Immunosuppressed Individuals Research Articles

Pathogenesis and clinical features of severe hepatitis E virus infection

The hepatitis E virus (HEV), a member of the Hepeviridae family, is a small, non-enveloped icosahedral virus divided into eight distinct genotypes (HEV-1 to HEV-8). Only genotypes 1 to 4 are known to cause diseases in humans. Genotypes 1 and 2 commonly spread via fecal-oral transmission, often through the consumption of contaminated water. Genotypes 3 and 4 are known to infect pigs, deer, and wild boars, often transferring to humans through inadequately cooked meat. Acute hepatitis caused by HEV in healthy individuals is mostly asymptomatic or associated with minor symptoms, such as jaundice. However, in immunosuppressed individuals, the disease can progress to chronic hepatitis and even escalate to cirrhosis. For pregnant women, an HEV infection can cause fulminant liver failure, with a potential mortality rate of 25%. Mortality rates also rise amongst cirrhotic patients when they contract an acute HEV infection, which can even trigger acute-on-chronic liver failure if layered onto pre-existing chronic liver disease. As the prevalence of HEV infection continues to rise worldwide, highlighting the particular risks associated with severe HEV infection is of major medical interest. This text offers a brief summary of the characteristics of hepatitis developed by patient groups at an elevated risk of severe HEV infection.

SARS-CoV-2 Humoral and Cellular Immune Responses in People Living with HIV.

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies, and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. Overall, 29.8% of PLWH had no SARS-CoV-2 serologic markers; they displayed significantly lower CD4 counts and higher HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (p = 0.0003), anti-S IgA (p < 0.0001) and lack of neutralizing activity against the Omicron variant (p < 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immune responses but retained specific cellular immunity.

Gene expression landscape of cutaneous squamous cell carcinoma progression.

Cutaneous squamous cell carcinomas (cSCCs) are the second most common human cancer and have been characterized by RNA sequencing (RNA-Seq); however, the transferability of findings from individual studies may be limited by small sample sizes and diverse analysis protocols. To define the transcriptome landscape at different stages in the progression of normal skin to cSCC via a meta-analysis of publicly available RNA-Seq samples. Whole-transcriptome data from 73 clinically normal skin samples, 46 actinic keratoses (AK) samples, 16 in situ SCC samples, 13 keratoacanthoma (KA) samples and 147 cSCC samples [including 30 samples from immunocompromised patients and 8 from individuals with recessive dystrophic epidermolysis bullosa (RDEB)] were uniformly processed to harmonize gene expression. Differential expression, fusion detection and cell-type deconvolution analyses were performed. Individual RNA-Seq studies of cSCC demonstrated study-specific clustering and varied widely in their differential gene expression detection. Following batch correction, we defined a consensus set of differentially expressed genes (DEGs), including those altered in the preinvasive stages of cSCC development, and used single-cell RNA-Seq data to demonstrate that DEGs are often - but not always - expressed by tumour-specific keratinocytes (TSKs). Analysis of the cellular composition of cSCC, KA and RDEB-cSCC identified an increase in differentiated keratinocytes in KA, while RDEB-cSCC contained the most TSKs. Compared with cSCC arising in immunocompetent individuals, cSCC samples from immunosuppressed patients demonstrated fewer memory B cells and CD8+ T cells. A comprehensive and unbiased search for fusion transcripts in cSCC and intermediate disease stages identified few candidates that recurred in >1% of all specimens, suggesting that most cSCC are not driven by oncogenic gene fusions. Finally, using Genotype-Tissue Expression (GTEx) data, we distilled a novel 300-gene signature of chronic sun exposure that affirms greater cumulative ultraviolet (UV) exposure in later stages of cSCC development. Our results define the gene expression landscape of cSCC progression, characterize cell subpopulation heterogeneity in cSCC subtypes that contribute to their distinct clinical phenotypes, demonstrate that gene fusions are not a common cause of cSCC and identify UV-responsive genes associated with cSCC development.

