Hemolytic Uremic Syndrome Research Articles

The potential for therapeutic drug monitoring of belatacept and other biologicals in solid organ transplantation.

In solid organ transplantation (SOT), biologicals such as recombinant therapeutic proteins, monoclonal antibodies, fusion proteins and conjugates are increasingly used for immunosuppression, desensitization, ABO (blood group) incompatibility, antibody-mediated rejections and atypical haemolytic uremic syndrome. In this paper, we review the medical evidence available for biologicals used in SOT and the potential for improvement by the application of therapeutic drug monitoring (TDM) and model-informed precision dosing. Biologicals are used for off-label indications within the field of SOT, building on the experience from their use on labelled indications. Dosing is currently mostly standard, and experience vs. effect and toxicity is limited. Pharmacokinetic characteristics of these large, partly also immunogenic molecules differ from those of traditional small molecules. Individualization by concentration measurements and modelling has mostly been proof-of-concept or feasibility studies that lack the power to provide evidence for improvement in clinical outcome. For some drugs such as alemtuzumab, eculizumab, rituximab, tocilizumab and belatacept, studies have demonstrated significant interindividual variability in pharmacokinetics. Variability in absorption from subcutaneous administration may increase interindividual variability. There is also an economic aspect of appropriate dosing that needs to be pursued. Available assays and models to refine interpretation are in place, but trials of adequate size to document the usefulness of TDM and MIPD are scarce. Collaboration within the TDM community seems mandatory to establish studies of sufficient strength to provide evidence for the use of biologicals that are currently used off-label in SOT and furthermore to identify the settings where TDM may be beneficial.

Kidney Transplantation in Patients With aHUS: A Comparison of Eculizumab Prophylaxis Versus Rescue Therapy.

Guidelines advise eculizumab prophylaxis for most kidney transplant recipients with atypical hemolytic uremic syndrome (aHUS). However, recurrence rates may be overestimated, and starting eculizumab at relapse ("rescue therapy") may prevent graft loss. Randomized controlled trials have not compared the efficacy, safety, and costs of different treatment strategies. We performed a comparative study, including a previously described Dutch cohort treated with rescue therapy and a UK cohort using eculizumab prophylaxis. In the Netherlands, we selected all adult patients with aHUS who received a kidney transplant between 2010 and 2021 in the Radboud University Medical Center (n = 30) and enriched this cohort with 8 patients who received rescue therapy in other centers. The UK cohort included all adult patients with aHUS at moderate or high risk of recurrence, transplanted between 2013 and 2017 with prophylactic eculizumab. We included 38 Dutch patients and 35 UK patients. Characteristics were comparable, although the UK cohort included more patients with a complement factor H SCR20 mutation or hybrid gene (31% versus 5%; P < 0.01), and more Dutch patients received living donor kidneys (66% versus 20%; P < 0.001). Follow-up was comparable (the Dutch patients 70.8 mo, range, 10-134; UK patients 55.4 mo, range, 2-95). Eighteen (47%) Dutch patients received rescue therapy. Death-censored graft survival was not significantly different (the Dutch patients 1 y, 3 y, and 6 y: 97.4%, 91.2%, and 87.1%, respectively; UK patients 1 y, 3 y, and 6 y: 97.1%, 88.2%, and 65.6%, respectively, log-rank P = 0.189). In a population characterized by low prevalence of "very high risk" genes, who were predominantly transplanted using an endothelial protective regime, death-censored graft survival with eculizumab rescue therapy was not inferior to prophylaxis.

Rapid and Sensitive Detection of Shiga Toxin-Producing Escherichia coli (STEC) from Food Matrices Using the CANARY Biosensor Assay.

