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1.
PLoS One ; 14(12): e0220483, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31881024

RESUMO

E. coli associated Hemolytic Uremic Syndrome (epidemic hemolytic uremic syndrome, eHUS) caused by Shiga toxin-producing bacteria is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury that cause acute renal failure in up to 65% of affected patients. We hypothesized that the mannose-binding lectin (MBL) pathway of complement activation plays an important role in human eHUS, as we previously demonstrated that injection of Shiga Toxin-2 (Stx-2) led to fibrin deposition in mouse glomeruli that was blocked by co-injection of the anti-MBL-2 antibody 3F8. However, the markers of platelet thrombosis in affected mouse glomeruli were not delineated. To investigate the effect of 3F8 on markers of platelet thrombosis, we used kidney sections from our mouse model (MBL-2+/+ Mbl-A/C-/-; MBL2 KI mouse). Mice in the control group received PBS, while mice in a second group received Stx-2, and those in a third group received 3F8 and Stx-2. Using double immunofluorescence (IF) followed by digital image analysis, kidney sections were stained for fibrin(ogen) and CD41 (marker for platelets), von-Willebrand factor (marker for endothelial cells and platelets), and podocin (marker for podocytes). Electron microscopy (EM) was performed on ultrathin sections from mice and human with HUS. Injection of Stx-2 resulted in an increase of both fibrin and platelets in glomeruli, while administration of 3F8 with Stx-2 reduced both platelet and fibrin to control levels. EM studies confirmed that CD41-positive objects observed by IF were platelets. The increases in platelet number and fibrin levels by injection of Stx-2 are consistent with the generation of platelet-fibrin thrombi that were prevented by 3F8.


Assuntos
Síndrome Hemolítico-Urêmica/metabolismo , Lectina de Ligação a Manose/metabolismo , Trombose/metabolismo , Lesão Renal Aguda/metabolismo , Animais , Plaquetas/metabolismo , Modelos Animais de Doenças , Células Endoteliais/metabolismo , Escherichia coli/metabolismo , Escherichia coli/patogenicidade , Infecções por Escherichia coli/microbiologia , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Rim/metabolismo , Glomérulos Renais/metabolismo , Lectina de Ligação a Manose/imunologia , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Toxina Shiga/metabolismo , Toxina Shiga II/metabolismo , Tromboembolia/metabolismo
2.
Pediatrics ; 144(4)2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31519792

RESUMO

BACKGROUND: In 2017, we conducted a multistate investigation to determine the source of an outbreak of Shiga toxin-producing Escherichia coli (STEC) O157:H7 infections, which occurred primarily in children. METHODS: We defined a case as infection with an outbreak strain of STEC O157:H7 with illness onset between January 1, 2017, and April 30, 2017. Case patients were interviewed to identify common exposures. Traceback and facility investigations were conducted; food samples were tested for STEC. RESULTS: We identified 32 cases from 12 states. Twenty-six (81%) cases occurred in children <18 years old; 8 children developed hemolytic uremic syndrome. Twenty-five (78%) case patients ate the same brand of soy nut butter or attended facilities that served it. We identified 3 illness subclusters, including a child care center where person-to-person transmission may have occurred. Testing isolated an outbreak strain from 11 soy nut butter samples. Investigations identified violations of good manufacturing practices at the soy nut butter manufacturing facility with opportunities for product contamination, although the specific route of contamination was undetermined. CONCLUSIONS: This investigation identified soy nut butter as the source of a multistate outbreak of STEC infections affecting mainly children. The ensuing recall of all soy nut butter products the facility manufactured, totaling >1.2 million lb, likely prevented additional illnesses. Prompt diagnosis of STEC infections and appropriate specimen collection aids in outbreak detection. Child care providers should follow appropriate hygiene practices to prevent secondary spread of enteric illness in child care settings. Firms should manufacture ready-to-eat foods in a manner that minimizes the risk of contamination.


Assuntos
Surtos de Doenças/estatística & dados numéricos , Infecções por Escherichia coli/epidemiologia , Escherichia coli O157 , Doenças Transmitidas por Alimentos/epidemiologia , Escherichia coli Shiga Toxigênica , Alimentos de Soja/microbiologia , Adolescente , Idoso , Criança , Creches/estatística & dados numéricos , Pré-Escolar , Infecções por Escherichia coli/microbiologia , Fast Foods/efeitos adversos , Fast Foods/microbiologia , Feminino , Manipulação de Alimentos , Doenças Transmitidas por Alimentos/microbiologia , Síndrome Hemolítico-Urêmica/epidemiologia , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Lactente , Masculino , Recall e Retirada de Produto , Alimentos de Soja/efeitos adversos , Estados Unidos/epidemiologia
3.
Artigo em Inglês | MEDLINE | ID: mdl-31297339

