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Introduction: Aspergillosis is a fungal infection commonly found in human lungs and takes several forms. Chronic pulmonary aspergillosis (CPA) commonly affects individuals with underlying disease, most usually lung tuberculosis (TB). Aspergillosis can cause the formation of a fungus ball in the lung cavity and can also manifest in the tracheobronchial area, although this is rarely seen in immunocompetent patients. Case: A 23-year-old woman came with persistent cough, hemoptysis, and shortness of breath for 4 months. The patient also had a significant weight loss and a history of lung TB 3 years ago. She had completed her lung TB medication. Physical examination showed increased respiratory rate and rhonchi on the left lung. GeneXpert showed no Mycobacterium tuberculosis (MTB) detected. The chest X-ray showed a cavity on the left superior lobe of the lung. Bronchoscopy showed multiple plaques along the trachea, carina, and left main bronchus. A chest computed tomography (CT) scan with contrast enhancement was performed, and a fungus ball was found inside the cavity in the left upper lobe of the lung. The patient was given intravenous fluconazole as therapy and continued with oral fluconazole when discharged. A second bronchoscopy was performed, and improvement was shown. Conclusion: Early detection and treatment should be applied to CPA patients since some studies showed poor prognosis and low five-year survival rates.

Abstract Background The performance and availability of invasive and non-invasive investigations for the diagnosis of Pneumocystis jirovecii pneumonia (PCP) vary across clinical settings. Estimating the pre-test probability of PCP is essential to the optimal selection and interpretation of diagnostic tests, such as the 1,3-β-D-glucan assay (BDG), for the prioritization of bronchoscopy, and to guide empiric treatment decisions. We aimed to develop a multivariable risk score to estimate the pre-test probability of PCP. Methods The score was developed from a cohort of 626 individuals who underwent bronchoscopy for the purposes of identifying PCP in a Canadian tertiary-care centre, between 2015 and 2018. We conducted a nested case-control study of 57 cases and 228 unmatched controls. Demographic, clinical, laboratory, and radiological data were included in a multivariable logistic regression model to estimate adjusted odds ratios for PCP diagnosis. A clinical risk score was derived from the multivariable model and discrimination was assessed by estimating the score’s receiver operating characteristic curve. Results Participants had a median age of 60 years (interquartile range [IQR] 49–68) and 115 (40%) were female; 40 (14%) had HIV and 49 (17%) had a solid organ transplant (SOT). The risk score included prior SOT or HIV with CD4 ≤ 200/µL (+ 2), serum lactate dehydrogenase ≥ 265.5 IU/mL (+ 2), radiological pattern typical of PCP on chest x-ray (+ 2) or CT scan (+ 2.5), and PCP prophylaxis with trimethoprim-sulfamethoxazole (-3) or other antimicrobials (-2). The median score was 4 points (IQR, 2-4.5) corresponding to a 28% probability of PCP. The risk prediction model had good discrimination with a c-statistic of 0.79 (0.71–0.84). Given the operating characteristics of the BDG assay, scores ≤ 3 in patients without HIV, and ≤ 5.5 in those with HIV, paired with a negative BDG, would be expected to rule out PCP with 95% certainty. Conclusion We propose the PCP Score to estimate pre-test probability of PCP. Once validated, it should help clinicians determine which patients to refer for invasive investigations, when to rely on serological testing, and in whom to consider pre-emptive treatment.

Histoplasmosis is a fungal disease associated with substantial mortality rates among persons with advanced HIV disease. Our systematic review synthesized data on the global prevalence of Histoplasma­-caused antigenuria in persons with HIV. We searched PubMed/Medline, Embase, and Scopus databases on January 3, 2023, to identify cross-sectional and cohort studies evaluating Histoplasma antigenuria prevalence among adults with HIV infection. We calculated point estimates and 95% CIs to summarize prevalence. Of 1,294 studies screened, we included 15. We found Histoplasma antigenuria among 581/5,096 (11%; 95% CI 11%–12%) persons with HIV and 483/3,789 persons with advanced HIV disease (13%; 95% CI 12%–14%). Among persons with HIV and symptoms consistent with histoplasmosis, Histoplasma antigenuria prevalence was 14% (95% CI 13%–15%; 502/3,631 participants). We determined that persons with advanced HIV disease, inpatients, and symptomatic persons might benefit from a systematic approach to early detection of histoplasmosis using urine antigen testing.

A 59-year-old immunocompetent male who initially presented with symptoms of stroke was found to have an incidental rim-enhancing lesion on magnetic resonance imaging (MRI) of the brain. This discovery led to a lumbar puncture to analyze the cerebrospinal fluid, resulting in the diagnosis of cryptococcoma. The patient was subsequently managed with liposomal amphotericin B, followed by consolidation and maintenance therapy with fluconazole. The patient achieved a positive outcome, demonstrating the effectiveness of early diagnosis and targeted treatment. The rarity of cryptococcoma in immunocompetent individuals makes this case particularly unusual and noteworthy. It underscores the need for more extensive research to enable prompt diagnosis and effective management.

Background: COVID-19-associated pulmonary aspergillosis (CAPA) has emerged as a relatively common complication. Multiple studies described this relationship in critical patients, however its incidence and outcome in other risk groups such as immunosuppressed patients remains unknown. In this sense, we aimed to evaluate the rates and outcomes of CAPA in hematological patients and according to the different hematological malignances, comparing to invasive pulmonary aspergillosis (IPA) in non-COVID-19 ones. Methods: Nationwide, population-based and retrospective observational cohort study including all adult patients with hematological malignancies admitted in Spain since March 1, 2020 to December 31, 2021. The main outcome variable was the diagnosis of IPA during hospitalization in hematological patients with or without COVID-19 at admission. The rate of CAPA compared to IPA in non-COVID-19 patients in each hematological malignancy was also performed, as well as survival curve analysis. Findings: COVID-19 was diagnosed in 3.85 % (4367 out of 113,525) of the hematological adult inpatients. COVID-19 group developed more fungal infections (5.1 % vs. 3 %; p

