Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link

Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.

Volume 31, Number 4—April 2025
Research

Case–Control Study of Factors Associated with Hemolytic Uremic Syndrome among Shiga Toxin–Producing Escherichia coli Patients, Ireland, 2017–2020

Diana Espadinha1Comments to Author , Melissa Brady1Comments to Author , Carina Brehony, Douglas Hamilton, Lois O’Connor, Robert Cunney, Suzanne Cotter, Anne Carroll, Patricia Garvey, and Eleanor McNamara
Author affiliation: European Programme for Public Health Microbiology Training, European Centre for Disease Prevention and Control, Solna, Sweden (D. Espadinha); National Reference Laboratory for STEC at Public Health Laboratory Health Service Executive, Cherry Orchard Hospital, Dublin, Ireland (D. Espadinha, A. Carroll, E. McNamara); European Programme for Intervention Epidemiology Training, European Centre for Disease Prevention and Control, Solna (M. Brady); Health Service Executive Health Protection Surveillance Centre, Dublin (M. Brady, C. Brehony, S. Cotter, P. Garvey); Health Service Executive National Social Inclusion Office, Dublin (D. Hamilton); Health Service Executive Public Health, Dr. Steevens’ Hospital, Dublin (L. O'Connor); Children's Health Ireland at Temple Street, Dublin (R. Cunney); Royal College of Surgeons in Ireland, Dublin (R. Cunney); Trinity College Dublin School of Medicine and Saint James's Hospital, Dublin (E. McNamara)

Main Article

Figure

Maximum-likelihood phylogenetic tree of HUS and non-HUS STEC isolates from study of HUS among patients with STEC, Ireland, 2017–2020. Tree was generated by using RaxML (23) on the basis of a multi-FASTA alignment of the core genes of the 531 STEC isolates. We annotated and visualized the final tree by using iTOL version 6.8.1 (https://itol.embl.de) (24). HUS cases (indicated by red stars) were distributed across several serogroups: O26 (36%), O157 (26%), O145 (14%), O103 (4.6%), O111 (2.8%), and O55 (5.6%). GWAS, genomewide association study; HUS, hemolytic uremic syndrome; MVA, multivariable logistic regression analysis; STEC, Shiga toxin–producing Escherichia coli.

Figure. Maximum-likelihood phylogenetic tree of HUS and non-HUS STEC isolates from study of HUS among patients with STEC, Ireland, 2017–2020. Tree was generated by using RaxML (23) on the basis of a multi-FASTA alignment of the core genes of the 531 STEC isolates. We annotated and visualized the final tree by using iTOL version 6.8.1 (https://itol.embl.de) (24). HUS cases (indicated by red stars) were distributed across several serogroups: O26 (36%), O157 (26%), O145 (14%), O103 (4.6%), O111 (2.8%), and O55 (5.6%). GWAS, genomewide association study; HUS, hemolytic uremic syndrome; MVA, multivariable logistic regression analysis; STEC, Shiga toxin–producing Escherichia coli.

