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.

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.

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.

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.

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.

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.

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.

Molecular and phenotypic reidentification of Sporothrix schenckii clinical isolates preserved under mineral oil for 34 to 64 years in a culture collection in Brazil.

Sporotrichosis is a subcutaneous mycosis worldwide distributed reaching hyperendemic proportions in Brazil. Many isolates from patients with sporotrichosis are preserved in culture collections by different methods around the world. The preservation methods are used to maintain the viability and the morphophysiological and genetic characteristics of isolates for long periods. In this study, we evaluated 34 isolates, previously, identified as S. schenckii by a classical identification method, initially preserved by periodical subcultures and then under mineral oil at culture collection of Oswaldo Cruz Institute/Fiocruz, to re-identify them by polyphasic identification. Our results showed that seven isolates remained viable for 34 to 64 years under oil, one isolate lost the ability to sporulate which was reverted by using a medium culture supplemented with rosebush branches and all of them were identified as Sporothrix schenckii sensu stricto by morphological, physiological, partial ß-tubulin gene sequencing and phylogenetic analysis.

Special Issue "Sporothrix and Sporotrichosis 2.0".

Sporotrichosis is a chronic fungal disease of humans and other mammals that often affects the skin and subcutaneous tissues and, rarely, deep-seated organs (most frequently in immunocompetent hosts) [...].

Ocular Sporotrichosis: Different Spectrums of Clinical Manifestations and a Review of the Literature.

We hereby describe two cases of patients with ocular sporotrichosis who presented with different spectrums of clinical manifestations. Both patients had an antecedent history of zoonotic and vegetative contact. The first patient presented with acute granulomatous anterior uveitis, and the second patient presented with granulomatous conjunctivitis. Patients received topical antibiotics, steroids, and cycloplegics. Systemic oral antifungals were added until full recovery was achieved. Both cases were treated without any episodes of relapse or recurrence.

Current Progress on Epidemiology, Diagnosis, and Treatment of Sporotrichosis and Their Future Trends.

Sporotrichosis, a human and animal disease caused by Sporothrix species, is the most important implantation mycosis worldwide. Sporothrix taxonomy has improved in recent years, allowing important advances in diagnosis, epidemiology, and treatment. Molecular epidemiology reveals that S. brasiliensis remains highly prevalent during the cat-transmitted sporotrichosis outbreaks in South America and that the spread of S. brasiliensis occurs through founder effects. Sporothrix globosa and S. schenckii are cosmopolitan on the move, causing major sapronoses in Asia and the Americas, respectively. In this emerging scenario, one-health approaches are required to develop a creative, effective, and sustainable response to tackle the spread of sporotrichosis. In the 21st century, it has become vital to speciate Sporothrix, and PCR is the main pillar of molecular diagnosis, aiming at the detection of the pathogen DNA from clinical samples through multiplex assays, whose sensitivity reaches remarkably three copies of the target. The treatment of sporotrichosis can be challenging, especially after the emergence of resistance to azoles and polyenes. Alternative drugs arising from discoveries or repositioning have entered the radar of basic research over the last decade and point to several molecules with antifungal potential, especially the hydrazone derivatives with great in vitro and in vivo activities. There are many promising developments for the near future, and in this review, we discuss how these trends can be applied to the Sporothrix-sporotrichosis system to mitigate the advance of an emerging and re-emerging disease.

Ocular sporotrichosis from a tertiary referral center in Malaysia and review of literature in Southeast Asia.

Ocular sporotrichosis is rare in Malaysia and Southeast Asia and is increasingly reported in endemic areas of Brazil and Peru. We describe six cases of ocular sporotrichosis involving the bulbar conjunctiva and lid with a literature review on ocular sporotrichosis in Southeast Asia. In these series, four patients presented with similar findings of granulomatous lesion at the palpebral conjunctiva within 1-3 weeks. There was one case mistakenly diagnosed as conjunctival concretion due to its multiple yellowish nodules on the palpebral conjunctiva and another case as chalazion due to swelling of the lower lid. All patients showed immunocompetence. Four patients had an immediate contact with sick cats, one patient had a history of skin scratched by a healthy cat, and another patient had a history of gardening without direct contact with cat. Culture from conjunctival biopsy obtained from five patients and from ruptured lower lid nodules of one patient yielded Sporothrix schenckii. The patients were successfully treated with oral itraconazole 200 mg twice daily. Two patients developed symblepharon after completing treatment, while four patients showed good results without any sequelae.

Epidemiology of Clinical Sporotrichosis in the Americas in the Last Ten Years.

BACKGROUND: Sporotrichosis is a fungal infection caused by species of the Sporothrix genus. Presently, the prevalence of sporotrichosis in the Americas is unknown, so this study aims to analyze the cases reported in the past 10 years. METHODS: An advanced search was conducted from 2012 to 2022 in English and Spanish in PUBMED, SciELO, and Cochrane, with the terms: "sporotrichosis", "lymphocutaneous sporotrichosis", "fixed sporotrichosis", "mycosis", "Sporothrix spp.", "Sporothrix complex", "S. schenckii sensu stricto", "S. schenckii sensu lato", "S. globose", "S. brasiliensis", "S. luriei". Sporotrichosis is a fungal infection caused by species of the Sporothrix genus associated with "pathogenicity" or "epidemiology". RESULTS: A total of 124 articles were found in the Americas, corresponding to 12,568 patients. Of these, 87.38% of cases were reported in South America, 11.62% in North America, and 1.00% in Central America and the Caribbean. Brazil, Peru, and Mexico had the highest number of cases. The most prevalent etiological agents were S. schenckii complex/Sporothrix spp. (52.91%), S. schenckii (42.38%), others (4.68%), and Not Determined (ND) (0.03%). The most frequent form of the disease was lymphocutaneous infection; however, the infection type was not determined in 5639 cases. Among the diagnostic methods, culture was the most used. CONCLUSIONS: There is a high occurrence of cases reported in the literature. South America is the region with the highest number of reports because of its environment (climate, inhalation of spores, etc.), zoonotic transmission (scratches and sneezes from contaminated animals), and possible traumatic inoculation due to outdoor activities (agriculture, gardening, and related occupations). Molecular diagnosis has not been sufficiently developed due to its high cost.

Cutaneous disseminated sporotrichosis in immunocompetent patient: Case report and literature review.

Sporotrichosis is a global occurring implantation (subcutaneous) mycosis, caused by Sporothrix species, usually affecting the skin and the lymphatic vessels, from where it can disseminate. Nowadays, the vast majority of sporotrichosis infections in Brazil are caused by zoonotic transmission of S. brasiliensis which is the main etiologic agent. We report a cutaneous disseminated case of this disease, observed in an immunocompetent farmer living in southern Brazil, the Sporothrix schenckii-infection was successfully treated with itraconazole.