Outbreak of Shiga Toxin–Producing Escherichia coli (STEC) O104:H4 Infection in Germany Causes a Paradigm Shift with Regard to Human Pathogenicity of STEC Strains

2012 ◽  
Vol 75 (2) ◽  
pp. 408-418 ◽  
Author(s):  
LOTHAR BEUTIN ◽  
ANNETT MARTIN
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Outbreak Strain ◽  
Fenugreek Seeds ◽  
E Coli ◽  
Aggregative Adherence ◽  
Uremic Syndrome ◽  
Enterocyte Effacement ◽  
The Way

An outbreak that comprised 3,842 cases of human infections with enteroaggregative hemorrhagic Escherichia coli (EAHEC) O104:H4 occurred in Germany in May 2011. The high proportion of adults affected in this outbreak and the unusually high number of patients that developed hemolytic uremic syndrome makes this outbreak the most dramatic since enterohemorrhagic E. coli (EHEC) strains were first identified as agents of human disease. The characteristics of the outbreak strain, the way it spread among humans, and the clinical signs resulting from EAHEC infections have changed the way Shiga toxin–producing E. coli strains are regarded as human pathogens in general. EAHEC O104:H4 is an emerging E. coli pathotype that is endemic in Central Africa and has spread to Europe and Asia. EAHEC strains have evolved from enteroaggregative E. coli by uptake of a Shiga toxin 2a (Stx2a)–encoding bacteriophage. Except for Stx2a, no other EHEC-specific virulence markers including the locus of enterocyte effacement are present in EAHEC strains. EAHEC O104:H4 colonizes humans through aggregative adherence fimbrial pili encoded by the enteroaggregative E. coli plasmid. The aggregative adherence fimbrial colonization mechanism substitutes for the locus of enterocyte effacement functions for bacterial adherence and delivery of Stx2a into the human intestine, resulting clinically in hemolytic uremic syndrome. Humans are the only known natural reservoir known for EAHEC. In contrast, Shiga toxin–producing E. coli and EHEC are associated with animals as natural hosts. Contaminated sprouted fenugreek seeds were suspected as the primary vehicle of transmission of the EAHEC O104:H4 outbreak strain in Germany. During the outbreak, secondary transmission (human to human and human to food) was important. Epidemiological investigations revealed fenugreek seeds as the source of entry of EAHEC O104:H4 into the food chain; however, microbiological analysis of seeds for this pathogen produced negative results. The survival of EAHEC in seeds and the frequency of human carriers of EAHEC should be investigated for a better understanding of EAHEC transmission routes.

scholarly journals Escherichia coli O157:H7 and O157:H−Strains That Do Not Produce Shiga Toxin: Phenotypic and Genetic Characterization of Isolates Associated with Diarrhea and Hemolytic-Uremic Syndrome

1999 ◽  
Vol 37 (11) ◽  
pp. 3491-3496 ◽  
Author(s):  
H. Schmidt ◽  
J. Scheef ◽  
H. I. Huppertz ◽  
M. Frosch ◽  
H. Karch
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Low Frequency ◽  
Diagnostic Methods ◽  
Gene Encoding ◽  
E Coli ◽  
Uremic Syndrome ◽  
Plasmid Genes ◽  
Phenotypic And Genetic Characterization

We have isolated one sorbitol-nonfermenting (SNF) Escherichia coli O157:H7 isolate and five sorbitol-fermenting (SF) E. coli O157:H− isolates that do not contain Shiga toxin (Stx) genes (stx). Isolates originated from patients with diarrhea (n = 4) and hemolytic-uremic syndrome (HUS) (n = 2). All isolates harbored a chromosomaleae gene encoding gamma-intimin as well as the plasmid genes E-hly and etp. The E. coliO157:H7 isolate was katP and espP positive. Respective sera obtained from the patient with HUS contained antibodies to the O157 lipopolysaccharide antigen. Thestx-negative E. coli O157:H7 isolate is genetically related to stx-positive SNF E. coliO157:H7. All stx-negative SF E. coliO157:H− isolates belong to the same genetic cluster and are closely related to stx-positive SF E. coliO157:H− isolates. Our data indicate thatstx-negative E. coli O157:H7/H−variants may occur at a low frequency and cannot be recognized by diagnostic methods that target Stx.