Insights into the genetic characteristics, clustering patterns, and phylogeographic dynamics of the JC polyomavirus, 1993 to 2023

The human JC polyomavirus (JCV) is a widespread, neurotropic, opportunistic pathogen responsible for progressive multifocal leukoencephalopathy (PML) as well as other diseases in immunosuppressed individuals, including granule cell neuronopathy, JCV-associated nephropathy, encephalitis, and meningitis in rare cases. JCV classification is still unclear, where the ICTV (International Committee on Taxonomy of Viruses) has grouped all the strains into human polyomavirus 2, with no classification on clade and subclade levels. Therefore, JCV strains were previously classified using different genomic regions, e.g., full-length, VP1, and the V-T intergenic region etc., and the strains were grouped into several types related to various geographic locations and human ethnicities. However, neither of these classifications and nomenclature contemplates all the groups described so far. Herein, we evaluated all the available full-length coding genomes, VP1, and large T antigen nucleotide sequences of JCV reported during 1993–2023 and classified them into four major phylogenetic clades, i.e., GI-GIV, where GI is further grouped into two types GI.1 and GI.2 with five sub-clades each (GI.1/GI.2 a-e), GII into three (GII a-c), GIII as a separate clade, and GIV into seven sub-clades (GIV a-g). Similarly, the phylogeographic network analysis indicated four major clusters corresponding to GI-GIV clades, each with multiple subclusters and mutational sub-branches corresponding to the subclades. GI and GIV clusters are connected via GI.1-e reported from Europe and America, GII, GIII and GIV clusters are connected by GII-b and GII-c strains reported from Africa, while GIV cluster strains are connected to the Russia-Italy JCV haplotype. Furthermore, we identified JCV-variant-GS/B-Germany-1997 (GenBank ID: AF004350.1) as an inter-genotype recombinant having major and minor parents in the GI.1-e and GII-a clades, respectively. Additionally, the amino acid variability analysis revealed high entropy across all proteins. The large T antigen exhibited the highest variability, while the small t antigen showed the lowest variability. Our phylogenetic and phylogeographic analyses provide a new approach to genotyping and sub-genotyping and present a comprehensive classification system of JCV strains based on their genetic characteristics and geographic distribution, while the genetic recombination and amino acid variability can help identify pathogenicity and develop effective preventive and control measures against JCV infections.

Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India.

Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at the National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM), and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n=8) and A. levis (n=1), from brain abscess (n=4), respiratory tract (n=3), and corneal scraping (n=2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the internal transcribed spacer ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed the lowest minimum inhibitory concentrations (MICs) for triazoles and the highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin, and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.

Incidence and potential risk factors of human cytomegalovirus infection in patients with severe and critical coronavirus disease 2019

BackgroundHuman cytomegalovirus (HCMV) infection occurs in immunosuppressed individuals and is known to increase mortality. Patients with coronavirus disease 2019 (COVID-19) are often treated with steroids, require intensive care unit (ICU) treatment, and may therefore be at risk for HCMV infection. However, which factors predispose severely ill patients with COVID-19 to HCMV infection and the prognostic value of such infections remain largely unexplored. This study aimed to examine the incidence and potential risk factors of HCMV infection in patients with severe or critical COVID-19 and evaluate the relationship between HCMV infection and mortality. Methods and findingsWe used administrative claims data from advanced treatment hospitals in Japan to identify and analyze patients with severe or critical COVID-19. We explored potential risk factors for HCMV infection using multivariable regression models and its contribution to mortality in patients with COVID-19. Overall, 33,151 patients who progressed to severe or critical COVID-19 illness were identified. The incidence of HCMV infection was 0.3–1.7 % depending on the definition of HCMV infection. Steroids, immunosuppressants, ICU admission, and blood transfusion were strongly associated with HCMV infection. Furthermore, HCMV infection was associated with patient mortality independent of the observed risk factors for death. ConclusionsHCMV infection is a notable complication in patients with severe or critical COVID-19 who are admitted to the ICU or receive steroids, immunosuppressants, and blood transfusion and can significantly increase mortality risk.