Summary: Background: Coccidioidomycosis, an emerging fungal disease in the western USA, exhibits seasonal patterns that are poorly understood, including periods of strong cyclicity, aseasonal intervals, and variation in seasonal timing that have been minimally characterized, and unexplained as to their causal factors. Coccidioidomycosis incidence has increased markedly in recent years, and our limited understanding of intra- and inter-annual seasonality has hindered the identification of important drivers of disease transmission, including climate conditions. In this study, we aim to characterize coccidioidomycosis seasonality in endemic regions of California and to estimate the relationship between drought conditions and coccidioidomycosis seasonal periodicity and timing. Methods: We analysed data on all reported incident cases of coccidioidomycosis in California from 2000 to 2021 to characterize seasonal patterns in incidence, and conducted wavelet analyses to assess the dominant periodicity, power, and timing of incidence for 17 counties with consistently high incidence rates. We assessed associations between seasonality parameters and measures of drought in California using a distributed lag nonlinear modelling framework. Findings: All counties exhibited annual cyclicity in incidence (i.e., a dominant wavelet periodicity of 12 months), but there was considerable heterogeneity in seasonal strength and timing across regions and years. On average, 12-month periodicity was most pronounced in the Southern San Joaquin Valley and Central Coast. Further, the annual seasonal cycles in the Southern San Joaquin Valley and the Southern Inland regions occurred earlier than those in coastal and northern counties, yet the timing of annual cycles became more aligned among counties by the end of the study period. Drought conditions were associated with a strong attenuation of the annual seasonal cycle, and seasonal peaks became more pronounced in the 1–2 years after a drought ended. Interpretation: We conclude that drought conditions do not increase the risk of coccidioidomycosis onset uniformly across the year, but instead promote increased risk concentrated within a specific calendar period (September to December). The findings have important implications for public health preparedness, and for how future shifts in seasonal climate patterns and extreme events may impact spatial and temporal coccidioidomycosis risk. Funding: National Institutes of Health.

ABSTRACT Invasive fungal infections (IFIs) caused by pathogenic fungi pose a significant public health concern, particularly for immunocompromised individuals. Mortality rates for IFIs remain high, and currently available treatment options are limited. Existing antifungal agents often suffer from limited clinical efficacy, poor fungicidal activity within the host, potential toxicity, and increasing ineffectiveness due to emerging resistance, especially against triazole drugs, the current mainstay of antifungal treatment. A recent study has identified MBX-7591, a small molecule with promising antifungal activity against Aspergillus fumigatus and other pathogenic fungi, including strains resistant to triazoles (C. Gutierrez-Perez, C. Puerner, J. T. Jones, S. Vellanki, E. M. Vesely, et al., mBio e01166-24, 2024, https://doi.org/10.1128/mbio.01166-24). This novel compound appears to inhibit stearoyl-CoA 9-desaturase, a key enzyme involved in fungal fatty acid biosynthesis. By disrupting the conversion of saturated fatty acids to oleic acid, MBX-7591 offers a unique mechanism of action, potentially reducing the risk of resistance development. Here, we now discuss the implications of these groundbreaking findings for overcoming antifungal drug resistance.

Background: In the Balkans, rising concerns about invasive fungal infections over the past decade stem from various factors. Primarily, there has been a notable uptick in immunocompromised individuals, including those with chronic illnesses like immunological and hematological diseases. Thus, it is essential to assess the region's laboratory capabilities and the availability of antifungals. This evaluation is vital for gauging the preparedness to diagnose and treat fungal infections effectively, thus minimizing their public health impact. Methods: Data were collected via an online questionnaire targeting healthcare professionals specializing in relevant fields across diverse healthcare settings in Balkan countries. The survey covered various aspects, including diagnostic methods, imaging techniques, and available antifungal armamentarium. Results: Responses were obtained from 50 institutions across the Balkans. While conventional diagnostic methods like microscopy (96 %) and culture (100 %) diagnostics were widely available, access to newer diagnostic tools such as molecular assays (61 %) were limited, often relying on outsourced services. Imaging modalities like ultrasound (100 %) and CT scans (93 %) were universally accessible. A variety of antifungal drugs were available, including amphotericin B formulations (80 %), echinocandins (79 %), and triazoles (100 %). However, access to newer agents like posaconazole (62 %) and isavuconazole (45 %) was inconsistent. Therapeutic drug monitoring (53 %) services were also limited. Conclusion: The study underscores the need for equitable access to diagnostic facilities and antifungal treatments across healthcare settings in the Balkan geographic region. Improving access to molecular diagnostic tools and essential antifungal drugs, as well as implementing therapeutic drug monitoring, would optimize the management of fungal infections in the region.

Background: Candida species, commonly present in the human body, can result in severe infections. Non-albicans Candida (NAC) species, with increasing antifungal resistance, pose a growing concern. Aims and Objectives: This study aims to evaluate candidiasis prevalence and antifungal susceptibility in isolated Candida species among suspected patients at tertiary care hospitals in Butwal, emphasizing early identification and appropriate treatment to avoid unnecessary use of toxic antifungal drugs. Materials and Methods: In a descriptive study on 303 patients with clinical symptoms of Candida infections, specimens underwent direct microscopic examination and culture on Sabouraud dextrose agar. Species identification involved phenotypic methods such as chromogenic character on CHROMagar Candida media, germ tube examination, and microscopic characteristics. Subsequently, isolated species were tested for antifungal susceptibility using the disc diffusion method. Results: Among the 303 samples tested, 80 (26.4%) were positive for candidal infection. NAC species were the most commonly isolated, with Candida albicans and Candida krusei being the most virulent. The isolates exhibited the highest sensitivity to fluconazole (77.5%) followed by itraconazole (75%), whereas amphotericin B showed the lowest effectiveness with 63.75% resistance. Conclusion: The rising prevalence of NAC species, particularly their growing resistance to Amphotericin B, has become a significant concern, as these species are frequently detected in various clinical samples. These findings underscore the importance of diligent monitoring and judicious selection of antifungal agents to ensure effective treatment strategies.

