Virulence factors of Shiga toxin-producing Escherichia coli and the risk of developing haemolytic uraemic syndrome in Norway, 1992-2013.

Shiga toxin-producing Escherichia coli (STEC) may cause haemolytic uraemic syndrome (HUS). Age ≤5 years and presence of stx2a and eae are risk factors for the development of HUS. In this study, we investigated STEC isolates for the presence of adhesins, toxins and molecular risk assessment (MRA) factors to identify virulence genes associated with HUS development. We included non-duplicate isolates from all STEC infections (n = 340, HUS = 32) reported to the Norwegian National Reference Laboratory (NRL) for Enteropathogenic Bacteria from 1992 to 2013. The most common STEC were O157:H7/H- (34%) and O103:H2 (14%). We retrospectively screened the isolates by three multiplex polymerase chain reactions (PCRs) for adhesins (n = 11), toxins (n = 5) and MRA (n = 15). We calculated odds ratios (ORs) and adjusted odds ratios (aORs) for associations with HUS development. On average, isolates were positive for 15 virulence genes (range: 1-24); two toxins (range: 0-4), five adhesins (range: 0-8) and eight MRA genes (range: 0-13). The gene combinations were clustered within serotypes. Isolates from HUS cases were positive for eae and IpfA O26, and negative for saa, eibG, astA, cnf, subA and pic. We identified 11 virulence genes with a significant association to HUS development. Multivariable analyses adjusted for age group and Shiga toxin identified nleH1-2 [aOR 8.4, 95% confidence interval (CI); 2.18-32.3] as an independent risk factor for the development of HUS from an STEC infection. This study demonstrated that the non-LEE effector protein nleH1-2 may be an important predictor for elevated risk of developing HUS from STEC infections. We recommend the NRL for Enteropathogenic Bacteria to consider including nleH1-2 screening as part of routine STEC surveillance.

Overview and Historical Perspectives.

In this overview, we describe the history of Shiga toxin (Stx)-producing Escherichia coli (STEC) in two phases. In phase one, between 1977 and 2011, we learned that E. coli could produce Shiga toxin and cause both hemorrhagic colitis and the hemolytic-uremic syndrome in humans and that the prototype STEC-E. coli O157:H7-adheres to and effaces intestinal epithelial cells by a mechanism similar to that of enteropathogenic E. coli. We also recognized that the genes for Stx are typically encoded on a lysogenic phage; that STEC O157:H7 harbors a large pathogenicity island that encodes the elements needed for the characteristic attaching and effacing lesion; and that the most severe cases of human disease are linked to production of Stx type 2a, not Stx type 1a. Phase two began with a large food-borne outbreak of hemorrhagic colitis and hemolytic-uremic syndrome in Germany in 2011. That outbreak was caused by a novel strain consisting of enteroaggregative E. coli O104:H4 transduced by a Stx2a-converting phage. From this outbreak we learned that any E. coli strain that can adhere tightly to the human bowel (either by a biofilm-like mechanism as in E. coli O104:H4 or by an attaching and effacing mechanism as in E. coli O157:H7) can cause severe diarrheal and systemic illness when it acquires the capacity to produce Stx2a. This overview provides the basis for the review of current information regarding these fascinating and complex pathogens.

[Historical stages of Hemolytic Uremic Syndrome in Argentina (1964-2009)]. / Etapas históricas del Síndrome Urémico- Hemolítico en la Argentina (1964-2009).

The aim is to present an historical time frame of Hemolytic Uremic Syndrome (HUS) in Argentina. From a public policy approach, the history of the disease is analyzed as an object of health policy and seeks to contribute in understanding the multiple dimensions of illness. As a medical and scientific issue, as a social problem and a matter of health policy, the article describes three phases ranging from its discovery up to the national program of HUS adopted in 2009. This article aims to provide an overview of developments in biomedical knowledge and the emergence of the issue in both social and political problem.

Tibor Greenwalt Award. The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome Registry: a program for patient care, education and research.

