Sporotrichosis Treatment: Overview and Update

Sporotrichosis, caused by several species from the genus Sporothrix, mainly affects men working in agricultural labor. It is reported mostly from endemic regions located in tropical and subtropical areas. Sporotrichosis usually affects subcutaneous tissue with no symptoms or mild symptoms, but it causes disseminated and even fatal disease if the patient is immunocompromised. Significant progress in the knowledge of etiologic agents of sporotrichosis has been achieved recently, but evaluations of treatment using well-designed clinical trials have been neglected. This article reviews the drugs currently used to treat subcutaneous disease, describing the differences in their efficacy, and reviews recent findings about the proposed new Sporothrix species of clinical interest, as well as the role of melanin as a virulence factor in Sporothrix schenckii.     

Disseminated sporotrichosis with immune reconstitution inflammatory syndrome in an HIV patient: Case report and review of the literature

BackgroundSporotrichosis has been occurring as outbreaks in Brazil, reaching epidemic levels in some regions. Zoonotic transmission is the main route to acquire Sporothrix.Case reportWe describe a case of disseminated sporotrichosis caused by Sporothrix brasiliensis in an HIV/AIDS patient, with the presentation of immune reconstitution inflammatory syndrome (IRIS).ConclusionsThis case reinforces that sporotrichosis should always be suspected in patients with IRIS from endemic regions, even in patients without the typical cutaneous lesions of this mycosis.     

Sporotrichosis in Rio de Janeiro,Brazil: Sporothrix brasiliensis Is Associated with Atypical Clinical Presentations

Background

There have been several recent changes in the taxonomy of Sporothrix schenckii as well as new observations regarding the clinical aspects of sporotrichosis. In this study, we determined the identification of the Sporothrix species associated with both classic and unusual clinical aspects of sporotrichosis observed in the endemic area of sporotrichosis in Rio de Janeiro, Brazil.

Methodology/Principal Findings

To verify whether S. brasiliensis is associated with clinical manifestations of sporotrichosis, a cross-sectional study was performed in which Sporothrix isolates from 50 patients with different clinical manifestations were analyzed and their isolates were studied by phenotypic and genotypic methods. Data from these patients revealed a distinct clinical picture and therapeutic response in infections caused by Sporothrix brasiliensis (n = 45) compared to patients with S. schenckii sensu stricto (n = 5). S. brasiliensis was associated with disseminated cutaneous infection without underlying disease, hypersensitivity reactions, and mucosal infection, whereas patients with S. schenckii presented with less severe and more often localized disease, similar to the majority of previously described sporotrichosis cases. Interestingly, S. brasiliensis-infected patients overall required shorter durations of itraconazole (median 16 weeks) compared to the individuals with S. schenckii (median 24 weeks).

Conclusions/Significance

These findings suggest that Sporothrix species are linked to different clinical manifestations of sporotrichosis and that S. brasiliensis is effectively treated with oral itraconazole.     

Prophylactic and therapeutic vaccines against sporotrichosis. Feasibility and prospects

Sporotrichosis is an emergent subcutaneous mycosis of humans and some animals caused by dimorphic fungi of the genus Sporothrix. The disease occurs worldwide but is endemic or hyperendemic in tropical and subtropical areas. The epidemiology of the disease is changing dramatically, and it is now considered an important zoonosis with high morbidity rates, principally in Brazil, and an opportunistic infection in immunocompromised patients. Due to the limited options currently available to treat invasive fungal infections, including sporotrichosis, and the emergence of drug resistance and toxicity, the development of anti-Sporothrix vaccines has become an area of great interest. This work provides a brief analysis of the feasibility of the development of prophylactic and therapeutic vaccines against sporotrichosis, the main advances achieved to date, future challenges and prospects.     

The spread of cat-transmitted sporotrichosis due to Sporothrix brasiliensis in Brazil towards the Northeast region