Abstract Background The polymer-based facile and effective drug carrier approach was developed to treat superficial fungal infected retinopathy infections. Methods Here, biotin-glutathione (B-GHS) functionalized with chitosan grafted proline (CS-g-P) moieties were fabricated with the loading of fluconazole (FLZ) for the treatment of retinopathy. FT-IR and XRD techniques were used to characterize chemical structural and phase changes of the prepared carriers The SEM results show that the sphere morphology with interconnection particle nature. Results The particle diameter was found as ~ 6.5 and ~ 8.6 nm for CS-g-P/B-GHS and FLZ-loaded CS-g-P/B-GHS carriers, respectively. The negative surface charge was found as the values of CS-g-P/B-GHS and FLZ-loaded CS-g-P/B-GHS, such as -20.7 mV and − 32.2 mV, from zeta potential analysis. The in-vitro FLZ releases from the CS-g-P/B-GHS were investigated at pH 7.4 (PBS) as the tear fluid environment, and it was observed at 85.02% of FLZ release in 8 h reaction time. The sustained release was observed, leading to the necessity for prolonged therapeutic effects. The antifungal effect of the carrier was studied by the minimum inhibitory concentration (MIC) and the percentage inhibition of viable fungal count against Candida albicans, and it observed 81.02% of the zone of inhibition by the FLZ carrier. Conclusion FLZ-loaded CS-g-P/B-GHS carrier could inhibit the biofilm formation in a concentration-dependent inhibition. Hence, A novel FLZ/B-GHS-CS-g-P carrier is a hopeful approach for effectively treating superficial fungal contaminations of the retina region.

A patient suffered from chronic ulcer due to recalcitrant fungal infection for 3.5 years. Five antifungal agents and 40 times of debridement—all failed. Finally, radical microscopic debridement was performed for eradication of fungal conidiospores. Since then, there was no recurrence at 2 years of follow-up. Scopulariopsis brevicaulis is one of the rarest pathogens of cutaneous fungal infections, for which multidrug resistance increased the complexity and difficulty of treatment. Radical excision, especially microscopic debridement, was the key for eradication of fungal conidiospores in this case.

We report a patient from Panama who had lobomycosis caused by Paracoccidioides (Lacazia) loboi. We used combined clinical-epidemiologic and phylogenetic data, including a new gene sequence dataset on this fungus in Panama, for analysis. Findings contribute useful insights to limited knowledge of this fungal infection in the Mesoamerican Biologic Corridor.

Fungal infections represent a growing public health problem, mainly stemming from two phenomena. Firstly, certain diseases (e.g., AIDS and COVID-19) have emerged that weaken the immune system, leaving patients susceptible to opportunistic pathogens. Secondly, an increasing number of pathogenic fungi are developing multi-drug resistance. Consequently, there is a need for new antifungal drugs with novel therapeutic targets, such as type I and II DNA topoisomerase enzymes of fungal organisms. This contribution summarizes the available information in the literature on the biology, topology, structural characteristics, and genes of topoisomerase (Topo) I and II enzymes in humans, two other mammals, and 29 fungi (including Basidiomycetes and Ascomycetes). The evidence of these enzymes as alternative targets for antifungal therapy is presented, as is a broad spectrum of Topo I and II inhibitors. Research has revealed the genes responsible for encoding the Topo I and II enzymes of fungal organisms and the amino acid residues and nucleotide residues at the active sites of the enzymes that are involved in the binding mode of topoisomerase inhibitors. Such residues are highly conserved. According to molecular docking studies, antifungal Topo I and II inhibitors have good affinity for the active site of the respective enzymes. The evidence presented in the current review supports the proposal of the suitability of Topo I and II enzymes as molecular targets for new antifungal drugs, which may be used in the future in combined therapies for the treatment of infections caused by fungal organisms.

Fungal infections (FIs) are spreading globally, raising a significant public health concern. However, its documentation remains sparse in Africa, particularly in Rwanda. This report provides a comprehensive review of FIs in Rwanda based on a systematic review of reports published between 1972 and 2022. The findings reveal a rich diversity of fungal pathogens, including Blastomyces, Candida, Cryptococcus, Histoplasma, Microsporum, Pneumocystis, Rhinosporidium, and Trichophyton caused human infections. Candida infections predominantly affect the vagina mucosa, while Histoplasma duboisi was linked to disseminated infections. Other pathogens, such as Blastomyces dermatitidis and Rhinosporidium seeberi, were associated with cerebellar and nasal mucosa infections, respectively. The widespread observation of soilborne fungi affecting bean crops highlights the pathogens’ threat to agricultural productivity, food security, and socioeconomic stability, as well as potential health impacts on humans, animals, and the environment. Of particular importance is that there is no information about FIs among animals in the country. Moreover, the analysis underscores significant limitations in the detection, reporting, and healthcare services related to FIs in the country, indicating gaps in diagnostic capacity and surveillance systems. This is underscored by the predominant use of traditional diagnostic techniques, including culture, cytology, and histopathology in the absence of integrating more sensitive and specific molecular tools in investigating FIs. Developing the diagnostic capacities and national surveillance systems are urgently needed to improve the health of crops, animals, and humans, as well as food security and socioeconomic stability in Rwanda. Also, it is important to indicate severe gaps in the evidence to inform policymaking, guide strategic planning, and improve healthcare and public health services, underscoring the urgent need to build national capacity in fungal diagnosis, surveillance, and research. Raising awareness among the public, scientific community, healthcare providers, and policymakers remains crucial. Furthermore, this report reveals the threats of FIs on public health and food insecurity in Rwanda. A multisectoral one health strategy is essential in research and intervention to determine and reduce the health and safety impacts of fungal pathogens on humans, animals, and the environment.

