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Background: Auranofin is an approved anti-rheumatic drug that has a broad-range inhibitory action against several microorganisms, including human pathogenic fungi. The auranofin activity against Histoplasma capsulatum, the dimorphic fungus that causes histoplasmosis, has not been properly addressed. Since there are few therapeutic options for this life-threatening systemic mycosis, this study evaluated the effects of auranofin on H. capsulatum growth and expression of virulence factors., Methodology/principal Findings: Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) of auranofin against 15 H. capsulatum strains with distinct genetic backgrounds were determined using the yeast form of the fungus and a microdilution protocol. Auranofin activity was also assessed on a macrophage model of infection and on a Tenebrio molitor invertebrate animal model. Expression of virulence-related genes was compared between auranofin treated and untreated H. capsulatum yeast cells using a quantitative PCR assay. Auranofin affected the growth of different strains of H. capsulatum, with MIC and MFC values ranging from 1.25 to 5.0 μM and from 2.5 to >10 μM, respectively. Auranofin was able to kill intracellular H. capsulatum yeast cells and conferred protection against the fungus in the experimental animal model of infection. Moreover, the expression of catalase A, HSP70, superoxide dismutase, thioredoxin reductase, serine proteinase, cytochrome C peroxidase, histone 2B, formamidase, metallopeptidase, Y20 and YPS3 proteins were reduced after six hours of auranofin treatment. CONCLUSIONS/SIGNIFICANCE: Auranofin is fungicidal against H. capsulatum and reduces the expression of several virulence-related genes, which makes this anti-rheumatic drug a good candidate for new medicines against histoplasmosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 de Abreu Almeida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Over the past two decades, zoonotic sporotrichosis transmitted by naturally infected cats has become hyperendemic in Rio de Janeiro, Brazil. Sporothrix brasiliensis is the main agent involved. However, there are other forms of transmission of sporotrichosis. The aim of this study was to evaluate and associate the epidemiological, clinical and therapeutic data and the susceptibility of Sporothrix spp. to antifungal drugs in 43 non-zoonotic sporotrichosis cases. Forty-three clinical strains of Sporothrix were identified by partial sequencing of the calmodulin gene. An antifungal susceptibility test of amphotericin B, terbinafine, itraconazole, posaconazole and isavuconazole was performed according to the broth microdilution method. Most patients were male (55.8%). Regarding the source of infection, 21 patients (48.8%) reported trauma involving plants and/or contact with soil. Sporothrix brasiliensis was the predominant species (n = 39), followed by S. globosa (n = 3) and S. schenckii (n = 1). Sporothrix brasiliensis was associated with all the sources of infection, reinforcing previous data showing the presence of this species in environmental sources, as well as with all the clinical forms, including severe cases. One clinical strain of Sporothrix brasiliensis was classified as a non-wild-type strain for amphotericin B and another for itraconazole. S. schenckii was classified as non-WT for all the antifungals tested. In this context, it is important to emphasize that non-zoonotic sporotrichosis still occurs in the state of Rio de Janeiro, with S. brasiliensis as the main etiological agent, primarily associated with infections acquired after traumatic inoculation with plants and/or soil contact, followed by S. globosa and S. schenckii . In addition, non-WT strains were found, indicating the need to monitor the antifungal susceptibility profile of these species. It is crucial to investigate other natural sources of S. brasiliensis to better understand this fungal pathogen and its environment and host cycle.

The drugs available to treat sporotrichosis, an important yet neglected fungal infection, are limited. Some Sporothrix spp. strains present reduced susceptibility to these antifungals. Furthermore, some patients may not be indicated to use these drugs, while others may not respond to the therapy. The anthelmintic drug niclosamide is fungicidal against the Sporothrix brasiliensis type strain. This study aimed to evaluate whether niclosamide also has antifungal activity against Sporothrix globosa, Sporothrix schenckii and other S. brasiliensis strains with distinct genotypes and antifungal susceptibility status. Minimal inhibitory and fungicidal concentrations (MIC and MFC, respectively) were determined using the microdilution method according to the CLSI protocol. The checkerboard method was employed to evaluate niclosamide synergism with drugs used in sporotrichosis treatment. Metabolic activity of the strains under niclosamide treatment was evaluated using the resazurin dye. Niclosamide was active against all S. brasiliensis strains (n = 17), but it was ineffective (MIC > 20 µM) for some strains (n = 4) of other pathogenic Sporothrix species. Niclosamide MIC values for Sporothrix spp. were similar for mycelial and yeast-like forms of the strains (P = 0.6604). Niclosamide was fungicidal (MFC/MIC ratio ≤ 2) for most strains studied (89%). Niclosamide activity against S. brasiliensis is independent of the fungal genotype or non-wild-type phenotypes for amphotericin B, itraconazole, or terbinafine. These antifungal drugs presented indifferent interactions with niclosamide. Niclosamide has demonstrated potential for repurposing as a treatment for sporotrichosis, particularly in S. brasiliensis cases, instigating in vivo studies to validate the in vitro findings., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

