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.

Clinical factors associated with systemic sporotrichosis in Brazil.

BACKGROUND: Systemic sporotrichosis occurs when organs, other than subcutaneous tissues and lymph nodes, are infected. Interestingly, systemic sporotrichosis in apparently immunocompetent individuals is increasing in Brazil, but data on clinical manifestations and risk factors are scarce. Most of the existing data on such condition relate to people living with HIV. We aimed to study the risk factors associated with systemic sporotrichosis among HIV-negative and HIV-positive patients. METHODS: We performed a retrospective cross-sectional study with 80 patients from Brazil, diagnosed between 2014 and 2021. The association between disease classification, clinical presentation and risk factors were analysed by logistic regression. RESULTS: Of the 80 patients, 29 (36.3%) presented with systemic sporotrichosis. All HIV-positive patients developed the systemic form, with increased mortality (p = .002). Alcohol ingestion (p = .009) and diabetes (p = .010) were associated with systemic disease. Alcohol ingestion seemed to favour pulmonary infection (p = .013) and, diabetes favoured osteoarticular (p = .009) and ocular involvement (p = .033). The occurrence of fever (p = .001) and weight loss (p = .006) were significantly associated with systemic sporotrichosis, while meningeal involvement (p = .001) increased mortality risk. Nine (11.3%) patients died from sporotrichosis. The presence of fungal structures in the mycological examination of the patients' lesions were associated with the systemic form (p = .017) and death (p = .002). CONCLUSION: Our study points to the factors that drive systemic sporotrichosis other than HIV, such as alcohol ingestion and diabetes. Considering the high number of patients presenting severe sporotrichosis, the recognising these factors may contribute to timely diagnosis and proper treatment.

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.

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.

Rising Incidence of Sporothrix brasiliensis Infections, Curitiba, Brazil, 2011-2022.

Zoonotic outbreaks of sporotrichosis are increasing in Brazil. We examined and described the emergence of cat-transmitted sporotrichosis (CTS) caused by the fungal pathogen Sporothrix brasiliensis. We calculated incidence and mapped geographic distribution of cases in Curitiba, Brazil, by reviewing medical records from 216 sporotrichosis cases diagnosed during 2011-May 2022. Proven sporotrichosis was established in 84 (39%) patients and probable sporotrichosis in 132 (61%). Incidence increased from 0.3 cases/100,000 outpatient visit-years in 2011 to 21.4 cases/100,000 outpatient visit-years in 2021; of the 216 cases, 58% (n = 126) were diagnosed during 2019-2021. The main clinical form of sporotrichosis was lymphocutaneous (63%), followed by localized cutaneous (24%), ocular (10%), multisite infections (3%), and cutaneous disseminated (<0.5%). Since the first report of CTS in Curitiba in 2011, sporotrichosis has increased substantially, indicating continuous disease transmission. Clinician and public awareness of CTS and efforts to prevent transmission are needed.

Seroprevalence of sporotrichosis infection in cats living in the Buenos Aires epizootic area.

This study aimed to perform a seroepidemiological survey on the prevalence of sporotrichosis among cats living in the Northern area of Buenos Aires, where a four-fold increase of Sporothrix brasiliensis infections were diagnosed during the last decade. For this purpose, an in-house indirect ELISA test sensitized with S. brasiliensis crude antigens was used. The ELISA test showed 100.0% sensitivity and 95.0% specificity. Antibodies against S. brasiliensis antigens were detected in 3.7% (9/241) of healthy cats evaluated, suggesting likely exposure or infection to this fungus. This ELISA test would be a valuable screening tool for diagnosing sporotrichosis and for seroepidemiological surveys.

S. brasiliensis is the primary cause of feline sporotrichosis in Argentina. The seroprevalence of sporotrichosis infection in urban localities of Buenos Aires province is reported for the first time. An ELISA test using S. brasiliensis crude antigens is also described.

Genotyping and antifungal susceptibility testing of Sporothrix brasiliensis isolates from Southern Brazil.