RESUMO

The most frequent form of hemolytic-uremic syndrome (HUS) is associated with infections caused by Shiga-like toxin-producing Enterohaemorrhagic Escherichia coli (STEC). In rarer cases HUS can be triggered by Streptococcus pneumoniae. While production of Shiga-like toxins explains STEC-HUS, the mechanisms of pneumococcal HUS are less well-known. S. pneumoniae produces neuraminidases with activity against cell surface sialic acids that are critical for factor H-mediated complement regulation on cells and platelets. The aim of this study was to find out whether S. pneumoniae neuraminidase NanA could trigger complement activation and hemolysis in whole blood. We studied clinical S. pneumoniae isolates and two laboratory strains, a wild-type strain expressing NanA, and a NanA deletion mutant for their ability to remove sialic acids from various human cells and platelets. Red blood cell lysis and activation of complement was measured ex vivo by incubating whole blood with bacterial culture supernatants. We show here that NanA expressing S. pneumoniae strains and isolates are able to remove sialic acids from cells, and platelets. Removal of sialic acids by NanA increased complement activity in whole blood, while absence of NanA blocked complement triggering and hemolytic activity indicating that removal of sialic acids by NanA could potentially trigger pHUS.


Assuntos
Neuraminidase/sangue , Neuraminidase/metabolismo , Streptococcus pneumoniae/enzimologia , Streptococcus pneumoniae/metabolismo , Proteínas de Bactérias/genética , Plaquetas/metabolismo , Proteínas do Sistema Complemento/efeitos dos fármacos , Eritrócitos , Células HEK293 , Hemólise , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Inflamação , Neuraminidase/genética , Neuraminidase/farmacologia , Infecções Pneumocócicas/microbiologia , Deleção de Sequência , Ácidos Siálicos
4.
Pediatr Blood Cancer ; 66(11): e27913, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31286658

RESUMO

Complement activation plays an important role in the pathogenesis of atypical hemolytic uremic syndrome. Eculizumab is a monoclonal antibody that blocks complement activity and has been approved for use in the treatment of atypical hemolytic uremic syndrome (HUS). Less well appreciated is the role of complement in Shiga toxin-induced HUS (Shiga toxin producing Escherichia coli [STEC]-HUS). To a limited extent, eculizumab has been used off label in patients with severe STEC-HUS with neurological involvement. Through a systematic search of available databases, we identified 16 reports describing the use of eculizumab in STEC-HUS (eight case reports/series, seven retrospective studies, and one prospective cohort study). All studies described its use in severe STEC-HUS with neurological or multiorgan dysfunction; none were randomized or blinded. Four studies used the control groups. Although the overall quality of evidence is low, some published studies showed positive clinical improvement after treatment with eculizumab in severe STEC-HUS with progressive neurological involvement.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Ativação do Complemento , Infecções por Escherichia coli/tratamento farmacológico , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Escherichia coli Shiga Toxigênica/isolamento & purificação , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Método Duplo-Cego , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/microbiologia , Previsões , Cardiopatias/etiologia , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Doenças do Sistema Nervoso/etiologia , Uso Off-Label , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Estudos Retrospectivos
5.
Life Sci Alliance ; 2(3)2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31243048

RESUMO

Shiga toxin 1 (STx1) and 2 (STx2), produced by Shiga toxin-producing Escherichia coli, cause lethal untreatable disease. The toxins invade cells via retrograde trafficking. Direct early endosome-to-Golgi transport allows the toxins to evade degradative late endosomes. Blocking toxin trafficking, particularly at the early endosome-to-Golgi step, is appealing, but transport mechanisms of the more disease-relevant STx2 are unclear. Using data from a genome-wide siRNA screen, we discovered that disruption of the fusion of late endosomes, but not autophagosomes, with lysosomes blocked the early endosome-to-Golgi transport of STx2. A subsequent screen of clinically approved lysosome-targeting drugs identified tamoxifen (TAM) to be a potent inhibitor of the trafficking and toxicity of STx1 and STx2 in cells. The protective effect was independent of estrogen receptors but dependent on the weak base property of TAM, which allowed TAM to increase endolysosomal pH and alter endosomal dynamics. Importantly, TAM treatment enhanced survival of mice injected with a lethal dose of STx1 or STx2. Thus, it may be possible to repurpose TAM for treating Shiga toxin-producing E. coli infections.


