Search Results (53)

Introduction: Cutaneous leishmaniasis (CL) poses a number of challenges when it comes to diagnosis and treatment, due to the variety of clinical presentations that mimic other conditions and hinder the choice of the most appropriate therapeutic approach, especially in the context of immunodepression. Case presentation: We present the case of a 63-year-old woman on anti-tumor necrosis factor (TNF) therapy, who underwent surgical excision for the diagnostic purposes of a chronic non-healing lesion located on her right arm. The histopathological examination revealed the presence of Leishmania amastigotes. CL relapsed in the following months, with new lesions appearing both close to the excision scar and at a different body site. At this point, in order to avoid another surgical intervention, cutaneous swabs for Leishmania Polymerase Chain Reaction (PCR) were performed on both lesions. Both samples yielded positive results, and the patient was treated with a 4-week course of miltefosine. Conclusions: These results support the use of cutaneous swabs as a highly sensitive and less invasive tool for the diagnostic workup of CL. In addition, our case prompts a reflection on the management of immunosuppressed patients with CL, with particular emphasis on the risk of reactivation or simultaneous involvement of multiple anatomical sites, thus suggesting the need for specific considerations and personalized management for this group of subjects. Full article

Background: Lymphomatoid granulomatosis (LYG) is a rare and atypical EBV-induced B-cell lymphoproliferative disorder. Clinical manifestations are mainly respiratory, with nodular infiltrates, varying in number and size, being responsible for respiratory distress. Cutaneous, hepatic, or neurological involvement is also possible. Although pathogenesis is not clearly elucidated, quantitative or qualitative cellular immunodepression is thought to be a main factor. Here, we report a case of concomitant LYG and pulmonary tuberculosis. Case presentation: An 80-year-old female patient presented to the emergency unit for steadily increasing dyspnea, with workup revealing bilateral pulmonary nodules and mediastinal lymph node enlargement on chest imaging. Empiric antibiotic therapy was initially started with amoxicillin-clavulanate, which was later combined with azithromycin following respiratory deterioration. A CT-guided lung biopsy showed grade 2 LYG. Treatment with corticosteroids and weekly rituximab was initiated, leading to rapid improvement of respiratory symptoms. After the second dose of rituximab, sputum cultures that were initially collected were found to be positive for Mycobacterium tuberculosis. Rituximab was suspended, and antituberculous treatment was initiated. Rituximab was restarted once tuberculosis was controlled. Follow-up imaging later showed adequate control of both tuberculosis and LYG, with at least a partial remission of the latter. Conclusions: Our case highlights the importance of a complete diagnostic workup when a diagnosis of LYG is made, to avoid missing a concomitant pulmonary disease, such as tuberculosis, even when definite pathologic and clinical features of the former are present. Full article

Pneumonia caused by Pneumocystis jirovecii poses a serious threat, particularly to immunocompromised patients such as those with HIV/AIDS, transplant recipients, or individuals undergoing chemotherapy. Its diagnosis is challenging because current methods, such as microscopy and certain molecular tests, have limitations in sensitivity and specificity, and require specialized equipment, which delays treatment initiation. In this context, CRISPR-Cas12-based methods offer a promising alternative: they are rapid, highly specific, sensitive, and low-cost, enabling more timely and accessible detection, even in resource-limited settings. We developed a simple and rapid detection platform based on the CRISPR-Cas12 coupled with lateral flow strips. A guide RNA was designed against DHPS, β-tubulin, and mtLSU rRNA genes. The guide corresponding to β-tubulin showed high sensitivity in the detection of P. jirovecii to produce a detectable fluorescence signal within the first 20–30 min. In addition, it demonstrated high specificity for P. jirovecii when DNA from other microorganisms was used. When coupled with lateral flow strips, high sensitivity and specificity were also observed for detecting positive samples, without the need for genetic amplification. CRISPR-Cas12 successfully detected P. jirovecii infection in an initial diagnostic application, demonstrating the potential of this method for integration into public health diagnostic systems, particularly in field, due to its adaptability, speed, and ease of use. Full article

Nakaseomyces glabratus is a medically important fungal pathogen responsible for various opportunistic, life-threatening, and fatal infections, mainly among immunodepressed patients worldwide. Herein, genotypes identified in Central Poland by multilocus sequence typing (MLST) are presented. Along with the genotyping, drug susceptibility was performed. The research was conducted on 30 non-redundant clinical strains, and 15 distinct sequence types (STs) were identified, including three novel STs: ST212, ST213, and ST214. The most prevalent sequence types were ST3, ST6, and ST10. Antifungal susceptibility testing revealed varied resistance rates to azoles, with fluconazole susceptibility at 16.7% and high susceptibility to amphotericin B. No correlation between ST and antifungals MIC were found. The study findings highlight the genetic diversity of N. glabratus in Central Poland and the role of surveillance and research to elucidate antifungals resistance and molecular epidemiology of N. glabratus. Full article