Sporotrichosis is a subcutaneous mycosis caused by pathogenic Sporothrix species. Among them, Sporothrix brasiliensis is the main species associated with endemic regions in South America, especially Brazil. It is highly virulent and can be spread through zoonotic transmission. Molecular epidemiological surveys are needed to determine the extent of genetic variation, to investigate outbreaks, and to identify genotypes associated with antifungal resistance and susceptibility. This study investigated the sequence variation of different constitutive genes and established a novel multilocus sequence typing (MLST) scheme for S. brasiliensis. Specific primers were designed for 16 genes using Primer-BLAST software based on the genome sequences of three S. brasiliensis strains (ATCC MYA-4823, A001 and A005). Ninety-one human, animal, and environmental S. brasiliensis isolates from different Brazilian geographic regions (South, Southeast, Midwest and Northeast) andtwo isolates from Paraguay were sequenced. The loci that presented the highest nucleotide diversity (π) were selected for the MLST scheme. Among the 16 studied genetic loci, four presented increased π value and were able to distinguish all S. brasiliensis isolates into seven distinct haplotypes. The PCR conditions were standardized for four loci. Some of the obtained haplotypes were associated with the geographic origin of the strains. This study presents an important advance in the understanding of this important agent of sporotrichosis in Brazil. It significantly increased the discriminatory power for genotyping of S. brasiliensis isolates, and enabled new contributions to the epidemiological studies of this human and animal pathogen in Brazil and in other countries., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Sporothrix brasiliensis causes sporotrichosis, an important infection in some groups of patients. Aims: This work was designed to investigate the effects of isavuconazole against this species. Methods: An antifungal susceptibility test was performed to compare MIC values with other antifungal drugs used to treat sporotrichosis. A checkerboard assay was performed to understand isavuconazole interactions. Furthermore, isavuconazole growth inhibition on an itraconazole-resistant strain was tested. Results: Isavuconazole had similar MICs to other azoles against S. brasiliensis , presenting fungistatic activity. Isavuconazole did not interact in vitro with antifungals or immunosuppressive drugs and inhibited the growth of an itraconazole-resistant strain. Conclusion: Isavuconazole inhibits S. brasiliensis , its pharmacologic characteristics make it a candidate for patients with sporotrichosis and it may be useful to combat sporotrichosis caused by resistant isolates.

Histoplasmosis is a frequent mycosis in people living with HIV/AIDS and other immunocompromised hosts. Histoplasmosis has high rates of mortality in these patients if treatment is unsuccessful. Itraconazole and amphotericin B are used to treat histoplasmosis; however, both antifungals have potentially severe pharmacokinetic drug interactions and toxicity. The present study determined the minimal inhibitory and fungicidal concentrations of mebendazole, a drug present in the NIH Clinical Collection, to establish whether it has fungicidal or fungistatic activity against Histoplasma capsulatum . Protein extracts from H. capsulatum yeasts, treated or not with mebendazole, were analyzed by proteomics to understand the metabolic changes driven by this benzimidazole. Mebendazole inhibited the growth of 10 H. capsulatum strains, presenting minimal inhibitory concentrations ranging from 5.0 to 0.08 µM. Proteomics revealed 30 and 18 proteins exclusively detected in untreated and mebendazole-treated H. capsulatum yeast cells, respectively. Proteins related to the tricarboxylic acid cycle, cytoskeleton, and ribosomes were highly abundant in untreated cells. Proteins related to the nitrogen, sulfur, and pyrimidine metabolisms were enriched in mebendazole-treated cells. Furthermore, mebendazole was able to inhibit the oxidative metabolism, disrupt the cytoskeleton, and decrease ribosomal proteins in H. capsulatum . These results suggest mebendazole as a drug to be repurposed for histoplasmosis treatment., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for approximately 6.8 million deaths worldwide, threatening more than 753 million individuals. People with severe coronavirus disease-2019 (COVID-19) infection often exhibit an immunosuppression condition, resulting in greater chances of developing co-infections with bacteria and fungi, including opportunistic yeasts belonging to the Saccharomyces and Candida genera. In the present work, we have reported the case of a 75-year-old woman admitted at a Brazilian university hospital with an arterial ulcer in the left foot, which was being prepared for surgical amputation. The patient presented other underlying diseases and presented positive tests for COVID-19 prior to hospitalization. She received antimicrobial treatment, but her general condition worsened quickly, leading to death by septic shock after 4 days of hospitalization. Blood samples collected on the day she died were positive for yeast-like organisms, which were later identified as Saccharomyces cerevisiae by both biochemical and molecular methods. The fungal strain exhibited low minimal inhibitory concentration values for the antifungal agents tested (amphotericin B, 5-flucytosine, caspofungin, fluconazole and voriconazole), and it was able to produce important virulence factors, such as extracellular bioactive molecules (e.g., aspartic peptidase, phospholipase, esterase, phytase, catalase, hemolysin and siderophore) and biofilm. Despite the activity against planktonic cells, the antifungals were not able to impact the mature biofilm parameters (biomass and viability). Additionally, the S. cerevisiae strain caused the death of Tenebrio molitor larvae, depending on the fungal inoculum, and larvae immunosuppression with corticosteroids increased the larvae mortality rate. In conclusion, the present study highlighted the emergence of S. cerevisiae as an opportunistic fungal pathogen in immunosuppressed patients presenting several severe comorbidities, including COVID-19 infection.

