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.

Plasma itraconazole concentrations during treatment of feline sporotrichosis.

Itraconazole (ITZ) is the most used drug to treat feline sporotrichosis; however, little is known about its pharmacokinetics in cats with this mycosis. The aim of this study was to determine plasma ITZ concentrations in cats with sporotrichosis treated with ITZ as monotherapy or in combination with potassium iodide (KI). Cats diagnosed with sporotrichosis received orally ITZ (100 mg/cat/day) or combination therapy with ITZ (100 mg/cat/day) and KI (2.5-5 mg/kg/day) in the case of worsening or stagnation of the clinical condition. At each monthly visit, blood samples were collected at an interval of 4 h for analysis of trough and peak plasma ITZ concentrations by HPLC. Clinical features and laboratory parameters were evaluated during follow-up. Sixteen cats were included in the study. The median plasma ITZ concentration of all cats was 0.75 µg/mL. The median plasma ITZ concentration was 0.5 µg/mL in cats that received ITZ monotherapy (n=12) and 1.0 µg/mL in those treated with ITZ+KI (n=4). The clinical cure rate was 56.3% (n=9) and the median treatment duration was 8 weeks. Nine cats (56.3%) developed adverse clinical reactions and hyporexia was the most frequent (n=8; 88.9%). Serum alanine aminotransferase was elevated in four cats (25%). The median plasma ITZ concentration detected in cats was considered to be therapeutic (>0.5 µg/mL) and was reached after 4 weeks of treatment. Plasma ITZ concentrations were higher in cats that received ITZ+KI compared to those treated only with ITZ, suggesting pharmacokinetic synergism between these drugs.

Itraconazole is the most common therapy for feline sporotrichosis and combination therapy with potassium iodide is used in cases non-responsive. Our study showed that all cats achieved a therapeutic plasma concentration of itraconazole, with higher levels in cats treated with the combination therapy.

Current situation of sporotrichosis in China.

Sporotrichosis, a mycosis resulting from cutaneous or subcutaneous infection with the dimorphic fungus Sporothrix, has been reported in China, particularly in the northeast region. In this review, we conducted a thorough examination of the recent advancements in sporotrichosis in China, encompassing aspects such as etiology, epidemiology, pathogenesis, clinical manifestations, diagnosis and treatment strategies. Within the Chinese context, fixed cutaneous sporotrichosis represents the prevailing clinical manifestation. Fungal culture stands as the gold standard for diagnosing sporotrichosis, while polymerase chain reaction techniques can enhance both the specificity and sensitivity of diagnosis. Besides conventional systemic antifungal agents, alternative modalities such as Chinese herbal medicines, photodynamic therapy and laser therapy show potential efficacy against sporotrichosis.

Sporotrichosis is a fungal infection on the skin. It is caused by a group of fungi called Sporothrix. Common symptoms are lesions on the skin, inflammatory papules, nodules and ulcers. These fungi live in the natural environment and cause infection by entering the body through a wound in the skin. China has a high prevalence of sporotrichosis, with northeast China the most seriously affected region. This review looks at the state of sporotrichosis in China.

Sporothrix brasiliensis-specific PCR for the diagnosis of cat and human sporotrichosis through non-invasive samples.

Zoonotic sporotrichosis caused by Sporothrix brasiliensis is an emerging mycosis in Latin America. One of the problems to quickly treat infected animals and break the transmission chain is associated with the time-consuming gold-standard diagnosis method (culture). We aimed to evaluate a species-specific polymerase chain reaction (PCR) for the diagnosis of sporotrichosis caused by S. brasiliensis using non-invasive samples. We performed a retrospective cross-sectional study using samples collected with swabs from humans and cats with clinical suspicion of sporotrichosis. DNA was extracted using a commercial kit, and a species-specific PCR for S. brasiliensis detection was performed. One-hundred ten samples were included. PCR showed a good concordance with culture (86% of agreement) for human and cat samples (Kappa coefficient = 0.722, and 0.727, respectively). In conclusion, our data shows that this adapted PCR using non-invasive samples can be applied to sporotrichosis diagnosis, being a good alternative mainly in regions with a lack of mycologists to identify the fungus in culture, contributing to the control of this emergent zoonosis.

