Nasal immunization with H7 flagellin protects mice against hemolytic uremic syndrome secondary to Escherichia coli O157:H7 gastrointestinal infection.

Introduction: Shiga-toxin (Stx) producing Escherichia coli (STEC) O157:H7 is the most frequent serotype associated with hemolytic uremic syndrome (HUS) after gastrointestinal infections. Protection against HUS secondary to STEC infections has been experimentally assayed through the generation of different vaccine formulations. With focus on patients, the strategies have been mainly oriented to inhibit production of Stx or its neutralization. However, few approaches have been intended to block gastrointestinal phase of this disease, which is considered the first step in the pathogenic cascade of HUS. The aim of this work was to assay H7 flagellin as a mucosal vaccine candidate to prevent the systemic complications secondary to E. coli O157:H7 infections. Materials and methods: The cellular and humoral immune response after H7 nasal immunization in mice were studied by the analysis of systemic and intestinal specific antibody production, as well as cytokine production and lymphocyte proliferation against H7 flagellin ex vivo. Results: Immunized mice developed a strong and specific anti-H7 IgG and IgA response, at systemic and mucosal level, as well as a cellular Th1/Th2/Th17 response. H7 induced activation of bone marrow derived dendritic cells in vitro and a significant delayed-type hypersensitivity (DTH) response in immunized mice. Most relevant, immunized mice were completely protected against the challenge with an E. coli O157:H7 virulent strain in vivo, and surviving mice presented high titres of anti-H7 and Stx antibodies. Discussion: These results suggest that immunization avoids HUS outcome and allows to elicit a specific immune response against other virulence factors.

Vigilancia de síndrome urémico hemolítico / Surveillance of hemolytic uremic syndrome

Se presenta de manera breve la situación de Síndrome Urémico Hemolítico hasta la Semana Epidemiológica 15 de 2022, según datos de la notificación al Sistema Nacional de Vigilancia Epidemiológica, Incluye datos de notificación de agentes etiológicos 2021-2022.

Analysis of scenarios to reduce the probability of acquiring hemolytic uremic syndrome associated with beef consumption.

The objective of this study was to develop a quantitative microbial risk assessment (QMRA) model to evaluate potential risk mitigation strategies to reduce the probability of acquiring hemolytic uremic syndrome (HUS) associated with beef consumption in Argentina. Five scenarios were simulated to evaluate the effect of interventions on the probability of acquiring HUS from Shiga toxin-producing Escherichia coli (STEC)-contaminated ground beef and commercial hamburger consumption. These control strategies were chosen based on previous results of the sensitivity analysis of a baseline QMRA model. The application of improvement actions in abattoirs not applying Hazard Analysis and Critical Control Points (HACCP) for STEC would result 7.6 times lower in the probability that consumers acquired HUS from ground beef consumption, while the implementation of improvements in butcher shops would lead to a smaller reduction. In abattoirs applying HACCP for STEC, the risk of acquiring HUS from commercial hamburger consumption was significantly reduced. Treatment with 2% lactic acid, hot water and irradiation reduced 4.5, 3.5 and 93.1 times the risk of HUS, respectively. The most efficient interventions, in terms of case reduction, being those that are applied in the initial stages of the meat chain.

The Deleterious Effects of Shiga Toxin Type 2 Are Neutralized In Vitro by FabF8:Stx2 Recombinant Monoclonal Antibody.

Hemolytic Uremic Syndrome (HUS) associated with Shiga-toxigenic Escherichia coli (STEC) infections is the principal cause of acute renal injury in pediatric age groups. Shiga toxin type 2 (Stx2) has in vitro cytotoxic effects on kidney cells, including human glomerular endothelial (HGEC) and Vero cells. Neither a licensed vaccine nor effective therapy for HUS is available for humans. Recombinant antibodies against Stx2, produced in bacteria, appeared as the utmost tool to prevent HUS. Therefore, in this work, a recombinant FabF8:Stx2 was selected from a human Fab antibody library by phage display, characterized, and analyzed for its ability to neutralize the Stx activity from different STEC-Stx2 and Stx1/Stx2 producing strains in a gold standard Vero cell assay, and the Stx2 cytotoxic effects on primary cultures of HGEC. This recombinant Fab showed a dissociation constant of 13.8 nM and a half maximum effective concentration (EC50) of 160 ng/mL to Stx2. Additionally, FabF8:Stx2 neutralized, in different percentages, the cytotoxic effects of Stx2 and Stx1/2 from different STEC strains on Vero cells. Moreover, it significantly prevented the deleterious effects of Stx2 in a dose-dependent manner (up to 83%) in HGEC and protected this cell up to 90% from apoptosis and necrosis. Therefore, this novel and simple anti-Stx2 biomolecule will allow further investigation as a new therapeutic option that could improve STEC and HUS patient outcomes.

Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome.

BACKGROUND: Haemolytic uraemic syndrome (HUS) is a common cause of acquired kidney failure in children and rarely in adults. The most important risk factor for development of HUS is a gastrointestinal infection by Shiga toxin-producing Escherichia coli (STEC). This review addressed the interventions aimed at secondary prevention of HUS in patients with diarrhoea who were infected with a bacteria that increase the risk of HUS. OBJECTIVES: Our objective was to evaluate evidence regarding secondary preventative strategies for HUS associated with STEC infections. In doing so, we sought to assess the effectiveness and safety of interventions as well as their potential to impact the morbidity and death associated with this condition. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 12 November 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Studies were considered based on the methods, participants, and research goals. Only randomised controlled trials were considered eligible for inclusion. The participants of the studies were paediatric and adult patients with diarrhoeal illnesses due to STEC. The primary outcome of interest was incidence of HUS. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as recommended by Cochrane. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: We identified four studies (536 participants) for inclusion that investigated four different interventions including antibiotics (trimethoprim-sulfamethoxazole), anti-Shiga toxin antibody-containing bovine colostrum, Shiga toxin binding agent (Synsorb Pk: a silicon dioxide-based agent), and a monoclonal antibody against Shiga toxin (urtoxazumab). The overall risk of bias was unclear for selection, performance and detection bias and low for attrition, reporting and other sources of bias. It was uncertain if trimethoprim-sulfamethoxazole reduced the incidence of HUS compared to no treatment (47 participants: RR 0.57, 95% CI 0.11-2.81, very low certainty evidence). Adverse events relative to this review, need for acute dialysis, neurological complication and death were not reported. There were no incidences of HUS in either the bovine colostrum group or the placebo group. It was uncertain if bovine colostrum caused more adverse events (27 participants: RR 0.92, 95% CI 0.42 to 2.03; very low certainty evidence). The need for acute dialysis, neurological complications or death were not reported. It is uncertain whether Synsorb Pk reduces the incidence of HUS compared to placebo (353 participants: RR 0.93, 95% CI 0.39 to 2.22; very low certainty evidence). Adverse events relevant to this review, need for acute dialysis, neurological complications or death were not reported. One study compared two doses of urtoxazumab (3.0 mg/kg and 1.0 mg/kg) to placebo. It is uncertain if either 3.0 mg/kg urtoxazumab (71 participants: RR 0.34, 95% CI 0.01 to 8.14) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) reduced the incidence of HUS compared to placebo (very low certainty evidence). Low certainty evidence showed there may be little or no difference in the number of treatment-emergent adverse events with either 3.0 mg/kg urtoxazumab (71 participants: RR 1.00, 95% CI 0.84 to 1.18) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) compared to placebo. There were 25 serious adverse events reported in 18 patients: 10 in the placebo group, and 9 and 6 serious adverse events in the 1.0 mg/kg and 3.0 mg/kg urtoxazumab groups, respectively. It is unclear how many patients experienced these adverse events in each group, and how many patients experienced more than one event. It is uncertain if either dose of urtoxazumab increased the risk of neurological complications or death (very low certainty evidence). Need for acute dialysis was not reported. AUTHORS' CONCLUSIONS: The included studies assessed antibiotics, bovine milk, and Shiga toxin inhibitor (Synsorb Pk) and monoclonal antibodies (Urtoxazumab) against Shiga toxin for secondary prevention of HUS in patients with diarrhoea due to STEC. However, no firm conclusions about the efficacy of these interventions can be drawn given the small number of included studies and the small sample sizes of those included studies. Additional studies, including larger multicentre studies, are needed to assess the efficacy of interventions to prevent development of HUS in patients with diarrhoea due to STEC infection.

Complement-Mediated Disorders in Pregnancy.

