Severity Of Fungal Infections Research Articles

A Novel One Health Approach concerning Yeast Present in the Oral Microbiome of the Endangered Rio Skate (Rioraja agassizii) from Southeastern Brazil.

The current climate change scenario caused by anthropogenic activities has resulted in novel environmental pressures, increasing the occurrence and severity of fungal infections in the marine environment. Research on fungi in several taxonomic groups is widespread although not the case for elasmobranchs (sharks and rays). In this context, the aim of the present study was to screen the oral fungal microbiota present in artisanally captured Rioraja agassizii, a batoid that, although endangered, is highly fished and consumed worldwide. Oropharyngeal samples were obtained by swabbing and the samples were investigated using morphological and phenotypic methods by streaking on Sabouraud Dextrose Agar (SDA) and subculturing onto CHROMagar Candida (BD Difco) and CHROMagar Candida Plus (CHROMagarTM), as well as molecular techniques by amplification of the ITS1-5.8S-ITS2 ribosomal DNA region and a MALDI-TOF MS assessment. The findings indicated the presence of Candida parapsilosis (seven isolates), Candida duobushaemulonii (one isolate) and Rhodotorula mucilaginosa (three isolates), several of these reported for the first time in Rioraja agassizii. In addition, a 100% agreement between the MALDI-TOF results and partial ITS region sequencing was noted, demonstrating that the MALDI-TOF MS is a rapid and effective alternative for yeast identification in Rioraja agassizii isolates and potentially in other elasmobranch species. These findings highlight the need for further research to determine the potential impact on elasmobranch health, ecology, and commercial fisheries. Furthermore, this research is paramount in a One Health framework and may be employed to predict elasmobranch responses to an evolving ocean, keep healthy populations in check, monitor species, and assess the public health consequences of consuming these species.

Analysis of risk factors of fungal superinfections in viral pneumonia patients: A systematic review and meta-analysis.

Infections with fungi, such as Aspergillus species, have been found as common complications of viral pneumonia. This study aims to determine the risk factors of fungal superinfections in viral pneumonia patients using meta-analysis. This study aims to determine the risk factors of fungal infection s in viral pneumonia patients using meta-analysis. We reviewed primary literature about fungal infection in viral pneumonia patients published between January 1, 2010 and September 30, 2020, in the Chinese Biomedical Literature, Chinese National Knowledge Infrastructure, Wanfang (China), Cochrane Central Library, Embase, PubMed, and Web of Science databases. These studies were subjected to an array of statistical analyses, including risk of bias and sensitivity analyses. In this study, we found a statistically significant difference in the incidence of fungal infections in viral pneumonia patients that received corticosteroid treatment as compared to those without corticosteroid treatment (p < .00001). Additionally, regarding the severity of fungal infections, we observed significant higher incidence of invasive pulmonary aspergillosis (IPA) in patients with high Acute Physiology and Chronic Health Evaluation(APACHE) II scores (p < .001), tumors (p = .005), or immunocompromised patients (p < .0001). Our research shows that corticosteroid treatment was an important risk factor for the development of fungal infection in patients with viral pneumonia. High APACHE II scores, tumors, and immunocompromised condition are also important risk factors of developing IPA. The diagnosis of fungal infection in viral pneumonia patients can be facilitated by early serum galactomannan (GM) testing, bronchoalveolar lavage fluidAspergillus antigen testing, culture, and biopsy.

Screening of Pandemic Response Box Library Reveals the High Activity of Olorofim against Pathogenic Sporothrix Species.

