Immunosuppressed Patients Research Articles

Development of an indirect ELISA for detecting Toxoplasma gondii IgG antibodies based on a recombinant TgIMP1 protein.

Toxoplasma gondii (T. gondii) is widely spread around the world, which can cause serious harm to immunosuppressed patients. Currently, the commercial test kits are poor at assessing T. gondii infection and vaccine effectiveness, making an urgent need to exploit effective enzyme-linked immunosorbent assay with great performance to compensate for this deficiency. Here, the TgIMP1 recombinant protein was expressed in E. coli BL(21) cells. The TgIMP1 was purified with affinity chromatography and the reactivity was retained with anti-TgIMP1 antibodies. The TgIMP1 was then used to develop an indirect ELISA (IMP1-iELISA) and the reaction conditions of IMP1-iELISA were optimized. As a result, the cut-off value was determined to be 0.2833 by analyzing the OD450nm values of forty T. gondii-negative sera. The coefficient of variation of 6 T. gondii-positive sera within and between runs were both less than 10%. The IMP1-iELISA was non-cross-reactive with the sera of cytomegalovirus, herpes virus, rubella virus, Cryptosporidium spp., Theileria spp., Neospora spp. and Plasmodium spp.. Furthermore, the sensitivity and specificity of IMP1-iELISA were 98.9% and 96.7%, respectively, based on testing 150 serum samples. The results suggest that this IMP1-iELISA is specific, sensitive, repeatable and can be applied to the detection of T. gondii infections in the medical and health industries.

Standardization via Post Column Infusion-A Novel and Convenient Quantification Approach for LC-MS/MS.

Mass spectrometry (MS) is a widely used analytical technique including medical diagnostics, forensic toxicology, food and water analysis. The gold standard for quantifying compounds involves using stable isotope-labeled internal standards (SIL-IS). However, when these standards are not commercially available, are prohibitively expensive, or are extremely difficult to synthesize, alternative external quantification techniques are employed. We hereby present a novel, convenient and cheap quantification approach-quantification via post column infusion (PCI). As a proof of concept, we demonstrated PCI quantification for the immunosuppressant tacrolimus in whole blood using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The validation results met the criteria according to the guideline on bioanalytical method validation of the European Medicine Agency (EMA), achieving imprecisions and inaccuracies with coefficient of variation and relative bias below 15%. Anonymized and leftover whole blood samples from immunosuppressed patients receiving tacrolimus were used for method comparison (PCI quantification vs. conventional internal standard (IS) quantification). Both methods showed strong agreement with a Pearson correlation coefficient of r = 0.9532. This novel PCI quantification technique (using the target analyte itself) expands the quantification options available in MS, providing reliable results, particularly when internal standards are unavailable or unaffordable. With the current paper, we aim to demonstrate that our innovative PCI technique has great potential to overcome practical issues in quantification and to provide guidance on how to incorporate PCI in existing or new LC-MS methods. Moreover, this study demonstrated a more convenient method for correcting matrix effects in comparison to alternative PCI techniques.

Porokeratoses: an update on pathogenesis and treatment.

Porokeratoses (PK) are a group of uncommon dermatoses characterized by abnormal epidermal differentiation due to a disorder of the mevalonate metabolic pathway. Several clinical subtypes exist that can be associated with the same patient or affect different patients within a family and could, therefore, be different expressions of one disease. All PK subtypes share a common histopathologic finding, the cornoid lamella, a vertical stack of parakeratotic corneocytes embedded in an orthokeratotic horny layer. PK often affects immunosuppressed patients, in whom the course may parallel the level of immunosuppression. The pathogenesis of PK, which had long remained mysterious, has been recently unraveled after discovering pathogenic variants of genes involved in the mevalonate metabolic pathway. The disease is due to germline pathogenic variants of genes of this pathway but requires a second-hit event to manifest; therefore, PK is considered a dominantly inherited but recessively expressed condition. The prognosis of PK is usually favorable, even though the lesions progress to keratinocyte carcinomas in 7%-16% of patients. The treatment of PK was based on physical (ablative) procedures and various (topical or systemic) treatments, whose efficacy is nevertheless inconsistent and often temporary. The discovery of the metabolic pathway involved in the pathogenesis of PK paved the way for the elaboration of new topical treatments (combination of statins and cholesterol), which are more regularly efficacious compared with older treatments, even though the management of some patients with PK may still be challenging.