Assuntos
Toxina Shiga I/metabolismo , Toxina Shiga II/metabolismo , Tamoxifeno/farmacologia , Autofagia , Endossomos/metabolismo , Complexo de Golgi/metabolismo , Células HeLa , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Síndrome Hemolítico-Urêmica/metabolismo , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Espaço Intracelular/metabolismo , Lisossomos/metabolismo , Transporte Proteico/efeitos dos fármacos , Transdução de Sinais
6.
Indian J Med Res ; 149(3): 412-417, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-31249208

RESUMO

Background & objectives: : Shiga toxin (Stx) is produced by Shigella dysenteriae, a Gram-negative, facultative anaerobic bacillus that causes shigellosis, haemolytic uraemic syndrome (HUS) and Reiter's syndrome. The detection methods for shiga toxin needs to be rapid, accurate, reliable and must be extensively evaluated under field conditions. The aim of this study was to develop rapid, sensitive and specific detection method for Stx. Methods: : Mice and rabbits were immunized with purified recombinant Shiga toxin B (rStxB). Using these antibodies dot ELISA, sandwich ELISA and flow through assay were developed. Results: : The high-titre antibodies specifically reacted with purified rStxB. Dot-ELISA, sandwich ELISA and flow-through assay were developed and standardized that could detect StxB with limit of detection (LOD) of 9.75, 9.7 ng/ml and 0.46 µg/cassette, respectively. Interpretation & conclusions: : The rStxB was used to produce antibodies to avoid handling of pathogen. The Flow through assay 'developed was specific, rapid and field amenable.


Assuntos
Disenteria Bacilar/diagnóstico , Síndrome Hemolítico-Urêmica/diagnóstico , Toxina Shiga/isolamento & purificação , Shigella dysenteriae/genética , Animais , Anticorpos Antibacterianos/genética , Anticorpos Antibacterianos/imunologia , Artrite Reativa/diagnóstico , Artrite Reativa/genética , Artrite Reativa/microbiologia , Disenteria Bacilar/genética , Disenteria Bacilar/microbiologia , Ensaio de Imunoadsorção Enzimática , Escherichia coli/genética , Síndrome Hemolítico-Urêmica/genética , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Camundongos , Toxina Shiga/genética , Shigella dysenteriae/patogenicidade
7.
Iran J Kidney Dis ; 13(3): 139-150, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31209187

RESUMO

Shiga toxin induced Escherichia Coli (STEC) is associated with chronic kidney disease or neurologic disability. The aim of this study is to determine the prevalence of STEC identified in human studies in Iran. Search engines of PubMed, EMBASE, OVID, SCOPUS, Web of Science, Google Scholar, IranMedex, MagIran, SID and ganj.irandoc were used. All human studies with stool or rectal swap samples evaluated for STEC and the outcome of HUS in Iran, which had been published between 1985 and 2017, were included. Chi-square and I2 statistic tests were applied to assess between-studies heterogeneity. Pooled prevalence and odd ratio were calculated using random effect models. A total of 30 articles containing 23379 samples were included for the final analysis. The design of study was cross sectional in 16, case control in 13 and one was cohort. The pooled prevalence of STEC was 7% (95% CI, 5 - 11; I2 = 98.3%). In subgroup analysis, the pooled prevalence was 8% (95% CI, 4 - 13; I2 = 97.55%) in children but 4% (95% CI, 2 - 7; I2 = 97.66%) in adults. The odds of patients with diarrhea having had STEC were 7.06 times the odds of healthy subjects (pooled OR = 7.06, 95% CI: 3.66-13.61). Patients with bloody diarrhea less likely to have positive STEC than patients with non-bloody diarrhea (pooled OR = 0.33, 95% CI: 0.10-1.02). STEC was prevalent in diarrheic patients and the rate increased in recent years. The highest contamination was seen in East-South of Iran. Public health intervention is mandatory to eliminate it effectively.


Assuntos
Infecções por Escherichia coli/epidemiologia , Gastroenterite/epidemiologia , Síndrome Hemolítico-Urêmica/epidemiologia , Escherichia coli Shiga Toxigênica/isolamento & purificação , Diarreia/diagnóstico , Diarreia/epidemiologia , Diarreia/microbiologia , Infecções por Escherichia coli/diagnóstico , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Gastroenterite/diagnóstico , Gastroenterite/microbiologia , Síndrome Hemolítico-Urêmica/diagnóstico , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Irã (Geográfico)/epidemiologia , Prevalência
8.
Artigo em Inglês | MEDLINE | ID: mdl-31083597

RESUMO

Shiga toxin-producing Escherichia Coli (STEC) infections routinely run as a common gastroenteritis, but in many cases they may evolve towards hemolytic uremic syndrome (HUS). HUS is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Gut microorganisms have a fundamental impact on human physiology, because they modulate normal intestinal functions and play a pivotal role in influencing the local and systemic immune responses. Despite surveillance established in many countries and major progresses in the understanding of STEC-HUS mechanisms, no specific treatment is currently available. Targeting the gut microbiota could represent a new potential therapeutic strategy in STEC infection. In this paper, we reviewed the current knowledge about microbiota characteristics of patients with STEC infections, as well as in vitro and in vivo evidence of probiotic supplementation in managing STEC gastroenteritis and in HUS onset prevention.


