scholarly journals Peripheral nervous system manifestations of Shiga toxin-producing E. coli-induced haemolytic uremic syndrome in children

2021 ◽  
Vol 47 (1) ◽  
Author(s):  
Luisa Santangelo ◽  
Giuseppe Stefano Netti ◽  
Diletta Domenica Torres ◽  
Giovanni Piscopo ◽  
Vincenza Carbone ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Functional Recovery ◽  
Shiga Toxin ◽  
Rehabilitation Program ◽  
Lower Limbs ◽  
Motor Deficit ◽  
E Coli ◽  
Renal Complication ◽  
Uremic Syndrome

Abstract Background The Neurological involvement is the most common extra-renal complication of Shiga toxin-producing E. coli-hemolytic uremic syndrome (HUS) or typical HUS. On brain magnetic resonance examination, main neurological signs encompass acute lesions of the basal ganglia and the white matter, which could usually regress after Eculizumab infusion. In contrast, peripheral nervous system (PNS) manifestations in typical HUS are very rare and, when occurring, they require a careful management of neurological sequelae and an intensive multidisciplinary neuro-rehabilitation program. Case presentation Here, we present two pediatric cases of severe and complicated typical HUS with PNS manifestations who required therapeutic treatment and an intensive multidisciplinary neuro-rehabilitation program. In both cases, PNS manifestations were followed by the recovery from typical HUS-related severe central neurological damage and manifested mainly with marked bilateral motor deficit and hyporeflexia/areflexia in the lower limbs. The peripheral polyneuropathy was treated with immunosuppressive therapy (methylprednisolone boluses, i.v. immunoglobulins, plasma exchange), followed by a prolonged intensive neuro-rehabilitation program. After 8 months of rehabilitation, both patients gained complete functional recovery. Conclusions PNS manifestations during typical HUS are a rare event and potentially leading to severe disability. A timely clinical assessment is mandatory to set up a prompt therapeutic and rehabilitation program and to obtain a complete clinical and functional recovery.

scholarly journals Peripheral neurological involvement in Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome (STEC-HUS) as a rare complication with a positive outcome in two consecutive children – Case Report

2021 ◽  
Author(s):  
Luisa Santangelo ◽  
Giuseppe Stefano Netti ◽  
Diletta Domenica Torres ◽  
Giovanni Piscopo ◽  
Vincenza Carbone ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Hemolytic Uremic Syndrome ◽  
Functional Recovery ◽  
Shiga Toxin ◽  
Rehabilitation Program ◽  
Lower Limbs ◽  
Motor Deficit ◽  
Neurological Involvement ◽  
Renal Complication ◽  
Uremic Syndrome

Abstract Background. The Neurological involvement is the most common extra-renal complication of Shiga toxin-producing Escherichia coli-hemolytic uremic syndrome (STEC-HUS). On brain magnetic resonance examination, main neurological signs encompass acute lesions of the basal ganglia and the white matter, which could usually regress after Eculizumab infusion. In contrast, STEC-HUS-related peripheral nervous system (PNS) involvement is very rare and, when occurring, it requires a careful management of neurological sequelae and an intensive multidisciplinary neuro-rehabilitation program.Case presentation. Here, we present two cases of severe and complicated STEC-HUS patients with PNS-involvement who successfully required therapeutic treatment and an intensive multidisciplinary neuro-rehabilitation program.In both cases, PNS-involvement followed the recovery from STEC-HUS-related severe central neurological damage and manifested mainly with marked bilateral motor deficit and hyporeflexia/areflexia in the lower limbs. The peripheral polyneuropathy was treated with immune-suppressive therapy (methylprednisolone pulses, i.v. immunoglobulins, therapeutic plasma exchange), followed by a prolonged intensive neuro-rehabilitation program. After 8 months of neuro-rehabilitation, both patients gained complete functional recovery.Conclusions. PNS involvement during STEC-HUS is a rare event and potentially leading to severe disability. A timely clinical assessment is mandatory to set up a prompt therapeutic and neuro-rehabilitation program and to obtain a complete clinical and functional recovery.

