Disseminated emergomyces orientalis infection in a patient with systemic lupus erythematosus.

A case of Eimonosis orientalis was reported in a 52-year-old male farmer who presented with cough, phlegm, fever, headache, and nausea for more than 4 days. Haemophilic cells and fungal spores were identified in the bone marrow smear and confirmed as Aemon orientalis by culture. The same bacteria were also isolated from blood cultures.

Metagenomic next-generation sequencing assisted in the successful treatment of pneumonia caused by Talaromyces marneffei in an immunocompetent patient.

INTRODUCTION: Talaromyces marneffei (T. marneffei), a kind of endemic opportunistic pathogen, was previously thought to occur in HIV-positive individuals and non-HIV hosts with impaired immune function. However, the infection of T. marneffei in patient with normal immune function was rarely reported. CASE PRESENTATION: We report a case of severe pneumonia caused by T. marneffei in an immunocompetent and HIV-negative patient, which was rapidly confirmed by metagenomics next-generation sequencing (mNGS) and treated successfully. The patient was a previously healthy 63-year-old male, who was admitted to hospital with fever for 11 days, cough and sputum for 1 week, and chest distress for 4 days. The infection of T. marneffei was quickly determined by alveolar lavage under bedside bronchoscope and mNGS test. RESULTS: Patient's condition improved rapidly after voriconazole treatment, and he was evaluated as a HIV-negative case of T. marneffei infection with normal immune function. This is a sporadic case of T. marneffei in non-endemic areas, and mNGS played a very important role in the treatment of the disease. The patient's immune function was relatively normal which was rare in clinical practice.

Fungal coinfection/superinfection in COVID-19 patients in a tertiary hospital in Mexico / Coinfección o sobreinfección fúngica en pacientes con COVID-19 en un hospital de tercer nivel en México

Introduction: Data on the prevalence of fungal coinfections/superinfections in patients with COVID-19 are limited. Objective: To describe the prevalence of fungal coinfections/superinfections in patients with COVID-19, as well as risk factors and demographic, clinical, and microbiological characteristics. Material and methods: We included patients with a confirmed COVID-19 diagnosis and a confirmed fungal infection hospitalized in the ICU from March 2020 to December 2021. We collected data on age, sex, comorbidities, hospital length of stay (days), laboratory (ferritin) and microbiological results, treatment for COVID-19, antifungal therapy, and outcomes obtained from the clinical records. Results: Only 11 out of 740 patients met the inclusion criteria. The coinfection rate was 0.3% and the superinfection was 1.2%. The most affected population was male adults. The coinfections/superinfections diagnosed were candiduria and candidemia, caused by Candida albicans, C. tropicalis, C. glabrata, C. lusitaniae, and Kluyveromyces marxianus (C. kefyr). In addition, tracheobronchitis due to Aspergillus fumigatus was found. The most used antifungals were fluconazole and caspofungin. The lethality in patients with fungal coinfections was 50% and superinfections, 22%. The length of hospital stay was 11-65 days. Eight patients required mechanical ventilation and six received corticosteroids. The main comorbidity was diabetes mellitus (81.8%). Conclusions: The rate of fungal coinfections/superinfections in COVID-19 patients was low, but the lethality found urges for routine fungal screening in patients with severe COVID-19 to timely detect fungal infections that may further compromise the patient's life.