Background: The increase in the zoonotic epidemic of sporotrichosis caused by Sporothrix brasiliensis, which started in the late 1990s in Rio de Janeiro and is now found in almost all Brazilian states, has been equally advancing in neighboring countries of Brazil. Changes in the clinical-epidemiological profile, advances in the laboratory diagnosis of the disease, and therapeutic difficulties have been observed throughout these almost 25 years of the epidemic, although there is no national consensus. The last international guideline dates from 2007., Objectives: Update the clinical classification, diagnostic methods and recommendations on the therapeutic management of patients with sporotrichosis., Methods: Twelve experts in human sporotrichosis were selected from different Brazilian regions, and divided into three work groups: clinical, diagnosis and treatment. The bibliographic research was carried out on the EBSCOHost platform. Meetings took place via electronic mail and remote/face-to-face and hybrid settings, resulting in a questionnaire which pointed out 13 divergences, resolved based on the opinion of the majority of the participants., Results: The clinical classification and laboratory diagnosis were updated. Therapeutic recommendations were made for the different clinical forms., Conclusion: Publication of the first national recommendation, carried out by the Brazilian Society of Dermatology, aimed at the Brazilian scientific community, especially dermatologists, infectologists, pediatricians, family medicine personnel, and laboratory professionals who work in the management of human sporotrichosis., (Copyright © 2022 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Feline-transmitted sporotrichosis has garnered attention due to the recent high incidence and the lack of efficient control in the epicenter of the epidemic, Rio de Janeiro, Brazil. Sporothrix brasiliensis is the major pathogen involved in feline-to-human sporotrichosis in Brazil and displays more virulent genotypes than the closely related species S. schenckii. Over the last two decades, several reports of antifungal-resistant strains have emerged. Sequencing and comparison analysis of the outbreak strains allowed us to observe that the azole non-wild-type S. brasiliensis strain CFP 1054 had significant chromosomal variations compared to wild-type strains. One of these variants includes a region of 231 Kb containing 75 duplicated genes, which were overrepresented for lipid and isoprenoid metabolism. We also identified an additional strain (CFP 1055) that was resistant to itraconazole and amphotericin B, which had a single nucleotide polymorphism in the tac1 gene. The patients infected with these two strains showed protracted clinical course and sequelae. Even though our sample size is modest, these results suggest the possibility of identifying specific point mutations and large chromosomal duplications potentially associated with antifungal resistance and clinical outcomes of sporotrichosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Sporothrix brasiliensis is the causative agent of zoonotic cases of sporotrichosis in Brazil and is associated with atypical and severe presentations in cats, dogs, and humans. Sporotrichosis treatment is usually time- and cost-consuming, sometimes with poor response and host toxicity. Schinus terebinthifolius has proven efficacy against bacteria and fungi of clinical interest., Objective: To determine the in vitro activity of S. terebinthifolius against S. brasiliensis., Methods: Five S. brasiliensis isolates and three reference strains were subjected to a hydroethanol extract derived from the leaves of S. terebinthifolius and its fractions. The minimal inhibitory concentration (MIC) was determined using the broth microdilution method according to the M38-A2 CLSI guidelines. Also, the fungicidal/fungistatic activity of the extract and fractions was studied., Findings: The crude extract of S. terebinthifolius inhibited the growth of S. brasiliensis (MIC: 0.5-1.0 µg/mL), while the partitioned extracts dichloromethane, ethyl acetate, and butanol demonstrated growth inhibition at 8 µg/mL due to a fungistatic activity., Main Conclusions: Due to its in vitro efficacy against S. brasiliensis and its known pharmacological safety, S. terebinthifolius is a candidate to be tested using in vivo models of sporotrichosis.

