A case of disseminated sporotrichosis.

Sporothrix schenckii is a thermally dimorphic fungus found in soil and in plant matter. Cutaneous sporotrichosis is the most common manifestation and disseminated sporotrichosis is the rarest. Delayed diagnoses are not uncommon. We report a case of disseminated sporotrichosis involving the skin, bones and joints, with subsequent joint destruction, tissue loss and permanent disability. Contribution: This case report highlights the debilitating potential of sporotrichosis and its often elusive nature regarding diagnosis.

Milteforan, a promising veterinary commercial product against feline sporotrichosis.

Sporotrichosis, the cutaneous mycosis most commonly reported in Latin America, is caused by the Sporothrix clinical clade species, including Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. Due to its zoonotic transmission in Brazil, S. brasiliensis represents a significant health threat to humans and domestic animals. Itraconazole, terbinafine, and amphotericin B are the most used antifungals for treating sporotrichosis. However, many strains of S. brasiliensis and S. schenckii have shown resistance to these agents, highlighting the importance of finding new therapeutic options. Here, we demonstrate that milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, is a possible therapeutic alternative for the treatment of sporotrichosis, as observed by its fungicidal activity in vitro against different strains of S. brasiliensis and S. schenckii. Fluorescent miltefosine localizes to the Sporothrix cell membrane and mitochondria and causes cell death through increased permeabilization. Milteforan decreases S. brasiliensis fungal burden in A549 pulmonary cells and bone marrow-derived macrophages and also has an immunomodulatory effect by decreasing TNF-α, IL-6, and IL-10 production. Our results suggest milteforan as a possible alternative to treat feline sporotrichosis. IMPORTANCE: Sporotrichosis is an endemic disease in Latin America caused by different species of Sporothrix. This fungus can infect domestic animals, mainly cats and eventually dogs, as well as humans. Few drugs are available to treat this disease, such as itraconazole, terbinafine, and amphotericin B, but resistance to these agents has risen in the last few years. Alternative new therapeutic options to treat sporotrichosis are essential. Here, we propose milteforan, a commercial veterinary product against dog leishmaniasis, whose active principle is miltefosine, as a possible therapeutic alternative for treating sporotrichosis. Milteforan decreases S. brasiliensis fungal burden in human and mouse cells and has an immunomodulatory effect by decreasing several cytokine production.

Emerging Cases of Cat-Transmitted Sporotrichosis Driven by Sporothrix brasiliensis in Northeast Brazil.

Cat-transmitted sporotrichosis is caused by the emerging fungal pathogen Sporothrix brasiliensis and constitutes a significant public health issue that affects people living in resource-poor urban centers in Brazil. The lack of knowledge about transmission dynamics makes it difficult to propose public health policies to contain the advance of sporotrichosis. We describe the recent emergence of 1,176 cases of sporotrichosis in cats (2016 to 2021) in the metropolitan region of Recife, Brazil, leading to significant zoonotic transmission and an overwhelming occurrence of S. brasiliensis as the etiological agent. Most cases were from cats in the cities of Olinda (408/1,176; 34.70%), Jaboatão dos Guararapes (332/1,176; 28.23%), and Recife (237/1,176; 20.15%). Molecular typing using amplified fragment length polymorphism (EcoRI-GA/MseI-AG) revealed low polymorphic information content (PIC = 0.2499) and heterozygosity (H = 0.2928), typical of an outbreak scenario. Dendrogram and multivariate cluster analysis revealed that isolates from Pernambuco are closely related to Rio de Janeiro isolates. We report a substantial occurrence of MAT1-2 idiomorphs in the metropolitan region of Recife (0:60 ratio; χ2 = 60.000, P < 0.0001). The limited population differentiation and genetic diversity of the isolates from Pernambuco suggest a recent introduction, possibly via a founder effect, from the parental population in Rio de Janeiro. Our findings emphasize the critical importance of molecular surveillance of S. brasiliensis for outbreak response. A comprehensive one-health strategy is mandatory to control the spread of cat-transmitted sporotrichosis driven by S. brasiliensis, encompassing sanitary barriers, quick diagnosis, and treatment.

Ocular Adnexal Manifestations of Sporotrichosis: A Report of Two Cases.