Assuntos
Infecções por Escherichia coli/tratamento farmacológico , Gastroenterite/tratamento farmacológico , Microbioma Gastrointestinal , Síndrome Hemolítico-Urêmica/tratamento farmacológico , Probióticos/uso terapêutico , Escherichia coli Shiga Toxigênica/fisiologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Gastroenterite/complicações , Gastroenterite/epidemiologia , Gastroenterite/microbiologia , Síndrome Hemolítico-Urêmica/epidemiologia , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Incidência
9.
J Med Microbiol ; 68(6): 930-939, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30994441

RESUMO

PURPOSE: This study describes the epidemiology of Shiga toxin-producing Escherichia coli (STEC) infections in a population in the South East of England. METHODS: From 1 November 2013 to 31 March 2017 participating diagnostic laboratories reported Shiga toxin gene (stx) positive real-time PCR results to local public health teams. Stx positive faecal samples/isolates were referred to the Gastrointestinal Bacteria Reference Unit (GBRU) for confirmation by culture and typing by whole genome sequencing (WGS). Key clinical information was collected by public health teams.Results/Key findings. Altogether, 548 faecal specimens (420 were non-travel associated) were stx positive locally, 535 were submitted to the GBRU. STEC were isolated from 42 %, confirmed by stx PCR in 21 % and 37 % were PCR negative. The most common non-travel associated STEC serogroups were O157, O26, O146 and O91. The annualized incidence of confirmed STEC infections (PCR or culture) was 5.8 per 100 000. The ratio of O157 to non-O157 STEC serogroups was 1:7. The annualized incidence of non-O157 haemolytic uraemic syndrome-associated Escherichia coli (HUSEC) strains was 0.4 per 100 000. Bloody diarrhoea was reported by 58 % of cases infected with E. coli O157, 33 % of cases infected with non-O157 HUSEC strains and 12 % of other lower risk non-O157 strains. Overall, 76 % of non-O157 HUSEC isolates possessed the eae virulence gene. CONCLUSIONS: HUSEC including serogroup O157 were uncommon and more likely to cause bloody diarrhoea than other STEC. The routine use of stx PCR testing can influence clinical management. Understanding the local epidemiology facilitates a proportionate public health response to STEC, based on clinical and microbiological characteristics including stx subtype(s).


Assuntos
Infecções por Escherichia coli/epidemiologia , Síndrome Hemolítico-Urêmica/epidemiologia , Toxina Shiga/metabolismo , Escherichia coli Shiga Toxigênica/imunologia , Diarreia/epidemiologia , Diarreia/microbiologia , Inglaterra/epidemiologia , Infecções por Escherichia coli/microbiologia , Fezes/microbiologia , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Incidência , Saúde Pública , Sorogrupo , Escherichia coli Shiga Toxigênica/isolamento & purificação , Escherichia coli Shiga Toxigênica/patogenicidade , Virulência
10.
PLoS One ; 14(4): e0214620, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30934002

RESUMO

Illnesses caused by Shiga toxin-producing Escherichia coli (STECs) can be life threatening, such as hemolytic uremic syndrome (HUS). The STECs most frequently identified by USDA's Microbiological Data Program (MDP) carried toxin gene subtypes stx1a and/or stx2a. Here we described the genome sequences of 331 STECs isolated from foods regulated by the FDA 2010-2017, and determined their genomic identity, serotype, sequence type, virulence potential, and prevalence of antimicrobial resistance. Isolates were selected from the MDP archive, routine food testing by FDA field labs (ORA), and food testing by a contract company. Only 276 (83%) strains were confirmed as STECs by in silico analysis. Foods from which STECs were recovered included cilantro (6%), spinach (25%), lettuce (11%), and flour (9%). Phylogenetic analysis using core genome MLST revealed these STEC genomes were highly variable, with some clustering associated with ST types and serotypes. We detected 95 different sequence types (ST); several ST were previously associated with HUS: ST21 and ST29 (O26:H11), ST11 (O157:H7), ST33 (O91:H14), ST17 (O103:H2), and ST16 (O111:H-). in silico virulome analyses showed ~ 51% of these strains were potentially pathogenic [besides stx gene they also carried eae (25%) or 26% saa (26%)]. Virulence gene prevalence was also determined: stx1 only (19%); stx2 only (66%); and stx1/sxt2 (15%). Our data form a new WGS dataset that can be used to support food safety investigations and monitor the recurrence/emergence of E. coli in foods.


