Search Results (528)

Mucormycosis is a rare invasive fungal disease in pediatric patients with hematological malignancies and is associated with poor outcomes. We present a fulminant and ultimately fatal case of rhino-orbito-cerebral mucormycosis, addressing important issues including clinical signs and symptoms, diagnostic approaches and the challenges of timely diagnosis. The patient was an 11-year old girl undergoing re-induction chemotherapy for Central Nervous System relapse of B-cell precursor acute lymphoblastic leukemia. She presented six days into the second course of chemotherapy in profound neutropenia with aggravating headaches, painful abducens nerve palsy and anisocoria. At first (day −3), no significant radiological or ophthalmological correlations were found, and methyl–prednisolone was started due to suspected vasculitis following ICU admission. After further clinical deterioration, a second MRI scan (day 0) revealed a prolonged occlusion of the left carotid artery, which was successfully stented in a neuroradiological intervention (day +1). However, during the next day the child developed clinical signs indicating severe cerebral dysfunction. An emergency CT scan showed complete infarction of the left hemisphere including a progredient perfusion deficit and beginning brain edema. Based on the unfavorable prognosis, best supportive care was initiated, and the patient deceased on day +2. Pathological and microbiological workup identified thrombotic infarction in all major cerebral arteries. While microscopy was suspicious for mucormycosis, nested PCR from retained blood specimens confirmed the genus Lichtheimia. Final NGS on brain tissue led to the identification of Lichtheimia ramosa. This case illustrates the rapidity and severity of Mucorales infection. It shows the importance of early clinical suspicion and the need for an aggressive laboratory testing algorithms. The stratification of risk factors and definition of red flags may be a future task fighting these infections. Full article

Infectious keratitis (IK), including bacterial, fungal, parasitic, and viral etiologies, continues to represent a significant cause of ocular morbidity in the United States and around the world. Corneal scraping for smears and cultures remains the gold standard in diagnosing IK; however, molecular diagnoses, including metagenomic deep sequencing (MDS), are promising emerging diagnostic tools. Despite recent interest in procedural treatment such as riboflavin photoactivated chromophore corneal collagen cross-linking (PACK-CXL) and Rose Bengal photodynamic antimicrobial therapy (RB-PDAT), medical treatment advances have remained stagnant. Methods: This review highlights IK pathogens obtained from corneal cultures at Bascom Palmer Eye Institute (BPEI) from 2011 to 2021 and provides the current BPEI algorithms for initial management of IK or as a referred clinically worsening patient. The roles of corticosteroid therapy, PACK-CXL, and RB-PDAT for IK are also summarized. Results: A total of 9326 corneal cultures were performed at BPEI between 2011 and 2021, and only 3609 (38.7%) had a positive organism identified, of which bacteria were the most common (83.4%). Fortified vancomycin and tobramycin are recommended as first-line medical therapy for IK patients based on culture sensitivity data for the top Gram-negative (Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. PACK-CXL and RB-PDAT may benefit IK patients with corneal melting and fungal IK, respectively. Conclusions: Drug holidays, minimizing contamination, and optimizing sample order are crucial to maximizing corneal culture positivity. PACK-CXL and RB-PDAT are promising procedural advancements for IK therapy. Full article

Aspergillosis in immunocompromised individuals is a serious and potentially life-threatening infection, as the weakened immune system cannot effectively fight the Aspergillus fungus. This review provides an in-depth examination of aspergillosis in patients with various conditions that compromise immunity, including hematological disorders, HIV, SARS-CoV-2 pneumonia, influenza, and those who have undergone solid organ transplants. The clinical manifestations of aspergillosis are influenced by factors such as the host’s underlying comorbidities, immune response, and immune suppression due to medications or treatments. The review delves into the epidemiology of aspergillosis, exploring various risk factors that predispose individuals to infection. It also discusses the wide range of clinical symptoms, highlighting the challenges in diagnosis and the importance of early detection. The review contrasts traditional diagnostic approaches with emerging molecular techniques, emphasizing the role of advanced diagnostics in improving outcomes. A proposed clinical decision-making flowchart is provided to assist healthcare professionals in managing suspected cases of aspergillosis. In addition to diagnostic challenges, the review addresses antifungal prophylaxis, pre-emptive therapy, and the growing concern of pharmacological resistance to antifungal agents. It concludes with a discussion of future research directions, underscoring the need for improved therapeutic strategies and preventative measures in immunocompromised patients to reduce the burden of this severe fungal infection. Full article