Avian reovirus (ARV) is one of the main causes of viral arthritis, tenosynovitis, malabsorption syndrome (MAS), runting-stunting syndrome, and immunodepression. In recent years, due to the emergence of new ARV strains, outbreaks of the disease have brought significant economic losses to chicken flocks. To determine the prevalence of ARV in China from 2010 to 2024, a total of 409 tissue samples from different breeding farms were collected from chickens presenting clinical signs of lameness and swollen joints in various flocks located in 18 provinces. As performed on these tissue samples, the ARV-specific reverse transcription-polymerase chain reaction (RT-PCR) assay indicated 111 ARV-positive samples with a positive rate of 27.14%. After viral isolation from the necropsied chicken samples, 69 ARV strains were isolated, and specific sigma C (σC) genes were amplified and sequenced. The sequence analysis of σC genes showed that these 69 isolates were grouped into six clusters, including 14 ARV isolates from cluster I (20.29%), 12 ARV isolates from cluster II (17.39%), 3 ARV isolates from cluster III (4.35%), 8 ARV isolates from cluster IV (11.59%), 3 ARV isolates from cluster V (4.35%), and 29 ARV isolates from cluster VI (42.03%). Except for cluster V, each of the other five clusters could be divided into two subclusters. Homology analysis showed that ARV isolates in clusters II–VI had only 50.3 to 60.8% homology with the commercial S1133 vaccine strain which is derived from cluster I. The ARVs in subcluster Ia had high homology with the S1133 vaccine strain (93.5–98.0%), while the ARVs in subcluster Ib had a low homology with the S1133 strain (73.4–76.4%). Further, the cluster VI viruses, the main epidemic genotype in China, had only 50.3–55.7% homology with the S1133 strain. The results of the pathogenicity test showed that the representative strains of the six different clusters all caused swelling of the footpads in SPF chickens, and the incidence rate was not significantly different. The present study will be helpful in the understanding the prevalence of ARV strains in China and revealed the genetic differences between the ARV isolates and the commercial vaccine strain. Full article

Background: Immunosuppressed patients still exhibit a high mortality rate due to SARS-CoV-2 infection, up to 21%. Persistent viral load replication and protracted viral symptoms result in a high risk of developing pneumonia, a potential risk of antiviral resistance, and a subsequent delay of onco-hematological treatments. Methods: Hematological patients and kidney transplant patients with SARS-CoV-2 infection, treated at GOM Niguarda Hospital (Milan) with combined antiviral therapy (remdesivir plus nirmatrelvir/ritonavir at standard doses) between November 2022 and March 2024, were retrospectively reviewed. Results: Thirty-four patients were analyzed. Twenty-four (71%) patients had pneumonia. The median duration of SARS-CoV-2 positivity before antiviral treatment was 40 (10–34) days. The median treatment duration was 11 (10–10) days. All patients went through clinical resolution. Thirteen patients were exposed to a new immune-chemotherapy cycle early after antiviral treatment (median 13, IQR 6–12 days), while five resumed a standard immunosuppressive regimen immediately after viral clearance. No relapse or recurrence of symptoms was reported for up to 226 (106–318) days of follow-up. Antiviral therapy was well tolerated, and no adverse events were observed. The 30-day overall survival was 94%, while the 90-day survival was 88%. No patient died of SARS-CoV-2 infection. Conclusions: The administration of nirmatrelvir/ritonavir and remdesivir lead to the complete resolution of SARS-CoV-2 pneumonia with no side effects in this cohort. The combination of these two antivirals may be a safe option in immunosuppressed population at risk of severe complications and prolonged SARS-CoV-2 infection in order to treat severe clinical presentation and to avoid viral recurrence after chemotherapy. Full article