Sporotrichosis is a subcutaneous mycotic infection, caused by the dimorphic fungi Sporothrix schenckii. Ocular sporotrichosis has both intraocular and adnexal forms. We describe two cases of sporotrichosis involving the conjunctiva of two healthy individuals after inoculation by their pet cats, with complete resolution of lesions after antifungal treatment.

Anti-Sporothrix Activity of Novel Copper-Itraconazole Complexes.

A series of new metal complexes, [Cu(ITZ)2Cl2] ⋅ 5H2O (1), [Cu(NO3)2(ITZ)2] ⋅ 3H2O ⋅ C4H10O (2) and [Cu(ITZ)2)(PPh3)2]NO3 ⋅ 5H2O (3) were synthesized by a reaction of itraconazole (ITZ) with the respective copper salts under reflux. The metal complexes were characterized by elemental analyses, molar conductivity, 1H and 13C{1H} nuclear magnetic resonance, UV-Vis, infrared and EPR spectroscopies. The antifungal activity of these metal complexes was evaluated against the main sporotrichosis agents: Sporothrix brasiliensis, Sporothrix schenkii, and Sporothrix globosa. All three new compounds inhibited the growth of S. brasiliensis and S. schenckii at lower concentrations than the free azole, with complex 2 able to kill all species at 4 µM and induce more pronounced alterations in fungal cells. Complexes 2 and 3 exhibited higher selectivity and no mutagenic effect at the concentration that inhibited fungal growth and affected fungal cells. The strategy of coordinating itraconazole (ITZ) to copper was successful, since the corresponding metal complexes were more effective than the parent drug. Particularly, the promising antifungal activity of the Cu-ITZ complexes makes them potential candidates for the development of an alternative drug to treat mycoses.

Sporotrichosis Cluster in Domestic Cats and Veterinary Technician, Kansas, USA, 2022.

We describe a feline sporotrichosis cluster and zoonotic transmission between one of the affected cats and a technician at a veterinary clinic in Kansas, USA. Increased awareness of sporotrichosis and the potential for zoonotic transmission could help veterinary professionals manage feline cases and take precautions to prevent human acquisition.

An Immune-Based Therapeutical Approach in an Elderly Patient With Fixed Cutaneous Sporotrichosis.

Sporotrichosis is a subcutaneous fungal infection caused by thermally dimorphic fungi from the Sporothrix genus, primarily prevalent in tropical regions of Latin America, Africa, and Asia. Mexico's Jalisco state is an endemic hotspot with a remarkable prevalence rate of 54.4%. Clinical presentation varies based on immune status and virulence. The most common form is cutaneous-lymphangitic (67%), with fixed cutaneous cases accounting for 28%. This case study explores a traditional therapeutic approach for fixed cutaneous sporotrichosis but introduces a distinct immunological perspective.

Oral mucosa sporotrichosis: Report of a rare case acquired by direct inoculation.

Sporotrichosis is a rare type of fungal infection caused by Sporothrix fungus. Transmissions are commonly by traumatic inoculation of the fungus through the skin and subcutaneous tissue either from environmental exposure or contact with infected animals. Due to its mode of transmission, it is commonly affecting the upper limbs. Definitive diagnosis can be obtained by fungal culture test on secretion fluids, pus, bloods or tissue biopsy. We report a rare presentation of this disease appearing as a solitary chronic ulcer of the lip which was successfully treated with itraconazole.

Milteforan, a promising veterinary commercial product against feline sporotrichosis.

Sporotrichosis, the cutaneous mycosis most commonly reported in Latin America, is caused by the Sporothrix clinical clade species, including Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In Brazil, S. brasiliensis represents a vital health threat to humans and domestic animals due to its zoonotic transmission. Itraconazole, terbinafine, and amphotericin B are the most used antifungals for treating sporotrichosis. However, many strains of S. brasiliensis and S. schenckii have shown resistance to these agents, highlighting the importance of finding new therapeutic options. Here, we demonstrate that milteforan, a commercial veterinary product against dog leishmaniasis whose active principle is miltefosine, is a possible therapeutic alternative for the treatment of sporotrichosis, as observed by its fungicidal activity in vitro against different strains of S. brasiliensis and S. schenckii, and by its antifungal activity when used to treat infected epithelial cells and macrophages. Our results suggest milteforan as a possible alternative to treat feline sporotrichosis.

