Skip to main content

Advertisement

SpringerLink
Log in

Epidemiology of Haemophilus influenzae in the Republic of Ireland, 2010–2018

  • Original Article
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

The purpose of this study was to investigate H. influenzae epidemiology in the Republic of Ireland. We performed serotyping, multi-locus sequence typing (MLST) and susceptibility testing on H. influenzae isolates received by the Irish Meningitis and Sepsis Reference Laboratory from 2010 to 2018. Three hundred sixty-seven invasive and 41 non-invasive infection (NII) isolates were received. Invasive isolates were mostly recovered from paediatric (21%) and elderly (42%) populations. Invasive disease was more prevalent in females of childbearing age (72%) compared with males the same age (28%). Non-typeable H. influenzae (NTHi) predominated among invasive (83%) and NII (95%). Invasive Hib disease isolates were infrequent (4%, n = 15). Among invasive disease, Hif was the commonest encapsulated serotype (10%, n = 37), and the only encapsulated serotype detected in NII (5%, 2/41). The first PCR-confirmed serotypes d and a in Ireland were characterised among invasive disease in 2017 and 2018, respectively. MLST revealed a diverse NTHi population, while encapsulated serotypes were clonal. Sequence type (ST) 103 (n = 14) occurred exclusively in invasive NTHi disease. Ampicillin resistance (AmpR) was 18% among invasive isolates and 22% in NII. β-Lactamase production was the main source of ampicillin resistance in invasive and NII isolates. We detected β-lactamase negative ampicillin resistance (BLNAR) among invasive isolates. We report an NTHi fluoroquinolone-resistant clone: ST1524 among invasive (n = 2) and NII isolates (n = 2). The Hib vaccine has positively impacted on Hib disease in Ireland, given the low frequency of Hib. The dominance of NTHi, emergence of serotypes a and d and BLNAR suggest a changing H. influenzae epidemiology in Ireland.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

Any request for further anonymous data or isolates used in the study may be requested from the corresponding author. The assembled genome data for H. influenzae isolates in this study that were genome sequenced can be found at https://pubmlst.org/hinfluenzae/.

References

  1. Peltola H (2000) 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 13(2):302–317

    Article  CAS  Google Scholar 

  2. European Centre for Disease Prevention and Control (2017) Haemophilus influenzae Annual Epidemiological Report for 2017. https://www.ecdc.europa.eu/en/publications-data/haemophilus-influenzae-annual-epidemiological-report-2017 (Accessed 22 June 2020)

  3. Giufre M, Cardines R, Accogli M, Pardini M, Cerquetti M (2013) Identification of Haemophilus influenzae clones associated with invasive disease a decade after introduction of H. influenzae serotype b vaccination in Italy. Clin Vaccine Immunol 20(8):1223–1229

    Article  CAS  Google Scholar 

  4. Giufre M, Cardines R, Caporali MG, Accogli M, D'Ancona F, Cerquetti M (2011) Ten years of Hib vaccination in Italy: prevalence of non-encapsulated Haemophilus influenzae among invasive isolates and the possible impact on antibiotic resistance. Vaccine 29(22):3857–3862

    Article  Google Scholar 

  5. Heliodoro CIM, Bettencourt CR, Bajanca-Lavado MP (2020) Molecular epidemiology of invasive Haemophilus influenzae disease in Portugal: an update of the post-vaccine period, 2011-2018. Eur J Clin Microbiol Infect Dis. https://doi.org/10.1007/s10096-020-03865-0

  6. Soeters HM, Blain A, Pondo T, Doman B, Farley MM, Harrison LH, Lynfield R, Miller L, Petit S, Reingold A, Schaffner W, Thomas A, Zansky SM, Wang X, Briere EC (2018) Current epidemiology and trends in invasive Haemophilus influenzae disease-United States, 2009-2015. Clin Infect Dis 67(6):881–889