The endemic mycoses blastomycosis, coccidioidomycosis, histoplasmosis, paracoccidioidomycosis, cryptococcosis, sporotrichosis, talaromycosis, adiaspiromycosis, and emergomycosis are mostly caused by geographically limited thermally dimorphic fungi (except for cryptococcosis), and their diagnoses can be challenging. Usual laboratory methods involved in endemic mycoses diagnosis include microscopic examination and culture of biological samples; however, serologic, histopathologic, and molecular techniques have been implemented in the last few years for the diagnosis of these mycoses since the recovery and identification of their etiologic agents is time-consuming and lacks in sensitivity. In this review, we focus on the immunologic diagnostic methods related to antibody and antigen detection since their evidence is presumptive diagnosis, and in some mycoses, such as cryptococcosis, it is definitive diagnosis.

Feline sporotrichosis has emerged as an important public health issue in some countries, especially Brazil. Currently, zoonotic transmission of Sporothrix brasiliensis by domestic cats is the major sporotrichosis spread form throughout this country. Sporotrichosis in Brazil is a good model for the One Health concept application, which connects the environment, human and animal health. Under this thinking, the aim of this study was to investigate the seroprevalence of sporotrichosis in cats from Rolim de Moura, Rondônia, Brazil, using antibody detection by an ELISA test previously validated for human diagnosis. For the standardization of this test, 30 serum samples from cats with proven sporotrichosis and 11 sera from healthy cats were used. The assay showed 87% sensitivity and 100% specificity for the diagnosis of feline sporotrichosis. After the standardization, 202 serum samples from distinct cats from Rolim de Moura were evaluated. The test was positive in 63 (31.19%) cats from the studied area. A multivariate analysis revealed that living far from forest or agricultural areas as well as pure breed animals had higher odds ratios (3.157 and 2.281, respectively) for the presence of detectable levels of anti-Sporothrix antibodies. These results show the applicability of this assay in the detection of anti-Sporothrix antibodies in feline serum samples and point to a putative new occurrence area of urban sporotrichosis dispersing to the North region of Brazil., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

The zoonotic transmission of sporotrichosis due to Sporothrix brasiliensis occurs largely in Rio de Janeiro state, Brazil since the 1990´s. Most patients infected with S. brasiliensis respond well to itraconazole or terbinafine. However, a few patients have a slow response or do not respond to the treatment and develop a chronic infection. The aim of this study was to analyze strains of S. brasiliensis against five different drugs to determine minimal inhibitory concentration distributions, to identify non-wild type strains to any drug evaluated and the clinical aspects of infections caused by them. This study evaluated 100 Sporothrix spp. strains obtained from 1999 to 2018 from the Evandro Chagas National Institute of Infectious Diseases, Fiocruz, which were identified through a polymerase chain reaction using specific primers for species identification. Two-fold serial dilutions of stock solutions of amphotericin B, itraconazole, posaconazole, ketoconazole and terbinafine prepared in dimethyl sulfoxide were performed to obtain working concentrations of antifungal drugs ranging from 0.015 to 8.0 mg/L. The broth microdilution reference method was performed according the M38-A2 CLSI guideline. All strains were identified as S. brasiliensis and thirteen were classified as non-wild type, two of them against different drugs. Non-wild type strains were identified throughout the entire study period. Patients infected by non-wild type strains presented prolonged treatment times, needed increased antifungal doses than those described in the literature and one of them presented a permanent sequel. In addition, three of them, with immunosuppression, died from sporotrichosis. Despite the broad use of antifungal drugs in hyperendemic areas of sporotrichosis, an emergence of non-wild type strains did not occur. The results of in vitro antifungal susceptibility tests should guide sporotrichosis therapy, especially in immunosuppressed patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bernardes-Engemann, Tomki, Rabello, Almeida-Silva, Freitas, Gutierrez-Galhardo, Almeida-Paes and Zancopé-Oliveira.)

Sporotrichosis is a cosmopolitan subcutaneous mycosis caused by Sporothrix species. Recently, this mycosis has gained notoriety due to the appearance of new endemic areas, recognition of new pathogenic species, changes in epidemiology, occurrence of outbreaks, and increasing numbers of cases. The purpose of this study is to analyze the peculiarities of sporotrichosis cases in Brazil since its first report in the country until 2020. In this work, ecological, epidemiological, clinical, and laboratorial characteristics were compiled. A systematic review of human sporotrichosis diagnosed in Brazil and published up to December 2020 was performed on PubMed/MEDLINE, SciELO, Web of Science, and LILACS databases. Furthermore, animal sporotrichosis and environmental isolation of Sporothrix spp. in Brazil were also evaluated. The study included 230 papers, resulting in 10,400 human patients. Their ages ranged from 5 months to 92 years old and 55.98% were female. The lymphocutaneous form was predominant (56.14%), but systemic involvement was also notably reported (14.34%), especially in the lungs. Besides, hypersensitivity manifestations (4.55%) were described. Most patients had the diagnosis confirmed by isolation of Sporothrix spp., mainly from skin samples. Sporothrix brasiliensis was the major agent identified. HIV infection, cardiovascular diseases, and diabetes were the most common comorbidities. Cure rate was 85.83%. Concerning animal sporotrichosis, 8538 cases were reported, mostly in cats (90.77%). Moreover, 13 Sporothrix spp. environmental strains were reported. This review highlights the burden of the emergent zoonotic sporotrichosis in Brazil, reinforcing the importance of "One Health" based actions to help controlling this disease., (© 2021. Sociedade Brasileira de Microbiologia.)