Background/Objectives: Opportunistic fungal infections are common among people living with HIV (PLHIV) and contribute substantially to morbidity, mortality, and hospitalization rates in this population. This study aimed to determine the prevalence of dermatological manifestations of fungal infections in HIV-positive patients and examine their association with demographic, clinical, and immunological characteristics. Methods: A retrospective review of medical records from 2500 PLHIV treated at the Infectious Diseases Unit of “Andreas Syggros” Hospital for Skin and Venereal Diseases between 1988 and 2017. Data from patients diagnosed with opportunistic fungal infections were analyzed. Participants were classified as either antiretroviral therapy (ART)-naïve or already receiving treatment. Recorded fungal infections were correlated with epidemiological variables and CD4+ T-cell counts. Results: Opportunistic fungal infections were identified in 859 patients (34.36%), with a marked male predominance. Candidiasis was the most frequently reported condition, with a higher prevalence among female patients. Lower CD4+ counts were significantly associated with an increased risk of cryptococcal meningitis, esophageal candidiasis, Pneumocystis jirovecii pneumonia (PJP), and oral candidiasis, whereas higher CD4+ counts were more common in patients with dermatophytosis, onychomycosis, and pityriasis/tinea versicolor. Conclusions: Opportunistic fungal infections remain highly prevalent in PLHIV, particularly among those with advanced immunosuppression. CD4+ T-cell counts are key diagnostic and prognostic markers, reinforcing their importance in monitoring disease progression and guiding clinical management. Full article

Background and Clinical Significance: Acute megakaryoblastic leukemia (AMKL) is a rare and aggressive hematologic malignancy. The presence of genetic abnormalities often increases the complexity of AMKL. Among these, patients with monosomy 7 constitute a high-risk group associated with a poorer prognosis and greater chemoresistance. We report the case of a 10-year-old boy who had AMKL along with monosomy 7 and familial GATA2 deficiency. The case highlights the diagnostic and therapeutic challenges faced, as well as the critical importance of early genetic screening and timely hematopoietic stem cell transplantation (HSCT). Case Presentation: A 10-year-old boy presented with easy bruising and pancytopenia. AMKL was diagnosed with the help of a bone marrow biopsy and immunophenotyping. Genetic testing showed a GATA2 mutation and monosomy 7. Two induction cycles with daunorubicin and cytarabine were administered but failed to eliminate residual disease. The patient also developed pneumonia of a fungal origin. HSCT was delayed due to liver toxicity and elevated minimal residual disease (MRD). Azacitidine and venetoclax stabilized the disease, thereby allowing for successful haploidentical HSCT. The patient achieved complete remission with full donor chimerism. Conclusions: This case emphasizes the importance of early molecular diagnostics in pediatric AMKL. Identifying GATA2 mutations and monosomy 7 early can help guide risk stratification and the timing of HSCT. Multimodal therapy, which includes the use of infection control and targeted agents, is important for improving the outcomes in high-risk patients. Full article

Invasive fungal infections (IFIs) are one of the most significant public health challenges worldwide. Yet, research and communication thereof were left behind for a long time, until the WHO published a priority pathogens list to guide research, development, and public health action in October 2022. Indeed, due to the rising number of immunocompromised patients at risk and the high level of morbidity, mortality, and economic burden they entail, especially in low- and middle-income countries, IFIs are a serious public health threat. Fungal infections due to dimorphic fungi face additional challenges such as limited knowledge outside of endemic areas and restricted availability of antifungal molecules in areas affected by these infections. The number of related deaths per year is estimated at 2.5 million, but non-governmental organisations make a wider estimation, due to the difficulties in early in vitro diagnostic and troublesome collection and analysis of epidemiological data. Despite this fact, the therapeutic toolbox addressing these infections remains limited, with only four main families of molecules available so far. The antifungal therapeutic supply is composed of very toxic polyenes, the weakly selective and nearly unused 5-fluorocytosine, and azoles, some of which are becoming increasingly inefficient against IFIs. In the 2000–2020s, the fourth arising family consisted of safer semisynthetic echinocandins. Unfortunately, nowadays, more and more fungal isolates encountered in intensive care units exhibit a low susceptibility to echinocandins or are even multiresistant. In this review, we expose the current treatments available to fight against invasive fungal infections. We recall the discovery and physico-chemical aspects of these substances leading to structure/activity and structure/properties relationships. We particularly focus on the to-date resistances and their molecular mechanisms. We finally list some of the most relevant antifungal drug candidates, as they were freshly overviewed by the World Health Organization in April 2025, highlighting the importance of the molecular dimension of this pursuit toward the expansion of the antifungal therapeutic toolbox. Full article