Sporotrichosis is an implantation mycosis caused by the dimorphic fungus Sporothrix and mostly involves cutaneous and subcutaneous tissues and the lymphatic vessels. Among more than 50 different species, only Sporothrix schenckii, Sporothrix globosa and Sporothrix brasiliensis are frequently reported to cause infections in humans. Sporothrix brasiliensis is remarkably virulent and has been spreading rapidly in Brazil and other Latin American countries. In this study, we aimed to determine the genetic relatedness and antifungal susceptibility of Sporothrix strains by analysing 89 isolates from humans and cats in Curitiba, Southern Brazil. Calmodulin sequencing identified 81 S. brasiliensis and seven S. schenckii isolates. Amplified fragment length polymorphism genotyping analysis showed feline and human isolates clustering together. In vitro susceptibility testing with seven antifungals demonstrated a broad activity against all tested S. brasiliensis isolates, with no significant differences in minimal inhibitory concentration (MIC) values between feline and human isolates. Resistance was solely observed in one human isolate against itraconazole and posaconazole, with MICs of ≥16 µg/mL against both antifungals. Whole genome sequencing (WGS) analysis on this isolate and two related susceptible isolates did not reveal any unique substitutions in resistance-associated genes, including cyp51, hmg and erg6, when compared to two related susceptible isolates. The novel antifungal olorofim exhibited excellent activity against this large isolate collection, with all isolates considered as susceptible. Altogether, we indicate zoonotic transmission based on genotyping and revealed a broad activity of seven common antifungals, including olorofim, against a large S. brasiliensis isolate collection.

Therapeutic efficacy of isavuconazole and potassium iodide in a cat with refractory sporotrichosis.

A seven-month-old, male, domestic short-hair cat was presented with nodular and ulcerative lesions, as well as respiratory signs, caused by Sporothrix brasiliensis infection. Owing to lack of response to oral itraconazole and potassium iodide, isavuconazole was substituted for itraconazole, leading to clinical cure after three months of treatment without adverse effects.

Un chat domestique mâle à poil court de 7 mois est présenté avec des lésions nodulaires et ulcéreuses, ainsi que des signes respiratoires, causés par une infection à Sporothrix brasiliensis. En raison de l'absence de réponse à l'itraconazole oral et à l'iodure de potassium, l'isavuconazole est substitué à l'itraconazole, ce qui conduit à une guérison clinique après 3 mois de traitement sans effets indésirables.

Um gato doméstico de pelo curto de sete meses de idade foi apresentado com lesões nodulares e ulcerativas, bem como sintomas respiratórios, causados por infecção por Sporothrix brasiliensis. Devido à pobre resposta ao tratamento com itraconazol oral e iodeto de potássio, itraconazol foi substituído por isavuconazol, levando à cura clínica após três meses de tratamento, sem efeitos adversos.

Un gato doméstico de pelo corto, macho, de 7 meses de edad, se presentó con lesiones nodulares y ulcerativas, así como signos respiratorios, causados por infección por Sporothrix brasiliensis. Ante la falta de respuesta a itraconazol y yoduro potásico orales, se sustituyó itraconazol por isavuconazol, con curación clínica tras 3 meses de tratamiento sin efectos adversos.

Single nucleotide polymorphisms and chromosomal copy number variation may impact the Sporothrix brasiliensis antifungal susceptibility and sporotrichosis clinical outcomes.

Feline-transmitted sporotrichosis has garnered attention due to the recent high incidence and the lack of efficient control in the epicenter of the epidemic, Rio de Janeiro, Brazil. Sporothrix brasiliensis is the major pathogen involved in feline-to-human sporotrichosis in Brazil and displays more virulent genotypes than the closely related species S. schenckii. Over the last two decades, several reports of antifungal-resistant strains have emerged. Sequencing and comparison analysis of the outbreak strains allowed us to observe that the azole non-wild-type S. brasiliensis strain CFP 1054 had significant chromosomal variations compared to wild-type strains. One of these variants includes a region of 231 Kb containing 75 duplicated genes, which were overrepresented for lipid and isoprenoid metabolism. We also identified an additional strain (CFP 1055) that was resistant to itraconazole and amphotericin B, which had a single nucleotide polymorphism in the tac1 gene. The patients infected with these two strains showed protracted clinical course and sequelae. Even though our sample size is modest, these results suggest the possibility of identifying specific point mutations and large chromosomal duplications potentially associated with antifungal resistance and clinical outcomes of sporotrichosis.

A Sporothrix spp. enolase derived multi-epitope vaccine confers protective response in BALB/c mice challenged with Sporothrix brasiliensis.