Convalescent Plasma for Immunocompromised Patients.

COVID-19 convalescent plasma (CCP) is an important therapeutic option for immunocompromised patients with COVID-19. Such patients are at increased risk for serious complications of infection and may also develop a unique syndrome of persistent infection. This article reviews the rationale for CCP utilization in immunocompromised patients and the evidence for its value in immunosuppressed patients with both acute and persistent COVID-19. Both historical precedence and understanding of the mechanisms of action of antibody treatment support this use, as do several lines of evidence derived from case series, comparative studies, randomized trials, and systematic reviews of the literature. A summary of recommendations from multiple practice guidelines is also provided.

Is a 3 mm Surgical Margin Safe for Basal Cell Carcinoma in the Head and Neck that is Less than 2 cm, Considering Different Risk Factors?

Background Basal cell carcinoma (BCC) is the most common type of nonmelanoma skin cancer. Typically, resection requires a safety margin of ≥4 mm. When removing tumor cells, achieving complete excision with minimal safety margins and reconstructing the defect to preserve the original appearance are important. In this study, we used a 3-mm resection margin to confirm recurrence and re-resection rates. Methods Electronic medical records and photographic data were obtained for patients with primary BCC lesions less than 2 cm in diameter who underwent wide excision with a 3-mm surgical margin from January 2015 to November 2021. We analyzed factors determining recurrence and re-resection rates, such as tumor size, location, age, sex, underlying diseases (including immunosuppression state), ethnicity, subtypes, tumor borders, etc. Results This study included 205 patients. The mean age and follow-up period were 73.0 ± 11.5 years and 10.2 ± 8.0 months, respectively. The recurrence and re-resection rates were 1.95% and 25.85%, respectively. A statistically significant correlation was found between recurrence rate and tumor border ( p = 0.013) and the re-resection rate was correlated statistically with location ( p = 0.022) and immunosuppressed patients ( p = 0.006). Conclusion We found that a 3-mm excision margin provided sufficient safety in small facial BCC, resulting in ease of surgery and better aesthetic outcomes. However, surgical margins must be determined case by case by integrating various patient factors. In particular, a surgical margin of ≥4 mm is required for BCC in high-risk areas, immunosuppressed patients, or poorly defined border.

Using virtual patient cohorts to uncover immune response differences in cancer and immunosuppressed COVID-19 patients.

The COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in millions of deaths globally. Adults with immunosuppression (e.g., solid organ transplant recipients) and those undergoing active cancer treatments experience worse infections and more severe COVID-19. It is difficult to conduct clinical studies in these populations, resulting in a restricted amount of data that can be used to relate mechanisms of immune dysfunction to COVID-19 outcomes in these vulnerable groups. To study immune dynamics after infection with SARS-CoV-2 and to investigate drivers of COVID-19 severity in individuals with cancer and immunosuppression, we adapted our mathematical model of the immune response during COVID-19 and generated virtual patient cohorts of cancer and immunosuppressed patients. The cohorts of plausible patients recapitulated available longitudinal clinical data collected from patients in Montréal, Canada area hospitals. Our model predicted that both cancer and immunosuppressed virtual patients with severe COVID-19 had decreased CD8+ T cells, elevated interleukin-6 concentrations, and delayed type I interferon peaks compared to those with mild COVID-19 outcomes. Additionally, our results suggest that cancer patients experience higher viral loads (however, with no direct relation with severity), likely because of decreased initial neutrophil counts (i.e., neutropenia), a frequent toxic side effect of anti-cancer therapy. Furthermore, severe cancer and immunosuppressed virtual patients suffered a high degree of tissue damage associated with elevated neutrophils. Lastly, parameter values associated with monocyte recruitment by infected cells were found to be elevated in severe cancer and immunosuppressed patients with respect to the COVID-19 reference group. Together, our study highlights that dysfunction in type I interferon and CD8+ T cells are key drivers of immune dysregulation in COVID-19, particularly in cancer patients and immunosuppressed individuals.