Shiga toxin-producing Escherichia coli (STEC) causes a wide spectrum of diseases including hemorrhagic colitis and hemolytic uremic syndrome (HUS). Previously, we developed a rapid, sensitive, and potentially portable assay that identified STEC by detecting Shiga toxin (Stx) using a B-cell based biosensor platform. We applied this assay to detect Stx2 present in food samples that have been implicated in previous STEC foodborne outbreaks (milk, lettuce, and beef). The STEC enrichment medium, modified Tryptone Soy Broth (mTSB), inhibited the biosensor assay, but dilution with the assay buffer relieved this effect. Results with Stx2a toxoid-spiked food samples indicated an estimated limit of detection (LOD) of ≈4 ng/mL. When this assay was applied to food samples inoculated with STEC, it was able to detect 0.4 CFU/g or 0.4 CFU/mL of STEC at 16 h post incubation (hpi) in an enrichment medium containing mitomycin C. Importantly, this assay was even able to detect STEC strains that were high expressors of Stx2 at 8 hpi. These results indicate that the STEC CANARY biosensor assay is a rapid and sensitive assay applicable for detection of STEC contamination in food with minimal sample processing that can complement the current Food Safety Inspection Service (US) methodologies for STEC.

Real-world analysis of the underdiagnosis, clinical outcomes and associated burden of hematopoietic stem cell transplantation-associated thrombotic microangiopathy (HSCT-TMA) in the United States

BackgroundThrombotic microangiopathy (TMA) associated with hematopoietic stem cell transplantation (HSCT-TMA) is a serious post-transplant complication. Diagnosis is difficult due to overlapping symptoms with other conditions and a lack of universally adopted diagnostic criteria.MethodsThis retrospective, observational study investigated HSCT-TMA incidence between July 2009–August 2020 using the TriNetX US Electronic Medical Record database. Patients who underwent autologous or allogeneic HSCT procedures and had conditioning agents were stratified as follows: confirmed TMA (≥1 hemolytic uremic syndrome (HUS)/TMA diagnosis code), suspected TMA [no HUS/TMA code but met modified published Cho (adult) or Jodele (pediatric) diagnostic criteria (further information in main text), and non-TMA (met neither criteria). Baseline demographics, clinical characteristics and outcomes, and all-cause unadjusted healthcare resource utilization (HCRU) within 12-months of HSCT, were assessed. Statistical comparisons were against the non-TMA cohort (p&amp;lt;0.05).ResultsThe study included 16,809 adults and 901 pediatrics. Of these, 125 adults (0.7%) and 30 pediatrics (3.3%) had confirmed TMA, 3029 (18.0%) adults and 94 (10.4%) pediatrics had suspected TMA; 13,655 (81.2%) adults and 777 (86.2%) pediatrics met non-TMA criteria. Confirmed and suspected TMA incidences were higher after allogeneic HSCT in adults. In pediatrics, confirmed TMA incidence was higher following autologous transplantation, and suspected TMA higher after allogeneic transplantation. Confirmed and suspected TMA patients had significantly higher Charlson Comorbidity Indexes pre-HSCT and more post-HSCT complications. In adults with confirmed and suspected TMA, mortality estimates within 12-months of HSCT were significantly higher compared to non-TMA patients, and numerically higher in pediatrics. All confirmed and suspected TMA patients had significantly more ER visits, inpatient stays and ICU admissions. HCRU within 12-months of HSCT was higher in all confirmed TMA patients; ≤0.1% of patients with suspected TMA, and 25.6–50.0% of patients with confirmed TMA, received complement inhibitors.ConclusionsOur results demonstrate that incidence of HSCT-TMA in the real world, as per billing codes, is low compared with historical literature. However, a proportion of suspected TMA cases, based on diagnosis criteria, share similarly poor outcomes and HCRU. HSCT-TMA is likely underdiagnosed, or under-coded, in real world practice. Our study highlights the need for greater vigilance to this severe complication.

