faucon G et al. Diversity of beta-lactam resistance-conferring amino acid substitutions in penicillin-binding protein 3 of Haemophilus influenzae. Antimicrob Agents Chemother 2002;46:2208–2218 [CrossRef][PubMed]
    [Google Scholar]
  43. Ubukata K, Shibasaki Y, Yamamoto K, Chiba N, Hasegawa K et al. Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae. Antimicrob Agents Chemother 2001;45:1693–1699 [CrossRef][PubMed]
    [Google Scholar]
  44. Slack MPE. The evidence for non-typeable Haemophilus influenzae as a causative agent of childhood pneumonia. Pneumonia 2017;9:9 [CrossRef][PubMed]
    [Google Scholar]
  45. Connor TR, Corander J, Hanage WP. Population subdivision and the detection of recombination in non-typable Haemophilus influenzae. Microbiology 2012;158:2958–2964 [CrossRef]
    [Google Scholar]
  46. Chien YW, Vidal JE, Grijalva CG, Bozio C, Edwards KM et al. Density interactions among Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus in the nasopharynx of young Peruvian children. Pediatr Infect Dis J 2013;32:72–77 [CrossRef][PubMed]
    [Google Scholar]
  47. Shukla SD, Sohal SS, O'Toole RF, Eapen MS, Walters EH. Platelet activating factor receptor: gateway for bacterial chronic airway infection in chronic obstructive pulmonary disease and potential therapeutic target. Expert Rev Respir Med 2015;9:473–485 [CrossRef][PubMed]
    [Google Scholar]
  48. Shakhnovich EA, King SJ, Weiser JN. Neuraminidase expressed by Streptococcus pneumoniae desialylates the lipopolysaccharide of Neisseria meningitidis and Haemophilus influenzae: a paradigm for interbacterial competition among pathogens of the human respiratory tract. Infect Immun 2002;70:7161–7164 [CrossRef][PubMed]
    [Google Scholar]
  49. Lysenko ES, Ratner AJ, Nelson AL, Weiser JN. The role of innate immune responses in the outcome of interspecies competition for colonization of mucosal surfaces. PLoS Pathog 2005;1:e1 [CrossRef][PubMed]
    [Google Scholar]
  50. Earle SG, Wu CH, Charlesworth J, Stoesser N, Gordon NC et al. Identifying lineage effects when controlling for population structure improves power in bacterial association studies. Nat Microbiol 2016;1:16041 [CrossRef][PubMed]
    [Google Scholar]
  51. Hiltke TJ, Schiffmacher AT, Dagonese AJ, Sethi S, Murphy TF. Horizontal transfer of the gene encoding outer membrane protein P2 of nontypeable Haemophilus influenzae, in a patient with chronic obstructive pulmonary disease. J Infect Dis 2003;188:114–117 [CrossRef][PubMed]
    [Google Scholar]
  52. Witherden EA, Bajanca-Lavado MP, Tristram SG, Nunes A. Role of inter-species recombination of the ftsI gene in the dissemination of altered penicillin-binding-protein-3-mediated resistance in Haemophilus influenzae and Haemophilus haemolyticus. J Antimicrob Chemother 2014;69:1501–1509 [CrossRef][PubMed]
    [Google Scholar]
  53. Cody AJ, Field D, Feil EJ, Stringer S, Deadman ME et al. High rates of recombination in otitis media isolates of non-typeable Haemophilus influenzae. Infect Genet Evol 2003;3:57–66 [CrossRef][PubMed]
    [Google Scholar]
  54. Lacross NC, Marrs CF, Gilsdorf JR. Population structure in nontypeable Haemophilus influenzae. Infect Genet Evol 2013;14:125–136 [CrossRef][PubMed]
    [Google Scholar]
  55. Waight PA, Andrews NJ, Ladhani SN, Sheppard CL, Slack MP 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 [CrossRef][PubMed]
    [Google Scholar]
  56. 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 [CrossRef][PubMed]
    [Google Scholar]
  57. Feikin DR, Kagucia EW, Loo JD, Link-Gelles R, Puhan MA et al. Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites. PLoS Med 2013;10:e1001517 [CrossRef][PubMed]
    [Google Scholar]
  58. Roca A, Hill PC, Townend J, Egere U, Antonio M et al. Effects of community-wide vaccination with PCV-7 on pneumococcal nasopharyngeal carriage in the Gambia: a cluster-randomized trial. PLoS Med 2011;8:e1001107 [CrossRef][PubMed]
    [Google Scholar]
  59. Ingels H, Rasmussen J, Andersen PH, Harboe ZB, Glismann S et al. Impact of pneumococcal vaccination in Denmark during the first 3 years after PCV introduction in the childhood immunization programme. Vaccine 2012;30:3944–3950 [CrossRef]
    [Google Scholar]
  60. Rodenburg GD, de Greeff SC, Jansen AG, de Melker HE, Schouls LM et al. Effects of pneumococcal conjugate vaccine 2 years after its introduction, the Netherlands. Emerg Infect Dis 2010;16:816–823 [CrossRef][PubMed]
    [Google Scholar]
  61. 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 [CrossRef][PubMed]
    [Google Scholar]
  62. Jauneikaite E, Jefferies JM, Hibberd ML, Clarke SC. Prevalence of Streptococcus pneumoniae serotypes causing invasive and non-invasive disease in South East Asia: a review. Vaccine 2012;30:3503–3514 [CrossRef]
    [Google Scholar]
  63. Weinberger DM, Malley R, Lipsitch M. Serotype replacement in disease after pneumococcal vaccination. Lancet 2011;378:1962–1973 [CrossRef][PubMed]
    [Google Scholar]
  64. Biesbroek G, Wang X, Keijser BJ, Eijkemans RM, Trzciński K et al. Seven-valent pneumococcal conjugate vaccine and nasopharyngeal microbiota in healthy children. Emerg Infect Dis 2014;20:201–210 [CrossRef][PubMed]
    [Google Scholar]
  65. Mika M, Maurer J, Korten I, Allemann A, Aebi S et al. Influence of the pneumococcal conjugate vaccines on the temporal variation of pneumococcal carriage and the nasal microbiota in healthy infants: a longitudinal analysis of a case–control study. Microbiome 2017;5:85 [CrossRef]
    [Google Scholar]
  66. Jefferies JM, Clarke SC, Webb JS, Kraaijeveld AR. Risk of red queen dynamics in pneumococcal vaccine strategy. Trends Microbiol 2011;19:377–381 [CrossRef][PubMed]
    [Google Scholar]
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