We aimed to evaluate a molecular method for diagnosing sporotrichosis caused by Sporothrix brasiliensis in humans and cats. We observed that the technique is in good agreement with the classic method and is a good alternative for assisting in the diagnosis and consequent control of this zoonosis.

The rising incidence of feline and cat-transmitted sporotrichosis in Latin America.

INTRODUCTION: Sporotrichosis is a subcutaneous mycosis caused by different species of thermodimorphic fungi belonging to the genus Sporothrix. These fungi may affect a wide range of warm-blooded animals, including humans, dogs and, mainly, cats. METHODS: In this article, we conducted a narrative literature review about the status of feline and cat-transmitted sporotrichosis in Latin American countries, with emphasis on Brazil. RESULTS: From a global perspective, Latin America is one of the main foci of human and feline sporotrichosis. In humans, the disease has been reported in several countries, with endemic transmission occurring in Brazil, Colombia, Costa Rica, Guatemala, Mexico and Uruguay. Sporothrix brasiliensis is the most common species identified in human cases in Brazil, whereas Sporothrix schenckii predominates in other countries. CONCLUSION: Domestic cats are the main source of infection in the zoonotic transmission cycle of sporotrichosis in Latin America. Cases of feline sporotrichosis have been reported in several countries, including Argentina, Brazil, Chile, Colombia, Mexico, Panama, Paraguay and Peru.

Outbreak of Feline Sporotrichosis with Zoonotic Potential in the Seventh Health District of Maceió-AL.

Sporotrichosis is a mycosis with zoonotic potential caused by species of Sporothrix. Once thought rare in northeastern Brazil, the disease has recently been spreading, leading to an emergency health issue. In this paper, we describe an outbreak of feline sporotrichosis in the Seventh Health District of Maceió-AL. We collected samples from 23 domiciled and non-domiciled felines without regard for age, breed, sex, and neutering state. Skin samples were analyzed cytologically under a light microscope and seeded onto Sabouraud dextrose agar at 25 °C for from 15 to 30 days. Fifteen of the twenty-three cats with suspected skin lesions were positive for Sporothrix spp. on either cytological or microbiological evaluation. Most of the infected cats were male, young adults, non-neutered, with free access to external areas, and living in environments with poor sanitation, a high population density, and an accumulation of garbage and organic matter. Three owners were bitten or scratched by infected cats and subsequently developed suspicious cutaneous lesions suggestive of sporotrichosis. The epidemiological features of feline sporotrichosis in the outbreaks of Maceió seemed to share similarities with the data obtained from outbreaks in current hyperendemic areas. Identifying geographical sites of infection and providing compulsory notification of the disease is essential for avoiding an epidemic in Alagoas.

Neutrophil Oxidative Burst Profile Is Related to a Satisfactory Response to Itraconazole and Clinical Cure in Feline Sporotrichosis.

Despite the central role of cats in the transmission and amplification of Sporothrix, studies regarding immune response in feline sporotrichosis are scarce. In cats with sporotrichosis, neutrophil-rich lesions are usually associated to good general condition and lower fungal burden. However, the role of neutrophils in anti-Sporothrix immunity has been little explored in cats. Thus, the aim of this study was to evaluate the neutrophil oxidative burst in the blood of cats with sporotrichosis. Cats with sporotrichosis included in the study were treated with itraconazole (ITZ) alone or combined with potassium iodide (KI). The neutrophil oxidative burst was evaluated through a flow-cytometry-based assay using dihydrorhodamine 123 (background) and stimulation with Zymosan and heat-killed Sporothrix yeasts. The cure rate was 50.0% in cats under treatment with ITZ monotherapy and 90.9% in cats treated with ITZ + KI (p = 0.014), endorsing the combination therapy as an excellent alternative for the treatment of feline sporotrichosis. Higher percentages of Sporothrix-stimulated neutrophils were associated with good general condition (p = 0.003). Higher percentages of Sporothrix- (p = 0.05) and Zymosan-activated (p = 0.014) neutrophils before and early in the treatment were related to clinical cure in ITZ-treated cats. The correlation between oxidative burst and successful use of KI could not be properly assessed given the low number of failures (n = 2) in this treatment group. Nasal mucosa involvement, typically linked to treatment failure, was related to lower percentages of activated neutrophils in the background at the treatment outcome (p = 0.02). Our results suggest a beneficial role of neutrophils in feline sporotrichosis and a positive correlation between neutrophil activation and the cure process in ITZ-treated cats.

