Cases Of Hemolytic Uremic Syndrome Research Articles

A novel multiplex and glycoprotein-based immunochromatographic serologic IgM test for the rapid diagnosis of Escherichia coli O157 and O145 causing bloody diarrhea and hemolytic uremic syndrome.

Shiga toxin-producing Escherichia coli (STEC) are the main etiological agents of hemolytic uremic syndrome (HUS). Good clinical management of STEC infections and HUS depends on early, rapid, and accurate diagnosis. Here, we have developed and evaluated the first multiplex and glycoprotein-based immunochromatographic test for the detection of IgM antibodies against the O-polysaccharide of the lipopolysaccharide of E. coli O157 and O145 in human serum samples. A retrospective study was carried out resulting in a diagnostic sensitivity of the E. coli O157/O145 LFIA (lateral flow immunoassay) of 97.1% and 98.9% for O157 and O145, respectively, and 97.9% for both serogroups. The diagnostic specificity was 98.7% for O157 and O145, and the overall specificity 97.4%. In samples obtained before 3 days after the onset of diarrhea, the detection percentage was 83%, increasing to 100% from 3 days onward. Finally, the association of bloody diarrhea (BD) or HUS cases to an STEC infection increased from 22.8% to 77.2% when stool culture and stx/Stx detection were combined with serology by LFIA. Our results demonstrate that the E. coli O157/O145 LFIA is a highly accurate and serospecific test for the early and rapid diagnosis of E. coli O157 and O145 infections in BD or HUS cases. This test allows the detection of specific IgM antibodies very early in the course of the infection, making it an ideal diagnostic tool to be implemented in pediatric emergencies and, thus, avoid delays in the application of the correct supportive or specific treatment and prevent complications associated with HUS.

The Role of the N-Terminal Domain of Thrombomodulin and the Potential of Recombinant Human Thrombomodulin as a Therapeutic Intervention for Shiga Toxin-Induced Hemolytic-Uremic Syndrome.

Hemolytic-uremic syndrome (HUS) is a rare complication of an infection with Shiga toxin (Stx)-producing Escherichia coli (STEC-HUS), characterized by severe acute kidney injury, thrombocytopenia and microangiopathic hemolytic anemia, and specific therapy is still lacking. Thrombomodulin (TM) is a multi-domain transmembrane endothelial cell protein and its N-terminal domain has been implicated in the pathophysiology of some cases of HUS. Indeed, the administration of recombinant human TM (rhTM) may have efficacy in HUS. We used a Stx-based murine model of HUS to characterize the role of the N-terminal domain of TM. We show that mice lacking that domain (TMLed (-/-)) are more sensitive to Stx, with enhanced HUS progression seen at 4 days and increased mortality at 7 days post-HUS induction. In spite of these changes, renal function was less affected in surviving Stx-challenged TMLed (-/-) mice compared to their wild-type counterparts TMLed (+/+) at 7 days. Contrary to few clinical case reports from Japan, the administration of rhTM (0.06 mg/kg) to wild-type mice (C57BL/6J) with HUS did not protect against disease progression. This overall promising, but also contradictory body of evidence, requires further systematic preclinical and clinical investigations to clarify the role of TM in HUS as a potential therapeutic strategy.

Severe Invasive Pneumococcal Disease Caused by Serotype 19A in Children Under Five Years in Tāmaki Makaurau Auckland, Aotearoa New Zealand.

Increases in childhood invasive pneumococcal disease (IPD) have been reported in several countries following the easing of COVID-19 pandemic mitigations. In Aotearoa New Zealand (AoNZ), a surge in IPD is occurring in young children concurrent with changes in pneumococcal vaccines and declining immunization coverage. We sought to examine epidemiologic and clinical features of IPD among children under 5 years in a large urban region of AoNZ in the 3 years post-COVID-19. Demographic, clinical and laboratory data were collated from children under 5 years with Streptococcus pneumoniae identified from normally sterile sites between January 1, 2021, and December 31, 2023, in Tāmaki Makaurau Auckland, AoNZ. We identified 93 episodes of IPD (annual incidence of 18-40 cases per 100,000 population per year). Serotype was identified in 68 episodes and 46 (68%) were serotype 19A. Incidence was higher in Pacific children compared with non-Māori, non-Pacific children (incidence rate ratio: 2.3; 95% confidence interval: 1.4-3.7). Bacteremia occurred in 65 (70%) episodes, empyema in 47 (51%), meningitis in 11 (12%) and hemolytic uremic syndrome in 7 (7.5%). All cases of hemolytic uremic syndrome and empyema were only among children with serotype 19A. Two children died, both had serotype 19A, and 13/91 survivors (14%) experienced serious sequelae. The use of the pneumococcal conjugate vaccine with lower valency and easing of COVID-19 containment measures each may have contributed to an increase in IPD in AoNZ. Serotype 19A is associated with empyema and causes severe disease in young children. Urgent efforts are required to improve PCV13 coverage in AoNZ.