Assuntos
Infecções por Escherichia coli/microbiologia , Microbiologia de Alimentos , Toxina Shiga/genética , Escherichia coli Shiga Toxigênica/classificação , Escherichia coli Shiga Toxigênica/genética , Virulência/genética , Técnicas de Tipagem Bacteriana , Infecções por Escherichia coli/epidemiologia , Alimentos/classificação , Contaminação de Alimentos/análise , Contaminação de Alimentos/legislação & jurisprudência , Contaminação de Alimentos/estatística & dados numéricos , Microbiologia de Alimentos/estatística & dados numéricos , Inocuidade dos Alimentos , Regulamentação Governamental , Análise de Perigos e Pontos Críticos de Controle , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Legislação sobre Alimentos , Tipagem de Sequências Multilocus , Filogenia , Toxina Shiga/classificação , Transcriptoma , Estados Unidos/epidemiologia , United States Food and Drug Administration/legislação & jurisprudência
13.
Pediatr Neonatol ; 60(1): 87-94, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-29807724

RESUMO

BACKGROUND AND AIMS: To describe the epidemiologic, clinical, microbiological, therapeutic and outcome characteristics of a HUS outbreak occurring in southern Romania from 2015 to 2016. METHODS: We retrospectively collected data from the medical records of all HUS cases hospitalized at the pediatric nephrology department of Marie Curie Children's Hospital of Bucharest, Romania. RESULTS: There were 32 HUS cases (19 girls/13 boys, 87.6% <2 years), all associated with diarrhea (bloody in 13, 40.6%). Thirteen (40.6%) and 4 (12.5%) patients had oliguria and anuria at admission. Extreme pallor, generalized edema, vomiting, dehydration, fever and seizures were found in 100%, 56.3%, 31.3%, 31.3%, 25% and 9.4% of patients, respectively. E. coli and STEC were identified in the stools of 6 and 8 patients, respectively; E. coli O26 and O157 infection were documented serologically in 10 and 3 children, respectively. There were 15/32 (46.9%) patients with confirmed HUS. Eighteen (56.3%) patients were hypertensive; other complications included infections, left ventricular hypertrophy, cardiopulmonary arrest, seizures and encephalopathy in 62.5%, 37.5%, 28.3%, 18.8% and 12.5%, respectively. Peritoneal dialysis and hemodialysis were performed in 23 (72%) and 2 patients, respectively. Three patients (9.4%) died early during hospitalization. A 6-12-month follow-up of 26 patients revealed that 65.4% had post-HUS sequelae (persistent hypertension and chronic renal failure in 34.6% and 30.8%, respectively). CONCLUSIONS: The principal STEC serotype involved was O26:H11 and the number of confirmed HUS cases reached half of the patients. Compared with the medical literature, this outbreak had a higher rate of complications and renal sequelae and was associated with a high fatality rate.


Assuntos
Surtos de Doenças , Síndrome Hemolítico-Urêmica/epidemiologia , Adolescente , Criança , Pré-Escolar , Feminino , Síndrome Hemolítico-Urêmica/microbiologia , Síndrome Hemolítico-Urêmica/terapia , Humanos , Lactente , Masculino , Estudos Retrospectivos , Romênia/epidemiologia
14.
J Pediatr Hematol Oncol ; 41(3): e179-e181, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29683956

RESUMO

Diarrhea-associated hemolytic uremic syndrome (HUS) is usually associated with shigatoxin-producing Escherichia coli or shigella infections. We report 2 cases of HUS, respectively, caused by salmonella and Campylobacter jejuni infections. None of these bacteria produce shigatoxins, and the underlying mechanism of HUS development remains unknown. In streptococcus pneumoniae-associated HUS, bacterial neuraminidase cleaves neuraminic acid and causes exposure of Thomsen-Friedenreich cryptantigen on the cell surface of, for example, erythrocytes, which induces an inflammatory response caused by binding of preformed IgM. Both campylobacter and salmonella bacteria also produce neuraminidase, and HUS development could be explained by a similar mechanism.