Complement-mediated disorders in pregnancy span a large spectrum and have been implicated in all three complement pathways: classical, lectin, and alternative. Our understanding of these disorders in recent years has advanced due to a better understanding of complement regulatory proteins, such as complement factor H, complement factor I, membrane cofactor protein, and thrombomodulin that particularly affect the alternative complement pathway. Enthusiasm in genotyping for mutations that encode these proteins has allowed us to study the presence of genetic variants which may predispose women to develop conditions such as pregnancy-associated hemolytic uremic syndrome (P-aHUS), thrombotic thrombocytopenic purpura, preeclampsia/hemolysis, elevated liver enzymes, low platelets (HELLP), systemic lupus erythematosus/antiphospholipid syndrome, and peripartum cardiomyopathy. The advent of the anti-C5-antibody eculizumab to quench the complement cascade has already proven in small case series to improve maternal kidney outcomes in complement-mediated obstetric catastrophes such as P-aHUS and HELLP. In this review, we will detail the pathogenesis behind these complement-mediated pregnancy disorders, the role of complement variants in disease phenotype, and the most up-to-date experience with eculizumab in this population.

Identification of lipid A deacylase as a novel, highly conserved and protective antigen against enterohemorrhagic Escherichia coli.

Enterohemorrhagic E. coli (EHEC) is a major cause of large outbreaks worldwide associated with hemorrhagic colitis and hemolytic uremic syndrome. While vaccine development is warranted, a licensed vaccine, specific for human use, against EHEC is not yet available. In this study, the reverse vaccinology approach combined with genomic, transcriptional and molecular epidemiology data was applied on the EHEC O157:H7 genome to select new potential vaccine candidates. Twenty-four potential protein antigens were identified and one of them (MC001) was successfully expressed onto Generalized Modules for Membrane Antigens (GMMA) delivery system. GMMA expressing this vaccine candidate was immunogenic, raising a specific antibody response. Immunization with the MC001 candidate was able to reduce the bacterial load of EHEC O157:H7 strain in feces, colon and caecum tissues after murine infection. MC001 is homologue to lipid A deacylase enzyme (LpxR), and to our knowledge, this is the first study describing it as a potential vaccine candidate. Gene distribution and sequence variability analysis showed that MC001 is present and conserved in EHEC and in enteropathogenic E. coli (EPEC) strains. Given the high genetic variability among and within E. coli pathotypes, the identification of such conserved antigen suggests that its inclusion in a vaccine might represent a solution against major intestinal pathogenic strains.

[Shiga-toxin associated hemolytic uremic syndrome: How to prevent it?] / Síndrome Hemolítico Urémico asociado a Shigatoxina: ¿Cómo preve nirlo?

Hemolytic uremic syndrome (HUS) associated with intestinal infection by Shiga toxin-producing bacteria, which mainly affects children, can cause severe acute morbidity, chronic sequelae in seve ral organs, and premature death in some of them. Given its zoonotic nature, adequate measures of agricultural management and proper hygiene of what we consume are essential to prevent infection. Once the HUS is triggered, medical management is currently mainly supportive. In recent years, va rious therapeutic strategies have been developed to prevent this disease from occurring or, at least, to mitigate its morbidity and mortality consequences. This article describes specific actions at different levels of prevention of this pathology.

Síndrome hemolítico urémico asociado a Shigatoxina: ¿Cómo prevenirlo? / Shiga-toxin associated hemolytic uremic syndrome: how to prevent it?

Resumen: El síndrome hemolítico urémico (SHU) asociado a infección intestinal por bacterias productoras de Shigatoxina, que afecta principalmente a población infantil, puede causar morbilidad aguda grave, secuelas crónicas en varios órganos, y la muerte prematura en algunos de ellos. Dado su carácter zoonótico, adecuadas medidas de manejo agropecuario y correcta higiene de lo que consumimos es indispensable a la hora de prevenir la infección. Actualmente, una vez gatillado el SHU el manejo es médico y, principalmente, de soporte. En los últimos años diversas estrategias terapéuticas se han ido desarrollando para evitar que esta enfermedad ocurra, o, al menos, que pueda ser atenuada en sus consecuencias de morbi-mortalidad. El presente artículo describe acciones específicas a diferentes niveles de prevención de esta patología.