Sporotrichosis is a cosmopolitan mycosis caused by pathogenic species of Sporothrix genus, that in Brazil is often acquired by zoonotic transmission involved infected cats with S. brasiliensis. Previous studies showed that the Sporothrix spp. recombinant enolase (rSsEno), a multifunctional protein with immunogenic properties, could be a promising target for vaccination against sporotrichosis in cats. Nevertheless, the considerable sequence identity (62%) of SsEno with its feline counterpart is a great concern. Here, we report the identification in silico, chemical synthesis and biological validation of six peptides of SsEno with low sequence identity to its cat orthologue. All synthesized peptides exhibit B-cell epitopes on the molecular surface of SsEno and proved to be highly reactive with the serum of infected mice with S. brasiliensis and sera of cats with sporotrichosis. Interestingly, our study revealed that anti-peptide sera did not react with the recombinant enolase from Felis catus (cats, rFcEno), thus, may not trigger autoimmune response in these felines if used as a vaccine antigen. The immunization with peptide mixture (PeptMix) formulated with Freund adjuvant (FA), induced high levels of antigen-specific IgG, IgG1 and IgG2b antibodies that conferred protection upon passive transference in infected BALB/c mice with S. brasiliensis. We also observed, that the FA+PeptMix formulation induced a Th1/Th2/Th17 cytokine profile ex vivo, associated with protecting effect against the experimental sporotrichosis. Our results suggest that the six SsEno-derived peptides here evaluated, could be used as safe antigens for the development of vaccine strategies against feline sporotrichosis, whether prophylactic or therapeutic.

Sporothrix pathogenic clade: Molecular analysis of animal and human clinical isolates.

Sporotrichosis is a subcutaneous mycosis that affects animals and humans. Varying in severity, occurrences range from local lesions to systemic involvement. It is caused by thermodimorphic and saprobic fungi from the Sporothrix pathogenic clade. This study aimed to identify the species and the sexual idiomorph distribution patterns responsible for diagnosed cases of sporotrichosis in São José do Rio Preto, Brazil. We included 188 isolates of Sporothrix sp. from feline lesions and 27 of human origin, which underwent molecular identification and genotyping for mating-type MAT1-1 and MAT1-2. The results showed that Sporothrix brasiliensis is the prevalent species in feline sporotrichosis outbreaks with the overwhelming presence of a single mating-type, MAT1-2 (P <.0001), suggesting a prevalently clonal form of spread. Morphological analyses did not discriminate among cryptic species in the genus Sporothrix, and molecular identification was essential for the correct identification of the species responsible for the observed cases of sporotrichosis. Distribution analyses of MAT1-2 isolates support the hypothesis of unidirectional migration from the current epidemics in São Paulo and Rio de Janeiro to the municipality of São José do Rio Preto.

This study aimed to identify the species and the sexual idiomorph distribution patterns responsible for diagnosed cases of sporotrichosis in São José do Rio Preto, Brazil. We included 188 isolates of Sporothrix sp. from feline lesions and 27 of human origin.

A lateral flow assay for the immunodiagnosis of human cat-transmitted sporotrichosis.

BACKGROUND: Cat-transmitted sporotrichosis (CTS) caused by Sporothrix brasiliensis has emerged as an important zoonosis in Brazil and neighbouring countries. OBJECTIVES: Evaluate the performance of a lateral flow assay (LFA) for the detection of anti-Sporothrix antibodies in human sera. METHODS: A LFA for the detection of anti-Sporothrix antibodies (Anti-Sporo LFA) in human sera, developed by IMMY, was evaluated using 300 human sera collected prospectively at the Hospital de Clínicas, Federal University of Paraná (HC-UFPR), in Curitiba, Brazil. These specimens included 100 sera from patients with CTS. CTS cases were classified as follows: 59 lymphocutaneous, 27 fixed cutaneous,13 ocular, and one mixed form. One-hundred specimens from patients with other mycoses, including cryptococcosis (n = 32), candidemia (n = 27), paracoccidioidomycosis (n = 14), aspergillosis (n = 10), histoplasmosis (n = 9), fusariosis (n = 4), lobomycosis (n = 1), chromoblastomycosis (n = 1), mucormycosis (n = 1) and trichosporonosis (n = 1). And 100 specimens from apparently healthy volunteers (AHV). RESULTS: The Anti-Sporo LFA showed a global sensitivity of 83% (95% confidence interval [CI] = 74%-90%), a global specificity of 82% (95% CI = 76%-87%), and accuracy of 82% (95% CI = 77%-86%). By clinical form sensitivity was as follows: Mixed form 100%, ocular 92%, lymphocutaneous 83% and fixed cutaneous 78%. False-positive results were observed in 11 specimens from people with other mycoses and 26 specimens from AHV. CONCLUSION AND DISCUSSION: This study presents the results of the evaluation of the first lateral flow assay for the detection of anti-Sporothrix antibodies in human sera. The findings here show evidence that IMMY's Anti-Sporo LFA is a promising tool for the rapid diagnosis of CTS.