Rapid Molecular Diagnosis of Sporotrichosis Directly from Biological Samples from a Reference Center in Brazil.

The gold standard diagnosis of sporotrichosis is the isolation of Sporothrix sp. in culture media, but this is a time-consuming test that is susceptible to contamination and can be affected by the fungal load. Molecular methods such as nested PCR are gaining more ground in the management of several infections as they are tools for the rapid and accurate identification of microorganisms from pure cultures or directly from biological samples. This study aimed to apply a nested PCR molecular protocol for the rapid detection of Sporothrix spp. directly from clinical samples. Thirteen samples-six from skin biopsies, five from skin exudates, and two from conjunctival secretions-were obtained from patients diagnosed with sporotrichosis due to S. brasiliensis. Calmodulin gene sequencing identified all the isolates as S. brasiliensis. Nested PCR was able to detect all the Sporothrix sensu lato directly from clinical samples as well as the CBS 120339 reference strain. The nested PCR protocol stands out as a diagnostic alternative, as it allows the identification of Sporothrix spp. directly from clinical samples without the need for fungal isolation.

Systematic review of literature to evaluate global distribution of species of the Sporothrix genus stored in culture collections.

Introduction: Sporotrichosis is a subcutaneous mycosis caused by fungi of the genus Sporothrix sp. Phenotypic and genotypic differences have been associated with their geographic distribution, virulence, or clinical manifestation of sporotrichosis. In the past decade, the interest in identifying species of the Sporothrix sp. has been increasing, due to its epidemiological importance and, in consequence, is important to know how to preserve them for future studies, in culture collection. Aims: The purposes of this study were to analyze the global distribution of environmental isolates and/or causal agents of sporotrichosis identified by polyphasic taxonomy, with mandatory use of molecular identification, and to evaluate the percentages and distribution of isolates stored in culture collections. Methods: A systematic review of articles on animal and human sporotrichosis and/or environmental isolation of the fungus, from 2007 to 2023, was done. Results: Our results demonstrated that, S. globosa, S. schenckii, and S. brasiliensis were the most identified species. With respect to the deposit and maintenance of species, we observed that only 17% of the strains of Sporothrix sp. isolated in the world are preserved in a culture collection. Conclusions: This systematic review confirmed a difficulty in obtaining the frequency of Sporothrix species stored in culture collection and insufficient data on the molecular identification mainly of animal sporotrichosis and isolation of Sporothrix sp. in environmental samples.

Drug to genome to drug: a computational large-scale chemogenomics screening for novel drug candidates against sporotrichosis.

Sporotrichosis is recognized as the predominant subcutaneous mycosis in South America, attributed to pathogenic species within the Sporothrix genus. Notably, in Brazil, Sporothrix brasiliensis emerges as the principal species, exhibiting significant sapronotic, zoonotic and enzootic epidemic potential. Consequently, the discovery of novel therapeutic agents for the treatment of sporotrichosis is imperative. The present study is dedicated to the repositioning of pharmaceuticals for sporotrichosis therapy. To achieve this goal, we designed a pipeline with the following steps: (a) compilation and preparation of Sporothrix genome data; (b) identification of orthologous proteins among the species; (c) identification of homologous proteins in publicly available drug-target databases; (d) selection of Sporothrix essential targets using validated genes from Saccharomyces cerevisiae; (e) molecular modeling studies; and (f) experimental validation of selected candidates. Based on this approach, we were able to prioritize eight drugs for in vitro experimental validation. Among the evaluated compounds, everolimus and bifonazole demonstrated minimum inhibitory concentration (MIC) values of 0.5 µg/mL and 4.0 µg/mL, respectively. Subsequently, molecular docking studies suggest that bifonazole and everolimus may target specific proteins within S. brasiliensis- namely, sterol 14-α-demethylase and serine/threonine-protein kinase TOR, respectively. These findings shed light on the potential binding affinities and binding modes of bifonazole and everolimus with their probable targets, providing a preliminary understanding of the antifungal mechanism of action of these compounds. In conclusion, our research advances the understanding of the therapeutic potential of bifonazole and everolimus, supporting their further investigation as antifungal agents for sporotrichosis in prospective hit-to-lead and preclinical investigations.