Anti-C5 monoclonal antibody treatment showing pathological resolution of complement-mediated atypical hemolytic uremic syndrome: a case report

BackgroundNo reports have shown histological changes before and after anti-C5 monoclonal antibody treatment in patients with atypical hemolytic uremic syndrome (aHUS). Here, we report a rare case of complement-mediated aHUS with a complement factor H (CFH) mutation and anti-CFH antibodies who underwent multiple kidney biopsies.Case presentationA 53-year-old woman developed aHUS with CFH gene mutation [c.3572C > T (p. Ser1191 Leu)] and anti-CFH antibodies. Her father had succumbed to acute kidney injury (AKI) in his 30 s. She exhibited AKI, thrombocytopenia, and hemolytic anemia with schistocytes. After improving the platelet count with one session of plasma exchange, a kidney biopsy was performed one month after the onset of symptoms. Blood vessel thrombosis, obvious endothelial swelling, endocapillary hypercellularity, and subendothelial exudative lesions in the glomeruli and arterioles were detected. Anti-C5 monoclonal antibody treatment with eculizumab immediately improved disease activity. A second biopsy 3 months later revealed marked improvement of endothelial injuries with residual membrane double contours and exudative lesions. A third biopsy at 17 months after gradual improvement of kidney function showed a further decrease of double contours along with alterations of the exudative lesions to fibrous intimal thickening.ConclusionsThis is the first report showing the pathophysiology of aHUS in the kidneys and the efficacy of anti-C5 monoclonal antibody treatment by presenting serial kidney pathological features before and after anti-C5 monoclonal antibody treatment. Since her CFH mutation was considered the most important pathological condition, treatment centered on eculizumab was administered, resulting in a good long-term prognosis. In addition, kidney pathological resolution in aHUS occurred over 1 year after anti-C5 monoclonal antibody treatment.

Cancer Related Atypical Hemolytic Uremic Syndrome with Cepacia Syndrome

Cancer Related Atypical Hemolytic Uremic Syndrome with Cepacia Syndrome

Hemolytic uremic syndrome in children: Clinical characteristics and predictors of outcome

BackgroundHemolytic uremic syndrome (HUS) is the most common thrombotic microangiopathy (TMA) occurring in children. ObjectivesTo study the clinico-laboratory profile and identify the potential outcome predictors in children with hemolytic uremic syndrome. MethodologyA retrospective observational study was conducted at a tertiary center in South India. Children diagnosed with HUS during the study period of 10 years were included. The demographic, clinical, and laboratory details, complications, and outcomes were recorded. Predictors of mortality were analyzed. ResultsAmong 44 children with HUS, 14 (31.8 %) children were diagnosed with D + HUS while 30 had D-HUS. The median age at diagnosis was 6.3 years. Male preponderance (55.9 %) was observed. Presenting symptoms included oliguria in 36 (86.4 %), followed by fever, observed in 34 (77.3 %). 12 (27.2 %) children had anuria. Seizures and altered sensorium were present in 12 (27.35) and 16 (36.4 %) children respectively. Hypertension was observed in 33 (75 %) children. Plasmapheresis was performed in 18 (13.6 %) children. 17 (38.6 %) children underwent hemodialysis, and 7 (15.9 %) underwent peritoneal dialysis. The median duration of hospital stay was 18 (9.7, 27.7) days. Complications observed during the study were CNS involvement was seen in 16 (36.4 %) children, while coagulopathy was observed in 3 (6.8 %) children. Mortality was observed in 16 children (36.4 %). Anuria at admission was more prevalent in non-survivors (10 out of 16 children; p 0.003). The median albumin and C3 levels were significantly low in non-survivors (p-value <0.001 and 0.008 respectively). A total leucocyte count >15,000 X 109 cells/L was independently associated with mortality even after adjustment with duration of symptoms before diagnosis >10 days and low C3 levels (adjusted OR [95 % CI]: 1.12 [1.02, 1.92] (p-value 0.03). ConclusionHypoalbuminemia and hypocomplementemia were observed in higher proportions among non-survivors. Elevated leucocyte count at admission was an independent predictor of mortality.

Deletion of Sphingosine Kinase 2 Attenuates Acute Kidney Injury in Mice with Hemolytic-Uremic Syndrome.