Mercury and Selenium Accumulation in the Tissues of Stranded Bottlenose Dolphins (Tursiops truncatus) in Northeast Florida, 2013-2021.

Bottlenose dolphins (Tursiops truncatus) are long-lived marine mammals, upper-level predators, and they inhabit near-shore environments, which increases their exposure to pollution. Mercury is a ubiquitous and persistent metal pollutant that can bioaccumulate and biomagnify up the food chain. Dolphins are known to accumulate mercury, and limited research has shown that mercury exposure can weaken the immune system of dolphins. The objectives of this study were to assess the mercury concentrations in the tissues (muscle, small intestine, liver) of stranded bottlenose dolphins and to compare the tissue mercury levels in dolphins that were stranded during the 2013-2015 morbillivirus Unusual Mortality Event (UME; immunosuppressed individuals) with the levels of those that were stranded at a normal rate (2016-2021). Selenium has been shown to reduce mercury toxicity in many animals; therefore, tissue selenium concentration and the molar ratio of selenium to mercury were also assessed. The tissue mercury (muscle, liver) and selenium (liver) concentrations increased with the age of the dolphins, with the liver accumulating the highest concentrations. No sex differences were observed in the mercury and selenium concentrations. While differences in tissue mercury concentrations were not observed due to the UME, the selenium accumulation profiles were significantly different between the two time periods. These results suggest that selenium may not have been as protective against mercury toxicity in the bottlenose dolphins that were stranded during the UME, possibly due to infection with morbillivirus.

P04 How fibroblasts and azathioprine prepare the soil for cutaneous squamous cell carcinoma

Abstract Introduction and aims DNA damage-inducing immunosuppressive drugs such as azathioprine (AZA) act synergistically with ultraviolet (UV)A radiation and photosensitize the skin of immunosuppressed individuals, such as organ transplant recipients. These individuals have an increased risk of developing cutaneous squamous cell carcinoma (cSCC). The specific combination of AZA and UVA causes oxidative DNA damage that leaves behind a characteristic mutational signature in tumour keratinocytes of patients treated with AZA. However, as UVA radiation can penetrate the dermis, the impact of AZA/UVA on cells of the tumour microenvironment, such as fibroblasts, also need to be addressed. Fibroblasts are crucial for cSCC development and progression as they can switch to a protumourigenic phenotype. Methods Cell viability and senescence assays were performed to investigate the impact of AZA in combination with or without UVA on neonatal (nonsun-exposed) and adult (sun-exposed) human dermal fibroblasts. In addition, the impact of AZA/UVA-treated fibroblasts on the clonal growth properties of different cSCC cell models was investigated using three-dimensional (co)culture models. Results We found that AZA and UVA synergistically reduce the viability of both UV-naïve neonatal and sun-exposed adult dermal fibroblasts. In addition, combined AZA and UVA treatments lead to an increased percentage of senescent fibroblasts. We hypothesize that the aberrant secretome of these senescent fibroblasts can impact the growth behaviour of tumour cells. In a soft agar assay, the more malignant cSCC cells (MET-1) formed more and larger clonal spheroids and were less dependent on growth factors compared with spheroids formed by premalignant (PM-1) keratinocytes. Conclusions AZA and UVA act synergistically and potentiate a UVA-induced senescent fibroblast phenotype. The changed characteristics of these fibroblasts can impact the stem cell-like properties from premalignant and malignant keratinocytes. Combining keratinocyte and fibroblast culture models enables us to study how AZA/UVA promote the initiation and progression of cSCC.