Background: Treatment of mycoses is often ineffective, usually prolonged, and has some side effects. These facts highlight the importance of discovering new molecules to treat fungal infections., Objectives: To search the Medicines for Malaria Venture COVID Box for drugs with antifungal activity., Methods: Fourteen human pathogenic fungi were tested against the 160 drugs of this collection at 1.0 µM concentration. We evaluated the ability of the drugs to impair fungal growth, their fungicidal nature, and morphological changes caused to cells., Findings: Thirty-four molecules (21.25%) presented antifungal activity. Seven are antifungal drugs and one is the agricultural fungicide cycloheximide. The other drugs with antifungal activity included antibiotics (n = 3), antimalarials (n = 4), antivirals (n = 2), antiparasitcs (n = 3), antitumor agents (n = 5), nervous system agents (n = 3), immunosuppressants (n = 3), antivomiting (n = 1), antiasthmatic (n = 1), and a genetic disorder agent (n = 1). Several of these drugs inhibited Histoplasma capsulatum and Paracoccidioides brasiliensis growth (15 and 20, respectively), while Fusarium solani was not affected by the drugs tested. Most drugs were fungistatic, but niclosamide presented fungicidal activity against the three dimorphic fungi tested. Cyclosporine affected morphology of Cryptococcus neoformans., Main Conclusions: These drugs represent new alternatives to the development of more accessible and effective therapies to treat human fungal infections.

Conventional systemic and topical treatments have proven ineffective for the treatment of onychomycosis caused by Neoscytalidium dimidiatum. Our aim was to evaluate the effectiveness and safety of laser monotherapy for the treatment of onychomycosis caused by this pathogen. Patients with clinical onychomycosis of the toenails and positive results both on direct mycological examination and N. dimidiatum culture underwent four 1064 nm Nd:YAG laser sessions with 6-week intervals between sessions. Participants were monitored by clinical examination supported by dermoscopy, measurement of diseased nail and the onychomycosis severity index (OSI), and by mycological examination for 12 months after completion of treatment. Treatment outcome was based on clinical and laboratory criteria and was divided in complete or partial cure, clinical improvement, treatment failure and relapse. No patient had complete or partial cure at any time during the study. Clinical improvement was observed in 40.6% of the patients at the end of the laser sessions; however, it did not persist during the follow-up. Treatment failure was observed in 64.7% of the patients at the end of 12 month follow-up period. Direct microscopy and culture results remained positive in most patients. Adverse events, in addition to treatment-related pain, were observed and considered severe in one case. The 1064 nm Nd:YAG laser was not able to cure onychomycosis caused by N. dimidiatum but temporarily improved the clinical appearance of the nail; however, adverse events may occur., (© The Authors 2017. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Improvement of laboratory diagnosis of onychomychosis is important so that adequate treatment can be safely implemented. To evaluate and compare the performance of mycological and histopathological examinations in onychomycoses caused by dermatophyte and non-dermatophyte moulds. Patients with lateral/distal subungual onychomycosis in at least one hallux were enrolled in the protocol and assessed via mycological and histopathological tests. The isolation of filamentous fungi was considered the gold standard. Test performance was evaluated through sensitivity, specificity and positive and negative predictive values. A total of 212 patients were enrolled in the study. Direct microscopy (DM) was positive in 57.5% patients, and cultures in 34.4%. Among these patients, 23.3% were positive for dermatophytes, with Trichophyton rubrum the most frequently isolated, and 86.3% were positive for non-dermatophytes, with Neoscytalidium dimidiatum predominance. Histopathology was positive in 41.0% samples. Direct microscopy showed better sensitivity for non-dermatophyte moulds (P=.000) and nail clipping was more specific for dermatophyte (P=.018). Histopathology of the distal nail plate is a valuable complementary tool for the diagnosis of onychomycosis caused by dermatophytes and direct microscopy is especially useful for non-dermatophyte molds., (© 2017 Blackwell Verlag GmbH.)