Typical hemolytic uremic syndrome (HUS) can occur as a severe systemic complication of infections with Shiga toxin (Stx)-producing Escherichia coli. Its pathology can be induced by Stx types, resulting in toxin-mediated damage to renal barriers, inflammation, and the development of acute kidney injury (AKI). Two sphingosine kinase (SphK) isozymes, SphK1 and SphK2, have been shown to be involved in barrier maintenance and renal inflammatory diseases. Therefore, we sought to determine their role in the pathogenesis of HUS. Experimental HUS was induced by the repeated administration of Stx2 in wild-type (WT) and SphK1 (SphK1-/-) or SphK2 (SphK2-/-) null mutant mice. Disease severity was evaluated by assessing clinical symptoms, renal injury and dysfunction, inflammatory status and sphingolipid levels on day 5 of HUS development. Renal inflammation and injury were found to be attenuated in the SphK2-/- mice, but exacerbated in the SphK1-/- mice compared to the WT mice. The divergent outcome appeared to be associated with oppositely altered sphingolipid levels. This study represents the first description of the distinct roles of SphK1-/- and SphK2-/- in the pathogenesis of HUS. The identification of sphingolipid metabolism as a potential target for HUS therapy represents a significant advance in the field of HUS research.

Case presentation: a severe case of cobalamin c deficiency presenting with nephrotic syndrome, malignant hypertension and hemolytic anemia

BackgroundThe etiology of nephrotic syndrome can vary, with underlying metabolic diseases being a potential factor. Cobalamin C (cblC) defect is an autosomal recessive inborn error of metabolism caused by mutations in the MMACHC gene, resulting in impaired vitamin B12 processing. While cblC defect typically manifests with hematological and neurological symptoms, renal involvement is increasingly recognized but remains rare.Case PresentationWe describe a 7-month-old male patient presenting with fatigue and edema. His initial laboratory findings showed anemia, thrombocytopenia, hypoalbuminemia and proteinuria. Further examinations reveals hemolysis in peripheral blood smear. During his follow up respiratory distress due to pleural effusion in the right hemithorax was noticed. And fluid leakage to the third spaces supported a diagnosis of nephrotic syndrome. The patient’s condition deteriorated, leading to intensive care admission due to, hypertensive crisis, and respiratory distress. High total plasma homocysteine and low methionine levels raised suspicion of cobalamin metabolism disorders. Genetic testing confirmed biallelic MMACHC gene mutations, establishing the diagnosis of cblC defect. Treatment with hydroxycobalamin, folic acid, and betaine led to remarkable clinical improvement.Discussion/ConclusionThis case underscores the significance of recognizing metabolic disorders like cblC defect in atypical presentations of nephrotic syndrome. Early diagnosis and comprehensive management are vital to prevent irreversible renal damage. While cblC defects are more commonly associated with atypical hemolytic uremic syndrome, this case highlights the importance of considering cobalamin defects in the differential diagnosis of nephrotic syndrome, especially when associated with accompanying findings such as hemolysis. Our case, which has one of the highest homocysteine levels reported in the literature, emphasizes this situation again.

Clinical characteristics and genetic profile of complement system in renal thrombotic microangiopathy in patients with severe forms of arterial hypertension