Key Clinical Message Invasive candidiasis may be one of the serious complications of transurethral lithotripsy. Candiduria before this procedure should be assessed, and antifungals should be prescribed. Abstract This case is about a 44‐year‐old diabetic female patient who, after trans‐urethral lithotripsy with double‐J stent insertion, was diagnosed with Candida pneumonia and Candida endophthalmitis.

Humans interact with a multitude of microorganisms in various ecological relationships, ranging from commensalism to pathogenicity. The same applies to fungi, long recognized for their pathogenic roles in infection–such as in invasive fungal diseases caused, among others, by Aspergillus fumigatus and Candida spp.–and, more recently, for their beneficial activities as an integral part of the microbiota. Indeed, alterations in the fungal component of the microbiota, or mycobiota, have been associated with inflammatory, infectious and metabolic diseases, and cancer. Whether acting as opportunistic pathogens or symbiotic commensals, fungi possess a complex enzymatic repertoire that intertwines with that of the host. In this metabolic cross-talk, fungal enzymes may be unique, thus providing novel metabolic opportunities to the host, or, conversely, produce toxic metabolites. Indeed, administration of fungal probiotics and fungi-derived products may be beneficial in inflammatory and infectious diseases, but fungi may also produce a plethora of toxic secondary metabolites, collectively known as mycotoxins. Fungal enzymes may also be homologues to human enzymes, but nevertheless embedded in fungal-specific metabolic networks, determined by all the interconnected enzymes and molecules, quantitatively and qualitatively specific to the network, such that the activity and metabolic effects of each enzyme remain unique to fungi. In this Opinion, we explore the concept that targeting this fungal metabolic unicity, either in opportunistic pathogens or commensals, may be exploited to develop novel therapeutic strategies. In doing so, we present our recent experience in different pathological settings that ultimately converge on relevant trans-kingdom metabolic differences.

Abstract Pulmonary scedosporiosis is a rare pulmonary infection that often presents with nonspecific symptoms and radiological findings. In this report, we present a case of localized pulmonary scedosporiosis in an immunocompetent patient and analyze a total of 25 immunocompetent patients with pulmonary scedosporiosis. Through this case and the literature, we highlight the importance of considering pulmonary scedosporiosis in patients with nonspecific clinical symptoms and radiological findings resembling aspergilloma. This case and the literature further emphasize the significance of surgical intervention. Regardless of the use of antifungal drugs, surgery should be conducted as soon as possible.

IntroductionInvasive candidiasis is a global public health problem as it poses a significant threat in hospital-settings. The aim of this study was to evaluate C14R, an analog derived from peptide BP100, as a potential antimicrobial peptide against the prevalent opportunistic yeast Candida albicans and the emergent multidrug-resistant yeast Candida auris.MethodsAntifungal susceptibility testing of C14R against 99 C. albicans and 105 C. auris clinical isolates from Colombia, was determined by broth microdilution. Fluconazole was used as a control antifungal. The synergy between C14R and fluconazole was assessed in resistant isolates. Assays against fungal biofilm and growth curves were also carried out. Morphological alterations of yeast cell surface were evaluated by scanning electron microscopy. A permeability assay verified the pore-forming ability of C14R.ResultsC. albicans and C. auris isolates had a geometric mean MIC against C14R of 4.42 µg/ml and 5.34 µg/ml, respectively. Notably, none of the isolates of any species exhibited growth at the highest evaluated peptide concentration (200 µg/ml). Synergistic effects were observed when combining the peptide and fluconazole. C14R affects biofilm and growth of C. albicans and C. auris. Cell membrane disruptions were observed in both species after treatment with the peptide. It was confirmed that C14R form pores in C. albicans’ membrane.DiscussionC14R has a potent antifungal activity against a large set of clinical isolates of both C. albicans and C. auris, showing its capacity to disrupt Candida membranes. This antifungal activity remains consistent across isolates regardless of their clinical source. Furthermore, the absence of correlation between MICs to C14R and resistance to fluconazole indicates the peptide’s potential effectiveness against fluconazole-resistant strains. Our results suggest the potential of C14R, a pore-forming peptide, as a treatment option for fungal infections, such as invasive candidiasis, including fluconazole and amphotericin B -resistant strains.

Background: Lonchocarpus capassa is a medicinal plant used to treat diseases such as fungal infections, diarrhoea, oral candidiasis, and stomach complaints in South Africa. Aim: The study aimed to investigate the cytotoxicity and antifungal compounds isolated from L. capassa leaf extracts. Setting: The study was conducted in Muduluni village, Makhado Local Municipality, Limpopo province. Methods: Leaf extracts were screened for antifungal activity against fungal pathogens: Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. Bioassay-guided fractionation using column chromatography of the acetone extract led to the isolation of six antifungal compounds. Nuclear Magnetic Resonance spectroscopy and Mass Spectrometry were used for the identification of compounds. The antioxidant activity of the plant extracts was investigated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) assays. Cytotoxicity of isolated compounds was determined using the 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay against Vero monkey kidney cells. Results: The plant extract had an excellent minimum inhibitory concentrations (MIC) value of 40 μg/mL against the microorganisms. Compound 1 was identified as Lupeol, Compound 3 as Friedelin, and Compound 4 as 6-(γ,γ-Dimethylallyl)-3’,4’-dimethoxy-6”,6”-dimethylpyrano-[2”,3”:7,8]-flavanone (Compound 4). Compounds 2 and 5 were not identified because of the presence of mixtures of long-chain fatty acids. Friedelin was the most active radical scavenger in the DPPH assay. The compounds were not toxic with an LC50 value of ˃ 0.2 mg/mL. Conclusion: Screening of medicinal plants could provide lead to the discovery of novel antifungal agents. Contribution: The results support the traditional use of L. capassa to combat fungal infections in humans.