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.

Multifocal Sporotrichosis Associated with Armadillo Hunting in Midwest Brazil: An In-Depth Case Study and Comprehensive Literature Analysis.

Sporotrichosis is a globally distributed subcutaneous mycosis caused by dimorphic Sporothrix species commonly found in soil, mosses, and decaying plant matter. The lymphocutaneous manifestation, historically associated with occupational activities and sapronotic transmission, has recently been observed to also occur through animal contact, particularly notable in Brazil. We describe a rare case of lymphocutaneous sporotrichosis with simultaneous pulmonary complications resulting from the scratching of a southern three-banded armadillo, Tolypeutes matacus, primarily inhabiting the arid forests of South America's central region. Speciation using multiplex quantitative polymerase chain reaction (qPCR) established the etiological agent as S. schenckii s. str., while amplified fragment length polymorphism (AFLP) analysis unveiled a novel genotype circulating in the Midwest of Brazil. The patient received treatment with itraconazole (200 mg/day) for two months, leading to substantial clinical improvement of cutaneous and pulmonary symptoms. This case highlights the critical role of animal-mediated transmission in sporotrichosis epidemiology, particularly within regions with diverse armadillo species. The unusual epidemiology and genetic characteristics of this case emphasize the need for enhanced awareness and diagnostic vigilance in atypical sporotrichosis presentations.

Sporotrichosis transmitted by domestic cats: A case report. / Esporotricosis transmitida por gato doméstico: a propósito de un caso.

Sporotrichosis is a subacute to chronic subcutaneous mycosis caused by dimorphic fungi of the Sporothrix spp. complex. It is considered the most frequent subcutaneous mycosis in Latin America and predominates in tropical areas. In Argentina, its prevalence is estimated at 0.01-0.02%. In half of the patients, it manifests as lymphocutaneous sporotrichosis. Infection results from the agent's inoculation on the skin or mucous membrane by trauma with contaminated plants. There are also cases of zoonotic transmission by contact with animals, such as armadillos, birds, rats, horses, fish, mosquitoes, and cats. Here we describe the case of a 14-year-old female patient who consulted due to nodular lymphangitic syndrome for two months and, given the lack of response to multiple antibiotic regimens, a biopsy was performed and a culture of the lesion was done, which confirmed the diagnosis of lymphocutaneous sporotrichosis.

La esporotricosis es una micosis subcutánea de evolución subaguda-crónica causada por hongos dimórficos del complejo Sporothrix spp. Es considerada la micosis subcutánea más frecuente en Latinoamérica y predomina en zonas tropicales. La prevalencia en Argentina se estima entre el 0,01 % y el 0,02 %. En la mitad de los pacientes, se manifiesta como una esporotricosis linfocutánea. La infección es consecuencia de la inoculación del agente en la piel o mucosas a partir un trauma con plantas contaminadas. Existen también casos de transmisión zoonótica por contacto con animales como armadillos, aves, ratas, caballos, peces, mosquitos y felinos. Presentamos el caso de una paciente de 14 años, que consultó por síndrome linfangítico nodular de dos meses de evolución y, ante la falta de respuesta a múltiples esquemas antimicrobianos, se decidió realizar biopsia y cultivo de la lesión, que confirmó el diagnóstico de esporotricosis linfocutánea.

Disasters pile up on the rubbing heel: Sporothrix globosa as secondary infection to Mycobacterium chelonae infection.

Mycobacterium chelonae and Sporothrix globosa, both of which are opportunistic pathogens, have been proved to be possible multidrug resistant. However, are all recurring symptoms in chronic infections related to decreasing susceptibility? Here we report a case of sporotrichosis secondary to M. chelonae infection. In addition, we find that the blackish-red spots under the dermoscopic view can be employed as a signal for the early identification and regression of subcutaneous fungal infection.