    Article  Google Scholar 

  7. Staples M, Graham RMA, Jennison AV (2017) Characterisation of invasive clinical Haemophilus influenzae isolates in Queensland, Australia using whole-genome sequencing. Epidemiol Infect 145(8):1727–1736

    Article  CAS  Google Scholar 

  8. Tsang RSW, Shuel M, Whyte K, Hoang L, Tyrrell G, Horsman G, Wylie J, Jamieson F, Lefebvre B, Haldane D, Gad RR, German GJ, Needle R (2017) Antibiotic susceptibility and molecular analysis of invasive Haemophilus influenzae in Canada, 2007 to 2014. J Antimicrob Chemother 72(5):1314–1319

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Ladhani SN, Collins S, Vickers A, Litt DJ, Crawford C, Ramsay ME, Slack MP (2012) Invasive Haemophilus influenzae serotype e and f disease, England and Wales. Emerg Infect Dis 18(5):725–732

    Article  Google Scholar 

  10. Resman F, Ristovski M, Ahl J, Forsgren A, Gilsdorf JR, Jasir A, Kaijser B, Kronvall G, Riesbeck K (2011) Invasive disease caused by Haemophilus influenzae in Sweden 1997-2009; evidence of increasing incidence and clinical burden of non-type b strains. Clin Microbiol Infect 17(11):1638–1645

    Article  CAS  Google Scholar 

  11. Andersson M, Resman F, Eitrem R, Drobni P, Riesbeck K, Kahlmeter G, Sundqvist M (2015) Outbreak of a beta-lactam resistant non-typeable Haemophilus influenzae sequence type 14 associated with severe clinical outcomes. BMC Infect Dis 15:581

    Article  Google Scholar 

  12. Deghmane AE, Hong E, Chehboub S, Terrade A, Falguieres M, Sort M, Harrison O, Jolley KA, Taha MK (2019) High diversity of invasive Haemophilus influenzae isolates in France and the emergence of resistance to third generation cephalosporins by alteration of ftsI gene. J Inf Secur 79(1):7–14

    Google Scholar 

  13. Giufre M, Cardines R, Brigante G, Orecchioni F, Cerquetti M (2017) Emergence of invasive Haemophilus influenzae type a disease in Italy. Clin Infect Dis 64(11):1626–1628

    Article  Google Scholar 

  14. Hammitt LL, Block S, Hennessy TW, Debyle C, Peters H, Parkinson A, Singleton R, Butler JC (2005) Outbreak of invasive Haemophilus influenzae serotype a disease. Pediatr Infect Dis J 24(5):453–456

    Article  Google Scholar 

  15. Honda H, Sato T, Shinagawa M, Fukushima Y, Nakajima C, Suzuki Y, Shiraishi T, Kuronuma K, Takahashi S, Takahashi H, Yokota SI (2018) Multiclonal expansion and high prevalence of beta-lactamase-negative Haemophilus influenzae with high-level ampicillin resistance in Japan and susceptibility to quinolones. Antimicrob Agents Chemother 62(9)

  16. Maddi S, Kolsum U, Jackson S, Barraclough R, Maschera B, Simpson KD, Pascal TG, Durviaux S, Hessel EM, Singh D (2017) Ampicillin resistance in Haemophilus influenzae from COPD patients in the UK. Int J Chron Obstruct Pulmon Dis 12:1507–1518

    Article  CAS  Google Scholar 

  17. Tristram S, Jacobs MR, Appelbaum PC (2007) Antimicrobial resistance in Haemophilus influenzae. Clin Microbiol Rev 20(2):368–389

    Article  CAS  Google Scholar 

  18. Health Protection Surveillance Centre (2018) Immunisation uptake at 12 and 24 months of age in Ireland, 2017. https://www.hpsc.ie/a-z/vaccinepreventable/vaccination/immunisationuptakestatistics/immunisationuptakestatisticsat12and24monthsofage/annualreports/Immunisation%20uptake%20at%2012%20and%2024%20months%20of%20age%20in%202017%20HPSC%20AnnRpt%20chapter%20v1.0%20final.pdf (Accessed 27th April 2020)