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 Prevalence and molecular detection of shiga toxin producing Escherichia coli from diarrheic cattle

2016 ◽  
Vol 14 (1) ◽  
pp. 63-68 ◽  
Author(s):  
MM Akter ◽  
S Majumder ◽  
KH MNH Nazir ◽  
M Rahman
Keyword(s):  
Escherichia Coli ◽  
Shiga Toxin ◽  
Molecular Detection ◽  
Chain Reaction ◽  
Specific Primers ◽  
Fecal Samples ◽  
E Coli ◽  
Uremic Syndrome ◽  
Polymerase Chain ◽  
Positive Isolate

Shiga toxin-producing Escherichia coli (STEC) are zoonotically important pathogen which causes hemorrhagic colitis, diarrhea, and hemolytic uremic syndrome in animals and humans. The present study was designed to isolate and identify the STEC from fecal samples of diarrheic cattle. A total of 35 diarrheic fecal samples were collected from Bangladesh Agricultural University (BAU) Veterinary Teaching Hospital. The samples were primarily examined for the detection of E. coli by cultural, morphological and biochemical characteristics, followed by confirmation of the isolates by Polymerase Chain Reaction (PCR) using gene specific primers. Later, the STEC were identified among the isolated E. coli through detection of Stx-1 and Stx-2 genes using duplex PCR. Out of 35 samples, 25 (71.43%) isolates were confirmed to be associated with E. coli, of which only 7 (28%) isolates were shiga toxin producers, and all of them were positive for Stx-1. However, no Stx-2 positive isolate could be detected. From this study, it may be concluded that cattle can act as a reservoir of STEC which may transmit to human or other animals.J. Bangladesh Agril. Univ. 14(1): 63-68, June 2016

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.

How Does Escherichia coli O157:H7 Testing in Meat Compare with What We Are Seeing Clinically?

2000 ◽  
Vol 63 (6) ◽  
pp. 819-821 ◽  
Author(s):  
DAVID W. K. ACHESON
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Shiga Toxin ◽  
Food Supply ◽  
The United States ◽  
Escherichia Coli O157 ◽  
Current Policy ◽  
E Coli ◽  
Different Types ◽  
Uremic Syndrome

Escherichia coli O157:H7 is but one of a group of Shiga toxin-producing E. coli (STEC) that cause both intestinal disease such as bloody and nonbloody diarrhea and serious complications like hemolytic uremic syndrome (HUS). While E. coli O157: H7 is the most renowned STEC, over 200 different types of STEC have been documented in meat and animals, at least 60 of which have been linked with human disease. A number of studies have suggested that non-O157 STEC are associated with clinical disease, and non-O157 STEC are present in the food supply. Non-O157 STEC, such as O111 have caused large outbreaks and HUS in the United States and other countries. The current policy in the United States is to examine ground beef for O157:H7 only, but restricting the focus to O157 will miss other important human STEC pathogens.

scholarly journals Peripheral Nervous System Involvement in Late-Onset Cobalamin C Disease?

2020 ◽  
Vol 11 ◽  
Author(s):  
Xujun Chu ◽  
Lingchao Meng ◽  
Wei Zhang ◽  
Jinjun Luo ◽  
Zhaoxia Wang ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Methylenetetrahydrofolate Reductase ◽  
Late Onset ◽  
Hot Spot ◽  
Axonal Neuropathy ◽  
Methylmalonic Aciduria ◽  
Lower Limbs ◽  
Compound Heterozygous ◽  
Limb Weakness

Background: Cobalamin C (cblC) has a fundamental role in both central and peripheral nervous system function at any age. Neurologic manifestations may be the earliest and often the only manifestation of hereditary or acquired cblC defect. Peripheral neuropathy remains a classical but underdiagnosed complication of cblC defect, especially in late-onset cblC disease caused by mutations in the methylmalonic aciduria type C and homocysteinemia (MMACHC) gene. So the clinical, electrophysiological, and pathological characteristics of late-onset cblC disease are not well-known.Methods: A retrospective study of patients with late-onset cblC disease was conducted at our hospital on a 3-year period. The neuropathy was confirmed by the nerve conduction study. Sural biopsies were performed in 2 patients.Results: Eight patients were identified, with a mean onset age of 16.25 ± 6.07 years. All patients had methylmalonic aciduria, homocysteinemia, compound heterozygous MMACHC gene mutations were detected in all patients, and 7/8 patients with c.482G&gt;A mutation. One patient concomitant with homozygote c.665C&gt;T mutation in 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. All patients showed limb weakness and cognitive impairment. Five patients had possible sensorimotor axonal polyneuropathy predominantly in the distal lower limbs. Sural biopsies showed loss of myelinated and unmyelinated fibers. Electro microscopy revealed crystalline-like inclusions bodies in Schwann cells and axonal degeneration.Conclusion: Late-onset cblC disease had possible heterogeneous group of distal axonal neuropathy. c.482G&gt;A mutation is a hot spot mutation in late-onset cblC disease.

