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Open Access 01-02-2013 | Intra-abominal Infections, Hepatitis, and Gastroenteritis (D Bobak, Section Editor)

Lessons Learned From Outbreaks of Shiga Toxin Producing Escherichia coli

Authors: Susanne Hauswaldt, Martin Nitschke, Friedhelm Sayk, Werner Solbach, Johannes K.-M. Knobloch

Published in: Current Infectious Disease Reports | Issue 1/2013

Abstract

In 2011, a large outbreak caused by a Shiga toxin producing E. coli (STEC) occurred in Northern Germany, with a satellite outbreak in Western France, including the highest number of hemolytic uremic syndrome (HUS) cases ever encountered during a STEC outbreak. The outbreak strain was characterized as an enteroaggregative E. coli of serotype O104:H4 expressing a phage-encoded Shiga toxin 2. The majority of STEC infections and HUS cases were observed in adults, with a preponderance of the female gender. The outbreak imposed huge challenges on clinicians, microbiologists, and epidemiologists but also provided important new insight for the understanding of STEC infection. Thus, novel therapeutic strategies in the treatment of HUS in adults and for decolonization of long-term STEC carriers were evaluated. This review highlights the unusual features of the recent O104:H4 outbreak and focuses on emerging new strategies in diagnostics and treatment of acute STEC-related disease, as well as STEC long-term carriage.

Karmali MA, Petric M, Lim C, Fleming PC, Steele BT. Escherichia coli cytotoxin, haemolytic-uraemic syndrome, and haemorrhagic colitis. Lancet. 1983;2:1299–300.PubMedCrossRef

Karmali MA, Steele BT, Petric M, Lim C. Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet. 1983;1:619–20.PubMedCrossRef

Chattaway MA, Dallman T, Okeke IN, Wain J. Enteroaggregative E. coli O104 from an outbreak of HUS in Germany 2011, could it happen again? J Infect Dev Ctries. 2011;5:425–36.PubMedCrossRef

Kaper JB, Nataro JP, Mobley HL. Pathogenic Escherichia coli. Nat Rev Microbiol. 2004;2:123–40.PubMedCrossRef

Scheutz F, Teel LD, Beutin L, Pierard D, Buvens G, Karch H, et al. Multicenter evaluation of a sequence-based protocol for subtyping shiga toxins and standardizing stx nomenclature. J Clin Microbiol. 2012;50:2951–63.PubMedCrossRef

Karmali MA, Mascarenhas M, Shen S, Ziebell K, Johnson S, Reid-Smith R, et al. Association of genomic O island 122 of Escherichia coli EDL 933 with verocytotoxin-producing Escherichia coli seropathotypes that are linked to epidemic and/or serious disease. J Clin Microbiol. 2003;41:4930–40.PubMedCrossRef

Beutin L, Zimmermann S, Gleier K. Human infections with Shiga toxin-producing Escherichia coli other than serogroup O157 in Germany. Emerg Infect Dis. 1998;4:635–9.PubMedCrossRef

Goldwater PN, Bettelheim KA. Treatment of enterohemorrhagic Escherichia coli (EHEC) infection and hemolytic uremic syndrome (HUS). BMC Med. 2012;10:12.PubMedCrossRef

Tarr PI, Gordon CA, Chandler WL. Shiga-toxin-producing Escherichia coli and haemolytic uraemic syndrome. Lancet. 2005;365:1073–86.PubMed

10.

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.PubMedCrossRef

11.

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.PubMedCrossRef

12.

Robert Koch Institut: EHEC-Erkrankungen. In Infektionsepidemiologisches Jahrbuch meldepflichtiger Krankheiten für 2010. Edited by Robert Koch Institut (RKI). Berlin; 2011.80–84.

13.

Frank C, Werber D, Cramer JP, Askar M, Faber M, an der Heiden M, et al. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med. 2011;365:1771–80.PubMedCrossRef

14.

• Robert Koch Institut: Report: Final evaluation and presentation of epidemiological findings of the EHEC O104:H4 outbreak, Germany 2011. Edited by RKI Department for Infectious Disease Epidemiology Division 35. Berlin: RKI-Print Shop; 2011. p. 2011. This report provides a complete overview of the epidemiology of the STEC O104:H4 outbreak in Germany while also describing the efforts of the Robert Koch institute in tracing the outbreak source.

15.

Buchholz U, Bernard H, Werber D, Böhmer MM, Remschmidt C, Wilking H, et al. German outbreak of Escherichia coli O104:H4 associated with sprouts. N Engl J Med. 2011;365:1763–70.PubMedCrossRef

16.

King LA, Nogareda F, Weill FX, Mariani-Kurkdjian P, Loukiadis E, Gault G, et al. Outbreak of Shiga toxin-producing Escherichia coli O104:H4 associated with organic fenugreek sprouts, France, June 2011. Clin Infect Dis. 2012;54:1588–94.PubMedCrossRef

17.