The increase in the prevalence and severity of fungal infections and the resistance to available antifungals highlights the imperative need for novel therapeutics and the search for new targets. High-content screening of libraries containing hundreds of compounds is a powerful strategy for searching for new drug candidates. In this study, we screened the Pandemic Response Box library (Medicines for Malaria Venture) of 400 diverse molecules against the Sporothrix pathogenic species. The initial screen identified twenty-four candidates that inhibited the growth of Sporothrix brasiliensis by more than 80%. Some of these compounds are known to display antifungal activity, including olorofim (MMV1782354), a new antifungal drug. Olorofim inhibited and killed the yeasts of S. brasiliensis, S. schenckii, and S. globosa at concentrations lower than itraconazole, and it also showed antibiofilm activity. According to the results obtained by fluorimetry, electron microscopy, and particle characterization analyses, we observed that olorofim induced profound alterations on the cell surface and cell cycle arrest in S. brasiliensis yeasts. We also verified that these morphophysiological alterations impaired their ability to adhere to keratinocytes in vitro. Our results indicate that olorofim is a promising new antifungal against sporotrichosis agents.

Cinnamyl Schiff bases: synthesis, cytotoxic effects and antifungal activity of clinical interest.

The aim of this study was to synthesize and investigate the in vitro antifungal properties of 23 cinnamyl Schiff bases. In addition, cytotoxic effects of such cinnamyl Schiff bases against human lung, kidney or red blood cells were also checked. The compounds were synthesized in a single-step, 2min of reaction under microwave irradiation produced up to 97% yield. Six of the 23 cinnamyl Schiff bases possessed antifungal activities against strains of Candida, Aspergillus, Fonsecaea and, particularly, Cryptococcus species. Indeed, cinnamyl Schiff bases 1 and 23 exhibited minimum inhibitory concentration (MIC) values more than twofold lower than fluconazole (FCZ) against all the Cryptococcus neoformans strains (MIC=1·33, 1·4 and 5·2µgml-1 , respectively) and Cryptococcus gattii strains (MIC=5·3, 2·8 and 9·2µgml-1 , respectively) (12 strains of each species) while cinnamyl Schiff base 11 was as potent as FCZ against all strains from both Cryptococcus species. No significant cytotoxic effects were observed for Schiff bases against human lung, kidney or red blood cells, all presenting selective indexes higher than 10. In conclusion, this study revealed cinnamyl Schiff bases, especially 1 and 23, as new lead anticryptococcal agents for the discovery of novel antifungal drugs. SIGNIFICANCE AND IMPACT OF THE STUDY: The occurrence and severity of fungal infections have increased in recent decades due to resistance to available antifungal drugs and the appearance of new emerging pathogens. Thus, the search for new antifungal agents is mandatory. From a series of 23 cinnamyl Schiff bases, two compounds (1 and 23) were interrogated as new anticryptococcal agents without significant cytotoxicity against human lung, kidney or red blood cells. In turns, these new Schiff bases are lead compounds for the discovery of novel antifungal drugs.

Advances in Understanding Human Genetic Variations That Influence Innate Immunity to Fungi.

Fungi are ubiquitous. Yet, despite our frequent exposure to commensal fungi of the normal mammalian microbiota and environmental fungi, serious, systemic fungal infections are rare in the general population. Few, if any, fungi are obligate pathogens that rely on infection of mammalian hosts to complete their lifecycle; however, many fungal species are able to cause disease under select conditions. The distinction between fungal saprophyte, commensal, and pathogen is artificial and heavily determined by the ability of an individual host's immune system to limit infection. Dramatic examples of commensal fungi acting as opportunistic pathogens are seen in hosts that are immune compromised due to congenital or acquired immune deficiency. Genetic variants that lead to immunological susceptibility to fungi have long been sought and recognized. Decreased myeloperoxidase activity in neutrophils was first reported as a mechanism for susceptibility to Candida infection in 1969. The ability to detect genetic variants and mutations that lead to rare or subtle susceptibilities has improved with techniques such as single nucleotide polymorphism (SNP) microarrays, whole exome sequencing (WES), and whole genome sequencing (WGS). Still, these approaches have been limited by logistical considerations and cost, and they have been applied primarily to Mendelian impairments in anti-fungal responses. For example, loss-of-function mutations in CARD9 were discovered by studying an extended family with a history of fungal infection. While discovery of such mutations furthers the understanding of human antifungal immunity, major Mendelian susceptibility loci are unlikely to explain genetic disparities in the rate or severity of fungal infection on the population level. Recent work using unbiased techniques has revealed, for example, polygenic mechanisms contributing to candidiasis. Understanding the genetic underpinnings of susceptibility to fungal infections will be a powerful tool in the age of personalized medicine. Future application of this knowledge may enable targeted health interventions for susceptible individuals, and guide clinical decision making based on a patient's individual susceptibility profile.