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.

Sporothrix brasiliensis on cats with skin ulcers in Southern Brazil.

Sporotrichosis is a disease caused by thermally dimorphic fungi belonging to the Sporothrix schenckii complex. We report the occurrence of multiple cases of sporotrichosis in cats in Porto Alegre (RS), Brazil, from 2015 to 2019. A set of 21 fungal isolates were collected and the partial sequence of calmodulin (CAL) gene compared. All isolates were identified at phenotypic and molecular level as S. brasiliensis. Phylogenetic analysis showed the isolates clustered in two distinct groups, suggesting the presence of multiple genetic variants of S. brasiliensis in the region.

Zoonotic sporotrichosis in renal transplant recipients from Rio de Janeiro, Brazil.

Sporotrichosis is the main subcutaneous mycosis in the world. In the last two decades, zoonotic sporotrichosis transmitted by cats has become hyperendemic in Rio de Janeiro, Brazil. Renal transplant recipients are subject to invasive fungal infection because of the effects of immunosuppressive therapy, but sporotrichosis is rarely reported. The authors conducted a retrospective study describing epidemiological, clinical, and therapeutic data related to adult renal-transplant-recipient patients diagnosed with sporotrichosis. The molecular identification of fungal isolates was performed. Minimal inhibitory concentration (MIC) of amphotericin B (AMB), itraconazole (ITZ), posaconazole (POS), isavuconazole, and terbinafine (TRB) against the strains was determined using the protocol described by the Clinical and Laboratory Standards Institute (CLSI). Six cases were identified from a cohort with 2429 sporotrichosis patients. They were five men and one woman, with a mean age of 44.2 years (range: 34-54 years). Four of them had cutaneous limited forms, and two patients had disseminated forms. The mean time between transplant and the onset of sporotrichosis symptoms was 25.5 (range: 6-36) months. Sporothrix brasiliensis was identified as the causative agent. The isolates were classified as wild type for all antifungal drugs tested. Treatment schemes included AMB (deoxycholate and liposomal), ITZ, and TRB. Five patients evolved to cure, and one died as a result of disseminated disease. Renal transplant recipients may be a vulnerable group for sporotrichosis in endemic countries. The authors highlight the importance of sporotrichosis prevention, early diagnosis, and treatment to prevent disseminated disease and poor prognosis.

Extracellular Vesicles From Sporothrix brasiliensis Yeast Cells Increases Fungicidal Activity in Macrophages.

Sporotrichosis is a subcutaneous mycosis and is distributed throughout the world, although most cases belong to endemic regions with a warmer climate such as tropical and subtropical areas. The infection occurs mainly by traumatic inoculation of propagules. Similarly, to other organisms, Sporothrix brasiliensis display many biological features that aid in its ability to infect the host, such as extracellular vesicles, bilayered biological structures that provides communication between host cells and between fungi cells themselves. Recently, research on Sporothrix complex have been focused on finding new molecules and components with potential for therapeutic approaches. Here, we study the relationship among EVs and the host's macrophages as well as their role during infection to assess whether these vesicles are helping the fungi or inducing a protective effect on mice during the infection. We found that after cocultivation with different concentrations of purified yeasts EVs from Sb, J774 macrophages displayed an increased fungicidal activity (Phagocytic Index) resulting in lower colony-forming units the more EVs were added, without jeopardizing the viability of the macrophages. Interleukins IL-6, IL-10, and IL-12 were measured during the infection period, showing elevated levels of IL-12 and IL-6 in a dose-dependent manner, but no significant change for IL-10. We also assessed the expression of important molecules in the immune response, such as MHC class II and the immunoglobulin CD86. Both these molecules were overexpressed in Sb yeasts infected mice. Our results indicate that EVs play a protective role during Sporothrix brasiliensis infections.

The interaction between Sporothrix schenckii sensu stricto and Sporothrix brasiliensis with Acanthamoeba castellanii.