Hyperthermia is a promising potential adjunct to treating sporotrichosis: A refractory case of HIV sporotrichosis and in vitro experiments on Sporothrix spp.

BACKGROUND: Hyperthermia is a common monotherapy for sporotrichosis, but only in patients with special conditions, such as pregnancy and nursing. However, hyperthermia has not been used more widely for sporotrichosis in clinical practice. PATIENTS/METHODS: An HIV-positive adult male with lymphocutaneous sporotrichosis caused by Sporothrix globosa that did not respond to conventional itraconazole therapy lasting >2 months received adjunctive therapy with local hyperthermia. To simulate the effects of heat exposure on the growth and morphology of Sporothrix spp. in vitro, S. globosa, S. schenckii and S. brasiliensis were exposed to intermittent heat (42°C) for 1 h a day for 7 or 28 days and observed under transmission electron microscopy. RESULTS: Itraconazole combined with local hyperthermia significantly improved the lesions, and the patient was successfully cured of sporotrichosis, with no recurrence after 2 years of follow-up. Cultures of Sporothrix spp. treated with 7 days of daily heat exposure in vitro showed obvious decreases in colony diameters, but not numbers, compared with untreated cultures (p < .001). After 28 days of heat exposure in vitro, Sporothrix spp. were unable to thrive (p < .001), and ultrastructural alterations, including loose cell wall structure, incomplete cell membrane, disrupted vacuoles and fragmented nuclei, were noticeable. CONCLUSIONS: Our case findings and in vitro experiments on Sporothrix spp., together with a literature review of previous sporotrichosis cases, suggest that hyperthermia has a clinical role as a treatment adjunct. Large-scale clinical trials are required to examine the utility of hyperthermia in various forms of cutaneous sporotrichosis.

First occurrence of feline sporotrichosis in a metropolitan area of Central-West Brazil

ABSTRACT Sporotrichosis is a neglected mycosis that affects human and animal hosts, including domestic cats. In Brazil, its most frequently diagnosed etiological agent is Sporothrix brasiliensis. Zoonotic transmission of S. brasiliensis occurs via direct contact between an infected cat and a susceptible human host. Notification of confirmed cases of feline sporotrichosis is not mandatory in Brazil. The metropolitan area of Goiania city can be considered a silent area for the occurrence of feline sporotrichosis. In this context, voluntary reporting of feline sporotrichosis cases is recommended for all healthcare professionals. This study aimed to report the first occurrence of S. brasiliensis in a cat from the metropolitan area of Goiania city. Cytopathology, mycology, thermal dimorphism and calmodulin gene amplification tests were performed. The mycological and molecular biological diagnoses corresponded to S. brasiliensis. The etiological agent of zoonotic sporotrichosis was detected in the metropolitan area of Goiania city, and therefore there is a risk of the emergence of new cases of cats infected with S. brasiliensis and the occurrence of zoonotic transmission of this fungus.

The Mating Type (MAT) and Virulence of Sporothrix schenckii sensu stricto Isolates Maintained in Culture Collection.

In an attempt to determine the mating type of different Sporothrix schenckii sensu stricto isolates that remained viable after a long period of preservation in a culture collection and to correlate them with the degree of virulence/pathogenicity, a PCR technique using primers designed for the sequences of MAT1-1-1 and MAT1-2-1 genes and a murine experimental model were used. The results showed that there was no correlation between the mating type and virulence among the isolates. Furthermore, different degrees of virulence/pathogenicity, ranging from high to low, were found among them based on different virulence parameters. It was assumed that the long period of preservation favored the changes, yielding the isolation of variants. Thus, we believe that new technologies for studies on factors can improve our knowledge of the pathogenesis of sporotrichosis.

Sporothrix schenckii sensu stricto related to zoonotic transmission in Thailand.

Two sporotrichosis cases were related to zoonotic transmission as their cats were diagnosed of feline sporotrichosis. The result of fungus culture as dimorphic fungi and flower-like arrangement of typical S. schenckii complex morphology confirms the diagnosis. The species were identified by Polymerase Chain Reaction (PCR) using species-specific primers of calmodulin gene (CAL). The result showed that etiological agents of these two cases in Northern Thailand are S. schenckii sensu stricto. One case was successfully treated with daily dose of 250 mg terbinafine, and the other was treated with daily dose of 100 mg itraconazole with an excellent outcome. 2012 Elsevier Ltd. All rights reserved.