  19. Meyler K, Meehan M, Bennett D, Mulhall R, Harrison O, Gavin P, Drew RJ, Cunney R (2019) Spontaneous capsule loss in Haemophilus influenzae serotype b associated with Hib conjugate vaccine failure and invasive disease. Clin Microbiol Infect 25(3):390–391

    Article  CAS  Google Scholar 

  20. Davis GS, Sandstedt SA, Patel M, Marrs CF, Gilsdorf JR (2011) Use of bexB to detect the capsule locus in Haemophilus influenzae. J Clin Microbiol 49(7):2594–2601

    Article  CAS  Google Scholar 

  21. Falla TJ, Crook DW, Brophy LN, Maskell D, Kroll JS, Moxon ER (1994) PCR for capsular typing of Haemophilus influenzae. J Clin Microbiol 32(10):2382–2386

    Article  CAS  Google Scholar 

  22. Hobson RP, Williams A, Rawal K, Pennington TH, Forbes KJ (1995) Incidence and spread of Haemophilus influenzae on an Antarctic base determined using the polymerase chain reaction. Epidemiol Infect 114(1):93–103

    Article  CAS  Google Scholar 

  23. Meats E, Feil EJ, Stringer S, Cody AJ, Goldstein R, Kroll JS, Popovic T, Spratt BG (2003) Characterization of encapsulated and noncapsulated Haemophilus influenzae and determination of phylogenetic relationships by multilocus sequence typing. J Clin Microbiol 41(4):1623–1636

    Article  CAS  Google Scholar 

  24. Francisco AP, Vaz C, Monteiro PT, Melo-Cristino J, Ramirez M, Carrico JA (2012) PHYLOViZ: phylogenetic inference and data visualization for sequence based typing methods. BMC Bioinformatics 13:87

    Article  Google Scholar 

  25. The European Committee on Antimicrobial Susceptibility Testing (2019) Breakpoint tables for interpretation of MICs and zone diameters, version 9.0, 2019. http://www.eucast.org/clinical_breakpoints/

  26. Simpson EH (1949) Measurement of diversity. Nature 163:688

    Article  Google Scholar 

  27. Health Protection Surveillance Centre (2018) Annual Epidemiological Report: Haemophilus influenzae, in Ireland, 2018. https://www.hpsc.ie/a-z/vaccinepreventable/haemophilusinfluenzae/guidancepublications/annualreports/Haemophilus%20Influenza%20in%20Ireland%202018.pdf (Accessed 22nd June 2020)

  28. Meyler KL, Meehan M, Bennett D, Cunney R, Cafferkey M (2012) Development of a diagnostic real-time polymerase chain reaction assay for the detection of invasive Haemophilus influenzae in clinical samples. Diagn Microbiol Infect Dis 74(4):356–362

    Article  CAS  Google Scholar 

  29. Collins S, Ramsay M, Slack MP, Campbell H, Flynn S, Litt D, Ladhani SN (2014) Risk of invasive Haemophilus influenzae infection during pregnancy and association with adverse fetal outcomes. JAMA 311(11):1125–1132

    Article  CAS  Google Scholar 

  30. Moloney AC, Fogarty J, Clarke P, Musser JM (1997) Invasive Haemophilus influenzae in the Republic of Ireland. Eur J Clin Microbiol Infect Dis 16(5):377–380

    Article  CAS  Google Scholar 

  31. Health Protection Surveillance Centre (2002) Invasive Haemophilus influenzae in Ireland, 1996–2002. https://www.hpsc.ie/a-z/vaccinepreventable/haemophilusinfluenzae/guidancepublications/annualreports/File,2422,en.pdf (Accessed 27th April 2020)

  32. Whittaker R, Economopoulou A, Dias JG, Bancroft E, Ramliden M, Celentano LP (2017) Epidemiology of invasive Haemophilus influenzae disease, Europe, 2007-2014. Emerg Infect Dis 23(3):396–404