In the late 90's there was a change in both the route of transmission and the people at risk for sporotrichosis. This zoonotic cat-man alternative transmission route elicited changes in strategies to control the epidemic. There was a progressive increase in the number of cases involving especially children and the elderly. In addition to becoming hyperendemic, uncommon clinical pictures like immunoreactive clinical presentations or severe systemic cases have emerged. New species were identified and classified through molecular tools using more virulent clinical isolates, like S. brasiliensis, compared to the environmental isolates. Likewise, different species of Sporothrix have been associated with different geographic regions. The serological and molecular techniques are used as an auxiliary tool for the diagnosis and/or for species identification, although the isolation and the identification of Sporothrix spp. in clinical specimen is still the gold standard. Currently sporotrichosis epidemics requires the knowledge of the epidemiological-molecular profile to control the disease and the specific treatment. Itraconazole, potassium iodide, terfinafine, and amphotericin B are the available drugs in Brazil to treat sporotrichosis. The drug of choice, its posology, and treatment duration vary according to the clinical presentation, the Sporothrix species, and host immune status. New treatment choices, including a vaccine, are being developed; nevertheless, more clinical trials are required to confirm its efficacy.

Neoscytalidium dimidiatum is an emerging fungus that causes a skin infection similar to dermatophytosis; it affects both immunocompetent and immunosuppressed individuals, and it may invade deeper tissues and organs and cause systemic disease. Little is known about the etiopathogenesis of the infection caused by this fungus, and no standard effective treatment is available. The aim of the present experimental study was to develop an animal model of skin infection with N. dimidiatum. BALB/c mice were inoculated with two fungal strains, and different routes of infection were tested. When challenged intradermally, N. dimidiatum strain HUPE164165 caused skin infection in 67% of the animals whereas strain HUPE115669 did it in 49%. Neoscytalidium dimidiatum was isolated from the skin of 25% of the animals inoculated via epidermal scarification and from 100% of the animals challenged via subcutaneous injection. Mice inoculated intradermally were followed-up during four weeks, and clinical samples were collected on days 3, 8, 15, and 29 after inoculation, corresponding to different stages of infection. The cutaneous infection rate, as measured by the recovery of N. dimidiatum strain HUPE164165 from skin biopsies of animals inoculated intradermally, revealed the presence of infection in 90% of the animals sacrificed at 3 days post-inoculation, 71% at 8, 85% at 15, and 33% at 29. Conidia and hyphae were observed in PAS-stained sections as well as a mild to moderate inflammatory infiltrate in haematoxylin-eosin, although it did not differ from animals inoculated either with T. quinckeanum or PBS. The intradermal route of inoculation was considered to be suitable for the study of skin infection with N. dimidiatum The animal model developed in this preliminary study is the first to allow the study of cutaneous infection with N. dimidiatum and may contribute to further investigations of the aetiology, immunology, pathogenesis and treatment targeting this emerging mycosis., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The first therapeutic choice for the treatment of cutaneous sporotrichosis is oral itraconazole; however, the increase in cases of zoonotic transmission outbreak necessitates a search for effective and safe treatment alternatives., Objective: To evaluate a new potassium iodide (KI) posology as an alternative for the treatment of limited cutaneous forms of sporotrichosis., Methods: One hundred and two patients with sporotrichosis diagnosed by isolation of Sporothrix sp. were included and were divided into 2 groups that received different doses of KI: group A received the conventional dose, and group B received the reduced dose. The cure criteria were based on clinical and serological data., Results: Seventy-nine patients (77.4%) reached clinical cure: 70.6% and 84.3% of groups A and B respectively. Sixteen patients (15.6%) were lost during follow-up, and seven changed drug therapy: five in group A and two in group B. The incidence of adverse events was similar for both groups (64.7%): predominantly metallic taste (44%), followed by mild gastrointestinal intolerance and acneiform eruption (10.7% each). No serious adverse events occurred, and there were no recurrences. Analysis of the results showed no statistically significant difference between groups (P = 0.9255). The improvement in serologic titres was significant in both treatment groups., Conclusion: Through statistical analysis, the usual posology was not shown to be superior to the one proposed in this study. Serology for sporotrichosis may be used as a valuable tool in the clinical monitoring of these patients., (© 2014 European Academy of Dermatology and Venereology.)

Sporothrix brasiliensis is the main species of the S. schenckii complex implicated in the zoonotic epidemics of sporotrichosis in Rio de Janeiro, Brazil. Epidemiological features have been already described, such as zoonotic transmission by cats and increased frequency of atypical clinical aspects. The involvement of the face by contact with cats is common in childhood; as a result, ophthalmic manifestations have increased. We report a case of acute dacryocystitis in a 9-year-old girl. A calmodulin-based molecular phylogeny was used to identify the agent as S. brasiliensis. This is a rare type of presentation, usually complicated with nasolacrimal duct occlusion. The patient was cured without sequelae after treatment with a low dose of saturated solution of potassium iodide and decompressive oculoplastic surgery. Therapeutic options and considerations of aetiological agents and serology are discussed., (© 2014 British Association of Dermatologists.)