Abstract Hemolytic uremic syndrome (HUS) associated with intestinal infection by Shiga toxin-producing bacteria, which mainly affects children, can cause severe acute morbidity, chronic sequelae in seve ral organs, and premature death in some of them. Given its zoonotic nature, adequate measures of agricultural management and proper hygiene of what we consume are essential to prevent infection. Once the HUS is triggered, medical management is currently mainly supportive. In recent years, va rious therapeutic strategies have been developed to prevent this disease from occurring or, at least, to mitigate its morbidity and mortality consequences. This article describes specific actions at different levels of prevention of this pathology.

Efficacy of a recombinant Intimin, EspB and Shiga toxin 2B vaccine in calves experimentally challenged with Escherichia coli O157:H7.

Escherichia coli O157:H7 is a zoonotic pathogen of global importance and the serotype of Shiga toxin-producing E.coli (STEC) most frequently associated with Hemolytic Uremic Syndrome (HUS) in humans. The main STEC reservoir is cattle. Vaccination of calves with the carboxy-terminal fraction of Intimin γ (IntC280) and EspB can reduce E.coli O157:H7 fecal shedding after experimental challenge. Shiga toxin (Stx) exerts local immunosuppressive effects in the bovine intestine and Stx2B fused to Brucella lumazine synthase (BLS-Stx2B) induces Stx2-neutralizing antibodies. To determine if an immune response against Stx could improve a vaccine's effect on fecal shedding, groups of calves were immunized with EspB + IntC280, with EspB + IntC280 + BLS-Stx2B, or kept as controls. At 24 days post vaccination calves were challenged with E.coli O157:H7. Shedding of E.coli O157:H7 was assessed in recto-anal mucosal swabs by direct plating and enrichment followed by immunomagnetic separation and multiplex PCR. Calves were euthanized 15 days after the challenge and intestinal segments were obtained to assess mucosal antibodies. Vaccination induced a significant increase of IntC280 and EspB specific antibodies in serum and intestinal mucosa in both vaccinated groups. Antibodies against Stx2B were detected in serum and intestinal mucosa of animals vaccinated with 3 antigens. Sera and intestinal homogenates were able to neutralize Stx2 verocytotoxicity compared to the control and the 2-antigens vaccinated group. Both vaccines reduced E.coli O157:H7 shedding compared to the control group. The addition of Stx2B to the vaccine formulation did not result in a superior level of protection compared to the one conferred by IntC280 and EspB alone. It remains to be determined if the inclusion of Stx2B in the vaccine alters E.coli O157:H7 shedding patterns in the long term and after recurrent low dose exposure as occurring in cattle herds.

Detection, Prevalence, and Pathogenicity of Non-O157 Shiga Toxin-Producing Escherichia coli from Cattle Hides and Carcasses.

Cattle are a major reservoir for Shiga toxin-producing Escherichia coli (STEC) and harbor these bacteria in the intestinal tract. The prevalence, concentration, and STEC serogroup isolated in cattle varies between individuals. Hide removal at slaughter serves as a major point of carcass contamination and ultimately beef products. Certain STEC serogroups, such as O26, O45, O103, O111, O121, O145, and O157, containing the intestinal adherence factor intimin, pose a large economic burden to food producers because of testing and recalls. Human infection with STEC can cause illnesses ranging from diarrhea to hemorrhagic colitis and hemolytic uremic syndrome, and is commonly acquired through ingestion of contaminated foods, often beef products. Previously, most studies focused on O157 STEC, but there is growing recognition of the importance of non-O157 STEC serogroups. This review summarizes detection methods, prevalence, and methods for prediction of pathogenicity of non-O157 STEC from cattle hides and carcasses. A synthesis of procedures is outlined for general non-O157 STEC and targeted detection of specific STEC serogroups. Standardization of sample collection and processing procedures would allow for more robust comparisons among studies. Presence of non-O157 STEC isolated from cattle hides and carcasses and specific factors, such as point of sample collection and season, are summarized. Also, factors that might influence STEC survival on these surfaces, such as the microbial population on hides and microbial adherence genes, are raised as topics for future investigation. Finally, this review gives an overview on studies that have used genetic and cell-based methods to identify specific phenotypes of non-O157 STEC strains isolated from cattle to assess their risk to human health.

[Development of a product anti-Shiga toxin for prevention of the hemolytic uremic syndrome]. / Desarrollo de un producto anti-toxina Shiga para la prevención del síndrome urémico hemolítico.