Talaromycosis caused by Talaromyces marneffei is a life-threatening mycosis in patients with acquired immunodeficiency syndrome (AIDS). The gold-standard diagnostic method relies on time-consuming cultures, which delay treatment and increase mortality. In this study, we developed a rapid and sensitive droplet digital PCR (ddPCR) assay targeting the internal transcribed spacer (ITS) gene for detecting T. marneffei and compared its performance with blood culture and quantitative PCR (qPCR) assays. The ddPCR assay had a detection limit of one copy/reaction, making it 10-fold more sensitive than qPCR. It demonstrated 100% specificity for T. marneffei, with no cross-reactivity to 15 other fungal pathogens, six bacterial pathogens, and plasma from 119 AIDS patients without talaromycosis. In 119 AIDS patients with talaromycosis, ddPCR exhibited better overall sensitivity (92.44%) than blood culture (86.55%) and qPCR (87.29%). The sensitivity of ddPCR was 97.8% (89/91) and 75% (21/28) in plasma collected before and after antifungal therapy, respectively. Moreover, fungal load measured by ddPCR negatively correlated with the time to blood culture positivity. Fungal loads in patients receiving antifungal therapy were significantly lower than those in untreated patients. These findings indicate that ddPCR facilitates rapid diagnosis of T. marneffei infection in AIDS patients and can assist clinicians in evaluating treatment efficacy by quantifying fungal load. Full article

Background/Objectives: Granulomatous lesions of the head and neck arise from diverse infectious and non-infectious causes, with tuberculosis (TB) being a predominant etiology. This retrospective study analyzed 42 cases from the archives of university of Baghdad, College of Dentistry (1975–2025). This study aimed to characterize the clinicopathological features of these lesions and to assess the diagnostic performance of histochemical stains and real-time PCR in identifying infectious etiologies—particularly Mycobacterium tuberculosis—in formalin-fixed, paraffin-embedded (FFPE) tissue samples. Methods: Definitive diagnoses included 25 TB cases confirmed through clinical, microbiological, and therapeutic follow-up at the Baghdad Tuberculosis Institute, and 17 non-TB cases classified by predefined clinicopathological criteria supported by relevant clinical data. Zieh–Neelsen (ZN), Periodic acid–Schiff (PAS), and Grocott methenamine silver (GMS) stains were employed to identify acid-fast bacilli and fungal organisms. Statistical analysis was performed using SPSS version 26, with significance set at p ≤ 0.05. Results: The mean patient age was 36.28 years (SD = 20.6), with a female predominance (59.5%). Necrotizing granulomas were identified in 69% of cases and were strongly associated with tuberculosis, which was detected in 59.5% of specimens. ZN staining showed a sensitivity of 16.7% for tuberculosis, while PCR sensitivity was highly dependent on sample age. The detection rate was 33.3% in samples archived for less than 10 years but only 10% in older samples, resulting in an overall sensitivity of 24.0% for tuberculous cases. Langhans-type giant cells were significantly more frequent in necrotizing granulomas and strongly associated with tuberculosis infection (p = 0.001). Fungal infections, predominantly aspergillosis, were confirmed by PAS and GMS in 11.9% and 9.5% of cases, respectively, and were confined to non-necrotizing granulomas. The mandible was the most commonly affected site, and soft tissue lesions were significantly associated with necrotizing granulomas (p = 0.004). Conclusions: These findings underscore the complementary role of histopathology, histochemical stains, and molecular diagnostics in improving the evaluation and diagnosis of granulomatous inflammation in head and neck lesions. Full article