Background: Neutralizing antibodies targeting the SARS-CoV-2 Spike protein reduce COVID-19-related risk of hospitalization, particularly in high-risk individuals. The COCOPREV-R study aimed to evaluate and compare clinical outcomes in high-risk SARS-CoV-2 patients treated with dual monoclonal antibody therapies and to identify associated virological factors. Methods: The COCOPREV-R study retrospectively collected real-world data from high-risk patients receiving Bamlanivimab/Etesevimab or Casirivimab/Imdevimab dual monoclonal antibody therapies (22 February 2021 to 15 June 2021). Results: The study included 1004 patients with COVID-19, of whom 691 received Bamlanivimab/Etesevimab and 313 received Casirivimab/Imdevimab. The alpha variant represented 90.1% of those for whom data were available. The risk of hospitalization within 30 days was lower with Bamlanivimab/Etesevimab (12.7%, CI 95% [9.9–16.3%]) compared to Casirivimab/Imdevimab (28.4%, CI 95% [22.7–35.1%) (p < 0.001). The 30-day mortality rates were comparable between both groups (p = 0.982). Analysis of SARS-CoV-2 PCR negativity showed no difference between the two treatment groups (95.2% [93.0–96.9%] and 93.5% [89.1–96.6%] until day 30, p = 0.851 for Bamlanivimab/Etesevimab and Casirivimab/Imdevimab, respectively). Among persistently positive samples with available sequencing results (n = 43), Spike protein changes occurred only in Bamlanivimab/Etesevimab (42.9%) vs. Casirivimab/Imdevimab (0.0%) groups. Q493R (25.0%) and E484K (12.5%) were the most common mutations selected by Bamlanivimab/Etesevimab in follow-up samples. Other factors (immunodepression, comorbidities, and age) did not appear to be associated with the occurrence of Spike protein mutations. Conclusions: A higher rate of hospitalization was seen with Casirivimab/Imdevimab (RONAPREVE^®) in comparison with Bamlanivimab/Etesevimab treatment, but with the emergence of Spike mutations only in the Bamlanivimab/Etesevimab group. Full article

Turkey Hemorrhagic Enteritis (THE) is an acute disease caused by a Siadenovirus that affects 4 week-aged and older turkeys, characterized by acute depression, bloody droppings, and a high mortality rate. The immunosuppressive attributes of THE can protract disease progression and create a predisposition in birds towards subsequent bacterial infectiodoralns involving Escherichia coli and Clostridium perfringens (necrotic enteritis). Turkey Hemorrhagic Enteritis Virus (THEV) predominantly affects turkeys and carries substantial economic implications for this industry. Macrophages and B lymphocytes are recognized as the predominant target cells for the virus, while the spleen is the principal site of viral replication. Infected cells have also been observed in various other tissues, including the intestines, bursa of Fabricius, cecal tonsils, thymus, liver, kidney, peripheral blood leukocytes, and lungs. The economic relevance of this disease is derived both from the high mortality rate, which can reach 60% depending on the virulence of the strain, and from subclinical disease responsible for poor performance in vaccinated animals. This review aims to provide a comprehensive overview of THE, spanning etiology, epidemiology clinical signs and gross lesions, prevention, and management. Full article

Reactivation and primary infection with a high Epstein Barr Virus (EBV) DNA level in kidney transplant patients could cause severe complications, including the development of Post-Transplantation Lymphoproliferative Disease (PTLD). While in the general population the reactivation of EBV after SARS-CoV-2 infection has been reported, very few data are available in transplant recipients. Our retrospective study aimed to evaluate a possible EBV reactivation in kidney transplant patients following SARS-CoV-2 infection and a possible impairment of the immune system. In addition, the effects of changes in immunosuppressive therapy on EBV DNA reactivation and vaccination were also evaluated. A total of 166 kidney transplant patients followed at the Kidney–Pancreas Transplant Ambulatory Nephrology Unit at Padova University Hospital were retrospectively considered for an observation period of 6 months from January 2020 to April 2023. EBV DNA level was measured by Rt-PCR and evaluated 6 months before and after SARS-CoV-2 infection. Patients’ serological states were established via quantification of anti-VCA and anti-EBNA (chemiluminescence). Patients’ immune systems were characterized by CD4⁺/CD8⁺ lymphocyte ratio (flow cytometry). EBV DNA was reactivated in 50% of the 166 patients with COVID-19 who completed the study. Older patients with more severe forms of COVID-19 had higher EBV reactivation (p < 0.05). EBV reactivation significantly increased in patients with severe SARS-CoV-2 infection requiring hospitalization compared to patients managed at home (p < 0.001). CD4⁺/CD8⁺ lymphocyte ratio was reduced in patients with a younger age of transplant (p < 0.01) and on a higher dose of steroids (p < 0.01). The results of our study confirm the role of immunodepression, especially in recent transplant patients and those on high steroids, in EBV reactivation. These results combined with the few available in the literature might contribute to providing an optimal management of immunosuppressive treatment for these patients in order to obtain an immune state unfavorable to the activation of latent viruses, including EBV. Full article