The typical hemolytic uremic syndrome (HUS) is an orphan disease caused by Shiga toxin(Stx) producing Escherichia coli strains and characterized by acute kidney damage, microangiopathic hemolytic anemia and low platelet count. It is endemic in Argentina, the country with the highest incidence of HUS in the world. Stx is essential for its development and therefore, HUS is considered a toxemic non-bacteremic disorder, which could be treated with antibodies. Herein we describe the development of a new treatment capable of neutralizing the toxic effect of Stx and its variants. The treatment consists of F(ab')2 fragments from an equine antiserum whose efficacy and potency against Stx1 and Stx2 were proved in different preclinical models. The product was shown to be safe in animals. Furthermore, the anti-Stx F(ab')2 pharmacokinetic was shown to be similar to that of analogous compounds and a therapeutic window for its administration was determined. Altogether, these preclinical results warrant testing in humans. The phase I clinical trial will be performed at the Hospital Italiano in Buenos Aires to evaluate the safety and pharmacokinetics of the product in healthy adult volunteers. Based on the results of this study, a phase II clinical trial will be planned in pediatric patients diagnosed with infection by Stx-producing E. coli strains.

Pneumococcal haemolytic uraemic syndrome in the postvaccine era.

OBJECTIVE: Pneumococcal infection is a leading cause of haemolytic uraemic syndrome (HUS) and is potentially vaccine preventable. Published data suggest high mortality and poor renal outcomes. The introduction of the 7-valent pneumococcal conjugate vaccine (PCV) has seen the emergence of disease caused by non-vaccine strains, particularly 19A. We sought to describe serotype prevalence and outcomes, particularly after the introduction of the 13-valent PCV. DESIGN AND SETTING: We performed a retrospective chart review, using hospital medical records to identify cases of HUS in a tertiary paediatric hospital in Australia over a 20-year period (January 1997-December 2016). Associated pneumococcal infection was identified, and serotype data were categorised according to vaccine era: prevaccine (January 1997-December 2004), PCV7 (January 2005-June 2011) and PCV13 (July 2011-December 2016). RESULTS: We identified 66 cases of HUS. Pneumococcal infection was proven in 11 cases, representing 4% (1/26) of cases prior to the introduction of PCV7, 20% (3/15) in the PCV7 era and 28% (7/25) in the PCV13 era. Subtype 19A was the most prevalent pneumococcal serotype (6/11). All four patients who received PCV7 were infected with a non-vaccine serotype. Four of the five patients who received PCV13 were classed as vaccine failures. Median follow-up was 14 (range 1-108) months. Chronic kidney disease was the most common complication (4/7). We observed no mortality, neurological sequelae or progression to end-stage kidney disease. CONCLUSIONS: Serotype 19A is most commonly associated with pneumococcal HUS, despite the introduction of the 13-valent vaccine. Chronic kidney disease is a significant complication of pneumococcal HUS.

Desarrollo de un producto anti-toxina shiga para la prevención del síndrome urémico hemolítico / Development of a product anti-Shiga toxin for prevention of the hemolytic uremic syndrome

El síndrome urémico hemolítico (SUH) típico es una enfermedad huérfana causada por cepas de Escherichia coli productoras de toxina Shiga (Stx) y caracterizada por daño renal agudo, anemia hemolítica microangiopática y plaquetopenia. Es endémico en Argentina, el país con mayor incidencia de SUH en el mundo. Debido al rol fundamental de la Stx en su patogenia, se puede considerar que, como otras toxemias conocidas, el SUH podría ser tratado con anticuerpos. Este trabajo describe el desarrollo de un nuevo tratamiento capaz de neutralizar el efecto tóxico de distintas variantes de la Stx. El tratamiento consiste en fragmentos F(ab')2 provenientes de un antisuero equino cuya eficacia y potencia contra Stx1 y Stx2 se comprobó en diferentes modelos preclínicos. El producto mostró ser seguro en animales, presentó la farmacocinética descripta para compuestos similares y se pudo establecer una posible ventana terapéutica para su adecuada administración. En conjunto, los resultados preclínicos obtenidos validan la realización de un estudio clínico de primer uso en humanos. En dicho estudio, que se realizará en el Hospital Italiano de Buenos Aires, se analizará la seguridad y la farmacocinética del producto en voluntarios adultos sanos. Estos resultados sentarán las bases para la realización del estudio clínico fase II en pacientes pediátricos con infección por cepas de E. coli productoras de Stx.