Oral mucosa problems in palliative care

Oral health problems appear in up to 80 % of palliative care patients. Almost all of these patients suffer from a dry mouth which is often the result of medication side effects. Even though a dry mouth is not a disease by itself, it enhances the risk of developing other more serious oral lesions and diseases. Stomatitis, an inflammatory response to radio- or oncological treatment induced lesions, is very painful and may interfere severely with the ingestion of food and fluids. Finally, oral fungal infections are very common in immunosuppressed patients. Each of these entities comes with specific symptoms and signs which may impair food and fluid intake but also have consequences on the quality of life in these patients. Hence, a systematic and standardized evaluation is essential and can be accomplished with little effort by all health care professionals.

High Rates of Seroprotection to Hepatitis B After a Hepatitis B Challenge Dose in Previously Vaccinated Patients with Inflammatory Bowel Disease on Immunosuppressive Therapy.

Healthy populations have high rates of sustained vaccine-induced seroprotection to hepatitis B virus, but previous studies in immunosuppressed patients with inflammatory bowel disease (IBD) have shown suboptimal seroprotection rates. A challenge dose of hepatitis B vaccine (HepB) is recommended in previously vaccinated individuals who are seronegative to elicit an anamnestic response and determine if they are seroprotected. The aim of our study was to determine sustained seroprotection rates to hepatitis B vaccine (HepB) in patients with IBD. This was a single-center prospective study of patients with IBD previously vaccinated with a three dose HepB series. Patients had a hepatitis B surface antibody (anti-HBs) drawn; if it was below 10 mIU/mL, they received a challenge dose of the HepB vaccine to assess for anamnestic response and sustained seroprotection. The primary outcome was to determine the rate of sustained seroprotection (anti-HBs ≥ 10). A total of 168 patients met inclusion criteria, mean age 35.7years ± 13.6 standard deviation (SD). Initially 120 (71.4%) had anti-HBs ≥ 10 mIU/mL, with median anti-HBs of 37 mIU/mL (interquartile range 0-234); 48 (28.6%) needed a challenge dose, of which 34 responded with anti-HBs ≥ 10 mIU/mL. In total, 154 (91.7%) demonstrated sustained seroprotection to HepB. Those not seroprotected were more likely to have been vaccinated on immunosuppressive therapy or after their diagnosis of IBD. Most vaccinated patients with IBD maintain sustained seroprotection to HepB despite prolonged exposure to immunosuppression. This contradicts prior studies and shows that immunosuppression does not lead to loss of seroprotection.

Associated Toxicity in Immunosuppressed Patients with Enfortumab Vedotin - An Essential Differential Diagnosis - Case Report

Enfortumab vedotin is an Antibody-Drug Conjugate (ADC) used to treat urothelial cancer. It has recently been associated with reports of Stevens Johnson syndrome/Toxic Epidermal Necrolysis (TEN). I report the clinical case of a 74-year-old man who developed an extensive skin lesion, clinically mimicking TEN. Considering differential diagnoses is essential as it can have implications for the prognosis and treatment of the disease. Further investigation is needed to ascertain real cases of toxic epidermal necrolysis versus opportunistic infections and/or other toxicities due to chemotherapy.

Babesiosis in the immunocompromised population: Results from a multicentric cohort study conducted in Italy

Human babesiosis is an emerging zoonotic disease; diffused especially in some regions of the United States, it has been less frequently observed in other continents, including Europe. Serological surveys suggest that babesiosis could be more frequent than expected in European countries, representing an emerging health-issue and a possible harm, especially in immunocompromised populations. Only one case of human babesiosis has been reported in Italy and data about the diffusion of the pathogen in this country are scant. We conducted a multicentric serological survey in 5 centers of North-Eastern Italy, aimed to detect the seroprevalence of Babesia spp. antibodies in 3 groups of immunocompromised patients: people living with HIV (PLHIV), rheumatologic patients undergoing immunosuppressive therapies and patients undergoing renal transplant. Among the 433 enrolled patients, 3 (0.7%) tested positive for Babesia spp. serology. All positive patients belonged to the PLHIV group, with a seroprevalence of 1.7% (3/180) in this population; the three serologically positive patients were all asymptomatic. They were all enrolled in the provinces of Bolzano and Trento, where seroprevalences of 3.1% and 3.6% were recorded, respectively. Our results suggest that further research is needed on this field, awareness should be raised toward the human disease in Europe, especially in immunocompromised patients, and this emerging health issue should be analyzed in a One-Health perspective to be fully understood.