Global Burden and Evolving Understanding of Hepatitis E Virus

Hepatitis E virus (HEV) is the leading cause of acute viral hepatitis worldwide, recognized as a significant global public health concern. Recent advancements in understanding the natural history of HEV infection have shed light on its epidemiology and clinical implications. The primary mode of HEV transmission is fecal-oral, occurring through contaminated water or food. Parenteral transmission, particularly through blood transfusions, was initially overlooked but has been increasingly recognized in both developing and industrialized countries. Acute HEV infection typically manifests as self-limiting jaundice, particularly in immunocompetent individuals. However, recent data suggest that acute infection can progress to a chronic form in various immunosuppressive conditions, including solid organ transplantation, hematological malignancies, and human immunodeficiency virus (HIV) infection. Chronic HEV can lead to cirrhosis, which may progress rapidly in some cases. Extrahepatic manifestations, particularly neurological complications, have also been reported. HEV remains underdiagnosed globally due to a lack of awareness among healthcare providers in many regions. Advances in serological and molecular assays have facilitated reliable diagnosis, both in immunocompetent and immunocompromised patients. Ribavirin monotherapy has proven effective in treating chronic HEV infection in immunosuppressed individuals and is currently widely recommended. However, its efficacy in acute HEV remains inconclusive. In 2011, an effective and well-tolerated HEV vaccine was developed and approved in China. This vaccine holds promise for high-risk populations, particularly individuals with cirrhosis and travelers to endemic regions.

Evaluation of Toll-Like Receptor Gene Expressions in Encephalitozoon intestinalis Infection

Microsporidia are obligate intracellular pathogens that can infect many vertebrate and invertebrate hosts. While the Microsporidia phylum was defined as protozoa until the 1990s, it has been associated with fungi in line with the data obtained as a result of phylogenetic and molecular analyzes in recent years. Although approximately 200 genera and 1400 Microsporidia species related to these genera have been reported to date, only 14 species are known to cause infection in humans. Encephalitozoon intestinalis is one of the most frequently detected species in humans and causes serious clinical conditions in immunosuppressed individuals. Little information is available about the immunology of this infection. This study was aimed to investigate the changes in Toll-Like receptor (TLR) gene expressions in Madin-Darby canine kidney (MDCK) cells treated with E.intestinalis spores. Three groups were formed in the study. In the first group, only the medium prepared for E.intestinalis was added to the MDCK cells. In the second group, 108 live spores waiting at +4 °C were added. In the third group, 108 heat-inactivated spores were added. All three groups were incubated at 37ºC with 5% CO2 . RNA isolation and cDNA synthesis were performed from samples taken from these groups at the 1st, 3rd, 6th, 12th and 24th hours. Expression of TLR1-10 genes from the obtained cDNAs was evaluated by real-time polymerase chain reaction (Rt-PCR). GAPDH and ACTB genes were used as housekeeping genes in the study. Target genes were normalized by taking the average of these two genes and statistical analysis was performed by applying the 2-ΔΔCt formula. Genes detected above the threshold value (threshold 1) were considered to have increased expression. Genes detected below the threshold value were considered to have decreased expression. The growth of the live and inactive spores were followed simultaneously with the experimental groups. Approximately two weeks after the start of the culture, it was observed that E.intestinalis grew in the culture with live spore, but did not grow in the culture with inactivated spores. No statistically significant change was observed in gene expressions in the inactivated spore group. In the live spore group, a significant increase was seen in the expression of only two genes. These genes were TLR3 and TLR4. It was observed that there was a significant increase in TLR3 gene expression at the first hour (1.6-fold of control group) but the expression level started to decrease at the third hour (1.4-fold of control group) and returned to the control level at the sixth hour. It was observed that TLR4 gene expression continued parallel to the control until the 24th hour and increased significantly (2.1-fold of control group) at the 24th hour. In conclusion, this study is the f irst report in which the changes in ten different TLR gene expressions were evaluated at different times in MDCK cells stimulated with E.intestinalis and the change in TLR3 gene expression.