The spectrum of diseases characterized by the development of renal thrombotic microangiopathy (TMA) encompasses the malignant hypertension (MHT). TMA in MHT has conventionally been regarded as a variation of secondary TMA, the treatment of which is restricted to the stabilization of blood pressure levels, a measure that frequently fails to prevent the rapid progression to end-stage renal disease in patients. Nevertheless, there exists a rationale to suggest that, in certain instances, endothelial damage in MHT might be rooted in the dysregulation of the complement system (CS), thereby presenting potential opportunities for the implementation of complement-blocking therapy. To study clinical manifestations and genetic profile of CS in patients with morphologically confirmed renal TMA combined with severe AH. 28 patients with morphologically verified renal TMA and severe AH were enrolled to the study. Patients with signs of microangiopathic hemolysis and thrombocytopenia were not included in the study due to possible compliance with the criteria for atypical hemolytic uremic syndrome (aHUS). The prevalence of rare genetic defects (GD) of the CS was assessed by molecular genetic analysis (search for mutations in the clinically significant part of the human genome - exome) by next-generation sequencing technology (NGS). GD of CS were detected in a quarter of patients. Rare genetic variants classified as "likely pathogenic" including defects in CFI, C3, CD46, CFHR4, CFHR5 genes were detected in five cases. Two patients were found to have chromosomal deletions containing CFH-related proteins genes (CFHR1, CFHR3). Rare variants of CS genes linked to aHUS were found in 25% of patients with renal TMA, the genesis of which was originally thought to be secondary and attributed to MHT, with partial or complete absence of hematological manifestations of microangiopathic pathology. The key to confirming TMA associated with MHT, particularly in the absence of microangiopathic hemolysis and thrombocytopenia, elucidating its nature, and potentially effective complement-blocking therapy in patients with GD of CS, appears to be a genetic study of CS combined with a morphological study of a renal biopsy.

Kidney involvement in rare hereditary diseases

Various rare inherited disorders can be associated with kidney involvement, including glomerulopathies, tubulopathies, multiple cysts, congenital anomalies of the kidneys and urinary tract, urolithiasis, malignant and benign tumors. Genetic nephropathy should be always considered in children, adolescents and young patients with the kidneys or urinary tract disorders and/or patients with positive family anamnesis. Extrarenal manifestations can be a valuable clue for diagnosis of certain hereditary diseases, e.g. neurosensory deafness in Alport syndrome or photofobia in nephropathic cystinosis. Diagnosis of monogenic inherited diseases should be verified by genetic testing. Specific drugs are available for treatment of certain hereditary diseases involving kidney, e.g. Fabry disease, cystinosis, primary hyperoxaluria I type and atypical hemolytic uremic syndrome.

Atypical hemolytic uremic syndrome during induction chemotherapy in neuroblastoma, a rare phenomenon or common congenital predisposition?

Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy sometimes associated with germline variants in genes of the complement system. Clinical findings of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury arise due to aberrant complement protein activation in the circulation. A 13-month-old boy with metastatic neuroblastoma (NB) developed aHUS during his first cycle of induction chemotherapy with germline testing revealing a complement factor H(CFH) gene mutation, currently classified as a variant of uncertain significance (VUS). Now he is in disease remission after successful complement blockade therapy, thus highlighting a unique presentation of aHUS in a patient with newly diagnosed NB.

A challenging STEC strain isolation from patients' stools: an O166:H15 STEC strain with the stx2 gene.

Shiga toxin-producing E. coli (STEC) infections can lead to severe complications such as bloody diarrhea and hemolytic uremic syndrome (HUS), especially in young children and the elderly. Strains that carry the shiga toxin 2 gene (stx2), such as O157:H7, have been mostly linked with severe disease outcomes. In recent years, outbreaks caused by non-O157:H7 strains have increased. E. coli O166:H15 has been previously reported causing a gastroenteritis outbreak in 1996 as a non-STEC strain, however the O166:H15 serotype we recovered carried the stx2 gene. It was particularly challenging to isolate this strain from stools by culture. Consequently, we tested immunomagnetic separation for the STEC recovery, which was a novel approach on clinical stools. Virulence genes were included for the characterization of these isolates.

Prevalence of Pathogenic E. coli 0157:H7 from Diverse Sources in Negele Town, West Guji, Ethiopia