Introducción: Los datos sobre la prevalencia de coinfecciones o sobreinfecciones fúngicas en pacientes con COVID-19 son limitados. Objetivo: Describir la prevalencia de coinfecciones o sobreinfecciones fúngicas en pacientes con COVID-19, así como los factores de riesgo y las características demográficas, clínicas y microbiológicas. Material y métodos: Se incluyeron pacientes con diagnóstico confirmado de COVID-19, hospitalizados en la unidad de cuidados intensivos y con infección fúngica confirmada entre marzo del 2020 y diciembre del 2021. Del expediente clínico se obtuvieron datos sobre edad, sexo, comorbilidades, días de estancia hospitalaria, resultados de laboratorio (ferritina) y microbiológicos, tratamiento contra COVID-19, terapia antifúngica y desenlace. Resultados: Once de 740 pacientes cumplieron con los criterios de inclusión. La tasa de coinfección fue del 0,3 % y la de sobreinfección fue del 1,2 %. La población más afectada fue la de hombres adultos. Las coinfecciones o sobreinfecciones diagnosticadas fueron candiduria y candidemia, causadas por Candida albicans, C. tropicalis, C. glabrata, C. lusitaniae y Kluyveromyces marxianus (C. kefyr). Además, se encontró una traqueobronquitis por Aspergillus fumigatus. Los antifúngicos más administrados fueron fluconazol y caspofungina. La letalidad en pacientes con coinfecciones fue del 50 % y con sobreinfecciones fúngicas, del 22 %. El tiempo de estancia intrahospitalaria fue de 11 a 65 días. Ocho de los pacientes requirieron asistencia respiratoria mecánica y seis recibieron corticoides. La principal comorbilidad fue diabetes mellitus (81,8 %). Conclusiones: La tasa de coinfecciones o sobreinfecciones por hongos en pacientes con COVID-19 fue baja, pero la letalidad de estas requiere, con urgencia, la realización de pruebas de rutina para detectar hongos en pacientes con COVID-19 grave para diagnosticar oportunamente infecciones fúngicas que puedan comprometer aún más la vida del paciente.

[Development of Lomentospora prolificans infection during induction therapy with venetoclax and azacitidine for acute myeloid leukemia].

Lomentospora prolificans is a rare filamentous fungus that causes invasive fungal disease (IFD) in immunocompromised patients with hematological malignancies, as well as hematopoietic cell or solid organ transplant recipients. A 75-year-old woman was diagnosed with acute myeloid leukemia, and started induction therapy with azacitidine and adjusted-dose venetoclax along with antifungal prophylaxis with fluconazole. On day 7, she became febrile and chest CT imaging showed multiple nodules in both lung fields, and the serum galactomannan antigen index became positive, indicating probable IFD. Anti-fungal therapy with liposomal amphotericin B was immediately initiated; however, the patient's condition rapidly deteriorated, and she died on day 15. L. prolificans was later identified in blood culture tests that had been repeatedly performed while she had been febrile. L. prolificans is generally resistant to most antifungal agents, which can make it fatal. As early definitive diagnosis is difficult, it may be appropriate to consider combination therapy when conventional anti-IFD therapy seems inadequate.

[Infections and liver cirrhosis]. / Infektionen und Leberzirrhose.

End-stage liver disease is a life-threatening clinical syndrome combined with a state of immune dysfunction. In this constellation patients are prone to bacterial, fungal and viral infections associated with markedly increased morbidity and mortality rates. Bacterial infections are the most prevalent kind of infection in patients with end-stage liver disease accounting for nearly 30%. The evolving rates of multidrug resistant organisms present enormous challenges in treatment strategies. Therefore, the urgent needs for prevention, early detection strategies and widespread treatment options are a necessity to handle the rising incidence of infection complications in end-stage liver disease.

Direct antiglobulin (Coombs) test in HIV-positive Talaromycosis marneffei patients.

Talaromycosis marneffei (T.M) is the primary opportunistic infection of AIDS patients, and its morbidity and mortality are extremely high. To further clarify the disease characteristics of patients and provide a solid basis for in-depth exploration of their pathogenic mechanisms, we retrospectively summarized and analyzed their clinical data. We included all T.M patients tested for direct antiglobulin test (DAT) in the study. Interestingly, we found that AIDS-T.M patients had an extremely high rate of DAT positivity (92/127, 72.44%). In univariate analysis, a positive DAT was associated with blood culture of TM (P = .021), hypoproteinemia (P = .001), anemia (P = .001), thrombocytopenia (P = .003), sepsis (P = .007), and Sequential Organ Failure Assessment (SOFA) (P = .001). Hypoproteinemia, anemia, SOFA, APTT > 32.6 s, and AST > 40 U/l were studied by logistic regression. Logistic regression revealed that SOFA (OR = 1.311, P = .043), hypoproteinemia (OR = 0.308, P = .021), and anemia (OR = 0.19, P = .044) were associated with positive DAT. Positive DAT was associated with severe disease manifestations such as sepsis, and the DAT test is crucial in patients with fungemia.