scholarly journals Serogroup-Specific Bacterial Engineered Glycoproteins as Novel Antigenic Targets for Diagnosis of Shiga Toxin-Producing-Escherichia coli-Associated Hemolytic-Uremic Syndrome

2014 ◽  
Vol 53 (2) ◽  
pp. 528-538 ◽  
Author(s):  
Luciano J. Melli ◽  
Andrés E. Ciocchini ◽  
Ana J. Caillava ◽  
Nicolás Vozza ◽  
Isabel Chinen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Diagnostic Procedures ◽  
Stool Culture ◽  
Human Infection ◽  
Healthy Children ◽  
Content Type ◽  
E Coli ◽  
Uremic Syndrome

Human infection with Shiga toxin-producingEscherichia coli(STEC) is a major cause of postdiarrheal hemolytic-uremic syndrome (HUS), a life-threatening condition characterized by hemolytic anemia, thrombocytopenia, and acute renal failure.E. coliO157:H7 is the dominant STEC serotype associated with HUS worldwide, although non-O157 STEC serogroups can cause a similar disease. The detection of anti-O157E. colilipopolysaccharide (LPS) antibodies in combination with stool culture and detection of free fecal Shiga toxin considerably improves the diagnosis of STEC infections. In the present study, we exploited a bacterial glycoengineering technology to develop recombinant glycoproteins consisting of the O157, O145, or O121 polysaccharide attached to a carrier protein as serogroup-specific antigens for the serological diagnosis of STEC-associated HUS. Our results demonstrate that using these antigens in indirect ELISAs (glyco-iELISAs), it is possible to clearly discriminate between STEC O157-, O145-, and O121-infected patients and healthy children, as well as to confirm the diagnosis in HUS patients for whom the classical diagnostic procedures failed. Interestingly, a specific IgM response was detected in almost all the analyzed samples, indicating that it is possible to detect the infection in the early stages of the disease. Additionally, in all the culture-positive HUS patients, the serotype identified by glyco-iELISAs was in accordance with the serotype of the isolated strain, indicating that these antigens are valuable not only for diagnosing HUS caused by the O157, O145, and O121 serogroups but also for serotyping and guiding the subsequent steps to confirm diagnosis.

scholarly journals Syntheses and Immunologic Properties ofEscherichia coli O157 O-Specific Polysaccharide and Shiga Toxin 1 B Subunit Conjugates in Mice

1999 ◽  
Vol 67 (11) ◽  
pp. 6191-6193 ◽  
Author(s):  
Edward Konadu ◽  
Arthur Donohue-Rolfe ◽  
Stephen B. Calderwood ◽  
Vince Pozsgay ◽  
Joseph Shiloach ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Conjugate Vaccines ◽  
E Coli ◽  
B Subunit ◽  
Specific Polysaccharide ◽  
Uremic Syndrome ◽  
Adult Volunteers ◽  
Immunologic Properties

ABSTRACT Escherichia coli O157 is the major cause of diarrhea-associated hemolytic uremic syndrome (HUS). Strains causing HUS contain either Shiga toxin 1 (Stx1) or Stx2, or both. In adult volunteers, conjugate vaccines of detoxified lipopolysaccharide (LPS) elicited bactericidal antibodies to E. coli O157. Here, the detoxified LPS was conjugated with improved schemes to the nontoxic B subunit of Stx1. Mice injected with these bivalent conjugates elicited both bactericidal antibodies to E. coli O157 and neutralization antibodies to Stx1.

scholarly journals Shiga toxin producing Escherichia coli-associated diarrhea and hemolytic uremic syndrome in young children in Romania

Gut Pathogens ◽  
2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Oana Falup-Pecurariu ◽  
Raluca Ileana Lixandru ◽  
Emanuela Cojocaru ◽  
Katalin Csutak ◽  
Vlad Monescu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Young Children ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Clinical Information ◽  
Surveillance Program ◽  
Industrialized Countries ◽  
E Coli ◽  
Uremic Syndrome ◽  
A Prospective Study