Assuntos
Campylobacter jejuni/patogenicidade , Síndrome Hemolítico-Urêmica/microbiologia , Salmonella/patogenicidade , Infecções por Campylobacter/complicações , Síndrome Hemolítico-Urêmica/etiologia , Humanos , Neuraminidase , Infecções por Salmonella/complicações , Toxina Shiga/toxicidade
16.
Ther Apher Dial ; 23(2): 118-125, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30324646

RESUMO

Shiga toxin-associated hemolytic uremic syndrome (STEC-HUS) is associated with significant mortality and morbidity. Case fatalities are often associated with severe neurological involvement in children and advanced age in adults but specific treatment is currently unavailable. Plasma exchange (PE) could theoretically enable removal of Shiga toxins, pro-inflammatory cytokines, and prothrombotic factors and has been used in deteriorating patients with STEC-HUS but the efficacy remains uncertain. In order to assess efficacy of PE in STEC-HUS, a literature review was performed. PubMed, Web of Science, Embase, and LiLACS were searched for reports describing the outcomes of patients with STEC-HUS treated with PE and 16 reports were included. Reports ranged from case reports to cohort studies and one case-control study with the largest study population coming from the 2011 German STEC-HUS outbreak. Outcomes were variable but seemed to point towards lower case fatality rates in the elderly and improved outcomes in children with STEC-HUS, treated with PE early in the course. However studies were mostly of low quality with risk of observation bias and confounding. Currently no definitive answers concerning the efficacy of PE in STEC-HUS can be given, highlighting the need for well performed randomized controlled trials.


Assuntos
Síndrome Hemolítico-Urêmica/terapia , Troca Plasmática/métodos , Escherichia coli Shiga Toxigênica/isolamento & purificação , Idoso , Criança , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/terapia , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Projetos de Pesquisa , Resultado do Tratamento
17.
Clin Exp Nephrol ; 23(4): 544-550, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30467800

RESUMO

OBJECTIVES: Interleukin (IL)-33 plays an important role in host defense, immune regulation, and inflammation. This study assessed IL-33's role in the pathogenesis of severe hemolytic uremic syndrome (HUS) induced by enterohemorrhagic Escherichia coli (EHEC). We also investigated the clinical significance of IL-33 and soluble ST2 (soluble form of IL-33 receptor) serum levels in patients with EHEC-induced HUS. METHODS: The role of IL-33 in Shiga toxin (STx)-2-induced endothelial injury was studied in human umbilical vein endothelial cells (HUVECs) in vitro. Blood samples were obtained from 21 HUS patients and 15 healthy controls (HC). The IL-33 and sST2 serum levels were quantified using an enzyme-linked immunosorbent assay. The results were compared to HUS' clinical features. RESULTS: Cytotoxic assays indicated that IL-33 enhanced STx2 toxicity in HUVECs. Serum IL-33 levels in most HUS patients were below the lowest detection limit. On the other hand, serum sST2 levels in patients during the HUS phase were significantly higher than those in HC and showed a correlation with disease severity. Serum sST2 levels in patients with encephalopathy were significantly higher than those in patients without it. A serum sST2 level > 63.2 pg/mL was associated with a high risk of encephalopathy. Serum sST2 levels significantly correlated with serum levels of inflammatory cytokines related to the development of HUS. CONCLUSIONS: Our results indicate that IL-33 contributes to the severity of EHEC-induced HUS. Serum sST2 level in HUS patients correlated with disease activity, which suggests its potential role as a marker for disease activity and development of encephalopathy in patients with EHEC-induced HUS.


Assuntos
Escherichia coli Êntero-Hemorrágica , Infecções por Escherichia coli/microbiologia , Síndrome Hemolítico-Urêmica/metabolismo , Síndrome Hemolítico-Urêmica/microbiologia , Proteína 1 Semelhante a Receptor de Interleucina-1/sangue , Interleucina-33/sangue , Adolescente , Adulto , Estudos de Casos e Controles , Células Cultivadas , Criança , Pré-Escolar , Infecções por Escherichia coli/complicações , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Lactente , Interleucina-6/sangue , Masculino , Curva ROC , Receptores Tipo I de Fatores de Necrose Tumoral/sangue , Receptores Tipo II do Fator de Necrose Tumoral/sangue , Índice de Gravidade de Doença , Toxina Shiga II/toxicidade , Transdução de Sinais , Adulto Jovem
18.
Int J Food Microbiol ; 292: 72-82, 2019 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-30579059