Main Article

References
  1. Health Service Executive Health Protection Surveillance Centre. VTEC infection in Ireland, 2017. 2019 [cited 2023 Feb 7]. https://www.hpsc.ie/a-z/gastroenteric/vtec/epidemiologicaldata/annualreportsonepidemiologyofverotoxigenicecoli/VTEC%20infection%20in%20Ireland%202017.pdf
  2. Health Service Executive Health Protection Surveillance Centre. Infectious intestinal disease: public health & clinical guidance, version 1.1. 2012 [cited 2023 Feb 7]. https://www.hpsc.ie/a-z/gastroenteric/gastroenteritisoriid/guidance/File,13492,en.pdf
  3. Brzuszkiewicz  E, Thürmer  A, Schuldes  J, Leimbach  A, Liesegang  H, Meyer  FD, et al. Genome sequence analyses of two isolates from the recent Escherichia coli outbreak in Germany reveal the emergence of a new pathotype: Entero-Aggregative-Haemorrhagic Escherichia coli (EAHEC). Arch Microbiol. 2011;193:883–91. DOIPubMedGoogle Scholar
  4. Hamilton  D, Cullinan  J. A practical composite risk score for the development of Haemolytic Uraemic Syndrome from Shiga toxin-producing Escherichia coli. Eur J Public Health. 2019;29:861–8. DOIPubMedGoogle Scholar
  5. Boerlin  P, McEwen  SA, Boerlin-Petzold  F, Wilson  JB, Johnson  RP, Gyles  CL. Associations between virulence factors of Shiga toxin-producing Escherichia coli and disease in humans. J Clin Microbiol. 1999;37:497–503. DOIPubMedGoogle Scholar
  6. Wong  CS, Mooney  JC, Brandt  JR, Staples  AO, Jelacic  S, Boster  DR, et al. Risk factors for the hemolytic uremic syndrome in children infected with Escherichia coli O157:H7: a multivariable analysis. Clin Infect Dis. 2012;55:33–41. DOIPubMedGoogle Scholar
  7. European Centre for Disease Prevention and Control. Shiga toxin/verocytotoxin–producing Escherichia coli (STEC/VTEC) infection annual epidemiological report for 2018. Stockholm; The Centre; 2020.
  8. Rice  T, Quinn  N, Sleator  RD, Lucey  B. Changing diagnostic methods and increased detection of verotoxigenic Escherichia coli, Ireland. Emerg Infect Dis. 2016;22:1656–7. DOIPubMedGoogle Scholar
  9. HSE Health Protection Surveillance Centre. Case definitions 2019 [cited 2024 May 7]. https://www.hpsc.ie/a-z/gastroenteric/vtec/casedefinitions
  10. European Union. Commission implementing decision (EU) 2018/945 of 22 June 2018 on the communicable diseases and related special health issues to be covered by epidemiological surveillance as well as relevant case definitions. 2018 [cited 2024 Aug 6]. https://eur-lex.europa.eu/eli/dec_impl/2018/945/oj
  11. Ethelberg  S, Olsen  KEP, Scheutz  F, Jensen  C, Schiellerup  P, Enberg  J, et al. Virulence factors for hemolytic uremic syndrome, Denmark. Emerg Infect Dis. 2004;10:842–7. DOIPubMedGoogle Scholar
  12. HSE Health Protection Surveillance Centre. VTEC enhanced surveillance form CIDR EVENT ID HSE ID 2018 [cited 2024 May 7]. https://www.hpsc.ie/a-z/gastroenteric/vtec/surveillanceinvestigativeforms/VTEC_EnhancedQs2018_v2.0 FINAL_20180219.pdf.
  13. Department of Health and Children. Health statistics 2002 LENUS (Irish Health Repository). Dublin; 2003 [cited 2023 Jan 18]. https://www.lenus.ie/handle/10147/241861
  14. Yang  X, Sun  H, Fan  R, Fu  S, Zhang  J, Matussek  A, et al. Genetic diversity of the intimin gene (eae) in non-O157 Shiga toxin-producing Escherichia coli strains in China. Sci Rep. 2020;10:3275. DOIPubMedGoogle Scholar
  15. Zhang  WL, Köhler  B, Oswald  E, Beutin  L, Karch  H, Morabito  S, et al. Genetic diversity of intimin genes of attaching and effacing Escherichia coli strains. J Clin Microbiol. 2002;40:4486–92. DOIPubMedGoogle Scholar