Development of loop-mediated isothermal amplification for rapid detection of sporotrichosis caused by Sporothrix schenckii.

Background and Aim: Sporothrix schenckii is the causative agent of sporotrichosis, which most commonly causes lymphocutaneous infections in immunocompromised hosts. This pathogen infects dogs, cats, cattle, and buffaloes and can potentially infect humans. Diagnosis by fungal culture is lengthy, and although there are several clinical diagnoses and molecular methods, these are complicated and time-consuming for veterinarians. This study aimed to develop a visual diagnostic assay that is less time-consuming and can be used by veterinarians to screen for sporotrichosis. Materials and Methods: To develop a loop-mediated isothermal amplification (LAMP) assay for sporotrichosis, primers specific for fragments of the 18S rRNA gene of S. schenckii were designed. Then, the time and temperature were optimized to successfully achieve LAMP. Ten-fold serial dilutions of DNA were used to determine the detection limit using both LAMP and nested polymerase chain reaction (nPCR) assays. Results: The optimal LAMP conditions were incubation at 73°C for 30 min. Agarose gel electrophoresis revealed a ladder-like pattern of the LAMP product, and a sky-blue color indicated a positive result. A comparison of the LAMP assay with nPCR revealed that it was 10 times more sensitive than nPCR, with a detection limit of 10 pg. The use of a heat box compared with a thermocycler gave the same results. Conclusion: Loop-mediated isothermal amplification gives good results and may represent a future alternative diagnostic tool for screening fungal pathogens before the results of conventional fungal cultures are received. However, this method should be further studied to clarify its use with clinical samples.

Phenotypic and Genotypic Characterization and Antifungal Susceptibility of Sporothrix schenckii sensu stricto Isolated from a Feline Sporotrichosis Outbreak in Bangkok, Thailand.

Sporotrichosis, an invasive fungal infection caused by Sporothrix schenckii, has emerged in Southeast Asia, affecting cats and posing a potential zoonotic risk to humans. We evaluated 38 feline sporotrichosis cases in and around Bangkok, Thailand, from 2017 to 2021. The isolates were phenotypically and genotypically characterized. The cats infected with sporotrichosis were mainly young adults, males, and domestic short hairs with uncontrolled outdoor access, and they lived in Bangkok. All isolates showed low thermotolerance and converted to the yeast phase at 35 °C. Based on the internal transcribed spacer region of rDNA sequences, our strains belonged to S. schenckii sensu stricto and clustered with clinical clade D. Based on the concatenated tree of calmodulin and beta-tubulin genes, five groups of S. schenckii were generated, and the monophyletic clade, Group II, of Thai strains was recognized. In vitro antifungal susceptibility testing demonstrated that the MIC50 of our isolates to amphotericin B, itraconazole, and posaconazole were within the limit of the species-specific epidemiological cutoff values, suggesting that the organisms were the wild type. Addressing the outbreak of feline sporotrichosis in Thailand by providing guidelines for diagnosis and effective treatment may help control the spread of disease and reduce the risk of cat-transmitted sporotrichosis to humans.

Relationship of Sporotrichosis and Infected Patients with HIV-AIDS: An Actual Systematic Review.

BACKGROUND: Sporotrichosis is a fungal infection that can affect both humans and animals, caused by a species of thermo-dimorphic fungi of the genus Sporothrix. This pathology can be acquired by subcutaneous traumatic inoculation through contact with contaminated plants, soil or decomposing organic matter, and/or by inhalation of conidia. The infection can progress to chronic skin infection, or it can even spread to blood vessels, lymph, muscles, bones, and other organs, such as the lungs and nervous system. Those disseminated types are usually associated with cellular immunodeficiency and infection by inhalation, which explains why people living with human immunodeficiency virus (PLHIV) get infected in such a manner. This virus changes the natural history of sporotrichosis, producing a greater fungal load. METHODS: The search was carried out in three databases: Pubmed, Scopus, and Scielo. Eligible articles were considered as those that described sporotrichosis in patients infected with HIV-AIDS, as well as case series. RESULTS: A total of 24 articles were selected, with a sum of 37 patients with sporotrichosis and HIV infection. Of these patients, 31 came from Brazil, two from the United States, one from South Africa, one from Bangladesh, and two from an unspecified region. Regarding epidemiology, a predominance of the male sex was found in 28 of the 37 cases (75.6%), while nine were female (24.3%). CONCLUSIONS: Sporotrichosis infection continues to present in a more severe and disseminated way among HIV-positive subjects with lower CD4+ counts.