Possible alteration in serum ferritin level in malaria infected HIV seropositive individuals in Nauth, Nnewi, Nigeria

The role of Ferritin in monitoring disease progression in immune compromised HIV individuals with an underlying active infection like malaria is a subject of growing research. Ferritin being an acute phase protein, plays important role in assessing the range of damage due to inflammation in immunosuppressed patients leaving in highly endemic malaria regions. The levels of serum ferritin in malaria infected HIV positive individuals in Nnamdi Azikiwe University teaching hospital (NAUTH), Nnewi, Anambra State, Nigeria, was assessed. Questionnaire was used to obtain the demographic details of the participants, and to rule out other inflammatory infections. 88 participants of the age group 18 - 65 years, comprising 24 with HIV infection, 22 with HIV and Malaria co-infection, 22 with Malaria infection, and a control group of 22 individuals with neither HIV nor malaria infection were randomly recruited. Ferritin level was determined using enzyme linked immunosorbent assay technique and a cross sectional prospective study design was used. A significantly high mean serum ferritin level was observed in HIV infected individuals with and/ or without malaria co-infection than in malaria positive and control group (p<0.05 respectively). Serum ferritin level was significantly higher in female participants than in male counterparts (p < 0.05). Serum ferritin level was significantly higher in individuals with CD4 count >500 than in CD4 count ≤ 500 (p < 0.05). Blood pressure was significantly higher in HIV infected and malaria positive individuals when compared with controls. The increased serum ferritin level and higher blood pressure in HIV infected participants suggests active inflammatory process, reduced immunity and hypertension which may have worsened by malaria co-infection. This may subsequently lead to vascular and endothelia damage causing disease severity.

Common Practice Patterns in the Diagnosis and Management of Acute Retinal Necrosis: A Survey Study of Uveitis Specialists

ABSTRACT Purpose Due to lack of large randomized clinical trials to determine best practices in treating acute retinal necrosis (ARN), there is not a clear consensus amongst ophthalmologists on how to best manage this potentially blinding condition. The aim of this study is to survey common practice patterns and analyze the factors that affect ophthalmologists’ management of ARN. Methods An anonymous survey was distributed to uveitis and retina specialists who are members of the American Uveitis Society (AUS) via email to query practice patterns regarding ARN. The survey included 22 questions with an additional 10 questions based on response. Survey question topics included demographic information, diagnostic testing, antiviral therapy, corticosteroids, and surgical procedures. Results 67 surveys were included for analysis. Most respondents (87%) always or frequently obtain intraocular aqueous fluid for diagnostic PCR testing. The majority of respondents would administer intravitreal antiviral injections to a unilateral immunocompetent ARN patient (67%), but would be even more likely to do so for a bilateral immunosuppressed ARN patient (87%). Respondents tend to treat ARN with systemic rather than local corticosteroids, with the majority (63%) of respondents initiating corticosteroid treatment 48 hours after treatment. Most respondents (79%) never perform a vitrectomy to manage ARN unless the patient has a retinal detachment or tear. The majority (63%) rarely or never perform prophylactic laser barricade, but may consider laser treatment if there is extensive retinal involvement. Conclusion Current practice patterns for diagnosis and management of ARN among AUS members generally align with the suggested practices outlined by the American Academy of Ophthalmology.