The gold standard for the diagnosis of sporotrichosis consists of the isolation and identification of the fungus from clinical exudates and/or biopsy specimens. However, new technologies offer several advantages over the traditional methods because they are noninvasive and more sensitive in the differential diagnosis of infectious diseases. In the present study, we performed a validation, impact evaluation, and analysis of the applicability of an enzyme-linked immunosorbent assay (ELISA) for the diagnosis of sporotrichosis in different groups of patients in comparison with the reference protocols for the evaluation of diagnostic tests for infectious diseases. We used 177 serum samples that were collected between 1998 and 2008 from patients in a geographic area related to the Rio de Janeiro outbreak of sporotrichosis. The ELISA had a low rate of cross-reactivity based on the reference values for diagnostic tests, and the analysis of the receiver operating characteristic curve revealed an area under the curve of 0.9154. Furthermore, higher accuracy was observed in the serodiagnosis of infections in special groups of patients such as pediatric and human immunodeficiency virus-positive patients. We concluded that this ELISA had a good clinical serological correlation and, therefore, can be considered a new diagnostic tool applicable to all clinical presentations of sporotrichosis., (© The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Potassium iodide, as a saturated solution, is a valuable drug in the dermatologist's therapeutic arsenal and is useful for the treatment of different diseases due to its immunomodulatory features. However, its prescription has become increasingly less frequent in dermatology practice. Little knowledge about its exact mechanism of action, lack of interest from the pharmaceutical industry, the advent of new drugs, and the toxicity caused by the use of high doses of the drug are some possible explanations for that. Consequently, there are few scientific studies on the pharmacological aspects, dosage and efficacy of this drug. Also, there is no conventional standard on how to manipulate and prescribe the saturated solution of potassium iodide, which leads to unawareness of the exact amount of the salt being delivered in grams to patients. Considering that dosage is directly related to toxicity and the immunomodulatory features of this drug, it is essential to define the amount to be prescribed and to reduce it to a minimum effective dose in order to minimize the risks of intolerance and thus improve treatment adherence. This review is relevant due to the fact that the saturated solution of potassium iodide is often the only therapeutic choice available for the treatment of some infectious, inflammatory and immune-mediated dermatoses, no matter whether the reason is specific indication, failure of a previous therapy or cost-effectiveness.

Onychomycosis constitutes up to 50% of all nail disorders. Toenails are generally affected, mostly due to dermatophytes. Terbinafine is the most potent antifungal agent in vitro against dermatophytes. There are few randomised controlled trials using a non-continuous dose of terbinafine. The aim of this open-label pilot study was to reduce the total drug amount, the collateral effects and, specially, the costs; albeit maintaining the same efficacy of the standard regimens. Compare the outcomes of two different intermittent regimens with the same total amount of the medication (42 tablets in 6 months). Forty-one patients were divided into the following groups: terbinafine 250 mg day(-1) , for 7 days, monthly or terbinafine 500 mg day(-1) , once daily, for 7 days, every 2 months, both plus nail abrasion during 6 months. The efficacy was evaluated at months 6, 12 and 18 using the disease free nail criteria. Total cure = group I: eight patients (44.4%) and group II: eight patients (44.4%). Partial cure = group I: five patients (27.8%) and group II: four patients (22.2%). Treatment failure = group I: five patients (27.8%) and group II: three patients (16.7%). Recurrence = group I: zero patients (0.0%) and group II: three patients (16.7%). Two intermittent dosing regimens of terbinafine plus nail abrasion proved to be an alternative statistically effective, safe and with reduced drug costs for dermatophytes toenail onychomycosis., (© 2012 Blackwell Verlag GmbH.)

A 32-year-old HIV negative male presented with multiple pulmonary cavitation and skin abscesses up to 15 cm in diameter mimicking tuberculosis. Sporothrix brasiliensis was isolated and patient responded well to amphotericin B followed by itraconazole, except the skin lesions that had to be surgical drained to obtain cure.