scholarly journals Genomic Subtraction To Identify and Characterize Sequences of Shiga Toxin-Producing Escherichia coli O91:H21

2002 ◽  
Vol 68 (5) ◽  
pp. 2316-2325 ◽  
Author(s):  
Nathalie Pradel ◽  
Sabine Leroy-Setrin ◽  
Bernard Joly ◽  
Valérie Livrelli
Keyword(s):  
Escherichia Coli ◽  
Dna Sequences ◽  
Shiga Toxin ◽  
Shigella Flexneri ◽  
Virulence Determinants ◽  
E Coli ◽  
Virulence Plasmids ◽  
Subtraction Procedure ◽  
Uremic Syndrome ◽  
Genomic Subtraction

ABSTRACT To identify Shiga toxin-producing Escherichia coli genes associated with severe human disease, a genomic subtraction technique was used with hemolytic-uremic syndrome-associated O91:H21 strain CH014 and O6:H10 bovine strains. The method was adapted to the Shiga toxin-producing E. coli genome: three rounds of subtraction were used to isolate DNA fragments specific to strain CH014. The fragments were characterized by genetic support analysis, sequencing, and hybridization to the genome of a collection of Shiga toxin-producing E. coli strains. A total of 42 fragments were found, 19 of which correspond to previously identified unique DNA sequences in the enterohemorrhagic E. coli EDL933 reference strain, including 7 fragments corresponding to prophage sequences and others encoding candidate virulence factors, such a SepA homolog protein and a fimbrial usher protein. In addition, the subtraction procedure yielded plasmid-related sequences from Shigella flexneri and enteropathogenic and Shiga toxin-producing E. coli virulence plasmids. We found that lateral gene transfer is extensive in strain CH014, and we discuss the role of genomic mobile elements, especially bacteriophages, in the evolution and possible transfer of virulence determinants.

scholarly journals Circulating microRNAs in Patients with Shiga-Toxin-Producing E. coli O104:H4 Induced Hemolytic Uremic Syndrome

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e47215 ◽  
Author(s):  
Johan M. Lorenzen ◽  
Jan Menne ◽  
Bernhard MW. Schmidt ◽  
Mascha Schmidt ◽  
Filippo Martino ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Circulating Micrornas ◽  
E Coli ◽  
Uremic Syndrome

scholarly journals Molecular Characterization of Shiga Toxin-Producing Escherichia coli Strains Isolated in Poland

2016 ◽  
Vol 65 (3) ◽  
pp. 261-269 ◽  
Author(s):  
Aleksandra Januszkiewicz ◽  
Waldemar Rastawicki
Keyword(s):  
Escherichia Coli ◽  
Virulence Factors ◽  
Shiga Toxin ◽  
Virulence Gene ◽  
Virulence Determinants ◽  
E Coli ◽  
Heat Stable ◽  
Food Borne ◽  
Wide Range ◽  
Uremic Syndrome

Shiga toxin-producing Escherichia coli (STEC) strains also called verotoxin-producing E. coli (VTEC) represent one of the most important groups of food-borne pathogens that can cause several human diseases such as hemorrhagic colitis (HC) and hemolytic – uremic syndrome (HUS) worldwide. The ability of STEC strains to cause disease is associated with the presence of wide range of identified and putative virulence factors including those encoding Shiga toxin. In this study, we examined the distribution of various virulence determinants among STEC strains isolated in Poland from different sources. A total of 71 Shiga toxin-producing E. coli strains isolated from human, cattle and food over the years 1996 – 2010 were characterized by microarray and PCR detection of virulence genes. As stx1a subtype was present in all of the tested Shiga toxin 1 producing E. coli strains, a greater diversity of subtypes was found in the gene stx2, which occurred in five subtypes: stx2a, stx2b, stx2c, stx2d, stx2g. Among STEC O157 strains we observed conserved core set of 14 virulence factors, stable in bacteria genome at long intervals of time. There was one cattle STEC isolate which possessed verotoxin gene as well as sta1 gene encoded heat-stable enterotoxin STIa characteristic for enterotoxigenic E. coli. To the best of our knowledge, this is the first comprehensive analysis of virulence gene profiles identified in STEC strains isolated from human, cattle and food in Poland. The results obtained using microarrays technology confirmed high effectiveness of this method in determining STEC virulotypes which provides data suitable for molecular risk assessment of the potential virulence of this bacteria.