The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome (TTP-HUS) Registry was created by collaboration of the Oklahoma Blood Institute and the Colleges of Medicine and Public Health of the University of Oklahoma Health Sciences Center, combining their respective strengths of community service, patient care, education, and clinical research methodology. The organization of the Registry is based on the fundamental principles of patient-oriented research: 1) all consecutive patients are identified at a uniform time early in the course of their disease; 2) analysis of clinical data requires quantitative and reproducible definitions; 3) patient follow-up is complete; and 4) therefore the data are generalizable to community practice. A summary of 15 years experience with 301 consecutive patients is presented. Some of these results and interpretations are different from other case series. These differences emphasize the distinct perspective of the Registry that includes all patients in the community who have had a clinical diagnosis of TTP or HUS and for whom plasma-exchange treatment was requested. The Oklahoma TTP-HUS Registry provides educational and research opportunities, in addition to improved patient care, and serves as a model for productive collaboration of community blood centers and universities.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS): the new thinking.

TTP and HUS are two disorders with many similarities. Though their first descriptions appeared at different time in history, there has been a trend among physicians to consider them as the same clinical entity. However, in recent years new research findings on the pathophysiology of TTP and HUS have revealed some differences between the two disorders. In this paper, we will review the current approaches to the clinical and laboratory diagnosis of TTP and HUS, as well as therapeutic strategies. We will also summarize the recent advances in three areas in the study of the pathophysiology of TTP and HUS, namely the newly discovered von Willebrand factor multimer-cleaving protease, endothelial cell apoptosis induced by serum from patients with TTP and atypical HUS and the activation of complement system. Since distinguishing and differentiating between TTP and HUS may help to develop more effective therapies targeted at key steps of the disease development, we will discuss possible ways of reclassifying the TTP-HUS disorders. In the end, we also present our views on possible future development.

Hemolytic uremic syndromes in childhood.

The hemolytic uremic syndrome (HUS) comprises hemolytic anemia, acute renal failure, and thrombocytopenia. It is the most frequent cause of acute renal failure in childhood. Ninety percent of the patients have a diarrheal prodrome, and are referred to as having typical HUS. Approximately 10% exhibit the so-called atypical HUS. Typical HUS is caused by shigatoxin-producing Escherichia coli. The toxin, bound to the globotriosyl ceramide cell receptor and internalized, interferes with protein synthesis, predominantly of endothelial cells. The main target is the kidney, but nearly every organ system can be involved. The most common extrarenal involvement is damage to the central nervous system. The central event is probably an insult to the endothelial cell with consecutive loss of antithrombogenic properties. The von Willebrand factor, activation of platelets via platelet-activating factor, other growth factors (e.g., interleukins 1, 6, 8), nitric oxide, lipopolysaccharides, activated polymorphonucleated neutrophils, and the metabolites of the arachidonic acid cascade (e.g., prostaglandin I2) are believed to be involved in the pathogenic cascade. Controlled therapeutic trials with heparin, dipyridamole, aspirin, and urokinase have not been associated with improved outcome. Antibiotics have not yielded any benefit. Plasma infusions and plasma exchange appear to be efficacious, and are justified in cases of atypical HUS and thrombotic thrombocytopenic purpura. Binding of the toxin to the intestinal lumen, and thereby inhibition of enteral reabsorption, is under investigation.

Sindrome Hemolítico Urémico

El Síndrome Hemolítico Urémico(SHU) es una causa frecuente de insuficiencia renal aguda en la infancia yen la niñez. Se clasifica en típico o epidémico y atípico. A pesar de su frecuencia, la etiología y la patogénesis no han sido completamente aclarads. Sin embargo, en los últimos años se ha dado un gran avanceen el entendimiento de los factores desencadenantes y en la fisiopatología de esta entidad, dentro de los cuales se han implicado el endotelio vascular, lasplaquetas y sus derivados (factor decrecimiento, serotonina y tromboglobulina), la prostaciclina, el tromboxano A2 y sus metabolitos, multímeros del factor Von-Willebrand y la verotoxina de laEscherichia coli,entre otros. Estos avances han facilitado un diagnóstico más temprano y un mejor manejo, con notable disminución de la morbimortalidad, mediante una terapia de soporte y otra específica

Síndrome hemolítico urémico post-parto / Post-partum hemolytic uremic

Se presenta un caso visto en el Hospital San Ignacio, informando las manifestaciones clínicas, los hallazgos histopatológicos, su manejo terapéutico, seguimiento y se hace una revisión literaria