Background: Onychomycosis by Neoscytalidium constitutes chronic infection of the nails, and its frequency has increased in recent decades. Currently, no effective standard treatment exists and literature data remain scarce. This work aimed to conduct a pilot project of combined treatment for this infection., Methods: Thirty patients were divided into three treatment groups: oral terbinafine plus ciclopirox nail lacquer twice a week; ciclopirox nail lacquer twice a week; and ciclopirox nail lacquer 5 days a week, all associated with nail abrasion when required, for 12 months, with 6 months posttreatment follow-up. Clinical and mycological criteria were used for evaluation., Results: Twenty-five patients completed the study. Significant clinical lesion reduction in disease occurred in all three treatment groups: 21 patients (84%) entered the study with more than 50% of diseased nail plate, at the end of treatment, and at 6-month follow-up, 84 and 96%, respectively, presented less than 25% nail lesion. Negative microscopy was observed in 36% of the patients at the end of treatment and in 24% of the patients at 6-month follow-up. At treatment completion (12 months), culture was negative in 21 patients (84%) and in 18 (72%) at follow-up. It was not possible to establish any clinical or mycological statistical differences between groups (p > 0.05). Global medical evaluation upon treatment completion revealed that one patient (4%) presented complete cure, 8 (32%) presented partial cure, 16 (64%) presented therapeutic failure. At the end of follow-up period, 6 patients (24%) were considered to have recurrence/reinfection., Conclusions: The results obtained at the 6-month period of follow-up showed marked improvement (96% of clinical improvement and 72% of negative culture) of the patients treated for onychomycosis caused by Neoscytalidium in the three tested groups with no statistical differences between them. Multicentric studies with greater number of patients enrolled are necessary to confirm these results.

Five cases of sporotrichosis occurring in pregnant women in a zoonotic epidemic in Rio de Janeiro, Brazil, are described. The main clinical features, as well as the challenging therapeutic choices for this specific group of patients, are discussed.

The main objective of this study is to standardize an ELISA for the diagnosis of feline sporotrichosis. Sporothrix schenckii is the etiological agent of human and animal sporotrichosis. Cats may act as reservoirs for S. schenckii and can transmit the infection to humans by a bite or scratch. There are few methods for the serological diagnosis of fungal diseases in animals. In this paper, an ELISA test for the diagnosis of cat sporotrichosis is proposed, which detects S. schenckii-specific antibodies in feline sera. Two different kinds of antigens were used: "SsCBF", a specific molecule from S. schenckii that consists of a Con A-binding fraction derived from a peptido-rhamnomannan component of the cell wall, and a S. schenckii crude exoantigen preparation. The ELISA was developed, optimized, and evaluated using sera from 30 cats with proven sporotrichosis (by culture isolation); 22 sera from healthy feral cats from a zoonosis center were used as negative controls. SsCBF showed 90% sensitivity and 96% specificity in ELISA; while crude exoantigens demonstrated 96% sensitivity and 98% specificity. The ELISA assay described here would be a valuable screening tool for the detection of specific S. schenckii antibodies in cats with sporotrichosis. The assay is inexpensive, quick to perform, easy to interpret, and permits the diagnosis of feline sporotrichosis., (Copyright © 2010 Elsevier B.V. All rights reserved.)

A previous work showed that an antigenic fraction of Sporothrix schenckii, SsCBF, was specifically recognized by IgG antibodies present in patients' clinical specimens. The objective of this investigation was to compare the reactivity of this antigen recovered from three S. schenckii strains. ROC curve analysis revealed a variation in the sensitivity and specificity of the antigen derived from each of the strains, with a higher AUC for strain 1099-18. Moreover, the presence of the main O-glycosidically-linked epitopes described in the SsCBF fraction was ascertained. A significant reduction in SsCBF reactivity of all the strains was observed after beta-elimination confirming the presence of O-glycan epitopes. The antigen isolated from strain 1099-18 proved to be a more accurate diagnostic tool for serodiagnosis of sporotrichosis.

Sporotrichosis is a generally cutaneous, granulomatous, chronic and benign infection. Less frequently the disease may affect the joints. Articular involvement is usually characterized by monoarthritis in the absence of systemic symptoms, generally preceded by skin lesions, and frequently affects immunosuppressed individuals. We describe here the case of a healthy patient presenting knee arthritis without skin lesions, diagnosed as sporotrichosis, and treated with oral itraconazole. Serology used in this case was an invaluable tool for the diagnosis of sporotrichosis arthritis lacking skin lesions.

We performed a serological study with sera from 92 patients with confirmed sporotrichosis registered between 1999 and 2004 in two hospitals in Rio de Janeiro State, Brazil. The clinical presentation of sporotrichosis was distributed as follows: lymphocutaneous, 67%; fixed cutaneous, 23%; disseminated cutaneous, 8%; and extracutaneous, 2%. Sera were assayed by ELISA against a cell wall antigen of Sporothrix schenckii, SsCBF, that we have previously described. The cross-reactivity was determined with 77 heterologous sera. The serological test showed a sensitivity of 90% and a global efficiency of 86%. A group of 55 patients with several clinical presentations of sporotrichosis was clinically and serologically followed-up for at least 6 months. We observed by ELISA data a decrease in the antibody serum titers which correlated with the progress in healing. An HIV-positive patient with meningeal sporotrichosis was serologically followed-up for over 2 years. Serum and cerebrospinal fluid specimens were examined and significant antibodies levels against the antigen SsCBF were detected. Our results strongly suggest that this serological test is valuable for the differential diagnosis and follow-up of all clinical forms of sporotrichosis.