E. coli O157: H7 is widely recognized as a major foodborne pathogen responsible for diarrhoea, haemorrhagic colitis, and haemolytic-uremic syndrome. This study was carried out in Negele town to determine the prevalence of E. coli O157: H7 in cow flesh, water streams, and soil. A systematic random sampling technique was utilized to gather samples, which were then transported to Bule Hora University's biology laboratory for isolation and identification of E. coli O157: H 7. The colonies identified as E. coli were streaked onto Sorbitol-MacConkey agar and cultured at 37°C for 24 hours. E. coli O157:H7 was verified using a latex agglutination kit. E. coli O157: H7 isolates were tested for antimicrobial susceptibility in vitro against nine different antibiotics. The data was analyzed using SPSS 21 software. The Pearson Chi-square test was used, and differences were judged significant at P ≤.05. Descriptive statistics such as crosstabulation were used to determine the percentage of prevalence in samples. From a total of samples, the overall prevalence of E. coli O157: H7 in cow meat, soils, and streams was determined to be 6.25%, 4%, and 6.66%. The abattoir stores had the highest prevalence of E. coli O157: H7 (3.3%) compared to retailer shops (1.7%). Doxycycline, Ciprofloxacin, and Gentamicin demonstrated the highest susceptibility. Tetracycline was shown to have the highest resistance. Multidrug resistance was shown to be common among isolates. This investigation confirmed a significant prevalence of E. coli O157:H7. Proper training and supervision of meat handlers, farmers, and health care personnel was strongly advised.

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

Efficacy and safety of eculizumab in children with Shiga-toxin-producing Escherichia coli haemolytic uraemic syndrome: the ECUSTEC RCT

BackgroundShiga-toxin-producingEscherichia colihaemolytic uraemic syndrome affects ~100 United Kingdom children each year. Around half need dialysis, a quarter develop serious complications with long-term consequences and ~3% die. No effective intervention is known; however, some studies report eculizumab, effective in atypical haemolytic uraemic syndrome, may be effective.ObjectivesTo determine whether the severity of Shiga-toxin-producingEscherichia colihaemolytic uraemic syndrome is less in those given eculizumab.DesignRandomised, double-blind, placebo-controlled, parallel-group trial with internal pilot phase and nested mechanistic laboratory studies.SettingPaediatric nephrology units in 12 United Kingdom hospitals.ParticipantsChildren aged 6 months to &lt; 19 years weighing ≥ 5 kg, with presumed Shiga-toxin-producingEscherichia colihaemolytic uraemic syndrome, including ‘injury’ or ‘failure’ category of the acute kidney injury paediatric risk/injury/failure/loss/end criteria.InterventionParticipants were randomised in a 1 : 1 ratio to receive intravenous eculizumab or placebo on day 1 and 8. All received meningococcal vaccination and prophylactic antibiotics.Main outcome measuresThe primary outcome measure was a multidomain clinical severity score, reflecting morbidity until day 60. Secondary outcome measures included survival, duration of renal replacement therapy, persistent neurological defect (day 60) and presence of chronic kidney disease at 1 year. Mechanistic studies assessed complement activation and vascular endothelial growth factor profiles in plasma ± urine samples. In vitro cell co-culture work assessed the effect of Shiga toxin on endothelial cells.ResultsThirty-six participants from 10 sites were randomised: 17 to eculizumab and 19 to placebo. The target sample size was 134 participants – recruitment stopped early due to low recruitment (factors included reduced incidence and limited out-of-hours research infrastructure) and the COVID-19 pandemic. The mean clinical severity score for participants randomised to eculizumab was 11.5 (standard deviation 8.4) compared to 14.6 (standard deviation 7.7) for participants randomised to placebo (adjusted mean difference: −2.5, 95% confidence interval −7.8 to 2.8,p= 0.3). Five participants (three eculizumab, two placebo) experienced an adverse event; there were seven serious adverse events in six participants (five eculizumab, one placebo). Urinary complement factor H and vascular endothelial growth factor levels were high initially and subsequently normalised. Shiga toxin caused a podocyte-dependent decrease in endothelial cell factor H levels.Conclusions and limitationsThere was no significant difference in mean clinical severity score between eculizumab and placebo groups – since the trial was underpowered, this cannot be interpreted as evidence of no effect. No significant safety concerns were observed. With further validation, the Eculizumab in Shiga-toxin-producingEscherichia coliHaemolytic Uraemic Syndrome clinical severity score may be an outcome measure for future trials. Our results imply that Shiga toxin causes complement-dependent glomerular endothelial cell injury through its action on podocytes and subsequent cellular cross-talk.Future workWe will continue to investigate cross talk between podocytes and endothelial cells after exposure to Shiga toxin and further develop plasma/urine biomarkers for diagnosis of Shiga-toxin-producingEscherichia colihaemolytic uraemic syndrome.Trial registrationThis trial is registered as EudraCT-2016-000997-39 and ISRCTN89553116.FundingThis award was funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 14/48/43) and is published in full inEfficacy and Mechanism Evaluation; Vol. 11, No. 11. See the NIHR Funding and Awards website for further award information.