The endocannabinoid system, with its intricate presence in numerous cells, tissues, and organs, offers a compelling avenue for therapeutic interventions. Central to this system are the cannabinoid receptors 1 and 2 (CB1R and CB2R), whose ubiquity can introduce complexities in targeted treatments due to their wide-ranging physiological influence. Injuries to the central nervous system (CNS), including strokes and traumatic brain injuries, induce localized pro-inflammatory immune responses, termed neuroinflammation. Research has shown that compensatory immunodepression usually follows, and these mechanisms might influence immunity, potentially affecting infection risks in patients. As traditional preventive treatments like antibiotics face challenges, the exploration of immunomodulatory therapies offers a promising alternative. This review delves into the potential neuroprotective roles of the cannabinoid receptors: CB1R’s involvement in mitigating excitotoxicity and CB2R’s dual role in promoting cell survival and anti-inflammatory responses. However, the potential of cannabinoids to reduce neuroinflammation must be weighed against the risk of exacerbating immunodepression. Though the endocannabinoid system promises numerous therapeutic benefits, understanding its multifaceted signaling mechanisms and outcomes remains a challenge. Full article

Background and objectives: One of the most severe forms of extrapulmonary tuberculosis (EPTB) is tuberculous meningitis (TBM), which is linked to significant morbidity and high mortality. It is well recognized that human immunodeficiency virus (HIV)-positive people are more likely to develop EPTB, including TBM, especially if they have severe immunodeficiencies. We aim to highlight the profile and the characteristics of TBM in HIV-infected patients. Material and methods: We conducted a retrospective clinical study based on hospital medical records of patients diagnosed with HIV/AIDS (acquired immunodeficiency syndrome) and TBM in Northeast Romania, hospitalized at “St. Parascheva” Clinical Hospital of Infectious Diseases of Iasi from 1 January 2010 to 1 December 2022. Results: From a total number of 1692 patients on record in our center, 195 had a HIV–tuberculosis (TB) coinfection, and 19 cases were HIV–TBM coinfected. Six cases were newly HIV-diagnosed late presenters, and thirteen patients’ names were already found in the center’s records with deficient immunological viral status (median CD4 lymphocyte level 47/mm³). The average age in the study group was 27 years old. The clinical manifestations and cerebrospinal fluid (CSF) variables were typical in most cases, despite the severe immunodepression of the patients. The Thwaites scoring system correctly identified 89.5% of the patients. The median admission period was 18 days; the lethality rate was 31.6%, despite access to ART and anti-TB drugs, and was associated with a more severe immunosuppression. No rifampicin resistance was detected. Conclusions: TBM appeared in a minority of our HIV cohort and affected severely immunodepressed patients; the clinical and CSF variables had a typical aspect in most cases, and the Thwaites scoring system performed well for this type of patient. The lethality rate was high and was correlated with a more severe immunodepression. Full article

(1) Background: Inducing experimental stroke leads to biphasic immune responses, where the early activation of immune functions is followed by severe immunosuppression accompanied by spleen and thymus atrophy. Nicotinamide, a water-soluble B-group vitamin, is a known neuroprotectant against brain ischemia in animal models. We examined the effect of nicotinamide on the central and peripheral immune response in experimental stroke models. (2) Methods: Nicotinamide (500 mg/kg) or saline was intravenously administered to C57BL/6 mice during reperfusion after transiently occluding the middle cerebral artery or after LPS injection. On day 3, the animals were examined for behavioral performance and were then sacrificed to assess brain infarction, blood–brain barrier (BBB) integrity, and the composition of immune cells in the brain, thymus, spleen, and blood using flow cytometry. (3) Results: Nicotinamide reduced brain infarction and microglia/macrophage activation following MCAo (p < 0.05). Similarly, in LPS-injected mice, microglia/macrophage activation was decreased upon treatment with nicotinamide (p < 0.05), suggesting a direct inhibitory effect of nicotinamide on microglia/macrophage activation. Nicotinamide decreased the infiltration of neutrophils into the brain parenchyma and ameliorated Evans blue leakage (p < 0.05), suggesting that a decreased infiltration of neutrophils could, at least partially, be the result of a more integrated BBB structure following nicotinamide treatment. Our studies also revealed that administering nicotinamide led to retarded B-cell maturation in the spleen and subsequently decreased circulating B cells in the thymus and bloodstream (p < 0.05). (4) Conclusions: Cumulatively, nicotinamide decreased brain inflammation caused by ischemia–reperfusion injury, which was mediated by a direct anti-inflammatory effect of nicotinamide and an indirect protective effect on BBB integrity. Administering nicotinamide following brain ischemia resulted in a decrease in circulating B cells. This warrants attention with respect to future clinical applications. Full article

