Highly Virulent Escherichia coli O26, Scotland

Kevin G.J. Pollock, Sheetal Bhojani, T. James Beattie, Lesley Allison, Mary Hanson, Mary E. Locking, and John M. Cowden
Author affiliations: Health Protection Scotland, Glasgow, Scotland (K.G.J. Pollock, M.E. Locking, J.M. Cowden); Yorkhill Hospital, Glasgow (T.J. Beattie, S. Bhojani); and Scottish E. coli O157/VTEC Reference Laboratory, Edinburgh, Scotland (L. Allison, M. Hanson)
Suggested citation for this article
To the Editor: Hemolytic uremic syndrome (HUS) is a rare disorder characterized by microangiopathic hemolytic anemia, microthrombi, and multiorgan injury. HUS is one of the commonest causes of acute renal failure in children worldwide and is most frequently precipitated by infection with verotoxin-producing Escherichia coli (VTEC) such as E. coli O157 (1). However, non-O157 VTEC serotypes have been increasingly found in the development of HUS (2–4).
Although previous surveillance of childhood HUS in Scotland identified E. coli O157 in >90% of cases, non-O157 serotypes have also been associated with HUS (5). In 2010, several particularly severe cases of HUS were reported to Health Protection Scotland by a consultant pediatric nephrologist. Subsequent tests identified the pathogen in these cases as E. coli O26. However, in a recent study of pediatric HUS cases in Europe, children infected with E. coli O26 did not exhibit different clinical signs and symptoms from patients infected with other VTEC serotypes (6). To establish whether the host pathophysiologic responses to E. coli O157 and E. coli O26 strains differed, we analyzed a cohort of children with HUS who were infected with these VTEC serotypes.
In Scotland, most patients with pediatric thrombotic microangiopathy are referred to a specialist pediatric hospital, which immediately reports cases of HUS to Health Protection Scotland as part of national surveillance. To test the hypothesis that E. coli O26 was more virulent than E. coli O157, we performed an age-matched, nested case–case study of HUS patients and compared host clinical markers, treatment, and outcomes from pediatric cases in 2010. Data collection has been described elsewhere (5). The statistical significances of associations between categorical variables were investigated by using χ², Fisher exact, Mann-Whitney, or t tests. All analyses were performed by using SPSS version 11 (SPSS Inc., Chicago, IL, USA) with a significance level of 5%.
Although initial signs and symptoms were similar for both sets of cases, i.e., bloody diarrhea and abdominal pain, statistical analysis showed that children with O26-HUS were more likely to have neurologic complications and diabetes mellitus and require admission to the intensive care unit than O157-HUS patients (p = 0.02 for neurologic complications and diabetes and p = 0.04 for admission to an intensive treatment unit; Table).
All patients with HUS were oligoanuric, and the 2 groups did not differ with respect to this parameter. However, O26-HUS patients had significantly longer periods of anuria than O157-HUS patients (p = 0.04; Table) and were more likely to require treatment with hemofiltration than with peritoneal or hemodialysis (p = 0.001; Table). One patient with O26-HUS also experienced cardiomyopathy resulting in reduced left ventricular function.
Our study illustrates the potential for increased severity of E. coli O26 infection in children. In Scotland, HUS is more commonly associated with E. coli O157 infection, and the outcome for children infected with this pathogen is much better than that reported in other studies (7,8). In this study, the clinical severity and outcomes for the children with O26-HUS were worse than for children requiring treatment for O157-HUS. We investigated the prehospital management of E. coli O157 and O26 patients in this cohort and found no difference in pharmacologic intervention or duration of delay in admission to hospital.
In our cohort, vtx₁ and vtx₂ genes were detected in isolates from 2 of 3 patients. A diagnosis was made in the third patient by detection of E. coli O26 lipopolysaccharide–specific immunoglobulin M in serum; it was therefore not possible to confirm the presence of vtx genes. However, it is not unusual for VTEC to be undetectable in stool samples from patients with HUS, most likely because of intrahost bacteriophage lysis. Therefore, serodiagnosis of VTEC is considered a necessary adjunct to bacteriological confirmation of infection (9). A recent study suggests E. coli O26 exists as a highly dynamic group of organisms that can undergo verotoxin gene loss and be transferred during infection in humans, resulting in new pathogenic clones (10). Therefore, vtx₂ gene acquisition by E. coli O26 may have contributed to increased virulence.
Our study was limited by the small number of patients with pediatric O26-HUS. However, given the severity of the complications experienced by the children in this cohort, we believe it is necessary to communicate these findings promptly to the international community.
We suggest that infection with E. coli O26 in children can result in more severe and complicated forms of HUS than those caused by E. coli O157. In contrast to the findings of Gerber et al., we found that there was a significant difference in neurologic complications between the 2 groups (2). Epidemiologic investigations found that 2 of the 3 children lived on farms and may have acquired infection while playing near their homes (the other was acquired through foreign travel). Risk communication of VTEC infection to parents of young children who live in farming communities remains problematic, perhaps because of the perception that immunity has been acquired. Although this suggestion may be true for adults, children are likely to be immunologically naive. Salient public health messages on simple precautionary behavior need to be regularly reinforced because prevention of VTEC infection prevents HUS.