Abstract Background Diarrheagenic Escherichia coli (E. coli) is an important cause of diarrheal diseases in both developing countries and industrialized countries. An outbreak of hemolytic uremic syndrome (HUS) in young children from southern Romania was reported in early 2016 and was attributed to Shiga toxin producing E. coli (STEC) O26 infection. The aim of this study was to determine the prevalence, demographic and clinical characteristics of STEC infections in children hospitalized with diarrhea in Brașov in the central region of Romania. We also described the occurrence of HUS among hospitalized children, close in time to the 2016 HUS outbreak in southern Romania. Methods A prospective study was conducted between March and December 2016 among 722 children aged 1–30 months hospitalized with acute diarrhea. Stool samples obtained from patients with diarrhea were tested for the presence of Shiga toxin type 1 (STX1) and type 2 (STX2) by an immunochromatographic assay, and other enteropathogens. Demographic and clinical information on cases of HUS diagnosed in the same hospital was obtained from medical records. Results Overall 46/722 (6.4%) children (mean age 10.3 months, 32.6% females) hospitalized with diarrhea tested positive for STX1 or STX2; of these 79% were positive for both STX1 and STX2, 16% for STX2 only, and 5% for STX1 only. Bloody diarrhea, vomiting and fever were documented in 32.6%, 52.1% and 50.0%, respectively of patients with STEC infection. Eleven confirmed HUS cases (mean age 20 months, five females) were identified between 2014 and 2016 with prodromal diarrhea reported in 10 of them. Three of the 11 HUS patients required hemodialysis. Conclusions STEC prevalence among young children with diarrhea in Romania was high and the risk of HUS is emerging. The establishment of a systematic laboratory-based surveillance program including identification of the circulating STEC strains coupled with epidemiological investigation of HUS patients is warranted to determine the source and mode of transmission of STEC and prevent of STEC-associated diarrhea and HUS.

scholarly journals Enteroaggregative, Shiga Toxin-ProducingEscherichia coli O111:H2 Associated with an Outbreak of Hemolytic-Uremic Syndrome

1998 ◽  
Vol 36 (3) ◽  
pp. 840-842 ◽  
Author(s):  
Stefano Morabito ◽  
Helge Karch ◽  
Patrizia Mariani-Kurkdjian ◽  
Herbert Schmidt ◽  
Fabio Minelli ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Virulence Factors ◽  
Shiga Toxin ◽  
E Coli ◽  
Uremic Syndrome ◽  
Large Plasmids

Shiga toxin-producing Escherichia coli O111:H2 strains from an outbreak of hemolytic-uremic syndrome showed aggregative adhesion to HEp-2 cells and harbored large plasmids which hybridized with the enteroaggregative E. coli probe PCVD432. These strains present a novel combination of virulence factors and might be as pathogenic to humans as the classic enterohemorrhagic E. coli.

scholarly journals International Comparison of Clinical, Bovine, and Environmental Escherichia coli O157 Isolates on the Basis of Shiga Toxin-Encoding Bacteriophage Insertion Site Genotypes

2008 ◽  
Vol 74 (23) ◽  
pp. 7447-7450 ◽  
Author(s):  
Joshua H. Whitworth ◽  
Narelle Fegan ◽  
Jasmin Keller ◽  
Kari S. Gobius ◽  
James L. Bono ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Clinical Case ◽  
Insertion Site ◽  
Escherichia Coli O157 ◽  
E Coli ◽  
Transmission Chain ◽  
Uremic Syndrome ◽  
Case Transmission

ABSTRACT Escherichia coli O157:H7 genotypes in the bovine reservoir may differ in virulence. The proportion of clinical genotypes among cattle isolates was weakly (P = 0.054) related to the international incidence of E. coli O157:H7-associated hemolytic-uremic syndrome, varied among clinical isolates internationally, and also differed along the putative cattle-hamburger-clinical case transmission chain.

scholarly journals Highly Virulent Non-O157 Enterohemorrhagic Escherichia coli (EHEC) Serotypes Reflect Similar Phylogenetic Lineages, Providing New Insights into the Evolution of EHEC

2015 ◽  
Vol 81 (20) ◽  
pp. 7041-7047 ◽  
Author(s):  
Inga Eichhorn ◽  
Katrin Heidemanns ◽  
Torsten Semmler ◽  
Bianca Kinnemann ◽  
Alexander Mellmann ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Shiga Toxin ◽  
Enterohemorrhagic Escherichia Coli ◽  
Toxin Gene ◽  
Content Type ◽  
E Coli ◽  
Healthy Humans ◽  
Uremic Syndrome ◽  
Enterocyte Effacement ◽  
Phylogenetic Lineages

