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Volume 21, Number 1—January 2015
Letter

Hemolytic Uremic Syndrome Associated with Escherichia coli O8:H19 and Shiga Toxin 2f Gene

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To the Editor: Gastroenteritis caused by Shiga toxin–producing Escherichia coli (STEC), associated with hemorrhagic colitis and hemolytic uremic syndrome (HUS), has been identified as a major health problem (1). Shiga toxin is essential for the development of HUS (2). Shiga toxin can be distinguished into Shiga toxin 1 (Stx1) and Shiga toxin 2 (Stx2). The stx2f STEC variant is a distinct group within STEC (regarding virulence genes) and is known to cause relatively mild disease, although reports of human illness are scarce (3).

During autumn 2013, a healthy 9-year-old boy in the Netherlands experienced fever, vomiting, and bloody diarrhea which persisted for days; he was admitted to the pediatric ward of a local hospital because of clinical signs of HUS with renal insufficiency: serum creatinine level 439 μmol/L (reference range 31–68 μmol/L); blood urea nitrogen concentration 34.1 mmol/L (reference range 3.3–5.6 mmol/L); thrombocytopenia (46 platelets/nL; reference range 150–450/nL); and low haptoglobin level. Hemoglobin levels decreased within 48 hours from 7.4 mmol/L to 5.5 mmol/L (reference range 6.9–8.4 mmol/L). His blood pressure was 127/82 (99th percentile for age and height). Renal insufficiency worsened over time, evidenced by maximum urea levels of 57.3 mmol/L and maximum creatinine levels of 744 μmol/L. Vomiting increased, and feeding became difficult. The boy was transferred to an academic nephrology center, where he received erythrocyte and thrombocyte infusions, then peritoneal dialysis. He received 1 prophylactic dose of cefazolin during insertion of the dialysis catheter. After 2 days, he entered a polyuric phase of renal failure; renal function normalized within a few weeks, however. To improve proteinuria, physicians prescribed a 3-month course of angiotensin-converting enzyme inhibitors after discharge.

A fecal sample tested positive for STEC by PCR in a local laboratory. Five isolates were sent to the National Institute for Public Health and the Environment (RIVM) as part of the national STEC surveillance. By using PCR, 1 of the 5 tested positive for the stx2f gene and the attaching and effacing gene (eae), and negative for the genes stx1, stx2a-e, H7, O157, and enterohemorrhagic E. coli hemolysin (hly). Serotyping identified O8:H19. The other 4 isolates tested negative for all of the above-mentioned genes and were not serotyped.

The family had stayed in a hotel in Turkey and returned to the Netherlands 5 days before onset of illness. The only reported contact with animals was with a parrot in the hotel. On return to the Netherlands, the boy had eaten filet américain, a sandwich spread made of raw beef. The day before disease onset, he attended a party where barbecue was served by a catering company.

Since 2007, besides this reported case, 8 cases of STEC O8 were registered within the STEC surveillance system in the Netherlands: O8:H– (4 cases), O8:H19 (2 cases), O8:H8 (1 case), and O8:H9 (1 case). All 8 isolates were stx2a-e-positive and stx1-, stx2f-, eae- and hly-negative. Disease associated with these cases was relatively mild. During 2007–2010, a total of 13,545 human STEC infections were reported in Europe: 20 were registered as STEC O8; HUS did not develop in these case-patients (4). HUS developed in 2 patients infected with STEC O8 (O8:H2, O8:H19) in Germany during 1996–2000 (5); these isolates and all other isolates from HUS and non-HUS case-patients in this period tested negative for stx2f. During 2008–2011, 87 stx2f STEC infections were registered in the Netherlands (3). These infections were relatively mild; no HUS cases were registered. The virulence genes seen in the isolate of the described case, stx2f and eae, but no hly or other toxin genes, were also seen in 97% of stx2f STEC infections reported in the Netherlands (3). Besides being detected in humans, stx2f STEC has only been detected in pigeons (6).

The cause of the severity of disease in this stx2f STEC case and the source of the infection could not be determined. The parrot in the hotel in Turkey could have been the source if birds are a reservoir of stx2f STEC. Conversely, the uncooked beef and barbecue cannot be ruled out, because O8:H19 has been found in cattle, pigs, and sheep (7). This case shows that STEC subgroups known to cause relatively mild disease can occasionally cause severe disease and that surveillance based upon a small group of serotypes underestimates the number of severe STEC infections and increases the chance of missing emerging serotypes.

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Ingrid H.M. FriesemaComments to Author , Mandy G. Keijzer-Veen, Marja Koppejan, Henk S. Schipper, Arjanne J. van Griethuysen, Max E.O.C. Heck, and Wilfrid van Pelt
Author affiliations: National Institute for Public Health and the Environment, Bilthoven, the Netherlands (I.H.M. Friesema, M.E.O.C. Heck, W. van Pelt); University Medical Center Utrecht, Utrecht, the Netherlands (M. G. Keijzer-Veen, H.S. Schipper); Gelderse Vallei Hospital, Ede, the Netherlands (M. Koppejan, H.S. Schipper, A.J. van Griethuysen)

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References

  1. Karmali  MA, Gannon  V, Sargeant  JM. Verocytotoxin-producing Escherichia coli (VTEC). Vet Microbiol. 2010;140:36070 . DOIPubMedGoogle Scholar
  2. Prager  R, Annemuller  S, Tschape  H. Diversity of virulence patterns among Shiga toxin—producing Escherichia coli from human clinical cases—need for more detailed diagnostics. Int J Med Microbiol. 2005;295:2938 . DOIPubMedGoogle Scholar
  3. Friesema  I, van der Zwaluw  K, Schuurman  T, Kooistra-Smid  M, Franz  E, van Duynhoven  Y, Emergence of Escherichia coli encoding Shiga toxin 2f in human Shiga toxin-producing E. coli (STEC) infections in the Netherlands, January 2008 to December 2011. [cited 2014 Nov 18]. Euro Surveill. 2014;19:20787 http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20787.PubMedGoogle Scholar
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  5. Friedrich  AW, Bielaszewska  M, Zhang  WL, Pulz  M, Kuczius  T, Ammon  A, Escherichia coli harboring Shiga toxin 2 gene variants: frequency and association with clinical symptoms. J Infect Dis. 2002;185:7484 . DOIPubMedGoogle Scholar
  6. Schmidt  H, Scheef  J, Morabito  S, Caprioli  A, Wieler  LH, Karch  H. A new Shiga toxin 2 variant (Stx2f) from Escherichia coli isolated from pigeons. Appl Environ Microbiol. 2000;66:12058 . DOIPubMedGoogle Scholar
  7. Bettelheim  KA. The non-O157 Shiga-toxigenic (verocytotoxigenic) Escherichia coli; under-rated pathogens. Crit Rev Microbiol. 2007;33:6787 . DOIPubMedGoogle Scholar

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DOI: 10.3201/eid2101.140515

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Please use the form below to submit correspondence to the authors or contact them at the following address:

Ingrid H.M. Friesema, RIVM-EPI, Centre for Infectious Disease Control, National Institute of Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, the Netherlands

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Page created: December 19, 2014
Page updated: December 19, 2014
Page reviewed: December 19, 2014
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.
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