Acknowledgments

We thank the staff of the renal unit, Royal Sick Children's Hospital, Yorkhill, UK, for their ongoing contributions to the clinical surveillance program and also staff at the Scottish E. coli O157/VTEC Reference Laboratory and Gastrointestinal Infections Reference Unit, Health Protection Agency, Colindale.

References

Tarr PI, Gordon CA, Chandler WL. Shiga toxin producing Escherichia coli and the haemolytic uraemic syndrome. Lancet. 2005;365:1073–86.
Gerber A, Karch H, Allerberger F, Verweyen HM, Zimmerhackl LB. Clinical course and the role of Shiga toxin-producing Escherichia coli infection in the hemolytic-uremic syndrome in pediatric patients, 1997–2000, in Germany and Austria: a prospective study.J Infect Dis. 2002;186:493–500. PubMed DOI
Aldick T, Bielaszewska M, Zhang W, Brockmeyer J, Schmidt H, Friedrich AW, et al. Hemolysin from Shiga toxin–negative Escherichia coli O26 strains injures microvascular endothelium. Microbes Infect. 2007;9:282–90. PubMed DOI
Johnson KE, Thorpe CM, Sears CL. The emerging clinical importance of non-O157 Shiga toxin-producing Escherichia coli. Clin Infect Dis. 2006;43:1587–95. PubMed DOI
Pollock KGJ, Young D, Beattie TJ, Todd WTA. Clinical surveillance of thrombotic microangiopathies in Scotland, 2003–2005.Epidemiol Infect. 2008;136:115–21. PubMed DOI
Zimmerhackl LB, Rosales A, Hofer J, Riedl M, Jungraithmayr T, Mellman A, et al. Enterohemorrhagic Escherichia coli O26:H11–associated hemolytic uremic syndrome: bacteriology and clinical presentation. Semin Thromb Hemost. 2010;36:586–93. PubMed DOI
Garg AX, Suri RS, Barrowman N, Rehman F, Matsell D, Rosas-Arellano MP, et al. Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. JAMA. 2003;290:1360–70. PubMed DOI
Weekly Report HPS. Clinical surveillance of haemolytic uraemic syndrome 2003–2009: renal prognosis at three-year follow up [cited 2011 Feb 1]. http://www.documents.hps.scot.nhs.uk/ewr/pdf2010/1010
Chart H, Cheasty T. Human infections with verocytotoxin-producing Escherichia coli O157—10 years of serodiagnosis. J Med Microbiol. 2008;57:1389–93. PubMed DOI
Bielaszewska M, Prager R, KöckR, Mellmann A, Zhang W, Tschäpe H, et al. Shiga toxin gene loss and transfer in vitro and in vivo during enterohemorrhagic Escherichia coli O26 infection in humans. Appl Environ Microbiol. 2007;73:3144–50. PubMed DOI