Innovative therapies for treatment of invasive fungal diseases

Invasive fungal diseases (IFD) are difficult to treat and pose a significant threat to immunocompromised individuals. Current antifungal agents face limitations, including antifungal resistance and adverse effects. This review aims to give a comprehensive overview of emerging treatment strategies.Novel drugs in development are Ibrexafungerp, an orally available triterpenoid inhibiting glucan synthesis, and Rezafungin representing the echinocandins with extended half-life and improved tissue penetration, both recently licensed for certain indications. Fosmanogepix targets glycosylphosphatidylinositol biosynthesis, while Olorofim, an orotomide, inhibits fungal nucleic acid synthesis, both currently assessed in advanced clinical trials.Immunotherapeutic approaches include immune checkpoint inhibitors to enhance immune response in immunosuppressed individuals and fungal-specific allogeneic CAR-T cell therapy. For prophylactic purpose in high-risk populations to develop IFD, monoclonal antibodies against different virulence factors of Candida spp. have been discovered but are not yet seen in clinical trials. Vaccines against distinct fungal antigens as well as pan fungal vaccines to prevent IFD are under development in preclinical stages, notably for Candida spp., Cryptococcus spp., and Aspergillus spp., however, their clinical value is still discussed.In summary, major advances to treat IFD have been observed, but challenges for their establishment in the clinical routine persist.

Epidemiological and Clinical Aspects of Cutaneous and Mucosal Leishmaniases in Portugal: Retrospective Analysis of Cases Diagnosed in Public Hospitals and Reported in the Literature between 2010 and 2020.

Leishmania infantum, a zoonotic vector-born parasite, is endemic in the Mediterranean region, presenting mostly as visceral (VL), but also as cutaneous (CL) and mucosal leishmaniasis (ML). This study aimed to describe the epidemiological and clinical aspects of the CL and ML cases diagnosed in mainland Portugal between 2010 and 2020. Collaboration was requested from every hospital of the Portuguese National Health System. Cases were screened through a search of diagnostic discharge codes or positive laboratory results for Leishmania infection. Simultaneously, a comprehensive literature search was performed. Descriptive statistics and hypothesis testing were performed using IBM® SPSS® Statistics. A total of 43 CL and 7 ML cases were identified, with a predominance of autochthonous cases (86%). In CL, immunosuppressed individuals constituted a significant proportion of patients (48%), and in this group, disseminated CL (22%) and simultaneous VL (54%) were common. In autochthonous cases, lesions, mostly papules/nodules (62%), were frequently observed on the head (48%). The approach to treatment was very heterogeneous. ML cases were all autochthonous, were diagnosed primarily in older immunosuppressed individuals, and were generally treated with liposomal amphotericin B. The findings suggest a need for enhanced surveillance and reporting, clinical awareness, and diagnostic capacity of these forms of leishmaniasis to mitigate underdiagnosis and improve patient outcomes. A holistic One Health approach is advocated to address the multifaceted challenges posed by leishmaniases in Portugal and beyond.

Decoding Immuno-Competence: A Novel Analysis of Complete Blood Cell Count Data in COVID-19 Outcomes.

While 'immuno-competence' is a well-known term, it lacks an operational definition. To address this omission, this study explored whether the temporal and structured data of the complete blood cell count (CBC) can rapidly estimate immuno-competence. To this end, one or more ratios that included data on all monocytes, lymphocytes and neutrophils were investigated. Longitudinal CBC data collected from 101 COVID-19 patients (291 observations) were analyzed. Dynamics were estimated with several approaches, which included non-structured (the classic CBC format) and structured data. Structured data were assessed as complex ratios that capture multicellular interactions among leukocytes. In comparing survivors with non-survivors, the hypothesis that immuno-competence may exhibit feedback-like (oscillatory or cyclic) responses was tested. While non-structured data did not distinguish survivors from non-survivors, structured data revealed immunological and statistical differences between outcomes: while survivors exhibited oscillatory data patterns, non-survivors did not. In survivors, many variables (including IL-6, hemoglobin and several complex indicators) showed values above or below the levels observed on day 1 of the hospitalization period, displaying L-shaped data distributions (positive kurtosis). In contrast, non-survivors did not exhibit kurtosis. Three immunologically defined data subsets included only survivors. Because information was based on visual patterns generated in real time, this method can, potentially, provide information rapidly. The hypothesis that immuno-competence expresses feedback-like loops when immunological data are structured was not rejected. This function seemed to be impaired in immuno-suppressed individuals. While this method rapidly informs, it is only a guide that, to be confirmed, requires additional tests. Despite this limitation, the fact that three protective (survival-associated) immunological data subsets were observed since day 1 supports many clinical decisions, including the early and personalized prognosis and identification of targets that immunomodulatory therapies could pursue. Because it extracts more information from the same data, structured data may replace the century-old format of the CBC.