RESUMO

The ever decreasing cost and increase in throughput of next generation sequencing (NGS) techniques have resulted in a rapid increase in availability of NGS data. Such data have the potential for rapid, reproducible and highly discriminative characterization of pathogens. This provides an opportunity in microbial risk assessment to account for variations in survivability and virulence among strains. A major challenge towards such attempts remains the highly dimensional nature of genomic data versus the number of isolates. Machine learning-based (ML) predictive risk modelling provides a solution to this "curse of dimensionality" while accounting for individual effects that are dependent on interactions with other genetic and environmental factors. This pilot study explores the potential of ML in the prediction of health endpoints resulting from shigatoxigenic E. coli (STEC) infection. Accessory genes in amino acid sequences were used as model input to predict and differentiate health outcomes in STEC infections including diarrhea, bloody diarrhea, hemolytic uremic syndrome and their combinations. Outcomes severity was also distinguished by hospitalization. A matrix of percent similarity between accessory genes and the E. coli genomes was generated and subsequently used as input for ML. The performances of ML algorithms random forest, support vector machine (radial and linear kernel), gradient boosting, and logit boost were compared. Logit boost was the best model showing an outcome prediction accuracy of 0.75 (95% CI: 0.60, 0.86), an excellent or substantial performance (Kappa = 0.72). Important genetic predictors of riskier STEC clinical outcomes included proteins involved in initial attachment to the host cell, persistence of plasmids or genomic islands, conjugative plasmid transfer and formation of sex pili, regulation of locus of enterocyte effacement expression, post-translational acetylation of proteins, facilitation of the rearrangement or deletion of sections within the pathogenic islands and transport macromolecules across the cell envelope. We propose further studies are proposed on the proteins with undefined or unclear functionality. One protein family in particular predicted HUS outcome. Toxin-antitoxin systems are potential stress adaptation markers which may mediate environmental persistence of strains in diverse sources. We foresee the application of ML approach to the set-up of real-time online analysis of whole genome sequence data to estimate the human health risk at the population or strain level. The ML approach is envisaged to support the prediction of more specific STEC clinical endpoints type by inputting isolate sequence data.


Assuntos
Diarreia/terapia , Infecções por Escherichia coli/terapia , Síndrome Hemolítico-Urêmica/terapia , Escherichia coli Shiga Toxigênica/genética , Adolescente , Adulto , Idoso , Criança , Diarreia/microbiologia , Infecções por Escherichia coli/epidemiologia , Proteínas de Escherichia coli/genética , Genômica/métodos , Síndrome Hemolítico-Urêmica/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Aprendizado de Máquina , Pessoa de Meia-Idade , Modelos Teóricos , Filogenia , Projetos Piloto , Plasmídeos/genética , Medição de Risco/métodos , Escherichia coli Shiga Toxigênica/isolamento & purificação , Resultado do Tratamento , Virulência/genética , Fatores de Virulência/genética , Sequenciamento Completo do Genoma , Adulto Jovem
19.
Georgian Med News ; (283): 123-129, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30516507

RESUMO

Shiga toxin-producing Escherichia coli (STEC) causes illness ranging from mild diarrhea to bloody diarrhea, to the hemolytic uremic syndrome (HUS), which manifests with a triad of microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure. Surveillance of HUS and bloody diarrhea is not performed in Georgia. The primary objective of our study was to determine the annual incidence of diarrheal diseases. The secondary objective was to assess epidemiological characteristics, etiology and risk factors of diarrhea and HUS in Georgia among children under 15. We collected a retrospective data on diarrheal diseases particularly bloody diarrhea and HUS among children in Georgia in 2009-2016 years. Laboratory, clinical and epidemiological data was entered into electronic database. Descriptive statistics, proportions, incidence rates, means and medians were calculated in R statistical language using statistical package R for windows v 3.4.3. A total of 316 cases of bloody diarrhea including 64 (20.2%) cases complicated with HUS under age 15 were identified from 2009 until 2016. From 316 patients 5 (1.6%) have died, all of them with diagnosis and severe complications of HUS. Average rate of HUS per 100,000 populations during 2009-2016 was 0.3 and for bloody diarrhea 2 per 100,000. High RR for food products consumed by children with bloody diarrhea either complicated with HUS or not were various ice-creams produced locally (RR 4.23 P<0.001), dairy products (RR 2.79 P = 0.01), ground beef products (RR 4.52 P<0.001). The another highest attack ratio was identified for fruits (RR 6.19 P<0.001) and vegetables (RR 3.45 P < 0.001). Different enteric pathogens including shiga toxin producing E. coli was detected as etiology of diarrheal diseases and HUS. Epidemiological data suggests that inadequately washed fruits, vegetables and eating undercooked food and ice-cream could be a possible risk factors of exposure with enteric pathogens and developing diarrhea and HUS among children. Further investigations of food products are required to determine epidemiology and source food products of bloody diarrhea and HUS among children in Georgia.