The typical hemolytic uremic syndrome (HUS) is an orphan disease caused by Shiga toxin(Stx) -producing Escherichia coli strains and characterized by acute kidney damage, microangiopathic hemolytic anemia and low platelet count. It is endemic in Argentina, the country with the highest incidence of HUS in the world. Stx is essential for its development and therefore, HUS is considered a toxemic non-bacteremic disorder, which could be treated with antibodies. Herein we describe the development of a new treatment capable of neutralizing the toxic effect of Stx and its variants. The treatment consists of F(ab')2 fragments from an equine antiserum whose efficacy and potency against Stx1 and Stx2 were proved in different preclinical models. The product was shown to be safe in animals. Furthermore, the anti-Stx F(ab')2 pharmacokinetic was shown to be similar to that of analogous compounds and a therapeutic window for its administration was determined. Altogether, these preclinical results warrant testing in humans. The phase I clinical trial will be performed at the Hospital Italiano in Buenos Aires to evaluate the safety and pharmacokinetics of the product in healthy adult volunteers. Based on the results of this study, a phase II clinical trial will be planned in pediatric patients diagnosed with infection by Stx-producing E. coli strains.

EspA-loaded mesoporous silica nanoparticles can efficiently protect animal model against enterohaemorrhagic E. coli O157: H7.

In the present study, the application of mesoporous silica nanoparticles (MSNPs) loaded with recombinant EspA protein, an immunogen of enterohaemorrhagic E. coli, was investigated in the case of BALB/c mice immunization against the bacterium. MSNPs of 96.9 ± 15.9 nm in diameter were synthesized using template removing method. The immunization of mice was carried out orally and subcutaneously. Significant immune responses to the antigen were observed for the immunized mice when rEspA-loaded MSNPs were administered in both routes in comparison to that of the antigen formulated using a well-known adjuvant, i.e. Freund's. According to the titretitre of serum IL-4, the most potent humoral responses were observed when the mice were immunized subcutaneously with antigen-loaded MSNPs (244, 36 and 14 ng/dL of IL-4 in the serum of mice immunized subcutaneously or orally by antigen-loaded MSNPs, and subcutaneously by Freund's adjuvant formulated-antigen, respectively). However, the difference in serum IgG and serum IgA was not significant in mice subcutaneously immunized with antigen-loaded MSNPs and mice immunized with Freund's adjuvant formulated-antigen. Finally, the immunized mice were challenged orally by enterohaemorrhagic E. coli cells. The amount of bacterial shedding was significantly reduced in faecesfaeces of the animals immunized by antigen-loaded MSNPs in both subcutaneous and oral routes.

[New regulations concerning EHEC/VTEC]. / Nya rutiner för smittskydds­åtgärder vid EHEC-infektion - Endast EHEC som bär på stx2-genen kan kopplas till HUS ­ dessa smittbärare måste avstängas från arbete eller förskola.

New regulations concerning EHEC/VTEC Hemolytic Uremic Syndrome (HUS) is the most severe complication to an infection with EHEC (enterohemorrhagic E. coli), also called VTEC (verocytotoxin-producing E. coli). Risk of severe complications such as HUS is an important reason why the Swedish Communicable Diseases Act (Smittskyddslag. 2004:168) includes infection with EHEC. With very few exceptions, only EHEC with the stx2 gene is associated with HUS. According to the law, persons working with unpackaged foods, infants or severely immunocompromised patients, and children attending preschool can be suspended awaiting negative test results for EHEC. Symptom free carriers of EHEC-infection only harbouring the stx1 gene and without an epidemiological association to HUS need not be suspended from work or preschool.

Use of Bacteriophages to Control Escherichia coli O157:H7 in Domestic Ruminants, Meat Products, and Fruits and Vegetables.

Escherichia coli O157:H7 is an important foodborne pathogen that causes severe bloody diarrhea, hemorrhagic colitis, and hemolytic uremic syndrome. Ruminant manure is a primary source of E. coli O157:H7 contaminating the environment and food sources. Therefore, effective interventions targeted at reducing the prevalence of fecal excretion of E. coli O157:H7 by cattle and sheep and the elimination of E. coli O157:H7 contamination of meat products as well as fruits and vegetables are required. Bacteriophages offer the prospect of sustainable alternative approaches against bacterial pathogens with the flexibility of being applied therapeutically or for biological control purposes. This article reviews the use of phages administered orally or rectally to ruminants and by spraying or immersion of fruits and vegetables as an antimicrobial strategy for controlling E. coli O157:H7. The few reports available demonstrate the potential of phage therapy to reduce E. coli O157:H7 carriage in cattle and sheep, and preparation of commercial phage products was recently launched into commercial markets. However, a better ecological understanding of the phage E. coli O157:H7 will improve antimicrobial effectiveness of phages for elimination of E. coli O157:H7 in vivo.