Innate Immune Responses to Sporothrix schenckii: Recognition and Elimination.

Sporothrix schenckii (S. schenckii), a ubiquitous thermally dimorphic fungus, is the etiological agent of sporotrichosis, affecting immunocompromised and immunocompetent individuals. Despite current antifungal regimens, sporotrichosis results in prolonged treatment and significant mortality rates in the immunosuppressed population. The innate immune system forms the host's first and primary line of defense against S. schenckii, which has a bi-layered cell wall structure. Many components act as pathogen-associated molecular patterns (PAMPs) in pathogen-host interactions. PAMPs are recognized by pattern recognition receptors (PRRs) such as toll-like receptors, C-type lectin receptors, and complement receptors, triggering innate immune cells such as neutrophils, macrophages, and dendritic cells to phagocytize or produce mediators, contributing to S. schenckii elimination. The ultrastructure of S. schenckii and pathogen-host interactions, including PRRs and innate immune cells, are summarized in this review, promoting a better understanding of the innate immune response to S. schenckii and aiding in the development of protective and therapeutic strategies to combat sporotrichosis.

Catalases in the pathogenesis of Sporothrix schenckii research.

Pathogenic fungal infection success depends on the ability to escape the immune response. Most strategies for fungal infection control are focused on the inhibition of virulence factors and increasing the effectiveness of antifungal drugs. Nevertheless, little attention has been focused on their physiological resistance to the host immune system. Hints may be found in pathogenic fungi that also inhabit the soil. In nature, the saprophyte lifestyle of fungi is also associated with predators that can induce oxidative stress upon cell damage. The natural sources of nutrients for fungi are linked to cellulose degradation, which in turn generates reactive oxygen species (ROS). Overall, the antioxidant arsenal needed to thrive both in free-living and pathogenic lifestyles in fungi is fundamental for success. In this review, we present recent findings regarding catalases and oxidative stress in fungi and how these can be in close relationship with pathogenesis. Additionally, special focus is placed on catalases of Sporothrix schenckii as a pathogenic model with a dual lifestyle. It is assumed that catalase expression is activated upon exposure to H2O2, but there are reports where this is not always the case. Additionally, it may be relevant to consider the role of catalases in S. schenckii survival in the saprophytic lifestyle and why their study can assess their involvement in the survival and therefore, in the virulence phenotype of different species of Sporothrix and when each of the three catalases are required. Also, studying antioxidant mechanisms in other isolates of pathogenic and free-living fungi may be linked to the virulence phenotype and be potential therapeutic and diagnostic targets. Thus, the rationale for this review to place focus on fungal catalases and their role in pathogenesis in addition to counteracting the effect of immune system reactive oxygen species. Fungi that thrive in soil and have mammal hosts could shed light on the importance of these enzymes in the two types of lifestyles. We look forward to encouraging more research in a myriad of areas on catalase biology with a focus on basic and applied objectives and placing these enzymes as virulence determinants.

Prevalencia de la infección por Sporothrix schenckii en agricultores del Cantón Shushufindi de la Provincia de Sucumbíos / Prevalence of Sporothrix schenckii infection in farmers of the Shushufindi Canton of the Sucumbíos Province