Candidemia is a highly prevalent invasive fungal infection caused primarily by C. albicans, C. parapsilosis, C. glabrata (currently Nakaseomyces glabratus), C. tropicalis, and C. krusei (currently Pichia kudriavzevii). Risk factors for the development of candidemia include steroid-induced immunosuppression used in solid organ or hematopoietic transplantation, and neutropenia secondary to infectious or tumorous processes. Alterations in the gut microbiota in people living with HIV, caused by antiretroviral therapy, increase the possibility of colonization by C. albicans. Likewise, the presence of a central venous catheter, parenteral nutrition, and abdominal surgery stand out as the main risk factors for the development of candidemia. New diagnostic tools have been developed for the diagnosis of this mycosis that allow the identification of the main species, from improvements in conventional stains such as calcofluor white, which increases sensitivity, as well as technologies such as T2 Candida, MoiM assay, biomarker panel (1,3 β-D-glucan, C-reactive protein, presepsin, and procalcitonin), and, more recently, the development of biosensors for the identification of Candida spp. Regarding treatment, the use of micafungin and anidulafungin in patients with obesity defined by a BMI > 30 kg/m² has shown higher survival rates and therapeutic success. Meanwhile, newer antifungals such as rezafungin and fosmanogepix have demonstrated excellent results in the treatment of these patients. Therefore, this review aims to update the epidemiology and risk factors of candidemia, as well as analyze the diagnostic tools and treatments currently available. Full article

Tan spot disease, caused by Pyrenophora tritici-repentis, poses a significant threat to wheat production worldwide. Early detection and precise fungicide application are essential for effective disease management. This study explores the potential of Raman spectroscopy—specifically surface-enhanced Raman spectroscopy (SERS) and coherent anti-Stokes Raman scattering (CARS)—as non-invasive tools for identifying fungal infection and assessing wheat’s biochemical response to propiconazole treatment. The methodology is entirely theoretical; no laboratory experiments were conducted. Instead, all spectral graphs and figures were generated through a collaborative process between the author and Microsoft Copilot, which served as a rendering tool. These AI-assisted visualizations simulate Raman responses based on known molecular interactions and literature data. The results demonstrate the conceptual feasibility of Raman-based diagnostics for precision agriculture, offering a sustainable approach to disease monitoring and fungicide management. Full article

Blastomycosis, caused by dimorphic fungi of the Blastomyces genus, is endemic to regions in North America, including the Great Lakes and other parts of Canada and the United States of America. The infection primarily occurs through the inhalation of airborne conidia from contaminated soil and decaying organic matter. Pulmonary involvement is most common, but dissemination to other organs such as the skin and bones can occur, especially in immunocompromised individuals. Diagnosis is challenging due to its clinical overlap with other diseases. Culture remains the gold-standard diagnostic method, but is time-consuming, with sensitivity ranging from 66.4% to 86%. Tissue histopathology offers quicker results but has sensitivities ranging from 36% to 85%. Antigen detection assays show high sensitivity from 76.3% to 91.3% but suffer from cross-reactivity with other fungi. PCR methods offer high specificity, with sensitivity ranging from 67.6% to 100%. In immunocompromised patients, blastomycosis is often more severe, with a mortality rate exceeding 30%. Multi-modal diagnostic approaches are crucial for accurate detection and management. Full article

Background: Graft-versus-host disease (GVHD) is a rare but serious complication following solid organ transplantation (SOT), particularly in transplants involving organs with a high volume of passenger donor T-lymphocytes. This case highlights the clinical course and diagnostic challenges of GVHD following simultaneous pancreas and pre-emptive kidney transplantation. Methods: A 51-year-old male with long-standing type 1 diabetes mellitus underwent simultaneous pancreas and kidney transplantation with induction therapy using rabbit anti-thymocyte globulin and methylprednisolone. Three months post-transplant, he presented with a diffuse lichenoid cutaneous eruption. Diagnostic evaluation included an extensive infectious workup, skin punch biopsy, liver and bone marrow biopsies, and microchimerism assay. Results: Skin biopsy revealed interface vacuolar dermatitis consistent with cutaneous GVHD. Subsequent liver and bone marrow biopsies confirmed GVHD involvement, with microchimerism assay showing 43% donor-origin T-cells in the bone marrow. Initial treatment with systemic and topical corticosteroids led to temporary improvement. However, the patient developed bone marrow suppression, recurrent bacteremia, and invasive fungal infection, resulting in a prolonged ICU stay and ultimately death. Conclusions: This case underscores the importance of considering SOT-GVHD in patients receiving organs rich in donor lymphocytes, such as pancreas transplants. Early recognition and multidisciplinary management are critical to improving outcomes in this rare but life-threatening condition. Full article