Two cases of typical HUS in adults treated with an anti-C5 monoclonal antibody: a new perspective?

Hemolytic uremic syndrome (HUS) is a rare clinical entity, especially in adults. In its typical form the causative factor that triggers the cascade of immunologic and inflammatory events is a Shiga toxin-producing pathogen, found in the patient's stool. Renal and neurologic involvement usually prevails and requires immediatecare. Regarding thispotentially life-threatening condition, little is known and the mainstay is supportive care. However, some interesting evidence has come up about the use of eculizumab, an anti-C5 monoclonal antibody, mainly in pediatric patients with typical HUS. Herein, we present two cases with typical HUS caused by two different strains of Escherichia coli (Shiga toxin-producing enterohemorrhagic and enteropathogenic) who were both treated effectively with anti-C5 monoclonal antibodies (eculizumab and ravulizumab).

A case of Haemolytic uraemic syndrome caused by Falciparum malaria, picked up in an urgent care setting

A case of Haemolytic uraemic syndrome caused by Falciparum malaria, picked up in an urgent care setting

Predictors of Prolonged Mechanical Ventilation in Pediatric Patients with Hemolytic Uremic Syndrome

AbstractThis study aimed to analyze factors associated with mechanical ventilation (MV) and prolonged MV (≥12 days) in pediatric hemolytic uremic syndrome (HUS) patients. Retrospective multicenter cohort study analyzed data from 3,831 pediatric HUS (age <18 years) patients between 2004 and 2018 from Pediatric Health Information System database. Multivariate logistic regression was used to pinpoint factors associated with MV and prolonged MV. Among 3,831 patients analyzed, 769 (20%) patients required MV, 166 (23.6%) of them were prolonged MV. Factors independently associated with prolonged MV include African American (adjusted odds ratio [aOR]: 1.98, 95% confidence interval [CI]: 1.11–3.54, p = 0.02), children aged between 1 and 5 years (aOR: 7.69, 95% CI: 3.71–15.93, p < 0.001), pneumonia (aOR: 2.54, 95% CI: 1.51–4.25, p < 0.001), pneumothorax (aOR: 2.41, 95% CI: 1.08–5.39, p = 0.032), liver dysfunction (aOR: 3.22, 95% CI: 1.68–6.16, p < 0.001), ileus with perforation (aOR: 1.83, 95% CI: 1.03–3.25, p = 0.039), and sepsis (aOR: 1.97, 95% CI: 1.26–3.08, p = 0.003). In pediatric HUS cases, 20% required MV, and 23.6% of them were prolonged MV. Factors associated with prolong MV include African American race, children aged between 1 and 5 years, pneumonia, pneumothorax, liver dysfunction, ileus with perforation, and sepsis.

Effect of Ground Beef Irradiation on Annual Nontyphoidal Salmonella and Escherichia coli O157 Burden and Direct Healthcare Costs in the United States: A Simulation Study