Clinical and virological features of SARS-CoV-2 Omicron variant-infected immunocompromised patients receiving immunosuppressive medications

BackgroundThe prognosis of immunocompromised individuals with COVID-19 remains a significant concern. Information regarding the clinical and virological characteristics of immunocompromised patients infected with SARS-CoV-2 during the Omicron variant period is limited.MethodsMedical records of patients admitted to our hospital with COVID-19 during the Omicron (BA.1–5) epidemic were retrospectively reviewed. Clinical, virological (nasopharyngeal swabs and blood), and serological data were compared between immunocompromised patients receiving immunosuppressive medications (calcineurin inhibitors, mycophenolate mofetil, or steroids) and control patients not receiving immunosuppressive medications.ResultsTwenty-eight immunocompromised patients (25 transplant recipients) and 26 control patients were included. Fourteen of the immunocompromised patients (50%) received monoclonal antibodies. The immunocompromised group included 15 mild/moderate (53.6%), 10 severe (35.7%), and three critical (10.7%) disease severities. The mortality rate due to COVID-19 during hospitalization was 3.6% (1/28) in the immunocompromised group, with no difference between the two groups. Three cases of re-exacerbation after discharge occurred in the immunocompromised group and none in the control group. Linear regression based on nasopharyngeal real-time-PCR cycle threshold (Ct) values according to the time since symptom onset showed markedly slower viral clearance in the immunocompromised group than in the control group (Pslope = 0.078). In the immunocompromised group, patients who received monoclonal antibodies showed faster viral clearance than those who did not receive monoclonal antibodies. The convalescent anti-spike IgG titers were comparable to those in the control group in patients who received monoclonal antibodies and significantly lower than those in the control patients in patients who did not receive monoclonal antibodies (P < 0.001). The prevalence of viremia at onset was significantly higher in the immunocompromised group than in the control group (35.7%, [10/28] vs. 11.5%, [3/26]; P = 0.003). All three patients with critical disease severity in the immunocompromised group exhibited viremia, one of whom died. All three patients with viremia in the control group were critical, of whom two died.ConclusionsImmunocompromised individuals receiving immunosuppressive medications are more likely to show delayed post-infection SARS-CoV-2 viral clearance and the development of viremia, potentially resulting in worsening severity and outcomes, especially in viremic patients, even during the Omicron epidemic.

Toxoplasma gondii in Wild Boars (Sus scrofa) in Germany: Serological Screening from Thuringia.

Game meat is an important source of meat borne parasitic infections. Due to its omnivorous diet, the wild boar is an important host of zoonotic parasites such as Toxoplasma gondii. T. gondii can cause severe to fatal disease in immunosuppressed patients, as well as congenital disorders in foetus and neonates. Consumption of undercooked infected meat is a main source of T. gondii infection. Information about the risk of toxoplasmosis through game meat is scarce. We collected serum samples from 42 wild boars from the federal state of Thuringia (Germany) between December 2017 and February 2018. Identification of anti-T. gondii IgG antibodies was conducted using a commercial indirect ELISA kit. Seropositivity was confirmed in 18 of the 42 samples (37.50%). From these, the highest seroprevalence was found in adult animals. This study joins another single database from wild boars in Brandenburg. The necessity of a country-wide database regarding T. gondii prevalence in wild boar and other game meat is pivotal for a profound risk analysis with its consequential impact in future mean hygiene policies.

Highly restrictive and directional penetration of the blood cerebral spinal fluid barrier by JCPyV.

The human polyomavirus JCPyV is an opportunistic pathogen that infects greater than 60% of the world's population. The virus establishes a persistent and asymptomatic infection in the urogenital system but can cause a fatal demyelinating disease in immunosuppressed or immunomodulated patients following invasion of the CNS. The mechanisms responsible for JCPyV invasion into CNS tissues are not known but direct invasion from the blood to the cerebral spinal fluid via the choroid plexus has been hypothesized. To study the potential of the choroid plexus as a site of neuroinvasion, we used an adult human choroid plexus epithelial cell line to model the blood-cerebrospinal fluid (B-CSF) barrier in a transwell system. We found that these cells formed a highly restrictive barrier to virus penetration either as free virus or as virus associated with extracellular vesicles (EVJC+). The restriction was not absolute and small amounts of virus or EVJC+ penetrated and were able to establish foci of infection in primary astrocytes. Disruption of the barrier with capsaicin did not increase virus or EVJC+ penetration leading us to hypothesize that virus and EVJC+ were highly cell-associated and crossed the barrier by an active process. An inhibitor of macropinocytosis increased virus penetration from the basolateral (blood side) to the apical side (CSF side). In contrast, inhibitors of clathrin and raft dependent transcytosis reduced virus transport from the basolateral to the apical side of the barrier. None of the drugs inhibited apical to basolateral transport suggesting directionality. Pretreatment with cyclosporin A, an inhibitor of P-gp, MRP2 and BCRP multidrug resistance transporters, restored viral penetration in cells treated with raft and clathrin dependent transcytosis inhibitors. Because choroid plexus epithelial cells are known to be susceptible to JCPyV infection both in vitro and in vivo we also examined the release of infectious virus from the barrier. We found that virus was preferentially released from the cells into the apical (CSF) chamber. These data show clearly that there are two mechanisms of penetration, direct transcytosis which is capable of seeding the CSF with small amounts of virus, and infection followed by directional release of infectious virions into the CSF compartment.