Candida spp. isolated from both humans and animals have a similar genotype. Properties of Candida spp. specific for different host species have not been isolated, followed by studies indicating that animals can be a reservoir of these fungi for humans. Occupational exposure concerns workers who have direct contact with farm animals, i.e., farmers, breeders, veterinarians, farm technicians. Hand dermatitis and fungal infection may be caused by prolonged exposure to water and occlusive gloves. The risk of fungal infection is estimated to be high for seafood workers, florists, hairdressers, bakers and cooks, gastronomy workers and healthcare workers. Even though Candida spp. are effective as saprophytic, in the event of a weakening of the function or disturbance of homeostasis, the risk of developing an additional form of candidiasis is increasing due to the intensification of animal production, environmental changes and the excessive use of antibiotics to treat infections in humans and animals. Employers and workers should adopt appropriate strategies to reduce factors conductive to Candida spp. infection at professional work. Med Pr Work Health Saf. 2023;74(5):425–33.

One third of patients were colonized by Candida auris during a point-prevalence survey in a neonatal unit during an outbreak in South Africa. The sensitivity of a direct PCR for rapid colonization detection was 44% compared with culture. The infection incidence rate decreased by 85% after the survey and implementation of isolation/cohorting.

Su-Fei Pan,* Shi-Mei Huang,* Lian Xie, Yuan-Yuan Zhang, Yu-Rong Tang, Xiao-Zhen Wang Department of Clinical Laboratory, Shengli Oilfield Central Hospital, Dongying, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Zhen Wang, Department of Clinical Laboratory, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying District, Dongying, Shandong, 257034, People’s Republic of China, Tel +86-18654610519, Email xiaozhenwang007@163.comAbstract: Scedosporium apiospermum (S. apiospermum) is typically reported to be involved in superficial and subcutaneous fungal infections but overlooked in invasive infections, which is associated with a high mortality rate. It poses a diagnostic challenge due to its confusable characteristics to other hyaline hyphomycetes. Here, we reported a psoriasis patient with an invasive S. apiospermum infection. The patient presents an abscess at the intermuscular space of the left hip and an increased C-reactive protein level. Pus culture showed white-greyish, cottonlike colonies with aerial mycelium and terminal oval conidia, suggesting S. apiospermum. This rare fungus was rapidly confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and RNA sequencing. The patient was successfully treated with voriconazole with no recurrence of the abscesses despite delayed treatment. This is the first such case infection report from China that described an unusual case of intermuscular space abscesses due to S. apiospermum. This report highlights the possibility of fungal infections in deeper tissue, as well as the necessity of thorough evaluation and microbiological diagnosis for invasive infections, particularly in immunocompromised patients.Keywords: fungi, fungal infections, infectious diseases, Scedosporium, abscesses, voriconazole

Fungi constitute a diverse group with highly positive and negative impacts in different environments, having several natural roles and beneficial applications in human life, but also causing several concerns. Fungi can affect human health directly, but also indirectly by being detrimental for animal and plant health, influencing food safety and security. Climate changes are also affecting fungal distribution, prevalence, and their impact on different settings. Searching for sustainable solutions to deal with these issues is challenging due to the complex interactions among fungi and agricultural and forestry plants, animal production, environment, and human and animal health. In this way, the “One Health” approach may be useful to obtain some answers since it recognizes that human health is closely connected to animal and plant health, as well as to the shared environment. This review aims to explore and correlate each of those factors influencing human health in this “One Health” perspective. Thus, the impact of fungi on plants, human, and animal health, and the role of the environment as an influencing factor on these elements are discussed.

Introduction: The involuntary flow of urine from the bladder is known as Urinary Incontinence (UI). Men and women of any age can experience incontinence, but it is more prevalent in older women. Several chronic illnesses and environmental variables increases incidence of UI in elderly adults. Most people in this modern era avoid seeking medical intervention early, due to financial worries as the current diagnostic and intervention methods are expensive. Aim: To use low-cost urinary diaper method for assessing the severity of UI and to study the effect of Kegel and therapeutic exercises in reducing the severity of UI in elderly women. Materials and Methods: This interventional study was conducted in an Inshape Physiotherapy Centre in Chennai, India. The duration of the study was five months, from August 2021 to December 2021. A total of 36 women with UI aged 55-75 years were included. The severity of UI among the participants was assessed using onehour Diaper Test (DPT), Hamilton Anxiety Rating Scale (HAM-A) and their level of fitness was evaluated using Senior Fitness Test (SFT). Kegel exercise, pelvic floor exercises were implemented following American College of Sports Medicine (ACSM) standards. Statistical analysis was carried out using the Statistical Package for Social Sciences (SPSS) version 20.0, and data collected was subjected to descriptive statistics and paired t-test. Results: The mean age of the study participants was 69.43±3.4 years. As a result of the intervention, 13 out of 36 participants, who initially had severe UI showed improvement (10 participants improved to moderate UI and three participants improved to mild UI). Out of seven participants, who initially had moderate UI, three participants improved to mild UI. Eight out of the 36 participants showed no UI after intervention, indicating complete recovery. There is an association between the Body Mass Index (BMI), HAM-A and UI, the intervention results in the changes of BMI, and HAM-A thus, reducing the severity of UI. Conclusion: The present study showed that, cost-effective diagnostic and non invasive intervention methods reduced the severity of the UI. The study also recommends regular physical activities to reduce stress and anxiety levels, which in turn helps to improve UI.