•• Menne J, Nitschke M, Stingele R, Abu-Tair M, Beneke J, Bramstedt J, et al. Validation of treatment strategies for enterohaemorrhagic Escherichia coli O104:H4 induced haemolytic uraemic syndrome: case–control study. BMJ. 2012;345:e4565. This multicentre retrospective case-control study of 298 patients with STEC O104:H4 induced HUS shows no benefit of either plasmapheresis or eculizumab treatment on short term outcome, on which there is otherwise very limited data.

18.

Magnus T, Röther J, Simova O, Meier-Cillien M, Repenthin J, Möller F, et al. The neurological syndrome in adults during the 2011 northern German E. coli serotype O104:H4 outbreak. Brain. 2012;135:1850–9.PubMedCrossRef

19.

Bell BP, Goldoft M, Griffin PM, Davis MA, Gordon DC, Tarr PI, et al. A multistate outbreak of Escherichia coli O157:H7-associated bloody diarrhea and hemolytic uremic syndrome from hamburgers. The Washington experience. JAMA. 1994;272:1349–53.PubMedCrossRef

20.

• Bielaszewska M, Mellmann A, Zhang W, Köck R, Fruth A, Bauwens A, et al. Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. Lancet Infect Dis. 2011;11:671–6. This study describes the “intermediate” virulence profile of STEC O104:H4 and the development of a multiplex PCR targeting characteristic genes of the outbreak strain.

21.

Scheutz F, Moller NE, Frimomodt-Moller J, Boisen N, Morabito S, Tozzoli R, et al. Characteristics of the enteroaggregative Shiga toxin/verotoxin-producing Escherichia coli O104:H4 strain causing the outbreak of haemolytic uraemic syndrome in Germany. Euro Surveill. 2011;16:19889.PubMed

22.

Rohde H, Qin J, Cui Y, Li D, Loman NJ, Hentschke M, et al. Open-source genomic analysis of Shiga-toxin-producing E. coli O104:H4. N Engl J Med. 2011;365:718–24.PubMedCrossRef

23.

Rasko DA, Webster DR, Sahl JW, Bashir A, Boisen N, Scheutz F, et al. Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany. N Engl J Med. 2011;365:709–17.PubMedCrossRef

24.

Mellmann A, Harmsen D, Cummings CA, Zentz EB, Leopold SR, Rico A, et al. Prospective genomic characterization of the German enterohemorrhagic Escherichia coli O104:H4 outbreak by rapid next generation sequencing technology. PLoS One. 2011;6:e22751.PubMedCrossRef

25.

Laing CR, Zhang Y, Gilmour MW, Allen V, Johnson R, Thomas JE, et al. A comparison of Shiga-toxin 2 bacteriophage from classical enterohemorrhagic Escherichia coli serotypes and the German E. coli O104:H4 outbreak strain. PLoS One. 2012;7:e37362.PubMedCrossRef

26.

Karch H, Denamur E, Dobrindt U, Finlay BB, Hengge R, Johannes L, et al. The enemy within us: lessons from the 2011 European Escherichia coli O104:H4 outbreak. EMBO Mol Med. 2012;4:841–8.PubMedCrossRef

27.

•• Nitschke M, Sayk F, Härtel C, Roseland RT, Hauswaldt S, Steinhoff J, et al. Association between azithromycin therapy and duration of bacterial shedding among patients with Shiga toxin-producing enteroaggregative Escherichia coli O104:H4. JAMA. 2012;307:1046–52. This study involving 65 STEC O104:H4 infected patients with or without HUS shows treatment with azithromycin to dramatically decrease the duration of STEC shedding without adverse effects, thereby challenging the absolute contraindication for antibiotics in any stage of STEC disease.

28.

Karch H, Russmann H, Schmidt H, Schwarzkopf A, Heesemann J. Long-term shedding and clonal turnover of enterohemorrhagic Escherichia coli O157 in diarrheal diseases. J Clin Microbiol. 1995;33:1602–5.PubMed

29.

Taormina PJ, Beuchat LR, Slutsker L. Infections associated with eating seed sprouts: an international concern. Emerg Infect Dis. 1999;5:626–34.PubMedCrossRef

30.

Michino H, Araki K, Minami S, Takaya S, Sakai N, Miyazaki M, et al. Massive outbreak of Escherichia coli O157:H7 infection in schoolchildren in Sakai City, Japan, associated with consumption of white radish sprouts. Am J Epidemiol. 1999;150:787–96.PubMedCrossRef

31.

Wood R, Donaghy M, Dundas S. Monitoring patients in the community with suspected Escherichia coli O157 infection during a large outbreak in Scotland in 1996. Epidemiol Infect. 2001;127:413–20.PubMed

32.

Dundas S, Todd WT, Stewart AI, Murdoch PS, Chaudhuri AK, Hutchinson SJ. The central Scotland Escherichia coli O157:H7 outbreak: risk factors for the hemolytic uremic syndrome and death among hospitalized patients. Clin Infect Dis. 2001;33:923–31.PubMedCrossRef

33.