Molecular analysis of bunch architecture in grapevine

A loose grape cluster is a desired trait in grapevine breeding, since it reduces the abundance and severity of fungal infections. This is the result of better coverage of the grape bunch by antifungal spraying agents and better air exchange within the grape cluster. The reduced exposure to high humidity acts as a physical barrier against pathogens that need high moisture to proliferate, e.g., Botrytis cinerea. The aim of this study was to identify genes that influence bunch architecture and to deduce molecular markers to accelerate the selection process in grapevine breeding. Bunch compactness was characterized by phenotyping of several subtraits. The experiment comprised plants of a mapping population (‘GF.GA-47-42’ × ‘Villard blanc’) and a set of ‘Pinot noir’ clones with loose as well as compact clusters. The latter were sampled from three different wine-growing regions in Germany. A genetic mapping and quantitative trait locus (QTL) analysis approach based on the trait-segregating population of 150 F1 individuals yielded many reproducible QTLs distributed along the genome. Some of them were concentrated in specific genomic regions. Further statistical evaluation revealed eight such QTL clusters to be of major relevance and identified flanking molecular markers for marker-assisted selection. In a transcriptional profiling approach, two loosely and two compactly clustered clones of ‘Pinot noir’ were compared. RNA from dormant winter buds and compound buds harvested during the growing period were used in differential gene expression experiments. RNA sequencing was performed at three different stages of development. Candidate genes found in these experiments were selected and re-analyzed in a more comprehensive set of ‘Pinot noir’ clones from the three different German growing locations. Finally, two genes appeared to be differentially expressed between the two groups of clones over the three locations.

Effect of Exogenous Application of Methyl Jasmonate on the Lipid and Carbohydrate Content and Composition of Winter Triticale ( Triticosecale Wittm.) Grain and the Severity of Fungal Infections in Triticale Plants and Grain.

Kernels of winter triticale ( Triticosecale Wittm. cv. Dinaro) were analyzed. In the autumn of 2015, the effect of methyl jasmonate (MJ) on the germination of triticale kernels and the development of triticale seedlings was analyzed in a laboratory before kernels were sown in experimental plots. Kernels harvested from plots in August 2016 were analyzed to determine their lipid and carbohydrate content and composition and the severity of fungal infections. Triticale grain was harvested at full maturity. The plots were sprayed with MJ at concentrations of 10-6 to 10-3 M in the stem elongation stage (200 L/ha) and in the early milk stage (300 L/ha). Other preventive treatments, fungicides, pesticides, or foliar fertilizers were not applied. Lipids of triticale kernels contained 20 fatty acids (FAs) with the highest proportion of linoleic acid. Methyl jasmonate did not exert a significant effect on the FA composition of kernel lipids treated with the plant hormone during the growing season. Statistical analysis did not reveal significant ( p < 0.05) differences in the total content of soluble carbohydrates in control kernels and in the kernels collected from triticale plants treated with MJ. Methyl jasmonate applied at a concentration of 10-3 M in BBCH stages 54 and 73 reduced the prevalence of stem base, leaf, and spike diseases. However, the severity of grain infections caused by mycotoxin-producing fungi increased in treatments where MJ was applied at a concentration of 10-5 M relative to the control treatment. The study describes the results noted in naturally infected plants and provides valuable inputs for agricultural practice, but further research is required to validate the presented findings.