scholarly journals Carboxypeptidase B2 Is Protective in a Mouse Model of Shiga Toxin-Induced Hemolytic Uremic Syndrome

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2804-2804
Author(s):  
Toshihiko Nishimura ◽  
John Morser ◽  
Zhifei Shao ◽  
Lawrence L. Leung
Keyword(s):  
Mouse Model ◽  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Conflicts Of Interest ◽  
Severe Thrombocytopenia ◽  
E Coli ◽  
Potential Efficacy ◽  
Significant Difference ◽  
Uremic Syndrome

Abstract Hemolytic uremic syndrome (HUS) is characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. The most common cause of HUS is Shiga toxin (STX)-producing E. coli, and eculizumab, a monoclonal antibody against complement C5, has shown clinical efficacy in some patients. Carboxypeptidase B2 (CPB2) is a metalloprotease activated by the thrombin/thrombomodulin complex that inactivates a number of inflammatory mediators, including complement C3a, and C5a by removing their C-terminal arginine. We hypothesized that in a murine model of STX-induced HUS, Cpb2-/- mice would have exacerbated disease compared to wild type (WT) mice due to excessive C3a and/or C5a in the absence of CPB2. A mouse model of STX-induced HUS was established by giving STX and LPS toxins intraperitoneally. Cpb2-/- mice had worse survival than WT (37% survival vs. 87% at 48h, p=0.0156). At 48h, severe thrombocytopenia developed in both WT and Cpb2-/- mice (WT: 0.096x106/μL; Cpb2-/-: 0.054x106/μL) compared to controls (1.2x106/μL; p>0.0001 vs. either WT or Cpb2-/-), with Cpb2-/- mice showing worse thrombocytopenia. Renal insufficiency was worse in Cpb2-/- mice than WT mice (BUN at 48h: 85 mg/dL vs. 37 mg/dL, p=0.0074; creatinine: 1.33 mg/dL vs. 0.23 mg/dL; p=0.0112, for Cpb2-/- and WT mice respectively, compared with normal baseline BUN and creatinine of 19 mg/dL and 0.1 mg/dL). Cpb2-/- mice developed worse anemia than WT (hemoglobin 9.8 g/dL vs. 12.4 g/dL, p=0.001 in Cpb2-/- vs. WT mice respectively). At 48h, liver function was worse in Cpb2-/- mice than WT mice, while plasma LDH was increased in Cpb2-/- mice more than WT mice. Using a standardized health score, the Cpb2-/- mice were worse than WT mice at all time points. Thus this model recapitulates STX-induced HUS with the Cpb2-/- mice having worse disease than WT. If the animals were treated with STX alone, there were no deaths in either genotype at 48h and only 37.5% mortality in Cpb2-/- mice by 60h compared with no deaths in WT mice. BUN, creatinine, liver enzymes and LDH were increased in both genotypes treated with STX alone compared to untreated mice, but there was no significant difference between the genotypes. Treatment with LPS alone caused thrombocytopenia in both WT and Cpb2-/- mice and LDH, BUN and creatinine levels were higher in Cpb2-/- mice than in WT mice, but there was no death at 48h and no drop in hemoglobin. Thus while either STX alone or LPS alone caused pathological conditions in the mice, the typical triad of HUS was only present when STX and LPS were given in combination. The Cpb2-/- mice had worse disease than WT mice consistent with our hypothesis on the role of CPB2 in inactivating C3a and/or C5a in STX-induced HUS. The potential efficacy of C3a and/or C5a blockade and anti-thrombotic agents will be tested in this model. Disclosures No relevant conflicts of interest to declare.

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