  16. Ooka  T, Seto  K, Kawano  K, Kobayashi  H, Etoh  Y, Ichihara  S, et al. Clinical significance of Escherichia albertii. Emerg Infect Dis. 2012;18:488–92. DOIPubMedGoogle Scholar
  17. Afgan  E, Nekrutenko  A, Grüning  BA, Blankenberg  D, Goecks  J, Schatz  MC, et al. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2022 update. Nucleic Acids Res. 2022;50(W1):W345–51.
  18. Seemann  T. Prokka: rapid prokaryotic genome annotation. Bioinformatics. 2014;30:2068–9. DOIPubMedGoogle Scholar
  19. Page  AJ, Cummins  CA, Hunt  M, Wong  VK, Reuter  S, Holden  MTG, et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics. 2015;31:3691–3. DOIPubMedGoogle Scholar
  20. Brynildsrud  O, Bohlin  J, Scheffer  L, Eldholm  V. Rapid scoring of genes in microbial pan-genome-wide association studies with Scoary. Genome Biol. 2016;17:1–9. DOIGoogle Scholar
  21. Bateman  A, Martin  MJ, Orchard  S, Magrane  M, Ahmad  S, Alpi  E, et al.; UniProt Consortium. UniProt: the Universal Protein Knowledgebase in 2023. Nucleic Acids Res. 2023;51(D1):D523–31. DOIPubMedGoogle Scholar
  22. Szklarczyk  D, Gable  AL, Nastou  KC, Lyon  D, Kirsch  R, Pyysalo  S, et al. The STRING database in 2021: customizable protein-protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res. 2021;49(D1):D605–12. DOIPubMedGoogle Scholar
  23. Stamatakis  A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics. 2014;30:1312–3. DOIPubMedGoogle Scholar
  24. Letunic  I, Bork  P. Interactive Tree Of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res. 2021;49(W1):W293–6. DOIPubMedGoogle Scholar
  25. Fox  J, Weisberg  S. An R companion to applied regression. 3rd ed. Thousand Oaks (CA): Sage Publications; 2018.
  26. Jay  M. R package generalhoslem [cited 2022 Jun 24]. https://cran.r-project.org/web/packages/generalhoslem
  27. Bursac  Z, Gauss  CH, Williams  DK, Hosmer  DW. Purposeful selection of variables in logistic regression. Source Code Biol Med. 2008;3:17. DOIPubMedGoogle Scholar
  28. Zhang  Z. Model building strategy for logistic regression: purposeful selection. Ann Transl Med. 2016;4:111. DOIPubMedGoogle Scholar
  29. Naseer  U, Løbersli  I, Hindrum  M, Bruvik  T, Brandal  LT. Virulence factors of Shiga toxin-producing Escherichia coli and the risk of developing haemolytic uraemic syndrome in Norway, 1992-2013. Eur J Clin Microbiol Infect Dis. 2017;36:1613–20. DOIPubMedGoogle Scholar
  30. Ylinen  E, Salmenlinna  S, Halkilahti  J, Jahnukainen  T, Korhonen  L, Virkkala  T, et al. Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli in children: incidence, risk factors, and clinical outcome. Pediatr Nephrol. 2020;35:1749–59. DOIPubMedGoogle Scholar
  31. Brandal  LT, Wester  AL, Lange  H, Løbersli  I, Lindstedt  BA, Vold  L, et al. Shiga toxin-producing escherichia coli infections in Norway, 1992-2012: characterization of isolates and identification of risk factors for haemolytic uremic syndrome. BMC Infect Dis. 2015;15:324. DOIPubMedGoogle Scholar
  32. Murphy  V, Carroll  AM, Forde  K, Broni  R, McNamara  EB. Verocytotoxin Escherichia coli–associated haemolytic uraemic syndrome. Ir Med J. 2020;113:5.PubMedGoogle Scholar
  33. Bai  X, Zhang  J, Hua  Y, Jernberg  C, Xiong  Y, French  N, et al. Genomic insights into clinical Shiga toxin–producing Escherichia coli strains: a 15-year period survey in Jönköping, Sweden. Front Microbiol. 2021;12:627861. DOIPubMedGoogle Scholar
  34. Public Health England. Interim public health operational guidance for Shiga toxin–producing Escherichia coli (STEC) including STEC (O157 and non-O157) infections. 2018 [cited 2021 Nov 1]. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/732569/Interim_public_health_operational_guidance_for_STEC_PDF.pdf