Antifungals therapeutic failure: Causes beyond steroid abuse

Abstract Severity of fungal infection can range from asymptomatic- mild mucocutaneous infections to potentially life threatening systemic disease. Socioeconomic and geoecologic characteristics and increasing number of at risk population are the main determinants of variation in incidence & prevalence of fungal infections. A variety of antifungal drugs are available, but the emerging issue of resistance is of paramount importance. Major factors implicated in Antifungal therapeutic failures and rising incidence of recurrent & relapse include overcrowding, poor hygienic condition, hot & humid climate, self medication, inappropriate and incomplete treatment, undiagnosed uncontrolled diabetes, malnutrition and obviously the issue of rampant steroid abuse. Keywords: Azoles, Anti fungal. Introduction Nearly a billion people have been estimated to have fungal infection of skin, nail, and hair and many 100’s of millions have mucosal candidiasis and more than 150 million.[1] people have serious fungal disease which have major impact on their lives, and can even be fatal. Severity of fungal infection can range from asymptomatic- mild mucocutaneous infections to potentially life threatening systemic disease. Socioeconomic and geoecologic characteristics and increasing number of at risk population are the main determinants of variation in incidence & prevalence of fungal infections. A variety of antifungal drugs are available, but the emerging issue of resistance is of paramount importance. Major factors implicated in Antifungal therapeutic failures and rising incidence of recurrent & relapse include overcrowding, poor hygienic condition, hot & humid climate, self medication, inappropriate and incomplete treatment, undiagnosed uncontrolled diabetes, malnutrition and obviously the issue of rampant steroid abuse. The evolution of drug resistance is an ubiquitous process, where microorganisms try to adapt and compete to survive the environmental stress. Variati

Blad-containing oligomer: a novel fungicide used in crop protection as an alternative treatment for tinea pedis and tinea versicolor.

The lack of novel antifungal drugs and the increasing incidence and severity of fungal infections are major concerns worldwide. Herein, we tested the activity of the Blad-containing oligomer (BCO), a new antifungal molecule already in use for agriculture, on Malassezia spp. and dermatophytes, the causal agents of human tinea versicolor and tinea pedis. Given the lack of a standard method for Malassezia susceptibility testing and the plethora of published methods, we also developed an improved method for this genus. The efficacy of BCO was assessed in vitro and compared to that of the drugs currently utilized in the treatment of tinea versicolor (fluconazole and itraconazole) and tinea pedis (itraconazole and terbinafine). For dermatophytes, the standard microdilution broth-based method was used, with small adjustments, and several broth formulations and inocula sizes were tested to develop an improved susceptibility method for Malassezia spp. We successfully developed a microdilution broth-based method with considerable advantages over other available methods, and used it for all in vitro susceptibility tests of Malassezia spp. isolates. We report that, on a molar basis, BCO was more effective than fluconazole or itraconazole on most strains of Malassezia spp. isolated from clinical samples (n=29). By contrast, BCO was less effective than itraconazole or terbinafine on the common dermatophytes Trichophyton rubrum and Trichophyton interdigitale. These data place BCO as a promising drug for the treatment of Malassezia-associated skin diseases. Further in vivo studies are now required to ascertain its applicability in the clinical setting.

Oral Candida colonization in HIV-infected patients in Londrina-PR, Brazil: antifungal susceptibility and virulence factors.

Host colonization by Candida species is an important predisposing factor to candidiasis, which seems to be more frequent in human immunodeficiency virus (HIV)-infected patients. Knowledge about the distribution, antifungal susceptibility, and virulence of oral Candida isolates is important for effective management of candidiasis. Oral rinses were collected from 242 HIV-infected patients without clinical evidence of candidiasis seen at the AIDS referral center in Londrina, Brazil. Species were identified by standard phenotypic and molecular methods, and characterized in vitro according to antifungal susceptibility, cell surface hydrophobicity, biofilm formation, and enzyme activities. Oral Candida colonization was detected in 50.4% of patients and combined use of antiretroviral therapy and protease inhibitor had a protective effect against colonization. Candida albicans (75.2%) was the most prevalent species. A high proportion of Candida spp. (39.9%) showed decreased susceptibility to fluconazole. Five isolates were resistant to nystatin. Protease and phospholipase activities were detected in 100% and 36.8% of isolates, respectively. Most isolates displayed a hydrophobic property that was associated with biofilm formation ability. A significant number of oral Candida species exhibiting decreased susceptibility to fluconazole were isolated from colonized HIV-infected individuals. Furthermore, all isolates expressed potential virulence attributes in vitro. Given the high incidence and severity of fungal infections in HIV-infected individuals, the results of this study reinforce the importance of antifungal susceptibility testing, which contributes to therapeutic strategies and highlights the need for continuous surveillance of Candida colonization in this population.