Abstract Background Patients with malignancy are at a higher risk of developing nosocomial infections. However, limited studies investigated the clinical features and prognostic factors of nosocomial infections due to fungi in cancer patients. Herein, this study aims to investigate the clinical characteristics of in-hospital fungal infections and develop a nomogram to predict the risk of in-hospital death during fungal infection of hospitalized cancer patients. Methods This retrospective observational study enrolled cancer patients who experienced in-hospital fungal infections between September 2013 and September 2021. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Variables demonstrating significant statistical differences in the multivariate analysis were utilized to construct a nomogram for personalized prediction of in-hospital death risk associated with nosocomial fungal infections. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. Results A total of 216 participants were included in the study, of which 57 experienced in-hospital death. C.albicans was identified as the most prevalent fungal species (68.0%). Respiratory infection accounted for the highest proportion of fungal infections (59.0%), followed by intra-abdominal infection (8.8%). The multivariate regression analysis revealed that Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 3–4 (odds ratio [OR] = 6.08, 95% confidence interval [CI]: 2.04–18.12), pulmonary metastases (OR = 2.76, 95%CI: 1.11–6.85), thrombocytopenia (OR = 2.58, 95%CI: 1.21–5.47), hypoalbuminemia (OR = 2.44, 95%CI: 1.22–4.90), and mechanical ventilation (OR = 2.64, 95%CI: 1.03–6.73) were independent risk factors of in-hospital death. A nomogram based on the identified risk factors was developed to predict the individual probability of in-hospital mortality. The nomogram demonstrated satisfactory performance in terms of classification ability (area under the curve [AUC]: 0.759), calibration ability, and net clinical benefit. Conclusions Fungi-related nosocomial infections are prevalent among cancer patients and are associated with poor prognosis. The constructed nomogram provides an invaluable tool for oncologists, enabling them to make timely and informed clinical decisions that offer substantial net clinical benefit to patients.

We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02–0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03–16], itraconazole [0.03–16], posaconazole [0.03–8], and isavuconazole [0.03–16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus.

Nannizzia polymorpha is a dermatophyte that rarely infects humans. We describe 2 case-patients from Asia who had an inflammatory type of tinea capitis and tinea manuum caused by infection with this fungus. The diagnosis was confirmed on the basis of the morphologic and molecular characteristics of the microorganism.

Infections represent the most common complication occurring during the evolution of the severely burned patient, hence requiring closer study and targeted result analysis. The fungal infections are one of the most aggressive types of existing infections, their opportunistic character enabling them to cause invasive infections, ultimately leading to a higher morbidity and a higher rate of mortality. The present study focuses on the presence of Candida spp. in 19 out of a total of 70 patients admitted to the Critical Care Burn Unit in the Clinical Emergency Hospital Bucharest, between 01.01.2019-31.12.2019. No other fungal species, besides Candida spp., were identified in this patient lot. The aim of this study was to analyze the risk factors and the dynamics of the biological parameters of the patients presenting Candida spp. infections, in order to determine how these contribute to the prognostic and final outcome of these patients. We can conclude that a precise diagnostic and prompt treatment can make a significant difference in the outcome of severely burnt patients presenting with a fungal infection.

Objective: To analyze the effect of methylene blue and 10% curcumin in fungi and bacteria through an in vitro study using photodynamic therapy (PDT). Methods: Curcumin and methylene blue were photosensitized by a Photon Lase III laser applied for 90 s in a dark environment within a laminar flow chamber. Enterococcus faecalis and Candida albicans strains were cultured and standardized. Then, a minimum inhibitory concentration (MIC) assay was conducted for these photosensitizers, with concentration variations and incubation to evaluate their antimicrobial activity. Results: With PDT, Curcumin had significant antibacterial activity against E. faecalis (MIC = 250 µg/mL). In contrast, methylene blue had antibacterial activity against E. faecalis (MIC < 12.5 µg/mL with PDT) and antifungal activity against C. albicans (MIC

Organ transplantation stands as a pivotal achievement in modern medicine, offering hope to individuals with end-stage organ diseases. Advancements in immunology led to improved organ transplant survival through the development of immunosuppressants, but this heightened susceptibility to fungal infections with nonspecific symptoms in recipients. This review aims to establish an intricate balance between immune responses and fungal infections in organ transplant recipients. It explores the fundamental immune mechanisms, recent advances in immune response dynamics, and strategies for immune modulation, encompassing responses to fungal infections, immunomodulatory approaches, diagnostics, treatment challenges, and management. Early diagnosis of fungal infections in transplant patients is emphasized with the understanding that innate immune responses could potentially reduce immunosuppression and promise efficient and safe immuno-modulating treatments. Advances in fungal research and genetic influences on immune-fungal interactions are underscored, as well as the potential of single-cell technologies integrated with machine learning for biomarker discovery. This review provides a snapshot of the complex interplay between immune responses and fungal infections in organ transplantation and underscores key research directions.

Summary: Disparities in social determinants of health (SDOH) play a significant role in causing health inequities globally. The physical environment, including housing and workplace environment, can increase the prevalence and spread of fungal infections. A number of professions are associated with increased fungal infection risk and are associated with low pay, which may be linked to crowded and sub-optimal living conditions, exposure to fungal organisms, lack of access to quality health care, and risk for fungal infection. Those involved and displaced from areas of armed conflict have an increased risk of invasive fungal infections. Lastly, a number of fungal plant pathogens already threaten food security, which will become more problematic with global climate change. Taken together, disparities in SDOH are associated with increased risk for contracting fungal infections. More emphasis needs to be placed on systematic approaches to better understand the impact and reducing the health inequities associated with these disparities.

Paracoccidioidomycosis is a systemic mycosis caused by the fungus Paracoccidioides sp. The genital cutaneous manifestation is rare, with few reports in the literature. We report a case of a male farmer, who presented with a genital cutaneous ulcer for 2 years, without respiratory symptoms. Clinical and histological findings showed paracoccidioidomycosis. This pathology must be considered as an etiology of an ulcerated lesion in the genital tract, even in the absence of respiratory or systemic manifestations.

We retrospectively reviewed physician diagnostic and treatment practices for pediatric tinea capitis at an academic institution over 16 years, in assessing adherence with published guidelines. We demonstrate the need to increase utilization of confirmatory testing and systemic therapy, and call for directed pediatrician education towards these goals.