Monitoring of Klebsiella pneumoniae as one of the criteria of microecological characterization of a water body

Introduction. Representatives of the family Enterobacteriaceae are ubiquitous in the environment, causing severe, including opportunistic diseases in immunocompromised individuals. The occurrence of antibiotic-sensitive bacteria of the Klebsiella genus within the recreational zone of a water body is potent of posing an epidemiologic danger to the inhabitants of the settlement. &#x0D; Materials and Methods. Water samples from the surface aquifers of the Don and Temernik rivers of Rostov-on-Don served as the material for the study. The sensitivity of isolates of Kl. pneumoniae isolates to fourteen antibacterial preparations were investigated by disk-diffusion method in accordance with the requirements of MUK 4.2.1980-04 and EUCAST v. 13.0 (2023). 13.0 (2023). Carbapenemase genes VIM, IMP, NDM, KPC, OXA-48, NDM were determined using commercial diagnostic kits AmpliSense MDR MBL-FL, AmpliSense MDR KPC/OXA-48-FL, AmpliSense MDR Ab-OXA-FL.&#x0D; Results. In 2022, 247 isolates of Klebsiella pneumoniae were isolated in 14 biotopes of water bodies of Rostov-on-Don. Biotopes of epidemiological significance were identified with the presence of antibiotic resistance genes in 28 isolates isolated above and below the sewage discharge site (sampling point #1 and #5) and strains isolated from the mouth of the Temernik River (sampling point #14). Phenotype of multidrug-resistant (MDR) in point No. 1 possessed 22%, point No. 5 – 26.9%, point No. 14 – 26%; phenotype of extreme drug resistance (XDR) in point No. 1 possessed 11.1 %, point No. 5 – 15.3%, point No. 14 – 13%; phenotype of pan-drug-resistant (PDR) in point No. 1 did not possess, point No. 5 – 3.8%, point No. 14 – 4.3%.&#x0D; Limitations. A limitation of the study is related to the location of water sampling from the river. Don and R. Temernik on the territory of Rostov-on-Don, covering from March to November 2022. In this article, we limited ourselves to sanitary-bacteriological and molecular genetic analysis.&#x0D; Conclusion. The detection of PDR, XDR, and MDR antibiotic-resistant phenotypes of Klebsiella pneumoniae, as well as the detection of resistance genes, indicates to an increased risk of water-associated acute intestinal infections, especially in immunosuppressed individuals.

Case Series: Efficacy of Polyclonal Intravenous Immunoglobulin for Refractory Clostridioides difficile Infection.

Intravenous immunoglobulin (IVIg) for Clostridioides difficile infection (CDI) no longer features in treatment guidelines. However, IVIg is still used by some clinicians for severe or recurrent CDI (rCDI) cases. The main objective of this study was to investigate the efficacy of IVIg and to identify possible predictors of disease resolution post IVIg administration for patients with CDI. This retrospective observational cohort study of patients ≥2 years old hospitalised with severe, relapsing, or rCDI treated with IVIg therapy was performed in a large UK tertiary hospital between April 2018 and March 2023. Scanned electronic notes from patient admissions and clinical reporting systems were used to collect relevant data. In total, 20/978 patients diagnosed with CDI over the 5-year study were treated with IVIg. Twelve (60%) had hospital-onset CDI. Eleven of the twenty patients (55%) responded to treatment, with a mean of 8.6 (SD 10.7) days to disease resolution. Sixteen (80%) patients were treated for severe CDI and four (20%) for rCDI (n = 3) and relapsing CDI (n = 1). There were no statistically significant differences in possible independent predictors of disease resolution post IVIg administration between groups. There was an average of 6.2 (4.9) days to IVIg administration after diagnosis with no difference between responders and non-responders (p = 0.88) and no further significant difference in additional indicators. Four (36%) of the responders were immunosuppressed compared to just one (11%) of the non-responders (p = 0.15). Six of the responders (two with recurrent and four with severe CDI) improved rapidly within 2 days, and three of these were immunosuppressed. We observed disease resolution post IVIg therapy in over 50% of patients with refractory CDI. Our data also support a potential enhanced effect of IVIg in immunosuppressed individuals. Thus, the role of IVIg for CDI treatment, particularly in the immunosuppressed, warrants future case-control studies coupled to mechanistic investigations to improve care for this ongoing significant healthcare-associated infection.