Talaromycosis marneffei (T.M) is the primary opportunistic infection of AIDS patients and causes high morbidity and mortality. AIDS-T.M patients who were positive for direct antiglobulin test had higher manifestations of inflammation, abnormal liver function, coagulation dysfunction, and hematologic abnormalities.

Isolated masseter muscle fungal invasion: unmasking the culprit.

This case report focusses on a unique and infrequently observed event where an isolated masseter muscle fungal invasion was seen. The patient's symptoms include facial swelling and restricted mouth opening. The rarity of this particular manifestation is emphasised by the fact that there are no previously reported cases where fungal infection was the cause of isolated masseter muscle involvement. This lack of documented cases underscores the novelty and significance of the current case.

Marrow talaromycosis as the initial presentation in a case of Burkitt lymphoma.

Talaromyces marneffei is a thermally dimorphic fungus which causes opportunistic infections in immunocompromised individuals. The diagnosis of T. marneffei infection rests on the microscopic demonstration of the fungus in the tissues and/or isolation of the fungus from clinical specimens. In this report, we discuss a case involving a 23-year-old man who presented with a history of intermittent fever, cough and constitutional symptoms. Clinically, the patient exhibited pallor, jaundice, generalized seborrhoeic dermatitis, hepatomegaly, and small palpable cervical lymph nodes. A computed tomography (CT) scan of the abdomen showed homogenous hypodense lesions in both liver lobes. HIV screening result was reactive. Microscopic examination of the bone marrow aspirate smear and trephine biopsy identified fungal bodies, and culture of the marrow aspirate confirmed the presence of T. marneffei. Notably, the liver biopsy revealed Burkitt lymphoma alongside fungal bodies. He was treated with intravenous Amphotericin B but ultimately succumbed to the illness due to severe metabolic acidosis and multiorgan failure. This case underscores the importance of presumptive diagnosis through morphological or histological examination of bone marrow samples, as microbiologic culture methods can be time-consuming. Timely diagnosis and aggressive treatment are critical in managing patients with T. marneffei infection.

Allergic Bronchopulmonary Mycosis with Eosinophilia Caused by Schizophyllum Infection.

BACKGROUND: As an opportunistic pathogenic fungus, Schizophyllum has been rarely reported to infect humans. By reporting a case of definite diagnosis of Schizophyllum infection, we aim to improve clinicians' understanding of this bacterium. METHODS: By reporting a case with cough and sputum as the main manifestations, after empirical antiinfective chest CT suggesting a more progressive inflammatory lesion and a mass-like lesion in the paratracheal area of the main airways, a diagnosis of Schizophyllum infection was finally made by bronchoscopy with the delivery of metagenomic next-generation sequencing (mNGS). RESULTS: The patient was finally diagnosed with rare Schizophyllum infection. After antifungal treatment, the symptoms improved, and the patient was discharged. CONCLUSIONS: Although Schizophyllum is a rare fungal infection, it should be taken seriously in patients with diabetes or who are immunocompromised. At the same time, mNGS plays a key role in the detection of rare and emerging pathogens, which is worthy of clinical interest.

Real-time application of ITS and D1-D3 nanopore amplicon metagenomic sequencing in fungal infections: Enhancing fungal infection diagnostics.