BackgroundSporotrichosis is a worldwide subcutaneous mycosis caused by Sporothrix spp. In the past, this infection was associated with armadillo hunting, horticulturists, miners, and gardeners, being considered an implantation mycosis acquired by plant debris injury. Nevertheless, since the late nineties, it has been considered a zoonotic disease in Brazil. Here we report a case series of 121 patients with cat-transmitted sporotrichosis seen in Northeast Brazil.Methodology/Principal findingsPatient’s demographic, clinical data, and length of treatment were recorded. In addition, a mycological examination and further PCR confirmation of species identification were performed. One hundred and twenty two patients were diagnosed with subcutaneous sporotrichosis from October 2016 to December 2019, while PCR revealed that 71 of them were due to S. brasiliensis. The majority of the individuals were female (n = 86; 70.5%). Patient’s age ranged from 5 to 87 years old. The clinical forms found were lymphocutaneous (58.2%) and fixed cutaneous (39.4%). Interestingly, 115 patients reported previous contact with cats diagnosed with sporotrichosis. Patients were successfully treated with itraconazole and potassium iodide.Conclusions/SignificanceOur study adds important contributions for the investigation of the spread of cat-transmitted subcutaneous sporotrichosis in Brazil, specifically towards the Northeast region of a continental-size country. It will also help clinicians to be aware of the existence and importance to accurately diagnose sporotrichosis and treat patients with this infectious disease in the lowest income region of Brazil.     

Successful Treatment of Canine Sporotrichosis with Terbinafine: Case Reports and Literature Review

Sporotrichosis occurs worldwide, and the metropolitan region of Rio de Janeiro, Brazil, is a main endemic area, with a large number of human and animal cases in the last 19 years. This mycosis is more frequently described in cats rather than in dogs. There are a limited number of oral antifungal agents for the treatment of sporotrichosis in animals. In this context, the effectiveness of terbinafine in the treatment of sporotrichosis in humans, as well as the promising results of in vitro susceptibility tests, inspired us to use this drug in the therapy of this mycosis in dogs. We reported for the first time the use of terbinafine in the treatment of two dogs with sporotrichosis caused by Sporothrix brasiliensis. Moreover, we provided an overview of therapeutic features of canine sporotrichosis cases reported since the 1960s. One of the dogs presented the fixed cutaneous form of the disease, while the other patient presented hyperemia of the nasal mucosa and respiratory signs only. Terbinafine showed high antifungal activity in vitro against the canine Sporothrix isolates. The dogs were successfully treated with terbinafine, with remission of all clinical signs initially presented. The current reports indicate that this drug can emerge as a therapeutic option for canine sporotrichosis.     

Squamous cell carcinoma subsequent to scarring caused by sporotrichosis: A case report

BackgroundSporotrichosis is a fungal disease caused by the Sporothrix schenckii species complex. It is usually acquired by trauma with plants. Lymphatic-cutaneous is the most common clinical manifestation.Case reportThe present case describes the development of an epidermoid carcinoma as a late complication on a long evolution sporotrichosis scar. During a period of 50 years, the patient had lesions in the right hand. Sporotrichosis was diagnosed and treated with potassium iodide. Eleven years after the healing of the lesions, a squamous cell carcinoma on the scar of this mycosis was diagnosed.ConclusionsThe chronic sporotrichosis injury was probably the cause of the tumor developed on the scar.     

Sporotrichosis After Tattooing Caused by Sporothrix brasiliensis

Sporotrichosis is a subcutaneous mycosis caused by pathogenic species of the genus Sporothrix. Since 1998, the number of cases of sporotrichosis due to Sporothrix brasiliensis has grown significantly in Rio de Janeiro, Brazil. Nearly all cases are related to cats as the main source of fungal infection. We report two cases of sporotrichosis following tattoos, a transmission form of S. brasiliensis not yet reported. The first patient, a 22-year-old female, had cutaneous sporotrichosis, fixed form, over a tattoo in her lumbar region. The lesion appeared 12 weeks after she was tattooed. The second patient, a 27-year-old female, had a lymphocutaneous sporotrichosis over a forearm tattoo. The lesion appeared two weeks after she was tattooed. In both cases there was no history of contact with cats or other plausible source of infection. The present study highlights that other non-zoonotic forms of transmission of S. brasiliensis may occur in endemic areas.

     

Sporotrichosis: Update on Diagnostic Techniques

Purpose of Review

Sporotrichosis, the disease caused by Sporothrix spp, ranges from subcutaneous infections to the severe disseminated or invasive diseases. The taxonomy of Sporothrix has been revised. The subcutaneous disease is suspected easily, but the extra-cutaneous disease is diagnosed by chance or with high suspicion. This review provides the overview of currently available diagnostic techniques.

Recent Finding

Enzyme-linked immunosorbent assay (ELISA) or latex agglutination test with partially purified antigens helps in the diagnosis of extra-cutaneous sporotrichosis. Molecular methods have been used for the identification and typing of the fungus. Calmodulin, beta tubulin, translation elongation factor and chitin synthase genes are targeted for species differentiation. MALDI-TOF MS has been standardized to identify the species.