The Prevalence and Risk Factors of Trichosporonosis at King Abdulaziz University Hospital.

Fungal infections, especially those caused have emerged as a significant medical concern over the past three decades, particularly among immunocompromised patients. However, recent studies have highlighted the increasing prevalence of fungal infections resembling yeast other than Candida, such as trichosporonosis, especially among immunosuppressed individuals worldwide. Trichosporon has been identified as a significant contributor to superficial and invasive infections. Invasive trichosporonosis, primarily affecting immunocompromised patients, poses a significant threat with high mortality rates. The current study aimed to explore the clinical epidemiology of Trichosporon spp at King Abdulaziz University Hospital (KAUH) in Saudi Arabia. This retrospective study aimed to assess the clinical epidemiology of Trichosporon spp. infections in microbiology cultures obtained from KAUH in Saudi Arabia. The study analyzed data from patients over a five-year period, focusing on demographic, clinical, and microbiological characteristics. This study encompassed 21 participants, categorized into four distinct age groups. Moreover, this study indicated T. asahii as the predominant species isolated, accounting for 90.5% of infections, followed by T. mucoides (9.5%). ICU hospitalization, diabetes mellitus, taking immunosuppressive drugs, and antifungal drugs, and the use of invasive medical equipment were identified as prominent risk factors for trichosporonosis. Urinary tract infections were the most common clinical presentation, particularly among male and elderly patients. Mortality rates were high, especially among older individuals. This study contributes valuable epidemiological insights into trichosporonosis, highlighting the need for enhanced surveillance and preventive strategies in healthcare settings. Further research is warranted to optimize treatment approaches and infection control measures, ultimately reducing the burden of Trichosporon infections on patient outcomes.

Emerging and reemerging human fungal pathogens that affect people with weakened immune systems: a systematic review

BACKGROUNDEmerging and reemerging human fungal pathogens are becoming more closely associated with morbidity and mortality, with 13 million infections and 1.5 million deaths per year. They are most often associated with critically ill and immunosuppressed patients. Therefore, this systematic review focused on emerging and reemerging human fungal pathogens that affect immunosuppressed individuals. METHODS A systematic literature search was performed using PubMed, ScienceDirect, Web of Science, Google Scholar, and other sources (Google engine and manual search using a reference list). The data were extracted in a structured format prepared using Microsoft Excel. RESULTSCryptococcus neoformans, Candida auris, Aspergillus fumigatus, Candida albicans, Nakaseomyces glabrata (Candida glabrata), Histoplasma spp., Mucorales (Rhizopus spp., Mucor spp., Lichtheimia spp., and others), Fusarium spp., Candida tropicalis, Candida parapsilosis, Pichia kudriavzevii (Candida krusei), Talaromyces marneffei and Pneumocystis jirovecii were emerging and reemerging fungal pathogens reported among critically ill and immunocompromised patients including but not limited to HIV patients and patients with infectious diseases such as influenza, COVID-19, and tuberculosis as well as chronic conditions or co-morbidities such as asthma, hepatic cirrhosis, cancer, diabetes, cystic fibrosis (CF), transplant recipients, and chronic obstructive pulmonary disease (COPD). Climate change, agricultural activities, occupational hazards, deforestation, migratory trends of people, soil dispersion, decreased immunity of patients, biofilm development, medication tolerance, and resistance to antifungal therapies are all factors that contribute to the emergence of fungal diseases. CONCLUSIONThis review makes recommendations for policymakers, public health experts, and other stakeholders to improve the response to these fungal infections, including laboratory capacity and surveillance, fostering sustainable research and innovation, implementing public health initiatives, and limiting the development of antifungal drug resistance.