While fungal infections cause considerable morbidity and mortality, the performance of the current diagnostic tests for fungal infection is low. Even though fungal metagenomics or targeted next-generation sequencing have been investigated for various clinical samples, the real-time clinical utility of these methods still needs to be elucidated. In this study, we used internal transcribed spacer (ITS) and D1-D3 ribosomal DNA nanopore amplicon metagenomic sequencing to assess its utility in patients with fungal infections. Eighty-four samples from seventy-three patients were included and categorized into 'Fungal infection,' 'Fungal colonization,' and 'Fungal contamination' groups based on the judgement of infectious disease specialists. In the 'Fungal infection' group, forty-seven initial samples were obtained from forty-seven patients. Three fungal cases detected not by the sequencing but by conventional fungal assays were excluded from the analysis. In the remaining cases, the conventional fungal assay-negative/sequencing-positive group (n=11) and conventional fungal assay-positive/sequencing-positive group (n=33) were compared. Non-Candida and non-Aspergillus fungi infections were more frequent in the conventional-negative/sequencing-positive group (p-value = 0.031). We demonstrated the presence of rare human pathogens, such as Trichosporon asahii and Phycomyces blakesleeanus. In the 'Fungal infection' group and 'Fungal colonization' group, sequencing was faster than culturing (mean difference = 4.92 days, p-value < 0.001/ mean difference = 4.67, p-value <0.001). Compared to the conventional diagnostic methods including culture, nanopore amplicon sequencing showed a shorter turnaround time and a higher detection rate for uncommon fungal pathogens.

Metagenomic Next-Generation Sequencing as an Effective Diagnostic Tool for Talaromycosis in HIV-Negative Patients.

The diagnosis of Talaromyces marneffei infection in HIV-negative patients remains challenging. There is an urgent need for rapid and convenient methods to diagnose this complicated disease. The aim of this study was to evaluate the diagnostic efficiency of metagenomic next-generation sequencing (mNGS) for talaromycosis in non-HIV-infected patients by comparing mNGS with traditional microbial culture. In total, 66 samples from 57 patients were analyzed via both mNGS and microbial culture. The ROC curve showed a sensitivity for mNGS of 97.22%, which was greater than that of microbial culture (61.11%). Samples from the respiratory tract, infectious skin lesions, and lymph nodes are recommended as routine samples for talaromycosis detection via mNGS. Furthermore, mNGS significantly reduced the diagnostic time compared to microbial culture. Overall, our study demonstrated that mNGS is a promising tool for rapid and accurate pathogenic detection in HIV-negative patients with talaromycosis.

Diagnostic accuracy of double density sign on CT scan of para-nasal sinuses for fungal sinusitis taking microbiology culture as gold standard.

Objectives: To compare double-density sign on non-contrast computed tomography scan of paranasal sinuses with fungal sinusitis on histopathology. METHODS: This prospective study was conducted at the Shifa International Hospital, Islamabad, Pakistan, from July 1, 2021, to June 30, 2023, and comprised patients of either gender aged 20-60 years who were set to undergo functional endoscopic sinus surgery. Demographic characteristics and non-contrast computed tomography scan findings were recorded preoperatively, while microbiological and histopathology results were recorded post-operatively. The microbiological finding was taken as the gold standard. Data was analysed using SPSS 23. RESULTS: Of the 201 patients, 123(61.2%) were males and 78(38.8%) were females. The overall mean age was 41.62±8.52 years. The diagnostic accuracy of a double-density sign on computed tomography scan showed sensitivity 90%, specificity 90.8%, positive predictive value 84%, and negative predictive value 94.4%. CONCLUSIONS: A higher rate of sensitivity and specificity indicated that non-contrast computed tomography scan was an effective modality that could be used for the diagnosis of fungal sinusitis.

Development of a TaqMan probe-based multiplex real-time PCR for the simultaneous detection of four clinically important filamentous fungi.