Over 20% of E. coli O157 illnesses and over 5% of Salmonella illnesses are estimated to be attributable to beef consumption in the United States. Irradiating ground beef is one possible method to reduce disease burden. We simulated the effect of ground beef irradiation on illnesses, hospitalizations, deaths, and direct healthcare costs from ground beef-associated E. coli O157 and Salmonella illnesses in the United States. To estimate the fraction of illnesses, hospitalizations, deaths, and direct healthcare costs preventable by ground beef irradiation, we multiplied the disease burden attributable to ground beef; the estimated percentage of ground beef sold that is not currently irradiated; the percentage of unirradiated ground beef that would be irradiated; and the percentage reduction in risk of illness after irradiation. We multiplied this fraction by estimates of burden and direct healthcare costs to calculate the numbers or amounts averted. Model inputs were obtained from the literature and expert opinion. We used Monte Carlo simulation to incorporate uncertainty in inputs into model estimates. Simulation outcomes were summarized with means and 95% uncertainty intervals (UI). Irradiating 50% of the currently unirradiated ground beef supply would avert 3,285 (95% UI: 624–9,977) E. coli O157 illnesses, 135 (95% UI: 24–397) hospitalizations, 197 (95% UI: 34–631) hemolytic uremic syndrome cases, 2 (95% UI: 0–16) deaths, and $2,972,656 (95% UI: $254,708–$14,496,916) in direct healthcare costs annually. For Salmonella, irradiation would avert 20,308 (95% UI: 9,858–38,903) illnesses, 400 (95% UI: 158–834) hospitalizations, 6 (95% UI: 0–18) deaths, and $7,318,632 (95% UI: $1,436,141–$26,439,493) in direct healthcare costs. Increasing ground beef irradiation could reduce E. coli O157 and Salmonella burden in the United States. Additional studies should assess whether targeted irradiation of higher-risk ground beef products could prevent similar numbers of illnesses with less total product irradiated.

Hemolytic uremic syndrome in a Pediatric Intensive Care Unit- Rapid review with case series

Hemolytic uremic syndrome (HUS) is a multiorgan clinical syndrome characterized by the simultaneous occurrence of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. This is the most important form of thrombotic microangiopathies in children and is considered the main cause of acute renal insufficiency in children, especially under the age of five. Over 90% of HUS in children is associated with infection, and the prodromal manifestation most often includes bloody diarrhea. Atypical hemolytic uremic syndrome (aHUS) is a rare but progressive, life-threatening condition that affects about 10% of HUS cases in children. It is predominantly caused by dysregulation of the alternative complement pathway and genetic predisposition. Conditions that enhance complement, such as some viral infections, malignancies, autoimmune diseases and transplantation may be comorbid in up to 70% of aHUS cases. The 2016 International Hemolytic Uremic Syndrome Group classification, based on the etiology, separates 4 groups: caused by infection, with coexisting conditions, due to cobalamin C disorders and due to complement dysregulation. Monoclonal antibody that effectively blocks complement activation, has significantly changed aHUS treatment and outcome. Early etiological recognition in order to start specific treatment as soon as possible is crucial for the outcome. This paper, through a rapid review and series of three children treated for HUS in our pediatric intensive care unit over a two-year period, aims to emphasize the complexity of the diagnosis and treatment of HUS, and the importance of a multidisciplinary team in order to to avoid complications, and achieve the best short- and long-term outcome

The Role of the Complement System in the Pathogenesis of Infectious Forms of Hemolytic Uremic Syndrome.

Hemolytic uremic syndrome (HUS) is an acute disease and the most common cause of childhood acute renal failure. HUS is characterized by a triad of symptoms: microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. In most of the cases, HUS occurs as a result of infection caused by Shiga toxin-producing microbes: hemorrhagic Escherichia coli and Shigella dysenteriae type 1. They account for up to 90% of all cases of HUS. The remaining 10% of cases grouped under the general term atypical HUS represent a heterogeneous group of diseases with similar clinical signs. Emerging evidence suggests that in addition to E. coli and S. dysenteriae type 1, a variety of bacterial and viral infections can cause the development of HUS. In particular, infectious diseases act as the main cause of aHUS recurrence. The pathogenesis of most cases of atypical HUS is based on congenital or acquired defects of complement system. This review presents summarized data from recent studies, suggesting that complement dysregulation is a key pathogenetic factor in various types of infection-induced HUS. Separate links in the complement system are considered, the damage of which during bacterial and viral infections can lead to complement hyperactivation following by microvascular endothelial injury and development of acute renal failure.

Combined usage of serodiagnosis and O antigen typing to isolate Shiga toxin-producing Escherichia coli O76:H7 from a hemolytic uremic syndrome case and genomic insights from the isolate.