Control of Anthracnose Caused by Colletotrichum musae on Curcuma alismatifolia Gagnep. Using Antagonistic Bacillus spp.

Over 400 bacterial strains, isolated from leaf surfaces of Curcuma alismatifolia Gagnep. and hot springs in the Chiang Mai province of northern Thailand, were screened in vitro for antagonistic activity against Colletotrichum musae, an anthracnose fungus. Three isolates provided greater than 75% growth inhibition of the fungus in vitro and were identified as Bacillus licheniformis, B. amyloliquefaciens and B. subtilis. Using in planta tests, B. amyloliquefaciens and B. subtilis were shown to efficiently colonize the curcuma bracts, provide a statistically significant growth suppression of C. musae over that of B. licheniformis, and all three isolates could provide 100% inhibition of conidial fungal germination. When B. licheniformis was co-inoculated in combination with either of the other two bacteria, the ability of B. amyloliquefaciens and B. subtilis to suppress the fungal disease was dramatically reduced. Both B. amyloliquefaciens and B. subtilis were found to contain an isoform of iturin A with antifungal activity against C. musae. As a preventative measure to control the spread of C. musae and reduce the severity of fungal infections, B. amyloliquefaciens could be used to inoculate curcuma flowers cost effectively and reduce the need for the toxic synthetic fungicides currently in use.

Methods for the Recovery and Purification of Polyene Antifungals

Despite the development of newer antifungal drugs, the polyene antifungals continue to be the most potent broad-spectrum fungicides available for clinical use. The incidence and severity of fungal infections are on the rise, underscoring the need for new and more effective antifungal drugs. Thus, the search for new polyene antifungals is ongoing. The limited solubility, polymorphic character, and inherent chemical instability of these compounds make their economical recovery and purification from mass culture challenging problems in biotechnology. This article provides a comprehensive review of the methods that have been developed for the recovery and purification of amphotericin B and nystatin, the two most important polyenes currently in clinical use.

Requirement for fungal prophylaxis in high-risk surgical patients: a randomized trial

Abstract Background In previous studies the authors have selected patients and surgical procedures with a high risk of fungal infection. Whether these patients and procedures require fungal prophylaxis was studied. Methods From June to December 1999, 850 surgical patients from two university hospitals were enrolled in a prospective open randomized study. Fifty were selected according to demographics (age, sex, co-morbidity) and surgical procedures (defined by GDRs and ICD9-CM) as at high risk of fungal infection according to a previously defined algorithm (presented to the Surgical Infection Society of Europe 1999). In these 50 patients the CD lymphocyte population was recollected, and urine, blood, sputum and wound (if infected) cultures were performed. Then, 25 were treated with nystatin wash and swallow, and the others with placebo. Fungal infection and fungal colonization were defined and used as the endpoint of the study. Results Patients not selected for the study did not develop fungal infection. Of the high-risk patients, 20 presented with fungal colonization (12 urine, seven wound and five bloodstream cultures) and 12 presented with subsequent fungal infections. Of these 20 colonized patients, only those with nystatin prophylaxis did not require fungal treatment, whereas controls required treatment. CD4 lymphocyte recount (below 300) was uniformly decreased in all patients with fungal infection. Conclusion Immunodepressed patients at high risk with concomitant fungal colonization develop fungal infections 2–5 days after high-risk surgical procedures. Nystatin prophylaxis in such patients may reduce the degree and severity of fungal infection. If fungal colonization is present and the CD4 lymphocyte count is below 300, fungal treatment might be advisable.