Summary

PCR-based molecular techniques and matrix-assisted laser desorption ionisation time of flight mass spectroscopy (MALDI-TOF MS) help in the identification of Sporothrix species, whereas ELISA helps in diagnosing extra-cutaneous form. Utility of molecular techniques for detection of Sporothrix directly from clinical specimen needs to be evaluated.

     

Isolation of Sporothrix schenckii From the Claws of Domestic Cats (Indoor and Outdoor) and in Captivity in São Paulo (Brazil)

Sporotrichosis is a subcutaneous mycosis and is also a zoonosis (sapro- and anthropozoonosis). The objective of the present study was to determine the occurrence of sporotrichosis in domestic cats and in wild or exotic felines in captivity through the isolation of Sporothrix spp. from claw impressions in a culture medium. The samples included 132 felines, of which 120 (91.0 %) were domestic cats, 11 (8.3 %) were wild felines, and one (0.7 %) was an exotic felid. Twenty-one (17.5 %) were outdoor cats. Of the total, 89 (67.4 %) had contact with other animals of the same species. It was possible to isolate Sporothrix schenckii from the claws of one (0.7 %) of the felids probed; this animal exhibited generalised sporotrichosis and had infected a female veterinarian. The potential pathogenic agents Microsporum canis and Malassezia pachydermatis were isolated in 12.1 and 5.3 % of the animals, respectively. The following anemophilous fungi, which were considered to be contaminants, were also isolated: Penicillium sp. (28 or 21.2 %), Aspergillus sp. (13 or 9.8 %), Rhodotorula sp. (5 or 3.8 %), Candida sp. (5 or 3.8 %), Trichoderma sp. (1 or 0.7 %), and Acremonium sp. (1 or 0.7 %). Due to the low magnitude of occurrence (0.7 %) of Sporothrix in feline claws, the potential of the cats evaluated in this study to be sources of infection in the city of São Paulo is considerably low.     

Molecular Identification and Antifungal Susceptibility of Clinical Isolates of Sporothrix schenckii Complex in Medellin,Colombia

Background

Sporotrichosis is a subcutaneous mycosis that affects humans and other animals. Infection prevails in tropical and subtropical countries. Until a few years ago, it was considered that two varieties of Sporothrix schenckii caused this mycosis, but by applying molecular taxonomic markers, it has been demonstrated that there are several cryptic species within S. schenckii complex which varies in susceptibility, virulence, and geographic distribution.

Objective

This study aimed to identify the clinical isolates of Sporothrix spp. from patients with sporotrichosis in Medellin, Colombia, using two markers and to evaluate the in vitro susceptibility to itraconazole.

Methods

Thirty-four clinical isolates of Sporothrix spp. from Colombia, three from Mexico, and one from Guatemala were identified through sequencing of the noncoding region ITS-1?+?5.8SDNAr?+?ITS-2 and of the fragment containing exons 3 and 4 of the β-tubulin gene. Clinical isolate sequences were compared with GenBank reference sequences using the BLASTN tool, and then, phylogenetic analysis was performed. Besides, the in vitro susceptibility to itraconazole was evaluated by determining the minimum inhibitory concentrations according to the CLSI M38-A2 method.

Results

Clinical isolates were identified by morphology as Sporothrix spp. Using the molecular markers, ITS and β-tubulin, isolates were identified as S. schenckii sensu stricto (25) and Sporothrix globosa (13). Susceptibility to itraconazole was variable among clinical isolates.

Conclusion

This is the first scientific publication that identifies species that cause sporotrichosis in Colombia, along with the antifungal susceptibility to itraconazole.

     

Proteomics-Based Characterization of the Humoral Immune Response in Sporotrichosis: Toward Discovery of Potential Diagnostic and Vaccine Antigens

Background

Sporothrix schenckii and associated species are agents of human and animal sporotrichosis that cause large sapronoses and zoonoses worldwide. Epidemiological surveillance has highlighted an overwhelming occurrence of the highly pathogenic fungus Sporothrix brasiliensis during feline outbreaks, leading to massive transmissions to humans. Early diagnosis of feline sporotrichosis by demonstrating the presence of a surrogate marker of infection can have a key role for selecting appropriate disease control measures and minimizing zoonotic transmission to humans.