Hemolytic uremic syndrome (HUS) is a life-threatening disease caused by Shiga toxin-producing Escherichia coli (STEC) infection. The treatment approaches for STEC-mediated typical HUS and atypical HUS differ, underscoring the importance of rapid and accurate diagnosis. However, specific detection methods for STECs other than major serogroups, such as O157, O26, and O111, are limited. This study focuses on the utility of PCR-based O-serotyping, serum agglutination tests utilizing antibodies against the identified Og type, and isolation techniques employing antibody-conjugated immunomagnetic beads for STEC isolation. By employing these methods, we successfully isolated a STEC strain of a minor serotype, O76:H7, from a HUS patient.

Public health risks of raw milk consumption: Lessons from a case of paediatric hemolytic uremic syndrome.

Pasteurization of raw milk is mandatory before sale in Canada and has been demonstrated to reduce the risk of food-borne illness associated with milk consumption. Consumption of raw milk sparks urgent concern from a public health perspective since it has been linked to numerous outbreaks by enteric organisms, particularly Escherichia coli-related illnesses and complications in pediatric populations. The sale and distribution of raw milk is illegal in Canada, based on these significant health risks, but growing popular interest and trends in consuming raw dairy products reflect changes in consumer preferences. Although the consumption of raw milk has been an ongoing issue, this new trend is alarming and action is needed to prevent serious consequences as seen in children and other populations with reduced immunity such as the elderly and pregnant people. This commentary explores key issues identified by a local public health unit during the investigation of a recent paediatric case of hemolytic uremic syndrome related to an E. coli O157:H7 infection that occurred within the context of consumption of raw milk. The main objective of this article is to highlight that the health risks and sequelae associated with consumption of raw milk far outweigh any potential benefits, with severe consequences particularly among children. Data and health impacts, distribution, regulation, pasteurization and proposed practice recommendations are also identified and discussed.

Detection of plasma anti-lipopolysaccharide (LPS) antibodies against enterohemorrhagic Escherichia coli (EHEC) in asymptomatic kindergarten teachers from Buenos Aires province

In Argentina, hemolytic uremic syndrome (HUS) caused by EHEC has the highest incidence in the world. EHEC infection has an endemo-epidemic behavior, causing 20–30% of acute bloody diarrhea syndrome in children under 5 years old. In the period 2016–2020, 272 new cases per year were notified to the National Health Surveillance System. Multiple factors are responsible for HUS incidence in Argentina including person-to-person transmission. In order to detect possible EHEC carriers, we carried out a preliminary study of the frequency of kindergarten teachers with anti-LPS antibodies against the most prevalent EHEC serotypes in Argentina. We analyzed 61 kindergarten teachers from 26 institutions from José C. Paz district, located in the suburban area of Buenos Aires province, Argentina. Fifty-one percent of the plasma samples had antibodies against O157, O145, O121 and O103 LPS: 6.4% of the positive samples had IgM isotype (n=2), 61.3% IgG isotype (n=19) and 32.3% IgM and IgG (n=10). Given that antibodies against LPS antigens are usually short-lived specific IgM detection may indicate a recent infection. In addition, the high percentage of positive samples may indicate a frequent exposure to EHEC strains in the cohort studied, as well as the existence of a large non-symptomatic population of adults carrying pathogenic strains that could contribute to the endemic behavior through person-to-person transmission. The improvement of continuous educational programs in kindergarten institutions could be a mandatory measure to reduce HUS cases not only in Argentina but also globally.

Escherichia coli encoding Shiga toxin subtype Stx2f causing human infections in England, 2015-2022.