Recurrent Atypical Hemolytic Uremic Syndrome: A Masquerade of Antibody-Mediated Rejection?

Abstract Atypical hemolytic uremic syndrome (aHUS) is a complement-mediated thrombotic microangiopathy (TMA) resulting from uncontrolled activation of the alternate complement pathway. It is necessary to distinguish a recurrent aHUS posttransplant from de novo aHUS, as the former is usually associated with complement abnormalities and has a poorer prognosis. Furthermore, COVID-19 is believed to unmask underlying complement defects triggering a relapse of aHUS. In this report, we present one such unique histologic presentation of recurrent TMA following a COVID-19 infection, which was not just a diagnostic challenge but could easily have been misdiagnosed as an antibody-mediated rejection.

Perinatal findings of women with pregnancy related haemolytic uremic syndrome: a case series from a single Italian tertiary perinatal care centre

Perinatal findings of women with pregnancy related haemolytic uremic syndrome: a case series from a single Italian tertiary perinatal care centre

A case report of atypical haemolytic-uremic syndrome (aHUS) in a patient with type IIB von Willebrand disease (VWD): management and differential diagnosis of thrombotic microangiopathies (TMA) disorders in pregnancy

A case report of atypical haemolytic-uremic syndrome (aHUS) in a patient with type IIB von Willebrand disease (VWD): management and differential diagnosis of thrombotic microangiopathies (TMA) disorders in pregnancy

Evaluation of the Humoral Response after Immunization with a Chimeric Subunit Vaccine against Shiga Toxin-Producing Escherichia coli in Pregnant Sows and Their Offspring.

Shiga toxin-producing Escherichia coli (STEC) poses a significant public health risk due to its zoonotic potential and association with severe human diseases, such as hemorrhagic colitis and hemolytic uremic syndrome. Ruminants are recognized as primary reservoirs for STEC, but swine also contribute to the epidemiology of this pathogen, highlighting the need for effective prevention strategies across species. Notably, a subgroup of STEC that produces Shiga toxin type 2e (Stx2e) causes edema disease (ED) in newborn piglets, economically affecting pig production. This study evaluates the immunogenicity of a chimeric protein-based vaccine candidate against STEC in pregnant sows and the subsequent transfer of immunity to their offspring. This vaccine candidate, which includes chimeric proteins displaying selected epitopes from the proteins Cah, OmpT, and Hes, was previously proven to be immunogenic in pregnant cows. Our analysis revealed a broad diversity of STEC serotypes within swine populations, with the cah and ompT genes being prevalent, validating them as suitable antigens for vaccine development. Although the hes gene was detected less frequently, the presence of at least one of these three genes in a significant proportion of STEC suggests the potential of this vaccine to target a wide range of strains. The vaccination of pregnant sows led to an increase in specific IgG and IgA antibodies against the chimeric proteins, indicating successful immunization. Additionally, our results demonstrated the effective passive transfer of maternal antibodies to piglets, providing them with immediate, albeit temporary, humoral immunity against STEC. These humoral responses demonstrate the immunogenicity of the vaccine candidate and are preliminary indicators of its potential efficacy. However, further research is needed to conclusively evaluate its impact on STEC colonization and shedding. This study highlights the potential of maternal vaccination to protect piglets from ED and contributes to the development of vaccination strategies to reduce the prevalence of STEC in various animal reservoirs.