  35. Public Health England. Shiga toxin–producing Escherichia coli 2019 [cited 2021 Nov 1]. https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/774291/STEC_O157_report.pdf
  36. Matussek  A, Mernelius  S, Chromek  M, Zhang  J, Frykman  A, Hansson  S, et al. Genome-wide association study of hemolytic uremic syndrome causing Shiga toxin-producing Escherichia coli from Sweden, 1994-2018. Eur J Clin Microbiol Infect Dis. 2023;42:771–9. DOIPubMedGoogle Scholar
  37. Koutsoumanis  K, Allende  A, Alvarez-Ordóñez  A, Bover-Cid  S, Chemaly  M, Davies  R, et al. Pathogenicity assessment of Shiga toxin–producing Escherichia coli (STEC) and the public health risk posed by contamination of food with STEC. EFSA J. 2020;18. DOIGoogle Scholar
  38. Hellinga  HW, Evans  PR. Nucleotide sequence and high-level expression of the major Escherichia coli phosphofructokinase. Eur J Biochem. 1985;149:363–73. DOIPubMedGoogle Scholar
  39. Zhang  D, Li  SH-J, King  CG, Wingreen  NS, Gitai  Z, Li  Z. Global and gene-specific translational regulation in Escherichia coli across different conditions. PLOS Comput Biol. 2022;18:e1010641. DOIPubMedGoogle Scholar
  40. Grass  G, Otto  M, Fricke  B, Haney  CJ, Rensing  C, Nies  DH, et al. FieF (YiiP) from Escherichia coli mediates decreased cellular accumulation of iron and relieves iron stress. Arch Microbiol. 2005;183:9–18. DOIPubMedGoogle Scholar
  41. Ouyang  A, Gasner  KM, Neville  SL, McDevitt  CA, Frawley  ER. MntP and YiiP contribute to manganese efflux in Salmonella enterica serovar Typhimurium under conditions of manganese overload and nitrosative stress. Microbiol Spectr. 2022;10:e0131621. DOIPubMedGoogle Scholar
  42. Lee  J, Hiibel  SR, Reardon  KF, Wood  TK. Identification of stress-related proteins in Escherichia coli using the pollutant cis-dichloroethylene. J Appl Microbiol. 2010;108:2088–102.PubMedGoogle Scholar
  43. Fukushima  K, Kumar  SD, Suzuki  S. YgiW homologous gene from Pseudomonas aeruginosa 25W is responsible for tributyltin resistance. J Gen Appl Microbiol. 2012;58:283–9. DOIPubMedGoogle Scholar
  44. Juárez-Rodríguez  MD, Torres-Escobar  A, Demuth  DR. ygiW and qseBC are co-expressed in Aggregatibacter actinomycetemcomitans and regulate biofilm growth. Microbiology (Reading). 2013;159:989–1001. DOIPubMedGoogle Scholar
  45. Pedersen  K, Gerdes  K. Multiple hok genes on the chromosome of Escherichia coli. Mol Microbiol. 1999;32:1090–102. DOIPubMedGoogle Scholar
  46. Lippert  C, Listgarten  J, Liu  Y, Kadie  CM, Davidson  RI, Heckerman  D. FaST linear mixed models for genome-wide association studies. Nat Methods. 2011;8:833–5. DOIPubMedGoogle Scholar
  47. Lees  JA, Galardini  M, Bentley  SD, Weiser  JN, Corander  J. pyseer: a comprehensive tool for microbial pangenome-wide association studies. Bioinformatics. 2018;34:4310–2. DOIPubMedGoogle Scholar
  48. Earle  SG, Wu  CH, Charlesworth  J, Stoesser  N, Gordon  NC, Walker  TM, et al. Identifying lineage effects when controlling for population structure improves power in bacterial association studies. Nat Microbiol. 2016;1:16041. DOIPubMedGoogle Scholar
  49. Farhat  MR, Freschi  L, Calderon  R, Ioerger  T, Snyder  M, Meehan  CJ, et al. GWAS for quantitative resistance phenotypes in Mycobacterium tuberculosis reveals resistance genes and regulatory regions. Nat Commun. 2019;10:2128. DOIPubMedGoogle Scholar

Main Article

1These authors were co–principal investigators, contributed equally to this work, and share first authorship.

Page created: February 28, 2025
Page updated: March 11, 2025
Page reviewed: March 11, 2025
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external