Filamentous fungi present significant health hazards to immunocompromised individuals globally; however, the prompt and precise identification of them during infection remains challenging. In this study, a TaqMan probe-based multiplex real-time PCR (M-qPCR) assay was developed to detect simultaneously the target genes of four important pathogenic filamentous fungi: ANXC4 gene of Aspergillus fumigatus, EF1-α gene of Fusarium spp., mitochondrial rnl gene of Mucorales, and hcp100 gene of Histoplasma capsulatum. In this M-qPCR assay, the limit of detection (LoD) to all four kinds of fungi was 100 copies and the correlation coefficients (R2) were above 0.99. The specificity of this assay is 100%, and the minimum detection limit is 100 copies/reaction. In conclusion, an M-qPCR detection assay was well established with high specificity and sensitivity for rapid and simultaneous detection on four important filamentous fungi in the clinic. IMPORTANCE: World Health Organization developed the first fungal priority pathogens list (WHO FPPL) in 2022. Aspergillus fumigatus, Mucorales, Fusarium spp., and Histoplasma spp. are the four types of pathogenic fungi with filamentous morphology in the critical priority group and high priority group of WHO FPPL. These four filamentous fungal infections have become more common and severe in immunocompromised patients with the increase in susceptible populations in recent decades, which resulted in a substantial burden on the public health system. However, prompt and precise identification of them during infection remains challenging. Our study established successfully a TaqMan probe-based multiplex real-time qPCR assay for four clinically important filamentous fungi, A. fumigatus, Fusarium spp., Mucorales, and Histoplasma capsulatum, with high sensitivity and specificity, which shows promising potential for prompt and precise diagnosis against fungal infection.

Exploring the potential of chitin and chitosan in nanobiocomposites for fungal immunological detection and antifungal action.

Chitin is a polymer of N-acetylglucosamine and an essential component of the fungal cell wall. Chitosan is the deacetylated form of chitin and is also important for maintaining the integrity of this structure. Both polysaccharides are widely distributed in nature and have been shown to have a variety of applications in biomedicine, including their potential in immune sensing and as potential antifungal agents. In addition, chitin has been reported to play an important role in the pathogen-host interaction, involving innate and adaptive immune responses. This paper will explore the role of chitin and chitosan when incorporated into nanobiocomposites to improve their efficacy in detecting fungi of medical interest and inhibiting their growth. Potential applications in diagnostic and therapeutic medicine will be discussed, highlighting their promise in the development of more sensitive and effective tools for the early diagnosis of fungal infections. This review aims to highlight the importance of the convergence of nanotechnology and biology in addressing public health challenges.

Value of MRI signal intensity in evaluation of allergic fungal rhinosinusitis compared with CT Hounsfield units: Retrospective study.

"Allergic fungal sinusitis (AFS)" is typically diagnosed using radiologic images like computed tomography (CT) scans and magnetic resonance imaging (MRI), with the "Hounsfield unit (HU)" in CT scans and T2-weighted images (T2WI) in MRI serving as reliable objective parameters. However, diagnosing AFS might be difficult because of possible signal changes and densities caused by variations in the secretion concentration in the sinus. Few studies have compared the diagnostic performance of MRI and CT scans. This study aimed to investigate the value of MRI signal intensity in evaluating AFS compared with CT HUs. This retrospective study included 111 patients with pathologically confirmed AFS who underwent CT imaging followed by MRI evaluation at King Saud Medical City, Riyadh, Saudi Arabia, from January 2012 to December 2022. Radiographic densities of sinus opacities on CT scan, including the mean HU values, and MRI findings, including signal voids on T1-weighted images and T2WI, were gathered and analyzed. To determine the efficacy of these radiographic characteristics in predicting the disease and the best cutoff value, we employed receiver operator characteristic curves. The mean age was 31.9 ±â€…15.6 years, and most patients were 74 females (66.7%). The main symptom was nasal obstruction in 73 patients (65.8%). In comparison, between HU and signal void on T2WI, there was moderate predictive performance [area under the curve: 0.856, P = .001]. An ideal HU cutoff value of 69.50 HU was obtained with a sensitivity of 100% and a specificity of 44.7%. However, the receiver operator characteristic for T1-weighted images could not be plotted, as no signal was avoided to predict AFS and it was not statistically significant (area under the curve: 0.566; P = .287). The study found a CT HU of 69.5 can predict MRI T2WI signal values with a void signal, aiding in diagnostic workup and evaluation for AFS.