La esporotricosis es una micosis subcutánea causada por la inoculación traumática en la piel de especies de hongos del género Sporothrix. La enfermedad tiene diferentes manifestaciones clínicas (cutáneas, linfocutáneas y diseminadas), y también puede progresar a una infección sistémica. A pesar de tener una distribución mundial, la esporotricosis es más frecuente en los países tropicales y subtropicales. La esporotricosis es la micosis subcutánea más frecuente en América Latina, donde se considera endémica. Ciertos grupos de personas pueden estar más expuestos al agente causal de la enfermedad, como los agricultores. Así, este trabajo tuvo como objetivo determinar la prevalencia de la esporotricosis en 3.133 agricultores, en el cantón de Shushufindi de la provincia de Sucumbíos, Ecuador. En este estudio, se utilizó una prueba de intradermorreacción con el antígeno esporotriquina obtenido del hongo Sporothrix schenckii. Los datos obtenidos mostraron una prevalencia de 35,45%. La distribución de la prevalencia de la esporotricosis con respecto a los grupos de edad no mostró diferencias estadísticas significativas (p=0,2054). Para la variable sexo, si hubo significancia estadística (p=0,01995). 51 de los casos positivos presentaron gomas y/o úlceras en alguno de sus miembros. La esporotricosis ha demostrado ser una de las micosis subcutáneas más frecuente en los trabajadores de la agricultura en la región ecuatoriana evaluada(AU)

Sporotrichosis is a subcutaneous mycosis caused by traumatic skin inoculation of fungal species of the genus Sporothrix. The disease has different clinical manifestations (cutaneous, lymphocutaneous, and disseminated), and it can also progress to a systemic infection. Despite having a worldwide distribution, sporotrichosis is more common in tropical and subtropical countries. Sporotrichosis is the most frequent subcutaneous mycosis in Latin America, where it is considered endemic. Certain groups of people may be more exposed to the causative agent of the disease, such as farmers. Thus, this work aimed to determine the prevalence of sporotrichosis in 3133 farmers, in the canton of Shushufindi in the province of Sucumbíos, Ecuador. In this study, an intradermal test was used with the sporotrichin antigen obtained from the fungus Sporothrix schenckii. The data obtained showed a prevalence of 35.45%. The distribution of the prevalence of sporotrichosis with respect to age groups did not show significant statistical differences (p=0.2054). For the sex variable, there was statistical significance (p=0.01995). 51 of the positive cases presented gums and/or ulcers in one of their members. Sporotrichosis has proven to be one of the most frequent subcutaneous mycoses in agricultural workers in the evaluated Ecuadorian region(AU)

Feline sporotrichosis caused by Sporothrix schenckii sensu stricto in Southern Thailand: phenotypic characterization, molecular identification, and antifungal susceptibility.

Feline sporotrichosis caused by the Sporothrix schenckii complex is a global subcutaneous mycosis, having higher prevalence in Latin America and Malaysia. However, its etiological agents have not been elucidated in Thailand, a neighboring country of Malaysia, where the cases are increasing. This study identified 38 feline isolates of S. schenckii from Southern Thailand, collected between 2018 and 2021, using phenotypic characterization and molecular identification using polymerase chain reaction (PCR)-sequencing of partial calmodulin (CAL) and ß-tubulin (Bt2) genes. Phenotypic characteristics proved that the isolates were S. schenckii sensu lato, with low thermotolerance. Based on partial CAL and Bt2-PCR sequencing, all isolates were identified as S. schenckii sensu stricto. Phylogenetic analyses revealed that the isolates were clustered with S. schenckii sensu stricto isolated from the cats in Malaysia. A low degree of genetic diversity was observed among the Thai feline isolates. The antifungal susceptibility of these isolates to antifungal agents, including itraconazole (ITC), ketoconazole (KTC), fluconazole (FLC), and amphotericin B (AMB), was investigated according to the M27-A3 protocol of the Clinical and Laboratory Standards Institute. Results showed low ITC, KTC, and AMB activities against S. schenckii sensu stricto isolates, with high minimum inhibitory concentration (MIC) ranges of 1-8, 1-8, and 2-16 µg/ml, respectively, whereas FLC exhibited MICs of 64 and > 64 µg/ml. This study indicated that S. schenckii sensu stricto is the causative agent responsible for feline sporotrichosis in Southern Thailand. Their phenotypic characteristics and in vitro antifungal susceptibility profiles will help to improve our understanding of this mycosis in Thailand.

Sporothrix schenckii sensu stricto is a causative agent of feline sporotrichosis in Southern Thailand identified by PCR-sequencing of calmodulin and ß-tubulin genes. Phenotypic tests are not recommended for species identification. All isolates showed low susceptibility to commonly used antifungals.