Assuntos
Diarreia/epidemiologia , Infecções por Escherichia coli/epidemiologia , Síndrome Hemolítico-Urêmica/epidemiologia , Escherichia coli Shiga Toxigênica/isolamento & purificação , Adolescente , Criança , Pré-Escolar , Diarreia/complicações , Diarreia/microbiologia , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/microbiologia , Feminino , República da Geórgia/epidemiologia , Síndrome Hemolítico-Urêmica/complicações , Síndrome Hemolítico-Urêmica/microbiologia , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Estudos Retrospectivos , Fatores de Risco
20.
Acta Biomed ; 89(9-S): 153-157, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30561409

RESUMO

BACKGROUND: Shiga-toxin Escherichia coli productor (STEC) provokes frequently an important intestinal damage that may be considered in differential diagnosis with the onset of Inflammatory Bowel Disease (IBD). The aim of this work is to review in the current literature about Hemolytic Uremic Syndrome (HUS) and IBD symptoms at the onset, comparing the clinical presentation and symptoms, as the timing of diagnosis and of the correct treatment of both these conditions is a fundamental prognostic factor. A focus is made about the association between typical or atypical HUS and IBD and a possible renal involvement in patient with IBD (IgA-nephropathy). METHODS: A systematic review of scientific articles was performed consulting the databases PubMed, Medline, Google Scholar, and consulting most recent textbooks of Pediatric Nephrology. RESULTS: In STEC-associated HUS, that accounts for 90% of cases of HUS in children, the microangiopathic manifestations are usually preceded by gastrointestinal symptoms. Initial presentation may be considered in differential diagnosis with IBD onset. The transverse and ascending colon are the segments most commonly affected, but any area from the esophagus to the perianal area can be involved. The more serious manifestations include severe hemorrhagic colitis, bowel necrosis and perforation, rectal prolapse, peritonitis and intussusception. Severe gastrointestinal involvement may result in life-threatening complications as toxic megacolon and transmural necrosis of the colon with perforation, as in Ulcerative Colitis (UC). Transmural necrosis of the colon may lead to subsequent colonic stricture, as in Crohn Disease (CD). Perianal lesions and strictures are described. In some studies, intestinal biopsies were performed to exclude IBD. Elevation of pancreatic enzymes is common. Liver damage and cholecystitis are other described complications. There is no specific form of therapy for STEC HUS, but appropriate fluid and electrolyte management (better hyperhydration when possible), avoiding antidiarrheal drugs, and possibly avoiding antibiotic therapy, are recommended as the best practice. In atypical HUS (aHUS) gastrointestinal manifestation are rare, but recently a study evidenced that gastrointestinal complications are common in aHUS in presence of factor-H autoantibodies. Some report of patients with IBD and contemporary atypical-HUS were found, both for CD and UC. The authors conclude that deregulation of the alternative complement pathway may manifest in other organs besides the kidney. Finally, searching for STEC-infection, or broadly for Escherichia coli (E. coli) infection, and IBD onset, some reviews suggest a possible role of adherent invasive E. coli (AIEC) on the pathogenesis of IBD. CONCLUSIONS: The current literature shows that gastrointestinal complications of HUS are quite exclusive of STEC-associated HUS, whereas aHUS have usually mild or absent intestinal involvement. Severe presentation as toxic megacolon, perforation, ulcerative colitis, peritonitis is similar to IBD at the onset. Moreover, some types of E. coli (AIEC) have been considered a risk factor for IBD. Recent literature on aHUS shows that intestinal complications are more common than described before, particularly for patients with anti-H factor antibodies. Moreover, we found some report of patient with both aHUS and IBD, who benefit from anti-C5 antibodies injection (Eculizumab).


Assuntos
Síndrome Hemolítico-Urêmica/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/terapia , Anemia Hemolítica/etiologia , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Apoptose , Síndrome Hemolítico-Urêmica Atípica/complicações , Terapia Combinada , Contraindicações de Medicamentos , Diagnóstico Diferencial , Diarreia/etiologia , Infecções por Escherichia coli/complicações , Infecções por Escherichia coli/tratamento farmacológico , Hemorragia Gastrointestinal/etiologia , Granuloma/etiologia , Síndrome Hemolítico-Urêmica/etiologia , Síndrome Hemolítico-Urêmica/microbiologia , Síndrome Hemolítico-Urêmica/terapia , Humanos , Doenças Inflamatórias Intestinais/complicações , Necrose , Escherichia coli Shiga Toxigênica/isolamento & purificação , Escherichia coli Shiga Toxigênica/patogenicidade , Trombocitopenia/etiologia
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