Abstract

The severity of human infection by one of the many Shiga toxin-producing Escherichia coli (STEC) is determined by a number of factors: the bacterial genome, the capacity of human societies to prevent foodborne epidemics, the medical condition of infected patients (in particular their hydration status, often compromised by severe diarrhea), and by our capacity to devise new therapeutic approaches, most specifically to combat the bacterial virulence factors, as opposed to our current strategies that essentially aim to palliate organ deficiencies. The last major outbreak in 2011 in Germany, which killed more than 50 people in Europe, was evidence that an effective treatment was still lacking. Herein, we review the current knowledge of STEC virulence, how societies organize the prevention of human disease, and how physicians treat (and, hopefully, will treat) its potentially fatal complications. In particular, we focus on STEC-induced hemolytic and uremic syndrome (HUS), where the intrusion of toxins inside endothelial cells results in massive cell death, activation of the coagulation within capillaries, and eventually organ failure.

Highlights

  • Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC-hemolytic and uremic syndrome (HUS)) belongs to the body of thrombotic microangiopathies [1], a heterogeneous group of diseases characterized by a triad of features: thrombocytopenia, mechanical hemolytic anemia with schistocytosis, and ischemic organ damage

  • These results could provide the rationale for the use of ART-123, a human recombinant thrombomodulin tested in the setting of disseminated intravascular coagulation [195] and acute exacerbations of idiopathic pulmonary fibrosis, in STEC-HUS

  • Likewise, during a diarrhea outbreak, rapid identification of enterohemorrhagic E. coli (EHEC) allows for timely epidemiological investigations and isolation measures that will prevent further spreading of the pathogen, as well as avoidance of antibiotic therapy and antimotility agents in cases of STEC-related disease [214]

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Summary

A Narrative Review

Adrien Joseph 1 , Aurélie Cointe 2 , Patricia Mariani Kurkdjian 2 , Cédric Rafat 1 and Alexandre Hertig 3, *. Received: 29 December 2019; Accepted: 17 January 2020; Published: 21 January 2020

Introduction
Historical Perspective
Purpose of the Review
Epidemiology and Microbiology
Nomenclature
Shiga Toxins
STEC-HUS as a Zoonosis
Propensity to Develop STEC-HUS
Pathogenesis
Colonization of the Bowel
Shiga Toxin Production and Effect
4: Thethe
Mechanisms
Activation of Complement Pathways
Endothelial Damage
Clinical Presentation
From Colitis to HUS
Clinical
Renal Involvement
Neurologic Involvement
Cardiac Involvement
STEC-HUS and Diabetes Mellitus
Recurrence
Unusual Invasive Infections
Thrombotic Microangiopathy
Inflammatory Features and Coagulation Activation
Biological Predictors of Evolution Towards HUS
Histopathology
Microbiology
Identification of EHEC
Identification of Shiga Toxin
5.10. Differential Diagnosis
Treatment
Primary Prevention
Secondary Prevention
Supportive Therapy
Blood Pressure Control
Transfusion
Detrimental Effect of Antimotility Agents
Specific Therapies
Plasma Exchange and Immunoadsorption
Complement Blockade Therapy
Manganese
Other Abandoned Therapies
Prognosis
Renal Sequelae
Extra-Renal Sequelae
Predicting the Risk of Long-Term Sequelae
Findings
Conclusions
Full Text
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