ABSTRACTEnterohemorrhagicEscherichia coli(EHEC) is the causative agent of bloody diarrhea and extraintestinal sequelae in humans, most importantly hemolytic-uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Besides the bacteriophage-encoded Shiga toxin gene (stx), EHEC harbors the locus of enterocyte effacement (LEE), which confers the ability to cause attaching and effacing lesions. Currently, the vast majority of EHEC infections are caused by strains belonging to five O serogroups (the “big five”), which, in addition to O157, the most important, comprise O26, O103, O111, and O145. We hypothesize that these four non-O157 EHEC serotypes differ in their phylogenies. To test this hypothesis, we used multilocus sequence typing (MLST) to analyze a large collection of 250 isolates of these four O serogroups, which were isolated from diseased as well as healthy humans and cattle between 1952 and 2009. The majority of the EHEC isolates of O serogroups O26 and O111 clustered into one sequence type complex, STC29. Isolates of O103 clustered mainly in STC20, and most isolates of O145 were found within STC32. In addition to these EHEC strains, STC29 also includedstx-negativeE. colistrains, termed atypical enteropathogenicE. coli(aEPEC), yet another intestinal pathogenicE. coligroup. The finding that aEPEC and EHEC isolates of non-O157 O serogroups share the same phylogeny suggests an ongoing microevolutionary scenario in which the phage-encoded Shiga toxin genestxis transferred between aEPEC and EHEC. As a consequence, aEPEC strains of STC29 can be regarded as post- or pre-EHEC isolates. Therefore, STC29 incorporates phylogenetic information useful for unraveling the evolution of EHEC.

scholarly journals Hemoconcentration and predictors in Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS)

2021 ◽  
Author(s):  
Sebastian Loos ◽  
Jun Oh ◽  
Laura van de Loo ◽  
Markus J. Kemper ◽  
Martin Blohm ◽  
...  
Keyword(s):  
Risk Factor ◽  
Serum Creatinine ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Neurological Symptoms ◽  
Fluid Loss ◽  
Good Prediction ◽  
E Coli ◽  
Complicated Course ◽  
Uremic Syndrome

Abstract Background Hemoconcentration has been identified as a risk factor for a complicated course in Shiga toxin-producing E. coli-hemolytic uremic syndrome (STEC-HUS). This single-center study assesses hemoconcentration and predictors at presentation in STEC-HUS treated from 2009–2017. Methods Data of 107 pediatric patients with STEC-HUS were analyzed retrospectively. Patients with mild HUS (mHUS, definition: max. serum creatinine < 1.5 mg/dL and no major neurological symptoms) were compared to patients with severe HUS (sHUS, definition: max. serum creatinine ≥ 1.5 mg/dL ± major neurological symptoms). Additionally, predictors of complicated HUS (dialysis ± major neurological symptoms) were analyzed. Results Sixteen of one hundred seven (15%) patients had mHUS. Admission of patients with sHUS occurred median 2 days earlier after the onset of symptoms than in patients with mHUS. On admission, patients with subsequent sHUS had significantly higher median hemoglobin (9.5 g/dL (3.6–15.7) vs. 8.5 g/dL (4.2–11.5), p = 0.016) than patients with mHUS. The product of hemoglobin (g/dL) and LDH (U/L) (cutoff value 13,302, sensitivity 78.0%, specificity of 87.5%) was a predictor of severe vs. mild HUS. Creatinine (AUC 0.86, 95% CI 0.79–0.93) and the previously published score hemoglobin (g/dL) + 2 × creatinine (mg/dL) showed a good prediction for development of complicated HUS (AUC 0.87, 95% CI 0.80–0.93). Conclusions At presentation, patients with subsequent severe STEC-HUS had a higher degree of hemoconcentration. This underlines that fluid loss or reduced fluid intake/administration may be a risk factor for severe HUS. The good predictive value of the score hemoglobin (g/dL) + 2 × creatinine (mg/dL) for complicated HUS could be validated in our cohort. Graphical abstract

scholarly journals Whole-genome characterization of hemolytic uremic syndrome-causing Shiga toxin-producing Escherichia coli in Sweden

Virulence ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 1296-1305
Author(s):  
Ying Hua ◽  
Milan Chromek ◽  
Anne Frykman ◽  
Cecilia Jernberg ◽  
Valya Georgieva ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Whole Genome ◽  
Genome Characterization ◽  
Uremic Syndrome
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