Introduction. Shiga toxin-producing Escherichia coli (STEC) belong to a diverse group of gastrointestinal pathogens defined by the presence of Shiga toxin genes (stx) of which there are at least ten subtypes (Stx1a-Stx1d and Stx2a-Stx2g).Gap Statement. Initially thought to be associated with mild symptoms, more recently STEC encoding stx2f have been isolated from cases of haemolytic uraemic syndrome (HUS) and the clinical significance and public health burden require further investigation.Aim. We analysed clinical outcomes and genome-sequencing data linked to patients infected with STEC encoding-stx2f in England to assess the risk to public health.Methodology. One hundred and twelve E. coli (n=58 isolates encoded stx2f; n=54 isolates E. coli belonging to CC122 or CC722 that had eae but were negative for stx) isolated from patients' faecal specimens between 2015 and 2022 were genome sequenced and linked to epidemiological and clinical outcome data. All isolates were investigated for the presence of virulence genes and a maximum-likelihood phylogeny of isolates belonging to CC122 and CC722 was constructed.Results. There were 52 cases infected with STEC harbouring stx2f between 2015 and 2022, with the majority identified in 2022. Most cases resided in the North of England (n=39/52, 75 %), were female (n=31, 59.6 %) and/or aged five and under (n=29, 55.8 %). Clinical outcome data were available for 40/52 cases (76.9 %) and 7/40(17.5 %) were diagnosed with STEC-HUS. In the two most common clonal complexes, CC122 and CC722, the presence of the stx2f-encoding prophage correlated with the presence of additional virulence genes, astA, bfpA and cdt, located on an 85kbp IncFIB plasmid.Conclusions. Certain serotypes of E. coli harbouring stx2f cause severe clinical outcomes, including STEC-HUS. Public health advice and possible interventions are limited, as little is known about the animal and environmental reservoirs and transmission routes. We recommend more comprehensive and standardized collection of microbiological and epidemiological data, and routine sharing of sequencing data between public health agencies worldwide.

Surveillance of Shiga toxin-producing Escherichia coli associated bloody diarrhea in Argentina

In Argentina, hemolytic uremic syndrome (HUS) caused by Shiga toxin-producing Escherichia coli (STEC-HUS) infection is endemic, and reliable data about prevalence and risk factors have been available since 2000. However, information about STEC-associated bloody diarrhea (BD) is limited. A prospective study was performed during the period October 2018–June 2019 in seven tertiary-hospitals and 18 referral units from different regions, aiming to determine (i) the frequency of STEC-positive BD cases in 714 children aged 1–9 years of age and (ii) the rate of progression of bloody diarrhea to HUS. The number and regional distribution of STEC-HUS cases in the same hospitals and during the same period were also assessed. Twenty-nine (4.1%) of the BD patients were STEC-positive, as determined by the Shiga Toxin Quik Chek (STQC) test and/or the multiplex polymerase chain reaction (mPCR) assay. The highest frequencies were found in the Southern region (Neuquén, 8.7%; Bahía Blanca, 7.9%), in children between 12 and 23 month of age (8.8%), during summertime. Four (13.8%) cases progressed to HUS, three to nine days after diarrhea onset. Twenty-seven STEC-HUS in children under 5 years of age (77.8%) were enrolled, 51.9% were female; 44% were Stx-positive by STQC and all by mPCR. The most common serotypes were O157:H7 and O145:H28 and the prevalent genotypes, both among BD and HUS cases, were stx2a-only or -associated. Considering the endemic behavior of HUS and its high incidence, these data show that the rate of STEC-positive cases is low among BD patients. However, the early recognition of STEC-positive cases is important for patient monitoring and initiation of supportive treatment.

Phenotypic and genotypic characterization of Shiga toxin-producing Escherichia coli strains recovered from bovine carcasses in Uruguay.