Sporotrichosis Mimicking Rosacea Lesions: A Case Report.

Sporotrichosis is a subacute or chronic infectious disease caused by sporothrix. It is mainly caused by Sporothrix inoculation after accidental skin injury during human labor. The clinical manifestations of sporotrichosis are variable, ranging from nodules, plaques, ulcers, verrucous lesions, and subcutaneous masses. Some reports indicate that sporotrichosis can mimic psoriasis-like lesions. We herein report a case of sporotrichosis mimicking rosacea lesions. In addition, the patient had a history of nasal trauma, and we believe that the patient was inoculated with Sporothrix after the nasal skin was damaged during labor activities. The patient was given itraconazole 200 mg orally daily for 3 months, which effectively resolved the rash.

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.

Combination therapy of itraconazole and an acylhydrazone derivative (D13) for the treatment of sporotrichosis in cats.

Acylhydrazone (AH) derivatives represent a novel category of anti-fungal medications that exhibit potent activity against Sporothrix sp., both in vitro and in a murine model of sporotrichosis. In this study, we demonstrated the anti-fungal efficacy of the AH derivative D13 [4-bromo-N'-(3,5-dibromo-2-hydroxybenzylidene)-benzohydrazide] against both planktonic cells and biofilms formed by Sporothrix brasiliensis. In a clinical study, the effect of D13 was then tested in combination with itraconazole (ITC), with or without potassium iodide, in 10 cats with sporotrichosis refractory to the treatment of standard of care with ITC. Improvement or total clinical cure was achieved in five cases after 12 weeks of treatment. Minimal abnormal laboratory findings, e.g., elevation of alanine aminotransferase, were observed in four cats during the combination treatment and returned to normal level within a week after the treatment was ended. Although highly encouraging, a larger and randomized controlled study is required to evaluate the effectiveness and the safety of this new and exciting drug combination using ITC and D13 for the treatment of feline sporotrichosis. IMPORTANCE: This paper reports the first veterinary clinical study of an acylhydrazone anti-fungal (D13) combined with itraconazole against a dimorphic fungal infection, sporotrichosis, which is highly endemic in South America in animals and humans. Overall, the results show that the combination treatment was efficacious in ~50% of the infected animals. In addition, D13 was well tolerated during the course of the study. Thus, these results warrant the continuation of the research and development of this new class of anti-fungals.

Low toxicity contributes to Sporothrix globosa invade the skin of patients in low-epidemic areas of China.

OBJECTIVE: This study aims to assess the clinical characteristics of sporotrichosis in low-endemic areas of China, including the prevalence geography, genotypic traits of patients, clinical manifestations, and strain virulence and drug sensitivities. The objective is to improve the currently used clinical management strategies for sporotrichosis. METHODS: Retrospective data were collected from patients diagnosed with sporotrichosis through fungal culture identification. The isolates from purified cultures underwent identification using CAL (Calmodulin) gene sequencing. Virulence of each strain was assessed using a Galleria mellonella (G. mellonella) larvae infection model. In vitro susceptibility testing against commonly used clinical antifungal agents for sporotrichosis was conducted following CLSI criteria. RESULTS: In our low-endemic region for sporotrichosis, the majority of cases (23) were observed in middle-aged and elderly women with a history of trauma, with a higher incidence during winter and spring. All clinical isolates were identified as Sporothrix globosa (S. globosa). The G. mellonella larvae infection model indicated independent and dose-dependent virulence among strains, with varying toxicity levels demonstrated by the degree of melanization of the G. mellonella. Surprisingly, lymphocutaneous types caused by S. globosa exhibited lower in vitro virulence but were more common in affected skin. In addition, all S.globosa strains displayed high resistances to fluconazole, while remaining highly susceptible to terbinafine, itraconazole and amphotericin B. CONCLUSION: Given the predominance of elderly women engaged in agricultural labour in our region, which is a low-epidemic areas, they should be considered as crucial targets for sporotrichosis monitoring. S. globosa appears to be the sole causative agent locally. However, varying degrees of melanization in larvae were observed among these isolates, indicating a divergence in their virulence. Itraconazole, terbinafine and amphotericin B remain viable first-line antifungal options for treating S.globosa infection.

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.