FUNGAL INFECTIONS IN PATIENTS WITH ACQUIRED IMMUNODEFICIENCY SYNDROME

The incidence and severity of fungal infections appear to increase with progression of HIV disease. Because of the significant morbidity and mortality associated with the mycoses discussed, knowledge of the clinical syndromes, early diagnosis, and prompt institution of therapy are crucial for a favorable outcome. For disseminated or invasive fungal infections, suppressive therapy must be continued to prevent relapse.

Plasma (1→3)-β-D-glucan assay and immunohistochemical staining of (1→3)-β-D-glucan in the fungal cell walls using a novel horseshoe crab protein (T-GBP) that specifically binds to (1→3)-β-D-glucan

A highly sensitive enzyme-linked immunosorbent assay specific to (1-->3)-beta-D-glucans (GBP-ELISA) has been developed using a novel (1-->3)-beta-D-glucan-binding protein (T-GBP), which was purified from the amebocyte lysate of the Japanese horseshoe crab, Tachypleus tridentatus. This method allowed quantitation of the glucans in a concentration range of 0.1-1,000 ng/ml, regardless of linear and branched structures, and was applied to determine the amounts of (1-->3)-beta-D-glucan in human and animal plasmas for diagnosis of fungemia. High levels of plasma glucan contents in clinical samples were found to be correlated closely with the severity of fungal infection. T-GBP was successfully utilized for indirect immunofluorescence staining of (1-->3)-beta-D-glucan in Candida albicans cell walls.

Quantification of Infection by Alternaria cassiae Using Leaf Immuno‐Autoradiography and Radioimmunosorbent Assays

AbstractThe severity of fungal infection is usually estimated visually as a rating of injury. A more quantitative method was needed to ascertain the effect of additives used to enhance the virulence of mycoherbicidal preparations. A sensitive and accurate serological method is presented for quantitative measurement of Alternaria cassiae infection of Cassia obtusifolia. An antiserum was prepared against a homogenate of mycelium of A. cassiae. A fast and simple procedure of leaf immuno‐autoradiography was developed for the visualization of A. cassiae mycelium on inoculated leaves. A radioimmunosorbent assay (RISA) was developed for quantification of the extent of fungal infection. As little as 1. 6 ng/ ml dry weight equivalent of mycelium could be detected by RISA. There was a linear relationship between the logarithm of the RISA values and the logarithm of fungus concentration up to 300 ng/ml. Reduced sensitivity of the assay was pronounced in extracts containing 400 μ g/ml or more fresh weight of leaves. There was 30–40 % cross‐reactivity of the antiserum with two other species of Alternaria, as well as with Monilinia fructicola, and almost no reactivity was found with three other fungi tested.

Fungal Infections in Solid-Organ Transplantation

Fungal infections following solid-organ transplantation remain a major cause of morbidity and death. Their incidence ranges from 5% among recipients of kidney transplants to as high as 40% among recipients of liver transplants. Species of Candida and Aspergillus account for more than 80% of fungal episodes. Moreover, more than 80% of fungal infections occur within the first 2 months after transplantation, with a resulting mortality of 30%-100%. The pathogenesis of infection and the risk factors involved depend on the type of transplant and the infecting microorganism. Cyclosporine has not significantly reduced the incidence or severity of fungal infections in this population. The value of surveillance cultures and fungal antigen detection in solid-organ transplant recipients remains to be determined. Amphotericin B is still a first-line drug, but its potential nephrotoxicity makes its use problematic, especially in renal transplant recipients. Fluconazole is a potential alternative for the treatment of infections due to Candida species and Cryptococcus neoformans. The role of antifungal compounds in the prophylaxis of fungal infection in recipients of solid-organ transplants needs to be established.