Purpose: Mucormycosis is a life-threatening fungal infection, where rapid diagnosis is critical. We developed a deep learning approach using paranasal computed tomography (CT) images to test whether mucormycosis can be detected automatically, potentially aiding or expediting the diagnostic process that traditionally relies on biopsy. Methods: In this retrospective study, 794 CT images (from patients with mucormycosis, nasal polyps, or normal findings) were analyzed. Images were resized and augmented for training. Two transfer learning models (ResNet50 and ConvNeXt Small) were fine-tuned to classify images into the three categories. We employed a 70/30 train-test split (with five-fold cross-validation) and evaluated performance using accuracy, precision, recall, F1-score, and confusion matrices. Results: The ConvNeXt Small model achieved 100% accuracy on the test set (precision/recall/F1-score = 1.00 for all classes), while ResNet50 achieved 99.16% accuracy (precision ≈0.99, recall ≈0.99). Cross-validation yielded consistent results (ConvNeXt accuracy ~99% across folds), indicating no overfitting. An ablation study confirmed the benefit of transfer learning, as training ConvNeXt from scratch led to lower accuracy (~85%) Conclusions: Our findings demonstrate that deep learning models can accurately and non-invasively detect mucormycosis from CT scans, potentially flagging suspected cases for prompt treatment. These models could serve as rapid screening tools to complement standard diagnostic methods (histopathology), although we emphasize that they are adjuncts and not replacements for biopsy. Future work should validate these models on external datasets and investigate their integration into clinical workflows for earlier intervention in mucormycosis. Full article

Sporotrichosis is a zoonotic fungal infection with increasing incidence in the Brazilian Amazon, primarily affecting domestic cats and posing risks to human health. This study characterized the clinical and epidemiological profiles of 29 feline sporotrichosis cases in Manaus and optimized molecular diagnostic methods for Sporothrix species identification. Most affected cats were young (86.2% aged 1–3 years), male (82.7%), and free-roaming or semi-indoor (44.8% each), frequently presenting cutaneous lesions localized at the nasal planum (23.3%), ears (7%), eyes (2.3%) and other facial areas (18.6%). Three DNA extraction methods were compared; the phenol–chloroform protocol yielded the highest DNA concentration and purity, and ITS1–ITS4 primers showed an adequate sensibility for PCR detection. In silico RFLP profiles using common restriction enzymes showed limited discriminatory power among Sporothrix species. ITS sequencing of four high-quality amplicons confirmed all isolates as Sporothrix brasiliensis. Antifungal susceptibility testing of all isolates revealed geometric mean MICs of 0.25 µg/mL for ketoconazole, 0.57 µg/mL for itraconazole, 7.27 µg/mL for amphotericin B, and 64 µg/mL for fluconazole, respectively. These findings provide clinical, molecular, and therapeutic information supporting the diagnosis and surveillance of feline sporotrichosis in the Amazon, reinforcing the need for ongoing veterinary and public health monitoring. Full article

Invasive candidiasis (IC), characterized by the most common clinical manifestation of candidemia, is a fungal infection with a high mortality rate and a significant impact on global public health. It is estimated that each year there are between 227,000 and 250,000 hospitalizations related to IC, with more than 100,000 associated deaths. In Latin America and the Caribbean (LA&C), the absence of a standardized surveillance system has led to multicenter studies documenting incidences ranging from 0.74 to 6.0 cases per 1000 hospital admissions, equivalent to 50,000–60,000 hospitalizations annually, with mortality rates of up to 60% in certain high-risk groups. Armed conflicts and structural violence in LA&C cause forced displacement, the collapse of health systems, and poor living conditions—such as overcrowding, malnutrition, and lack of sanitation—which increase vulnerability to opportunistic infections, such as IC. Insufficient specialized laboratories, diagnostic technology, and trained personnel impede pathogen identification and delay timely initiation of antifungal therapy. Furthermore, the empirical use of broad-spectrum antibiotics and the limited availability of echinocandins and lipid formulations of amphotericin B have promoted the emergence of resistant non-albicans strains, such as Candida tropicalis, Candida parapsilosis, and, in recent outbreaks, Candidozyma auris. Full article