Shiga toxin-producing Escherichia coli (STEC) is a zoonotic pathogen that cause food-borne diseases in humans. Cattle and derived foodstuffs play a known role as reservoir and vehicles, respectively. In Uruguay, information about the characteristics of circulating STEC in meat productive chain is scarce. The aim was to characterize STEC strains recovered from 800 bovine carcasses of different slaughterhouses. To characterize STEC strains we use classical microbiological procedures, Whole Genome Sequencing (WGS) and FAO/WHO risk criteria. We analyzed 39 STEC isolated from 20 establishments. They belonged to 21 different O-groups and 13 different H-types. Only one O157:H7 strain was characterized and the serotypes O130:H11(6), O174:H28(5), and O22:H8(5) prevailed. One strain showed resistance in vitro to tetracycline and genes for doxycycline, sulfonamide, streptomycin and fosfomycin resistance were detected. Thirty-three strains (84.6%) carried the subtypes Stx2a, Stx2c, or Stx2d. The gene eae was detected only in two strains (O157:H7, O182:H25). The most prevalent virulence genes found were lpfA (n = 38), ompA (n = 39), ompT (n = 39), iss (n = 38), and terC (n = 39). Within the set of STEC analyzed, the majority (81.5%) belonged to FAO/WHO's risk classification levels 4 and 5 (lower risk). Besides, we detected STEC serotypes O22:H8, O113:H21, O130:H11, and O174:H21 belonged to level risk 2 associate with diarrhea, hemorrhagic colitis or Hemolytic-Uremic Syndrome (HUS). The only O157:H7 strain analyzed belonged to ST11. Thirty-eight isolates belonged to the Clermont type B1, while the O157:H7 was classified as E. The analyzed STEC showed high genomic diversity and harbor several genetic determinants associated with virulence, underlining the important role of WGS for a complete typing. In this set we did not detect non-O157 STEC previously isolated from local HUS cases. However, when interpreting this findings, the low number of isolates analyzed and some methodological limitations must be taken into account. Obtained data suggest that cattle constitute a local reservoir of non-O157 serotypes associated with severe diseases. Other studies are needed to assess the role of the local meat chain in the spread of STEC, especially those associated with severe diseases in humans.

Pharmacological Management of Atypical Hemolytic Uremic Syndrome in Pediatric Patients: Current and Future.

Atypical hemolytic uremic syndrome is a thrombotic microangiopathy characterized by hemolysis, thrombocytopenia, and acute kidney injury, usually caused by alternative complement system overactivation due to pathogenic genetic variants or antibodies to components or regulatory factors in this pathway. Previously, a lack of effective treatment for this condition was associated with mortality, end-stage kidney disease, and the risk of disease recurrence after kidney transplantation. Plasma therapy has been used for atypical hemolytic uremic syndrome treatment with inconsistent results. Complement-blocking treatment changed the outcome and prognosis of patients with atypical hemolytic uremic syndrome. Early administration of eculizumab, a monoclonal C5 antibody, leads to improvements in hematologic, kidney, and systemic manifestations in patients with atypical hemolytic uremic syndrome, even with apparent dialysis dependency. Pre- and post-transplant use of eculizumab is effective in the prevention of atypical hemolytic uremic syndrome recurrence. Evidence on eculizumab use in secondary hemolytic uremic syndrome cases is controversial. Recent data favor the restrictive use of eculizumab in carefully selected atypical hemolytic uremic syndrome cases, but close monitoring for relapse after drug discontinuation is emphasized. Prophylaxis for meningococcal infection is important. The long-acting C5 monoclonal antibody ravulizumab is now approved for atypical hemolytic uremic syndrome treatment, enabling a reduction in the dosing frequency and improving the quality of life in patients with atypical hemolytic uremic syndrome. New strategies for additional and novel complement blockage medications in atypical hemolytic uremic syndrome are under investigation.

Haemolytic uraemic syndrome in children England, Wales, Northern Ireland, and Ireland: A prospective cohort study.

Haemolytic uraemic syndrome (HUS) caused by infection with Shiga toxin-producing Escherichia coli (STEC) is a relatively rare but potentially fatal multisystem syndrome clinically characterised by acute kidney injury. This study aimed to provide robust estimates of paediatric HUS incidence in England, Wales, Northern Ireland, and the Republic of Ireland by using data linkage and case reconciliation with existing surveillance systems, and to describe the characteristics of the condition. Between 2011 and 2014, 288 HUS patients were included in the study, of which 256 (89.5%) were diagnosed as typical HUS. The crude incidence of paediatric typical HUS was 0.78 per 100,000 person-years, although this varied by country, age, gender, and ethnicity. The majority of typical HUS cases were 1 to 4 years old (53.7%) and female (54.0%). Clinical symptoms included diarrhoea (96.5%) and/or bloody diarrhoea (71.9%), abdominal pain (68.4%), and fever (41.4%). Where STEC was isolated (59.3%), 92.8% of strains were STEC O157 and 7.2% were STEC O26. Comparison of the HUS case ascertainment to existing STEC surveillance data indicated an additional 166 HUS cases were captured during this study, highlighting the limitations of the current surveillance system for STEC for monitoring the clinical burden of STEC and capturing HUS cases.