Intestinal parasitic infections in patients with aids in northeast Brazil: an historical series from 2017 to 2022

Opportunistic infections are a major cause of death in patients with acquired immunodeficiency syndrome (AIDS). Intestinal parasitic infections (IPIs) may aggravate the clinical condition of immunosuppressed patients and they may increase the risk of death. The goal of the present study was to determine the epidemiological profile of patients with AIDS and IPIs who visited a reference hospital for contagious diseases in Northeast Brazil from 2017 through 2022. It was an observational, transverse, descriptive, and analytical study. Medical records were assessed, epidemiological questionnaires were administered to identify risk factors for IPI, and coproparasitological examinations were performed to detect IPI. Of the 248 patients included in this study, 30.6% (76/ 248) tested positive for IPI. Entamoeba histolytica/ dispar (16.5%) and Strongyloides stercoralis (14.4%) were the most prevalent protozoa and helminths identified. Diarrheic consistency was observed in 25.8% of the feces samples, and mucus or blood were present in 19.4%. Analysis of the sociodemographic profiles of patients with IPIs showed that most were female, lived in small cities, earned up to two minimum wages, had an incomplete primary education, and were single. We conclude that to control parasite transmission in patients with HIV/AIDS, public policies related to human and environmental health, routine coproparasitological exams, and acceptance of antiretroviral therapy are necessary. KEY WORDS: Acquired immunodeficiency syndrome; opportunistic infections; intestinal parasite infections; public health.

Invasive pulmonary aspergillosis evaluation in hematology patients: Three years results of tertiary hospital.

Invasive pulmonary aspergillosis (IPA) is the most frequent invasive fungal disease occurring in patients with hematological malignancies. Serum galactomannan (GM) antigen monitoring is thought to be helpful in the diagnosis of IPA. The aim of this study was to determine the role of a GM assay in serum samples for the diagnosis of IPA in patients with hematological disease. The data of 366 immunosuppressed patients that were hospitalized and followed up in the hematology clinic from January 2017 to December 2019 were retrospectively analyzed. The clinical and radiological findings of the patients and the GM results, requested twice a week, were evaluated. In this study, the incidence of probable and possible IPA was determined to be 15.3% (56/366). Of the cases detected, 28 (50.0%) were patients diagnosed with acute myeloid leukemia (AML), and 34 (60.7%) patients who had compatible clinical and examination findings were started on antifungal treatment. Additionally, area under the curve (AUC) values were calculated by receiver operating characteristic (ROC) analysis, and it was determined that the diagnostic efficiency was more predictive when the cut-off was 0.5 in the GM test for IPA disease. The detection of GM antigen in serum is a very useful and rapid method for diagnosing IPA disease in immunosuppressed hematology patients. However, GM results should be evaluated together with clinical and radiological findings for early diagnosis, and the treatment approach should be determined accordingly.

Molecular Identification of Encephalitazoon intestinalis and the Prevalence of Renal Microsporidiosis in Renal Transplant Recipients in Türkiye.