Methodology

We explored the presence and diversity of serum antibodies (IgG) specific against Sporothrix antigens in cats with sporotrichosis and evaluated the utility of these antibodies for serodiagnosis. Antigen profiling included protein extracts from the closest known relatives S. brasiliensis and S. schenckii. Enzyme-linked immunosorbent assays and immunoblotting enabled us to characterize the major antigens of feline sporotrichosis from sera from cats with sporotrichosis (n = 49), healthy cats (n = 19), and cats with other diseases (n = 20).

Principal Findings

Enzyme-linked immunosorbent assay-based quantitation of anti-Sporothrix IgG exhibited high sensitivity and specificity in cats with sporotrichosis (area under the curve, 1.0; 95% confidence interval, 0.94–1; P<0.0001) versus controls. The two sets of Sporothrix antigens were remarkably cross-reactive, supporting the hypothesis that antigenic epitopes may be conserved among closely related agents. One-dimensional immunoblotting indicated that 3-carboxymuconate cyclase (a 60-kDa protein in S. brasiliensis and a 70-kDa protein in S. schenckii) is the immunodominant antigen in feline sporotrichosis. Two-dimensional immunoblotting revealed six IgG-reactive isoforms of gp60 in the S. brasiliensis proteome, similar to the humoral response found in human sporotrichosis.

Conclusions

A convergent IgG-response in various hosts (mice, cats, and humans) has important implications for our understanding of the coevolution of Sporothrix and its warm-blooded hosts. We propose that 3-carboxymuconate cyclase has potential for the serological diagnosis of sporotrichosis and as target for the development of an effective multi-species vaccine against sporotrichosis in animals and humans.     

Molecular Diagnosis of Pathogenic Sporothrix Species

Background

Sporotrichosis is a chronic (sub)cutaneous infection caused by thermodimorphic fungi in the order, Ophiostomatales. These fungi are characterized by major differences in routes of transmission, host predilections, species virulence, and susceptibilities to antifungals. Sporothrix species emerge in the form of outbreaks. Large zoonoses and sapronoses are ongoing in Brazil and China, respectively. Current diagnostic methods based on morphology and physiology are inaccurate due to closely related phenotypes with overlapping components between pathogenic and non-pathogenic Sporothrix. There is a critical need for new diagnostic tools that are specific, sensitive, and cost-effective.

Methodology

We developed a panel of novel markers, based on calmodulin (CAL) gene sequences, for the large-scale diagnosis and epidemiology of clinically relevant members of the Sporothrix genus, and its relative, Ophiostoma. We identified specific PCR-based markers for S. brasiliensis, S. schenckii, S. globosa, S. mexicana, S. pallida, and O. stenoceras. We employed a murine model of disseminated sporotrichosis to optimize a PCR assay for detecting Sporothrix in clinical specimens.

Results

Primer-BLAST searches revealed candidate sequences that were conserved within a single species. Species-specific primers showed no significant homology with human, mouse, or microorganisms outside the Sporothrix genus. The detection limit was 10–100 fg of DNA in a single round of PCR for identifying S. brasiliensis, S. schenckii, S. globosa, S. mexicana, and S. pallida. A simple, direct PCR assay, with conidia as a source of DNA, was effective for rapid, low-cost genotyping. Samples from a murine model of disseminated sporotrichosis confirmed the feasibility of detecting S. brasiliensis and S. schenckii DNA in spleen, liver, lungs, heart, brain, kidney, tail, and feces of infected animals.

Conclusions

This PCR-based method could successfully detect and identify a single species in samples from cultures and from clinical specimens. The method proved to be simple, high throughput, sensitive, and accurate for diagnosing sporotrichosis.     

Diagnostic performance of mycologic and serologic methods in a cohort of patients with suspected sporotrichosis

BackgroundThe gold standard for the sporotrichosis diagnosis is culture; however, serologic approaches have been recently implemented to aid in the sporotrichosis diagnosis. Nevertheless, the clinical consequences of the introduction of serologic tests are poorly addressed.AimsTo correlate the results of culture and serology of patients with suspected sporotrichosis.MethodsA retrospective study of 198 patients with suspected sporotrichosis was conducted. Information about culture isolation of Sporothrix from clinical samples and antibody detection by an enzyme-linked immunosorbent assay (ELISA) were obtained from the medical records of the patients.ResultsPositive culture and antibody detection was observed in the samples of 84 patients (42.4%). Forty-one samples (20.7%) showed negative results with both techniques and divergent results were obtained in the samples of 73 patients (36.9%). False negative results in the ELISA were observed with 23 patients (31.5%), 78.3% of them with less than 30 days of infection (p = 0.0045). Among the initial false positive ELISA in the sera of 50 patients, four samples in culture yielded the growth of Sporothrix, and 27 improved with itraconazole. At the end of follow-up, a diagnosis of proven or probable sporotrichosis was established in 139 patients, and possible sporotrichosis in 11 patients. The treatment of the patients with probable sporotrichosis with antifungal drugs resulted in clinical cure for these individuals.ConclusionsThese two techniques are complementary in the diagnosis of sporotrichosis, making diagnosis and clinical decision more precise.     