Atypical Presentation of Shiga Toxin Haemolytic Uremic Syndrome (STEC-HUS)

Shiga-toxin producing Escherichia coli (STEC) infection is the most common cause of haemolytic uremic syndrome (HUS) in children. It should be noted that 5% of STEC-HUS patients have no prodromal diarrhoea, while it may be present in up to 30% of atypical HUS (aHUS) cases. In patients at risk for aHUS, STEC infection may act as a trigger rather than playing a causative role. Presently, eculizumab is the first-line therapy for children presenting with aHUS, whereas treatment of children with STEC-HUS is mainly supportive. We report the case of a child with STEC-HUS who had a severe presentation, requiring renal replacement therapy in the acute phase and surgical treatment for a colonic stricture that arose as a late extra-renal complication of the disease. We aim to review the diagnostic workup of children presenting with HUS, stressing the resources available in our setting. In Portugal, O157 E. coli isolation medium is widely available in clinical laboratories. Non-O157 STEC identification requires specific testing, which is increasingly relevant as non-O157 STEC is becoming a more common cause of STEC-HUS than serogroup O157. The National Health Institute Doutor Ricardo Jorge (INSA) has the capacity to identify verotoxin genes and to proceed to verotxin-producing E. coli (VTEC) pathogenicity assessment using multiplex polymerase chain reaction. Fresh stool samples must be obtained early in the disease course to be sent for culture in O157 E. coli isolation medium and for non-O157 E. coli identification assays.

Etiological diagnosis of post-diarrheal hemolytic uremic syndrome (HUS): humoral response contribution.

Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolysis, thrombocytopenia, and thrombus formation leading to tissue injury. HUS is classified according to its etiology as post-diarrheal or atypical HUS. Differential diagnosis of both entities continues to be a challenge for pediatric physicians. The aim was to improve the rapid etiological diagnosis of post-diarrheal HUS cases based on the detection of Shiga toxin (Stx)-producing Escherichia coli (STEC) infection by screening of stx1/stx2 and rfbO157 in cultured stools by multiplex PCR, and the additional detection of anti-lipopolysaccharide (anti-LPS) O157, O145, and O121 antibodies by Glyco-iELISA test. In addition, we studied patients' relatives to detect circulating pathogenic strains that could contribute to HUS diagnosis and/or lead to the implementation of measures to prevent dissemination of familial outbreaks. This study describes the diagnosis of 31 HUS patients admitted to Hospital Municipal de Niños Prof Dr Ramón Exeni during the 2017-2020 period. Stool PCR confirmed the diagnosis of STEC associated with HUS in 38.7% of patients (12/31), while anti-LPS serology did in 88.9% (24/27). In those patients in which both methods were carried out (n = 27), a strong association between the results obtained was found. We found that 30.4% of HUS patients had at least one relative positive for STEC. We could identify 96.3% (26/27) of HUS cases as secondary to STEC infections when both methods (genotyping and serology) were used. The results demonstrated a high circulation of STEC in HUS families and the prevalence of the STEC O157 serotype (83%) in our pediatric cohort. A higher-resolution version of the Graphical abstract is available as Supplementary information.

Hemolytic uremic syndrome: An updated review

Hemolytic uremic syndrome (HUS) is a microangiopathic thrombotic disease. HUS is classified into typical, secondary, and atypical types. All types are characterized by thrombocytopenia, acute kidney impairment, and hemolysis. Infection with Shiga toxin from Escherichia coli causes typical HUS. Atypical HUS is frequently caused by abnormal complement activation via the alternative pathway because of gene mutations or autoantibodies synthesis. Secondary HUS accompanies post-transplantation, autoimmunity, cancer, etc. Endothelial cell injury initiates cells destruction stimulates procoagulant state, which activates platelet and thrombus generation, producing ischemic tissue injury.
 HUS pathogenesis is the result of an ineffective complement activation cycle that causes endothelial cells damage, activating platelet and thrombus formation. In some atypical HUS cases, interrupting the pathogenesis cycle of HUS by inhibiting complement activation might be beneficial, but not in those with gene mutations and patients with typical or secondary HUS. Hence, the pathogenesis of HUS types understanding is required; therefore, a comprehensive review of the differences and resemblances between the HUS types will be discussed and updated.