The long Pentraxin PTX3 serves as an early predictive biomarker of co-infections in COVID-19.

BACKGROUND: COVID-19 clinical course is highly variable and secondary infections contribute to COVID-19 complexity. Early detection of secondary infections is clinically relevant for patient outcome. Procalcitonin (PCT) and C-reactive protein (CRP) are the most used biomarkers of infections. Pentraxin 3 (PTX3) is an acute phase protein with promising performance as early biomarker in infections. In patients with COVID-19, PTX3 plasma concentrations at hospital admission are independent predictor of poor outcome. In this study, we assessed whether PTX3 contributes to early identification of co-infections during the course of COVID-19. METHODS: We analyzed PTX3 levels in patients affected by COVID-19 with (n = 101) or without (n = 179) community or hospital-acquired fungal or bacterial secondary infections (CAIs or HAIs). FINDINGS: PTX3 plasma concentrations at diagnosis of CAI or HAI were significantly higher than those in patients without secondary infections. Compared to PCT and CRP, the increase of PTX3 plasma levels was associated with the highest hazard ratio for CAIs and HAIs (aHR 11.68 and 24.90). In multivariable Cox regression analysis, PTX3 was also the most significant predictor of 28-days mortality or intensive care unit admission of patients with potential co-infections, faring more pronounced than CRP and PCT. INTERPRETATION: PTX3 is a promising predictive biomarker for early identification and risk stratification of patients with COVID-19 and co-infections. FUNDING: Dolce & Gabbana fashion house donation; Ministero della Salute for COVID-19; EU funding within the MUR PNRR Extended Partnership initiative on Emerging Infectious Diseases (Project no. PE00000007, INF-ACT) and MUR PNRR Italian network of excellence for advanced diagnosis (Project no. PNC-E3-2022-23683266 PNC-HLS-DA); EU MSCA (project CORVOS 860044).

Clinico-mycological characteristics and outcomes of rare yeast infections.

Unusual fungi, encountered infrequently in practice, present a significant diagnostic challenge, leading to potential delays in diagnosis and treatment. This study aims to describe a number of cases, where infections were caused by rare yeast pathogens. Organisms isolated included rare Candida species, Geotrichum, Lodderomyces and Trichosporon species. The mean duration of the outcome of the patients from microbiological diagnosis was 20 days. A total of 3 patients succumbed to their illness. This study aims to shed light on the varied clinical presentation and outcome of infections caused by rare yeast pathogens.

SCHIZANGIELLA INFECTIONS IN AN EASTERN RATSNAKE (PANTHEROPHIS ALLEGHANIENSIS) AND A TIMBER RATTLESNAKE (CROTALUS HORRIDUS).

This report describes Schizangiella infections in colubrid and viperid snakes. A captive eastern ratsnake (Pantherophis alleghaniensis) was presented for a large intraoral mass associated with the mandible. The mass was debulked and histologic examination revealed severe, granulomatous stomatitis with intralesional fungi exhibiting morphologic features consistent with Schizangiella serpentis. PCR and sequencing of affected tissues confirmed S. serpentis. Because of declining health, the ratsnake was euthanized and postmortem examination identified a disseminated S. serpentis infection involving the skeletal musculature, lung, kidney, mesentery, and mandible. A wild-caught timber rattlesnake (Crotalus horridus) was presented for cutaneous lesions, weakness, and lethargy and later died. Postmortem examination revealed a mass-like structure in the esophagus characterized by high numbers of Schizangiella-like fungi associated with extensive granulomatous inflammation; the snake also had cutaneous mycosis suggestive of ophidiomycosis. This is the first report to document the unique morphologic features of S. serpentis in tissues and the presentation of schizangiellosis in snakes. Schizangiellosis should be considered as a differential diagnosis for nodular lesions involving the oral cavity and/or the gastrointestinal tract of snakes.