Microbiological and serological control of Escherichia coli O157: H7 in kindergarten staff in Buenos Aires city and suburban areas.

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections are implicated in the development of the life-threatening hemolytic-uremic syndrome (HUS). Despite the magnitude of the social and economic problems caused by HUS, no licensed vaccine or effective therapy is currently available for human use. Prevention of STEC infections continues being the most important measure to reduce HUS incidence. This is especially true for Argentina where HUS incidence among children is extremely high and shows an endemic pattern. The aim of this work was to investigate serologically adult staff of kindergartens in Buenos Aires city and suburban areas in order to detect possible carriers, and to educate personnel about good practices to reduce HUS transmission. We also assessed the microbiological quality of water and meal samples from the same kindergartens. We tested 67 healthy adults, 13 water supplies and 6 meals belonging to 6 public kindergartens. We analysed hand swabs for isolation of STEC and serum samples for the presence of antibodies against Stx and lipopolysaccharide (LPS) of O157 serogroup. We identified 46 Stx2-positive individuals, but only 7 for O157 LPS. No presence of STEC pathogens was detected in hands of staff, water or meal samples.

Microbiological and serological control of Escherichia coli O157: H7 in kindergarten staff in Buenos Aires city and suburban areas

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections are implicated in the development of the life-threatening hemolytic-uremic syndrome (HUS). Despite the magnitude of the social and economic problems caused by HUS, no licensed vaccine or effective therapy is currently available for human use. Prevention of STEC infections continues being the most important measure to reduce HUS incidence. This is especially true for Argentina where HUS incidence among children is extremely high and shows an endemic pattern. The aim of this work was to investigate serologically adult staff of kindergartens in Buenos Aires city and suburban areas in order to detect possible carriers, and to educate personnel about good practices to reduce HUS transmission. We also assessed the microbiological quality of water and meal samples from the same kindergartens. We tested 67 healthy adults, 13 water supplies and 6 meals belonging to 6 public kindergartens. We analysed hand swabs for isolation of STEC and serum samples for the presence of antibodies against Stx and lipopolysaccharide (LPS) of O157 serogroup. We identified 46 Stx2-positive individuals, but only 7 for O157 LPS. No presence of STEC pathogens was detected in hands of staff, water or meal samples.

Las infecciones bacterianas con Escherichia coli productor de toxina Shiga (Stx) (STEC) están implicadas en el desarrollo del síndrome urémico hemolítico (SUH). A pesar de la magnitud del problema social y económico causado por el SUH, actualmente no existe un tratamiento específico o una vacuna eficaz para uso humano. Por lo tanto, la prevención de las infecciones por STEC es la tarea central para reducir la incidencia del SUH. Esto es especialmente cierto para Argentina en donde el SUH muestra un comportamiento endémico y presenta una incidencia extremadamente alta entre los niños. En efecto, la mediana de casos notificados en menores de 5 años para el periodo 2010-2015 fue 306, mientras que la tasa de notificación fue 8.5 casos cada 100 000 menores/año (http://www.msal.gob.ar/images/stories/boletines/boletin_integrado_vigilancia_N335-SE45.pdf). El objetivo de este trabajo fue analizar serológicamente al personal adulto de jardines de infantes de la ciudad de Buenos Aires y el área suburbana con el fin de detectar portadores, y brindarles formación sobre las buenas prácticas para reducir la transmisión de infecciones con STEC y así evitar el SUH. También se evaluó la calidad microbiológica de las muestras de agua y de la comida elaborada en los mismos jardines. Hemos estudiado 67 adultos, a través del hisopado de manos para la búsqueda de STEC y suero para la presencia de anticuerpos contra Stx y el lipopolisacárido (LPS) de serogrupo O157. También se analizaron 13 suministros de agua y 6 muestras de comida pertenecientes a 6 jardines de infantes públicos. Se identificaron 46 individuos positivos para Stx2, pero solo 7 para LPS-O157. No se detectó presencia de patógenos STEC en las muestras de las manos del personal, ni en los reservorios de agua o muestras de comida.