    Article  Google Scholar 

  33. Kaur R, Chang A, Xu Q, Casey JR, Pichichero ME (2011) Phylogenetic relatedness and diversity of non-typable Haemophilus influenzae in the nasopharynx and middle ear fluid of children with acute otitis media. J Med Microbiol 60(Pt 12):1841–1848

    Article  Google Scholar 

  34. Mansson V, Skaare D, Riesbeck K, Resman F (2017) The spread and clinical impact of ST14CC-PBP3 type IIb/A, a clonal group of non-typeable Haemophilus influenzae with chromosomally mediated beta-lactam resistance-a prospective observational study. Clin Microbiol Infect 23(3):209 e201–209 e207

    Article  Google Scholar 

  35. Berndsen MR, Erlendsdottir H, Gottfredsson M (2011) Evolving epidemiology of invasive Haemophilus infections in the post-vaccination era: results from a long-term population-based study. Clin Microbiol Infect 18(9):918–923

    Article  Google Scholar 

  36. Ulanova M, Tsang RSW (2014) Haemophilus influenzae serotype a as a cause of serious invasive infections. Lancet Infect Dis 14(1):70–82

    Article  Google Scholar 

Download references

Acknowledgements

We wish to thank all the laboratories in the Republic of Ireland for submitting isolates to the Irish Meningitis and Sepsis Reference Laboratory. We would like to thank Piaras O’Lorcain in the Health Protection Surveillance Centre, all the staff in the IMSRL diagnostic and epidemiology sections and the microbiology staff at CHI at Temple Street. This publication made use of the Haemophilus influenzae MLST website (https://urldefense.proofpoint.com/v2/url?u=https-3A__pubmlst.org_&=DwIGaQ&c=vh6FgFnduejNhPPD0fl_yRaSfZy8CWbWnIf4XJhSqx8&r=V6lgvsp7_YQfpNLaAUf0CSwfDDoh9Qwwv5DOzn76mjE&m=vmBsrBzN335wAnspLuFULOHx-XoNaElC2bRSeeDfswI&s=oisFn7sNhaBQgdjlf8udKqyzcgXvsKxo9YHkYQlsYOY&e=hinfluenzae/) sited at the University of Oxford (Jolley et al. Wellcome Open Res 2018, 3:124 [version 1; referees: 2 approved]). The development of this site has been funded by the Wellcome Trust.

Author information

Authors and Affiliations

  1. Irish Meningitis and Sepsis Reference Laboratory, Children’s Health Ireland at Temple Street, Dublin, Ireland

    Martha McElligott, Kenneth Meyler, Désirée Bennett, Robert Mulhall, Richard J. Drew & Robert Cunney

  2. Clinical Innovation Unit and Department of Clinical Microbiology Rotunda Hospital Dublin, Dublin, Ireland

    Richard J. Drew

  3. Royal College of Surgeons in Ireland, Dublin, Ireland

    Richard J. Drew & Robert Cunney

Authors
  1. Martha McElligott
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenneth Meyler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Désirée Bennett
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert Mulhall
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard J. Drew
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Robert Cunney
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Martha McElligott.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

H. influenzae isolates were received as part of a routine activity of the IMSRL for performing national surveillance of the invasive H. influenzae disease in the Republic of Ireland and were analysed anonymously.

Consent to participate

Not applicable.

Consent for publication

All authors have approved the manuscript and agree to its submission to the European Journal of Clinical Microbiology & Infectious Diseases.

Code availability

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Martha McElligott and Kenneth Meyler are joint first authors

Electronic supplementary material

ESM 1

(DOCX 401 kb)

ESM 2

(DOCX 43 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

McElligott, M., Meyler, K., Bennett, D. et al. Epidemiology of Haemophilus influenzae in the Republic of Ireland, 2010–2018. Eur J Clin Microbiol Infect Dis 39, 2335–2344 (2020). https://doi.org/10.1007/s10096-020-03971-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-020-03971-z

Keywords

Search

Navigation