European sea bass production has increased in recent decades. This increase is associated with an annually rising demand for sea bass, which encourages the aquaculture industries to increase their production to meet that demand. However, this intensification has repercussions on the animals, causing stress that is usually accompanied by dysbiosis, low feed-conversion rates, and immunodepression, among other factors. Therefore, the appearance of pathogenic diseases is common in these industries after immunodepression. Seeking to enhance animal welfare, researchers have focused on alternative approaches such as probiotic application. The use of probiotics in European sea bass production is presented as an ecological, safe, and viable alternative in addition to enhancing different host parameters such as growth performance, feed utilization, immunity, disease resistance, and fish survival against different pathogens through inclusion in fish diets through vectors and/or in water columns. Accordingly, the aim of this review is to present recent research findings on the application of probiotics in European sea bass aquaculture and their effect on growth performance, microbial diversity, enzyme production, immunity, disease resistance, and survival in order to help future research. Full article

In the 100 years since its discovery, lysozyme has become an important molecule, both as model for studies in different fields and as a candidate for the therapy of various pathological conditions. Of the dozens of known lysozymes, in this review we focus on one in particular, lysozyme extracted from hen egg white (HEWL), and its interaction with the immune system when it is administered orally. Experimental data show that there is an axis that directs immune system activation from GALT (gut-associated lymphoid tissue) and the intestinal lymphocyte clusters. Although a contribution of peptidoglycans from digestion of the bacterial cell wall in the intestinal lumen cannot be excluded, immune stimulation is not dependent on the enzymatic activity of HEWL. The immune responses suggest that HEWL is able to recover from immunodepression caused by tumor growth or immunosuppressants, and that it also improves the success of chemotherapy. The positive results obtained in a small Phase 2 study in patients, the ease of oral administration of this protein, and the absence of adverse effects suggest that HEWL may play an important role in all diseases where the immune system is weakened or where its enhancement plays a critical role in the resolution of the pathology. Full article

Evidence-based, standard antibiotic therapy for ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii (CRAB) is a relevant unmet clinical need in the intensive care unit (ICU). We aimed to evaluate the effectiveness of first-line therapy with old and novel CRAB active antibiotics in monomicrobial VAP caused by CRAB. A prospective, observational study was performed in a mixed non-COVID-19 ICU. The primary outcome measure was clinical failure upon first-line targeted therapy. Features independently influencing failure occurrence were also investigated via Cox proportional multivariable analysis. To account for the imbalance in antibiotic treatment allocation, a propensity score analysis with an inverse probability treatment weighting approach was adopted. Of the 90 enrolled patients, 34 (38%) experienced clinical failure. Compared to patients who experienced a clinical resolution of VAP, those who had clinical failure were of an older age (median age 71 (IQR 64–78) vs. 62 (IQR 52–69) years), and showed greater burden of comorbidities (median Charlson comorbidity index 8 (IQR 6–8) vs. 4 (IQR 2–6)), higher frequency of immunodepression (44% vs. 21%), and greater clinical severity at VAP onset (median SOFA score 10 (IQR 9–11) vs. 9 (IQR 7–11)). Lower rates of use of fast molecular diagnostics for nosocomial pneumonia (8.8% vs. 30.3%) and of timely CRAB active therapy administration (65% vs. 89%), and higher rates of colistin-based targeted therapy (71% vs. 46%) were also observed in patients who failed first-line therapy. Overall, CRAB active iv regimens were colistin-based in 50 patients and cefiderocol-based in 40 patients, both always combined with inhaled colistin. According to the backbone agent of first-line regimens, clinical failure was lower in the cefiderocol group, compared to that in the colistin group (25% vs. 48%, respectively). In multivariable Cox regression analysis, the burden of comorbid conditions independently predicted clinical failure occurrence (Charlson index aHR = 1.21, 95% CI = 1.04–1.42, p = 0.01), while timely targeted antibiotic treatment (aHR = 0.40, 95% CI = 0.19–0.84, p = 0.01) and cefiderocol-based first-line regimens (aHR = 0.38, 95% CI = 0.17–0.85, p = 0.02) strongly reduced failure risk. In patients with VAP caused by CRAB, timely active therapy improves infection outcomes and cefiderocol holds promise as a first-line therapeutic option. Full article