Esporotricosis: prevalencia,perfil clínico y epidemiológico en un centro de referencia en Colombia

BackgroundSporotrichosis is a subacute and chronic infection caused by Sporothrix schenckii, which affects humans and other mammals. Clinical and epidemiological information in Colombia is scarce.ObjectiveTo describe clinical and socio-demographic findings and diagnostic tests in patients with sporotrichosis from 1996 to 2005 in a national reference center in Colombia, and to determine the institutional prevalence from 2002 to 2005.Material and methodsThis was a prevalence study, including patients with clinical diagnosis of sporotrichosis and at least one of the following criteria: positive culture with S. schenckii, pathologic diagnosis suggestive of sporotrichosis, or response to treatment with potassium iodide.ResultsSixty cases were included, 67% were male, and 25% of them were farmers. The most affected anatomical areas were the forearms and hands (32.5% and 22.8% respectively). Most cases came from the Cundinamarca and Boyacá areas. The cases presented as fixed cutaneous sporotrichosis and lymphangitic sporotrichosis. Differential diagnoses with: leishmaniasis and chromoblastomycosis were performed in most of the cases. All patients were treated with potassium iodide. The prevalence for our center from 2002 to 2005 was 8 cases per 100,000 patients.ConclusionsThe characteristics of our patients are similar to those described in other populations, with some differences. The culture continues to be the gold standard for diagnosis purposes. Potassium iodide is the treatment of choice in our center.     

Variation in Genotype and Higher Virulence of a Strain of <Emphasis Type="Italic">Sporothrix schenckii</Emphasis> Causing Disseminated Cutaneous Sporotrichosis

Sporotrichosis is usually a localized, lymphocutaneous disease, but its disseminated type was rarely reported. The main objective of this study was to identify specific DNA sequence variation and virulence of a strain of Sporothrix schenckii isolated from the lesion of disseminated cutaneous sporotrichosis. We confirmed this strain to be S. schenckii by^® tubulin and chitin synthase gene sequence analysis in addition to the routine mycological and partial ITS and NTS sequencing. We found a 10-bp deletion in the ribosomal NTS region of this strain, in reference to the sequence of control strains isolated from fixed cutaneous sporotrichosis. After inoculated into immunosuppressed mice, this strain caused more extensive system involvement and showed stronger virulence than the control strain isolated from a fixed cutaneous sporotrichosis. Our study thus suggests that different clinical manifestation of sporotrichosis may be associated with variation in genotype and virulence of the strain, independent of effects due to the immune status of the host.     

Sporotrichosis in sub-himalayan India

Sporotrichosis is endemic in the Sub-Himalayan belt, which ranges from the northern to the north-eastern Indian subcontinent. Similar to many parts of the developing world, sporotrichosis is commonly recognized clinically in this region however consolidated epidemiological data is lacking. We report epidemiological, clinical and microbiological data from a hundred culture positive cases of sporotrichosis. Out of 305 clinically suspicious cases of sporotrichosis, a total of 100 isolates were identified as Sporothrix schenckii species complex (S. schenckii) on culture. Out of the culture proven cases 71% of the cases presented with lymphocutaneous type of lesions while 28% had fixed localized type and 1% had disseminated sporotrichosis. Presentation with lesions on hands was most frequently seen in 32% with arm (23%) and face (21%) in that sequence. The male to female ratio was 1∶1.27. Age ranged from 1 ½ years to 88 years. Mean age was 43.25 years. Disease was predominantly seen in the fourth to sixth decade of life with 58% cases between 31 and 60 years of age. Since the first report from the region there has been a steady rise in the number of cases of sporotrichosis. Seasonal trends reveal that most of the patients visited for consultation in the beginning of the year between March and April. This is the first study, from the most endemic region of the Sub-Himalayan belt, to delve into epidemiological and clinical details of such a large number of culture proven cases over a period of more than eighteen years which would help in the understanding of the local disease pattern of sporotrichosis.