Determination of anti-COVID-19 IgG and IgM seroprevalence among pregnant women at Pietersburg Hospital, Limpopo Province, South Africa

Background. COVID-19 has been a major public health concern globally, leading to a higher mortality rate, especially among immunosuppressed individuals, who include pregnant women, people with HIV and people living with other comorbidities. Pregnant women are considered to be a special population group owing to their specific susceptibility to some infectious diseases. Objective. To determine the seroprevalence of anti-SARS-CoV-2 antibodies among pregnant women attending an antenatal clinic. Method. This was a descriptive cross-sectional study that tested blood samples from pregnant women who attended the antenatal clinic from March to July 2022 using the Orient Gene Biotech lateral flow immune-chromatographic assay according to manufacturer instructions. The assay detects IgM and IgG antibodies against SARS-CoV-2. Results. A total of 2 649 blood samples were tested; 2 039 (77.0%) samples tested positive for IgG, 7 (0.3%) tested positive for IgM, and 100 (3.7%) tested positive for both IgG and IgM. The study found a seroprevalence of 80.7% of IgG. Conclusion. The study findings showed evidence of acute COVID-19 infection in our patient population despite the consensus that COVID-19 infection is dissipating.

Therapy of Mycobacterium abscessus Infections in Solid Organ Transplant Patients.

Mycobacterium abscessus complex (MABC), a rapidly growing Mycobacterium, is one of the most common causes of non-tuberculous mycobacteria (NTM) infections in the United States of America, and it has been associated with a wide spectrum of infections in immunocompetent and immunosuppressed individuals. Eradicating MABC is very challenging, even with prolonged combination therapies. The management of MABC infections in solid organ transplant (SOT) patients is usually complex given their net state of immunosuppression, associated comorbidities, and potential drug-drug interactions, among other things. In this manuscript, we discussed the antimicrobial management of pulmonary and extrapulmonary MABC infections. In addition, we reviewed promising novel therapies such as clofazimine, omadacycline, bedaquiline, and inhaled tigecycline that could join the existing antimicrobial armamentarium to fight this infection associated with significant morbidity and mortality. However, further studies are needed, especially among the immunocompromised host.

Clinical features of atypical presentations of mucocutaneous herpes simplex virus infection observed in immunosuppressed individuals. Part II: the knife-cut sign.

The knife-cut sign is a distinctive manifestation of herpes simplex virus (HSV) type 1 or HSV type 2 infection that has been described in at least 10 immunocompromised patients. It appears as an extremely painful linear erosion or fissure in an intertriginous area such as the body folds beneath the breast, or within the abdomen, or in the inguinal region. Also, concurrent HSV infection at other mucocutaneous sites, or viscera, or both have been observed. The patients had medical conditions (at least 9 patients) and/or immunosuppressive drug therapy (6 patients). The diagnosis of HSV infection was confirmed by viral culture (8 patients), biopsy (4 patients), direct fluorescence antibody testing (3 patients), immunohistochemistry staining (2 patients), polymerase chain reaction (2 patients), or Western blot serologic assay (1 patient). Knife-cut sign-associated HSV infection is potentially fatal; three patients died. However, clinical improvement or complete healing occurred in the patients who received oral valacyclovir (1 patient), or intravenous acyclovir (2 patients), or intravenous acyclovir followed by foscarnet (1 patient). In summary, HSV infection associated with a positive the knife-cut sign is a potentially fatal variant of HSV infection that occurs in the intertriginous areas of immunocompromised patients and usually requires intravenous antiviral therapy.