In patients with end-stage kidney disease, kidney transplantation is the kidney replacement therapy option that provides the most successful survival. However, immunosuppression agents administered after kidney transplantation can increase the risk of opportunistic infections. Microsporidia are obligate intracellular pathogens that can be fatal in immunosuppressed patients. The present study aimed to determine the prevalence of microsporidia in kidney transplantation recipients and the molecular characterization of the detected species. To evaluate the prevalence of renal microsporidiosis in kidney transplant recipients, the urine samples from a total of 325 patients were analyzed by real-time and nested polymerase chain reaction for Encephalitozoon spp. and Enterocytozoon bieneusi. Only one (0.4%) sample from the adult patient was positive for the Encephalitozoon species, while no positivity was found in pediatric patients. It was determined as Encephalitozoon intestinalis by ITS rRNA gene region sequence analysis. A microsporidia species obtained from humans in Türkiye has been characterized for the first time and registered in GenBank. Our epidemiological results show that the prevalence of renal microsporidiosis in kidney transplant recipients is very low. In addition, as a result of the phylogenetic analysis of the detected isolate, it was observed that it was 100% identical to the isolates reported from dogs in Kayseri, Türkiye. This situation provided essential data regarding the zoonotic transmission dynamics of microsporidia.

Hepatitis E virus infection in immunosuppressed patients and its clinical manifestations

Background & AimsHepatitis E virus (HEV) is a main cause of acute hepatitis globally. However, immunosuppressed patients regularly develop chronic courses. The aim of this study was to analyse the current status of HEV diagnostics, characterize clinical manifestations and identify risk factors for complicated HEV infections. MethodsIn this retrospective study at two large hospitals, 512 patients with borderline and positive anti-HEV-IgM and 94 patients with positive HEV-PCR between January 1999 and May 2023 were included. ResultsDetection by anti-HEV-IgM-ELISA led to a positive HEV-PCR in only 17.9 %. Amongst patients with positive HEV-PCR, 61 had underlying immunosuppression and 23 were patients after solid organ transplantation (SOT). All 13 patients with chronic HEV infections were immunosuppressed. Generally, immunosuppression led to higher HEV-RNA concentrations and a higher probability of receiving immediate treatment. However, all fulminant courses with liver failure happened in patients without immunosuppression. Immunocompetent patients showed symptoms more frequently and primarily had higher bilirubin levels indicating more severe liver damage. A risk factor for delayed or failed viral clearance after SOT was the administration of mTOR inhibitors. ConclusionsFulminant HEV infections happen primarily in immunocompetent patients. Nevertheless, immunosuppressed patients bear the risk of undetected, prolonged HEV infections, reflected by the rare occurrence of symptoms.

Peptide derived from plant defensins: A promising 68Ga radiolabelled agent for diagnostic of infection foci in PET.

The development of new radiopharmaceuticals for the detection of hidden infection foci has great relevance for early detection and the selection of the correct treatment, particularly in immunosuppressed patients. In that sense, the labelling of antimicrobial peptides (AMPs) that are capable of binding specifically to the pathogenic microorganism which causes the infection, should provide a sufficiently specific agent, able to distinguish an infection from a sterile inflammation. Defensins are particularly interesting molecules with antimicrobial activity, the EcgDf1 defensin was identified from the genome of a Uruguayan native plant, Erythrina crista-galli, the 'Ceibo' tree. Our group has previously reported a synthetic biologically active short analogue EcgDf21 (ERFTGGHCRGFRRRCFCTKHC) successfully labelled with 99mTc. Herein we present a shorter analogue which also preserves the γ-core domain, as a pharmacophore for a potential infection detection agent. This peptide was derivatized with the bifunctional chelating agent 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) through a lysine linker in the amino-terminal group (NOTA-KGHCRGFRRRC) and radiolabelled with 68Ga ([68Ga]Ga-NOTA-K-EcgDf1(10)). The [68Ga]Ga-NOTA-K-EcgDf1(10) labelling procedure rendered a product with high radiochemical purity and stability in the labelling milieu. The Log P value indicated that the complex has a hydrophilic behaviour, confirmed by the biodistribution profile. The [68Ga]Ga-NOTA-K-EcgDf1(10) complex demonstrated specific binding to cultures of Candida albicans and Aspergillus niger. Its biodistribution showed renal elimination and low accumulation in the rest of the body. It was possible to successfully differentiate sterile inflammation from infection by PET images in nude mice with a target/non-target ratio of 3.3 for C. albicans and 3.7 for A. niger, respectively.