Piercefield EW, Bradley KK, Coffman RL, Mallonee SM. Hemolytic Uremic Syndrome After an Escherichia coli O111 Outbreak. Arch Intern Med. 2010;170:1656–63.PubMedCrossRef

34.

Boudailliez B, Berquin P, Mariani-Kurkdjian P, Ilef D, Cuvelier B, Capek I, et al. Possible person-to-person transmission of Escherichia coli O111–associated hemolytic uremic syndrome. Pediatr Nephrol. 1997;11:36–9.PubMedCrossRef

35.

Morabito S, Karch H, Mariani-Kurkdjian P, Schmidt H, Minelli F, Bingen E, et al. Enteroaggregative, Shiga toxin-producing Escherichia coli O111:H2 associated with an outbreak of hemolytic-uremic syndrome. J Clin Microbiol. 1998;36:840–2.PubMed

36.

Trachtman H, Austin C, Lewinski M, Stahl RA. Renal and neurological involvement in typical Shiga toxin-associated HUS. Nat Rev Nephrol. 2012. doi: 10.1038/nrneph.2012.196.

37.

Michael M, Elliott EJ, Ridley GF, Hodson EM, Craig JC. Interventions for haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura. Cochrane Database Syst Rev. 2009. CD003595.

38.

German Society of Nephrology. Advice of the German Society of Nephrology on the use of Eculizumab during the 2011 EHEC HUS outbreak, 04.06.2011. http://www.dgfn.eu/aktuell/ehec-informationen/fuer-das-fachpublikum/advice-on-the-use-of-ecilizumab.html. 2011.

39.

Lapeyraque AL, Malina M, Fremeaux-Bacchi V, Boppel T, Kirschfink M, Oualha M, et al. Eculizumab in severe Shiga-toxin-associated HUS. N Engl J Med. 2011;364:2561–3.PubMedCrossRef

40.

Dundas S, Murphy J, Soutar RL, Jones GA, Hutchinson SJ, Todd WT. Effectiveness of therapeutic plasma exchange in the 1996 Lanarkshire Escherichia coli O157:H7 outbreak. Lancet. 1999;354:1327–30.PubMedCrossRef

41.

Loos S, Ahlenstiel T, Kranz B, Staude H, Pape L, Härtel C, et al. An Outbreak of Shiga Toxin-Producing Escherichia coli O104:H4 Hemolytic Uremic Syndrome in Germany: Presentation and Short-term Outcome in Children. Clin Infect Dis. 2012;55:753–9.PubMedCrossRef

42.

Rosales A, Hofer J, Zimmerhackl LB, Jungraithmayr TC, Riedl M, Giner T, et al. Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. Clin Infect Dis. 2012;54:1413–21.PubMedCrossRef

43.

Greinacher A, Friesecke S, Abel P, Dressel A, Stracke S, Fiene M, et al. Treatment of severe neurological deficits with IgG depletion through immunoadsorption in patients with Escherichia coli O104:H4-associated haemolytic uraemic syndrome: a prospective trial. Lancet. 2011;378:1166–73.PubMedCrossRef

44.

Smith KE, Wilker PR, Reiter PL, Hedican EB, Bender JB, Hedberg CW. Antibiotic treatment of Escherichia coli O157 infection and the risk of hemolytic uremic syndrome, Minnesota. Pediatr Infect Dis J. 2012;31:37–41.PubMedCrossRef

45.

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.PubMedCrossRef

46.

Parker C. Eculizumab for paroxysmal nocturnal haemoglobinuria. Lancet. 2009;373:759–67.PubMedCrossRef

47.

Albert RK, Connett J, Bailey WC, Casaburi R, Cooper Jr JA, Criner GJ, et al. Azithromycin for prevention of exacerbations of COPD. N Engl J Med. 2011;365:689–98.PubMedCrossRef

48.

• Bielaszewska M, Idelevich EA, Zhang W, Bauwens A, Schaumburg F, Mellmann A, et al. Effects of antibiotics on Shiga toxin 2 production and bacteriophage induction by epidemic Escherichia coli O104:H4 strain. Antimicrob Agents Chemother. 2012;56:3277–82. This study examines the effect of different antibiotics on Stx-harbouring phage induction in STEC O104:H4 in vitro in order to predict their potential benefit or harm to STEC infected patients.

49.

Corogeanu D, Willmes R, Wolke M, Plum G, Utermöhlen O, Krönke M. Therapeutic concentrations of antibiotics inhibit Shiga toxin release from enterohemorrhagic E. coli O104:H4 from the 2011 German outbreak. BMC Microbiol. 2012;12:160.PubMedCrossRef

Title: Lessons Learned From Outbreaks of Shiga Toxin Producing Escherichia coli
Authors: Susanne Hauswaldt
Martin Nitschke
Friedhelm Sayk
Werner Solbach
Johannes K.-M. Knobloch
Publication date: 01-02-2013
Publisher: Current Science Inc.
Published in: Current Infectious Disease Reports / Issue 1/2013
Print ISSN: 1523-3847
Electronic ISSN: 1534-3146
DOI: https://doi.org/10.1007/s11908-012-0302-4

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