Abstract Fungi exhibit three adverse effects on human health: inflammatory, allergic and toxic effects, these implications affect mainly immunodepressed patients. The objective of this work was to analyze the fungal microbiota of the ambient air of an Intensive Care Unit. Three collections were carried out in an Intensive Care Unit in the city of Rio Branco, Acre, Western Amazon, Brazil from March to May 2017. 126 Petri dishes were exposed with the culture medium Agar Sabouraud with chloramphenicol and Agar Mycosel, considering the distribution of the 21 air conditioners, split residential model. The plates were incubated for seven days at room temperature and the growth of Colony Forming Units was observed. Colony counting and isolation for the morphological characterization of the granted fungi was performed. After quantification, the concentration of fungi per cubic meters of air (CFU.m-3) was settled. The third collection had a larger number of colony forming units with 48.6%. In the total of the analyzed samples, filamentous fungi (85.5%) and yeasts (14.5%) were isolated. Thirteen genera of fungi were identified, with the most frequent filaments being Cladosporium spp. 33.0%, Aspergillus spp. 30.4% and Penicillium spp. 19.6%, and yeasts Candida spp. 52.6%, Trichosporon spp. 36.9%. The colony-forming unit per cubic meter (CFU.m-3) did not shown any difference between the Cores in the same collection period, however in the 1st and 3rd collection, Core 1 had the highest average. The fungal microbiota of this Unit presented thirteen different genera potentially pathogenic, revealing the need for monitoring microorganisms and prevention actions.

Abstract Background Emerging fungal pathogens pose important threats to global public health. The World Health Organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL, Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal infections. Methods We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keyword Cryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance of C. neoformans to approved antifungal drugs. Results There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health burden. Conclusion The rising threat of C. neoformans is compounded by accumulating evidence for its ability to infect immunocompetent individuals and the emergence of antifungal-resistant variants. Emphasis should be placed on further understanding the mechanisms of pathogenicity and of antifungal resistance and tolerance. The development of novel management strategies through the identification of new drug targets and the discovery and optimization of new and existing diagnostics and therapeutics are key to reducing the health burden.

A 65-year-old man with HIV sought treatment for fever, weight loss, and productive cough after returning to the United States from Liberia. Fungal cultures grew Emergomyces pasteurianus, and the patient’s health improved after beginning voriconazole. We describe the clinical case and review the literature, treatment, and susceptibilities for E. pasteurianus.

Amphotericin B (AmB) has long stood as a cornerstone in the treatment of invasive fungal infections (IFIs), especially among immunocompromised patients. However, the landscape of antifungal therapy is evolving. New antifungal agents, boasting novel mechanisms of action and better safety profiles, are entering the scene, presenting alternatives to AmB’s traditional dominance. This shift, prompted by an increase in the incidence of IFIs, the growing demographic of immunocompromised individuals, and changing patterns of fungal resistance, underscores the continuous need for effective treatments. Despite these challenges, AmB’s broad efficacy and low resistance rates maintain its essential status in antifungal therapy. Innovations in AmB formulations, such as lipid complexes and liposomal delivery systems, have significantly mitigated its notorious nephrotoxicity and infusion-related reactions, thereby enhancing its clinical utility. Moreover, AmB’s efficacy in treating severe and rare fungal infections and its pivotal role as prophylaxis in high-risk settings highlight its value and ongoing relevance. This review examines AmB’s standing amidst the ever-changing antifungal landscape, focusing on its enduring significance in current clinical practice and exploring its potential future therapeutic adaptations.

In recent years, the incidence of fungal infections in humans has increased dramatically, accompanied by an expansion in the number of species implicated as etiological agents, especially environmental fungi never involved before in human infection. Among fungal pathogens, Candida species are the most common opportunistic fungi that can cause local and systemic infections, especially in immunocompromised individuals. Candida albicans (C. albicans) is the most common causative agent of mucosal and healthcare-associated systemic infections. However, during recent decades, there has been a worrying increase in the number of emerging multi-drug-resistant non-albicans Candida (NAC) species, i.e., C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. auris, and C. ciferrii. In particular, Candida ciferrii, also known as Stephanoascus ciferrii or Trichomonascus ciferrii, is a heterothallic ascomycete yeast-like fungus that has received attention in recent decades as a cause of local and systemic fungal diseases. Today, the new definition of the S. ciferrii complex, which consists of S. ciferrii, Candida allociferrii, and Candida mucifera, was proposed after sequencing the 18S rRNA gene. Currently, the S. ciferrii complex is mostly associated with non-severe ear and eye infections, although a few cases of severe candidemia have been reported in immunocompromised individuals. Low susceptibility to currently available antifungal drugs is a rising concern, especially in NAC species. In this regard, a high rate of resistance to azoles and more recently also to echinocandins has emerged in the S. ciferrii complex. This review focuses on epidemiological, biological, and clinical aspects of the S. ciferrii complex, including its pathogenicity and drug resistance.

Heat shock protein 90 (HSP90) is a critical target for anticancer and anti-fungal-infection therapies due to its central role as a molecular chaperone involved in protein folding and activation. In this study, we developed in vitro Förster Resonance Energy Transfer (FRET) assays to characterize the binding of C. albicans HSP90 to its co-chaperone Sba1, as well as that of the homologous human HSP90α to p23. The assay for human HSP90α binding to p23 enables selectivity assessment for compounds aimed to inhibit the binding of C. albicans HSP90 to Sba1 without affecting the physiological activity of human HSP90α. The combination of the two assays is important for antifungal drug development, while the assay for human HSP90α can potentially be used on its own for anticancer drug discovery. Since ATP binding of HSP90 is a prerequisite for HSP90-Sba1/p23 binding, ATP-competitive inhibitors can be identified with the assays. The specificity of binding of fusion protein constructs—HSP90-mNeonGreen (donor) and Sba1-mScarlet-I (acceptor)—to each other in our assay was confirmed via competitive inhibition by both non-labeled Sba1 and known ATP-competitive inhibitors. We utilized the developed assays to characterize the stability of both HSP90–Sba1 and HSP90α–p23 affinity complexes quantitatively. Kd values were determined and assessed for their precision and accuracy using the 95.5% confidence level. For HSP90-Sba1, the precision confidence interval (PCI) was found to be 70–120 (100 ± 20) nM while the accuracy confidence interval (ACI) was 100–130 nM. For HSP90α-p23, PCI was 180–260 (220 ± 40) nM and ACI was 200–270 nM. The developed assays were used to screen a nucleoside-mimetics library of 320 compounds for inhibitory activity against both C. albicans HSP90-Sba1 and human HSP90α-p23 binding. No novel active compounds were identified. Overall, the developed assays exhibited low data variability and robust signal separation, achieving Z factors > 0.5.