BACKGROUND: Sporotrichosis is a group of zoonotic subcutaneous mycoses, found worldwide and caused by fungi belonging to the genus Sporothrix. Protozoans of the genus Acanthamoeba are widely distributed, and some species may be pathogenic and/or opportunistic. These organisms coexist in the same environment and may interact. OBJECTIVES: This study determined the profile of interactions of S schenckii sensu stricto and S brasiliensis with A castellanii, using an in vitro co-culture model to evaluate the intrinsic characteristics of the two Sporothrix species and A castellanii. METHODS: We compared the rate of phagocytosis of S schenckii sensu stricto and S brasiliensis by A castellanii; the viability of S schenckii sensu stricto and S brasiliensis after contact with A castellanii; the viability of the amoeba after contact with a fungal species; and the influence of S schenckii sensu stricto and S brasiliensis on the encystment process of A castellanii. RESULTS: The analyses indicated that A castellanii phagocytised both S schenckii and S brasiliensis, with significantly more S schenckii than S brasiliensis in the first two hours of contact. Our results showed a significant increase in conidia and hyphae count after 72 hours of co-culture of A castellanii with S brasiliensis, and the amoebae lysed after they ingested the fungi, indicating that the fungi probably used the amoebae as a source of nutrition. CONCLUSIONS: Our results were obtained in vitro and these organisms may not behave similarly in vivo; in vivo studies of co-infections are necessary in order to gain a thorough understanding of this relationship.

The threat of emerging and re-emerging pathogenic Sporothrix species.

Sporotrichosis is a neglected subcutaneous mycosis of humans and animals acquired by traumatic inoculation of soil and plant material (classical route) contaminated with infectious propagules of the pathogen or being bitten/scratched by infected cats (alternative route). Within a genus composed of 53 species displaying an essentially environmental core, there are only a few members which have considerable impacts on human or animal health. Infections are typically caused by S. brasiliensis, S. schenckii or S. globosa. Rare mammal pathogens include members of the S. pallida and S. stenocereus complexes. To illustrate the tremendous impact of emerging zoonotic sporotrichosis on public health, we discuss the main features of the expanding epidemics driven by S. brasiliensis in cats and humans. The cat entry in the transmission chain of sporotrichosis, causing epizooties (cat-cat) or zoonosis (cat-human), has contributed to the definition of new paradigms in Sporothrix transmission, reaching epidemic levels, making the disease a serious public health problem. Indeed, S. brasiliensis infection in humans and animals is likely to become even more important in the future, with projections of its expansion in biogeographic domains and host range, as well as greater virulence in mammals. Therefore, lessons from a long-standing outbreak in the state of Rio de Janeiro about the source and distribution of the etiological agents among outbreak areas can be used to create better control and prevention plans and increase awareness of sporotrichosis as a serious emerging zoonotic disease.

The importance of Toll-like receptor 4 during experimental Sporothrix brasiliensis infection.

Here we investigated the importance of Toll-like receptor 4 (TLR-4) in innate immune response to Sporothrix brasiliensis, a virulent fungus of Sporothrix spp. In vitro assays, using C57Bl/6 (wild type [WT]) bone marrow-derived macrophages (BMDMs), and TLR-4 knockout (TLR-4-/-) showed that the absence of TLR-4 resulted in impaired phagocytosis and lower levels of tumor necrosis factor α (TNF-α), interleukin (IL)-6, and nitric oxide. In vivo assays were also performed, and the mice (WT and TLR-4-/-) were intraperitoneally infected with S. brasiliensis yeast ATCC MyA-4831 and euthanized on days 7, 14, and 28 postinfection, with the following parameters evaluated: fungal burden in liver, spleen, kidney, and brain, and the production of cytokines interferon γ (IFN-γ), TNF-α, IL-2, IL-4, IL-6, and IL-10. The results demonstrate the macrophages dependency on TLR-4 for inflammatory activation and in the absence of TLR-4 during experimental S. brasiliensis infection enhanced dissemination occurred after 14 and 28 days. These data show that TLR-4 signals are important for the recognition of S. brasiliensis by macrophages, and their absence promotes the persistence of the infection.

Human sporotrichosis: A zoonotic outbreak in southern Brazil, 2012-2017.

Zoonotic sporotrichosis has undergone a geographical expansion in Brazil in the last decade. Rio Grande do Sul (RS) is the second state of the country in which a number of feline sporotrichosis cases have been described. Since cats are the main zoonotic source of infection, this study aimed to describe 100 cases of human sporotrichosis occurring in the last 5 years in the southern region of RS, Brazil. In addition, we aimed to illustrate the zoonotic importance of the disease, describing four cases in the same family due to transmission by their cat. This great number of human cases in a short period of evaluation highlights the severity of sporotrichosis as a public health problem in the region, suggesting that a possible outbreak is occurring that requires immediate public intervention actions to weaken its impact.