Over 60% of emerging infectious diseases in humans are zoonotic, often originating from wild animals. This long-standing ecological phenomenon has accelerated due to human-induced environmental changes. Recent data show a significant increase in fungal infections, with 6.5 million cases annually leading to 3.7 million deaths, indicating their growing impact on global health. Despite the vast diversity of fungal species, only a few are known to infect humans and marine mammals. Fungal zoonoses, especially those involving marine mammals like cetaceans, are of global public health concern. Increased human–cetacean interactions, in both professional and recreational settings, pose risks for zoonotic disease transmission. This review focuses on the epidemiology, clinical manifestations, and zoonotic potential of major fungal pathogens shared in humans and cetaceans, highlighting their interspecies transmission capability and the challenges posed by antifungal resistance and environmental changes. It underscores the need for enhanced awareness and preventative measures in high-risk settings to protect public health and marine ecosystems.

Using a large US hospital database, we describe 192 Candida auris‒associated hospitalizations during 2017–2022, including 38 (20%) C. auris bloodstream infections. Hospitalizations involved extensive concurrent conditions and healthcare use; estimated crude mortality rate was 34%. These findings underscore the continued need for public health surveillance and C. auris containment efforts.

Human pathogenic fungi are responsible for causing a range of infection types including mucosal, skin, and invasive infections. Life-threatening and invasive fungal infections (FIs) are responsible for mortality and morbidity, especially for individuals with compromised immune function. The number of currently available therapeutic agents against invasive FIs is limited compared to that against bacterial infections. In addition, the increased mortality and morbidity caused by FIs are linked to the limited number of available antifungal agents, antifungal resistance, and the increased toxicity of these agents. Currently available antifungal agents have several drawbacks in efficiency, efficacy, toxicity, activity spectrum, and selectivity. It has already been demonstrated with numerous metallic nanoparticles (MNPs) that these nanoparticles can serve as an effective and alternative solution as fungicidal agents. MNPs have great potential owing to their intrinsic antifungal properties and potential to deliver antifungal drugs. For instance, gold nanoparticles (AuNPs) have the capacity to disturb mitochondrial calcium homeostasis induced AuNP-mediated cell death in Candida albicans. In addition, both copper nanoparticles and copper oxide nanoparticles exerted significant suppressive properties against pathogenic fungi. Silver nanoparticles showed strong antifungal properties against numerous pathogenic fungi, such as Stachybotrys chartarum, Mortierella alpina, Chaetomium globosum, A. fumigatus, Cladosporium cladosporioides, Penicillium brevicompactum, Trichophyton rubrum, C. tropicalis, and C. albicans. Iron oxide nanoparticles showed potent antifungal activities against A. niger and P. chrysogenum. It has also been reported that zinc oxide nanoparticles can significantly inhibit fungal growth. These NPs have already exerted potent antifungal properties against a number of pathogenic fungal species including Candida, Aspergillus, Fusarium, and many others. Several strategies are currently used for the research and development of antifungal NPs including chemical modification of NPs and combination with the available drugs. This review has comprehensively presented the current and innovative antifungal approach using MNPs. Moreover, different types of MNPs, their physicochemical characteristics, and production techniques have been summarized in this review.

Introduction: Fungal infections of the central nervous system present a variety of clinical syndromes, such as meningitis, encephalitis, raised intracranial pressure with a nonspecific presentation, and, in the last two decades, have increased the incidence of these fungal infections. Fungal meningoencephalitis is frequently associated with Cryptococcus, but this report stands out for presenting one species of Penicillium genus. Objectives: Here, we present the first case of meningoencephalitis associated with brain injury caused by Penicillium chrysogenum, in a patient who is immunocompetent and was admitted to Hospital Naval Marcílio Dias, Rio de Janeiro, Brazil. Methods: To identify the fungal species, we performed phenotypic and genotypic methodologies, from the culture to the sequencing of internal transcribed spacer region, and β-tubulin gene, a rare fungus in cerebrospinal fluid cultures, belonging to the genus Penicillium, was identified. Conclusion: We highlight the importance of the first report of meningoencephalitis caused by P. chrysogenum in a patient who is immunocompetent, registered in Brazil. We also emphasize the need for further studies to determine an effective treatment with the least possible side effects for patients infected by fungi that are rarely related to the most severe forms of invasive infections.

Introduction: Information on epidemiologic trends of dermatophytosis and its causative agents is essential for the healthcare system to improve its knowledge of associated complications. The main purpose of this study was to determine the distribution of fungal strains and the infection sites of patients with dermatophytosis. Materials and Methods: In this cross-sectional study, the demographical data and clinical characteristics of 641 patients with a positive fungal culture who were referred to Razi pathobiological laboratory, Rasht, Iran, between 2016-2021 were collected. All data were analyzed using SPSS software version 21 by a significant level of < 0.05. Results: Out of 641 patients, 70% were female and the mean age of patients was 43.98 ± 16.99 years. Laboratory analysis demonstrated that Candida Albicans (44/9%), Aspergillus (31/8%), and Dermatophytes (18%) were the most common causes of superficial cutaneous fungal infections. Among the dermatophytes, the most common pathogens were Trichophyton mentagrophytes (53%) and Trichophyton Rubrum (20.8%), also, the most common site of infection was nail (64.4%). Conclusion: Considering the high prevalence of Candida Albicans and Aspergillus, especially in females, it is important to determine preventive protocols for fungal infections and better clinical management of the patients involved.