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Background: Pregnant women constitute a vulnerable population occasionally affected by zoonotic sporotrichosis. Treatment is challenging due to potentially teratogenic oral medications (itraconazole and saturated potassium iodide solution) or lack of clinical experience during pregnancy (terbinafine). Literature is scarce on sporotrichosis and pregnancy, mainly consisting of case reports., Methodology/principal Findings: This study consists of a cohort of 58 cases of pregnant women with sporotrichosis attended in a reference center in Rio de Janeiro from 1998 to 2023. The median age was 27 years old; the majority were black (64.4%); comorbidities prior to pregnancy were reported by 20.7% (including two people living with HIV/AIDS-PLHIV) and 6.8% developed conditions that are unique to pregnancy. In 75.9% of patients, they were pregnant when they acquired sporotrichosis, with a median gestational age of 17 weeks, and 24.1% became pregnant during treatment for sporotrichosis. The lymphocutaneous form occurred in 63.8% of patients, followed by the fixed form (19%), disseminated cutaneous form (12%) and extracutaneous/disseminated forms (5.2%). Thermotherapy was indicated for all (except 2) patients and cryosurgery was performed in 22 (37.9%). Amphotericin B was indicated for a patient with external ocular sporotrichosis and for the PLHIV with osteomyelitis in the right tibia. Cure occurred in 100% of those followed (n = 44) with the remainder lost to follow-up (n = 14)., Conclusions: Pregnant women with cutaneous sporotrichosis in this study recovered following physical therapies, suggesting these therapies may be effective. In cases of extracutaneous and disseminated forms, amphotericin B was indicated due to its safety profile in this population. Management of sporotrichosis during pregnancy requires a delicate assessment of the balance between maternal benefit and fetal risks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Freitas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Sporotrichosis diagnosis involves a series of analyses, including culture and antibody detection in serum samples. Serologic methods may sometimes yield false-negative or false-positive results, leading to inaccurate diagnoses. This study assessed specific patient groups in which antibody detection of different isotypes and subclasses may lack sensitivity. An enzyme-linked immunosorbent assay (ELISA) with Sporothrix brasiliensis exoantigens was used to investigate IgM, IgG, IgG1, IgG2, IgG3, IgG4, IgA, IgA1 and IgA2 antibodies in human serum samples. Eighty serum samples from patients with different sporotrichosis clinical manifestations, including cutaneous forms with and without hypersensitivity manifestations, extracutaneous forms (bone, ocular, meningeal and pulmonary), disseminated cutaneous forms and disseminated forms in individuals living with HIV/AIDS, diabetics and alcoholics, were evaluated. The ELISA sensitivities in the detection of different antibodies ranged from 0.85 to 0.60 for the detection of IgG2 and IgG3, respectively. The antibodies with higher area under ROC curves were IgG2, IgG, IgA and IgA1. There were no significant differences in the immunological reactivity of the tested antibodies among different clinical forms of sporotrichosis. The data revealed a higher likelihood of a false-negative outcome in patients with lesions in the nasal mucosa regarding the detection of IgM and a lower likelihood in patients with lymphocutaneous sporotrichosis regarding the detection of IgG3. Patients with hypersensitivity manifestations had a 3.71 odds ratio to yield negative results in total IgG detection. In conclusion, we identified specific patient groups in which antibody detection may lack sensitivity, thus contributing to a better understanding of the diagnostic challenges associated with this condition., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Twenty-five years have passed since the initial observation of endemic zoonotic sporotrichosis in Rio de Janeiro, Brazil. Since then, this disease has spread throughout South America. Accompanying the emergence of this mycosis, some progress has been made, including the expansion of a research network in this field and higher visibility of sporotrichosis within government authorities and funding agencies. However, there are still some challenges to curbing the expansion of this disease in the coming years. These include the development of rapid and accurate diagnostic tests, new antifungal drugs, particularly for the treatment of extracutaneous manifestations of sporotrichosis, and more comprehensive care for cats with sporotrichosis. Including these actions in the sporotrichosis research agenda is required so as to change the development of this disease in the years to come.

Background: causes sporotrichosis, an important infection in some groups of patients. Sporothrix brasiliensis causes sporotrichosis, an important infection in some groups of patients. Aims: An antifungal susceptibility test was performed to compare MIC values with other antifungal drugs used to treat sporotrichosis. A checkerboard assay was performed to understand isavuconazole interactions. Furthermore, isavuconazole growth inhibition on an itraconazole-resistant strain was tested. Methods: An antifungal susceptibility test was performed to compare MIC values with other antifungal drugs used to treat sporotrichosis. A checkerboard assay was performed to understand isavuconazole interactions. Furthermore, isavuconazole growth inhibition on an itraconazole-resistant strain was tested. Results: Isavuconazole had similar MICs to other azoles against S. brasiliensis , presenting fungistatic activity. Isavuconazole did not interact in vitro with antifungals or immunosuppressive drugs and inhibited the growth of an itraconazole-resistant strain. Conclusion: , its pharmacologic characteristics make it a candidate for patients with sporotrichosis and it may be useful to combat sporotrichosis caused by resistant isolates.S. brasiliensis , its pharmacologic characteristics make it a candidate for patients with sporotrichosis and it may be useful to combat sporotrichosis caused by resistant isolates.

Sporotrichosis is an emergent public health problem. The mycological diagnosis of this infection is based on culture, which is fastidious and may represent a biohazard for technicians. Although not widely implemented in routine diagnosis, molecular methodologies are fast, have good accuracy, and can be easily standardized, aiding in the early diagnosis of neglected mycoses. This study aimed at implementing a new pan-Sporothrix quantitative reverse transcription PCR (RT-qPCR) assay, and then validating it on clinical samples from confirmed human sporotrichosis cases. A total of 68 human samples with culture-confirmed diagnosis of sporotrichosis were collected from 64 patients followed at a Brazilian reference center for endemic mycoses. These samples were submitted to whole nucleic acid extraction, followed by an RT-qPCR protocol. The limit of detection was 244 fg, the efficiency was 2.0 (100%), and the assay could amplify the genetic material of the three major clinically relevant species of the genus Sporothrix. Among the 68 samples analyzed, 62 were positive in RT-qPCR, showing an overall sensitivity of 91.18%, which variated according to the type of biological sample: 96.72% in skin samples (n = 61) and 100% in respiratory samples (n = 3), whereas all cerebrospinal fluid specimens (n = 4) were negative. The specificity was 100% when tested in 25 samples from patients with other mycoses and tuberculosis. In addition, DNA from 93 fungal species did not yield positive results, confirming the high specificity of this test. Our RT-qPCR presented high sensitivity and specificity, representing an excellent tool for a fast and reliable diagnosis of human sporotrichosis., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology.)

Background: Sporotrichosis is a subcutaneous or implantation mycosis caused by some species of the genus Sporothrix. Rio de Janeiro state, Brazil, experiences hyperendemic levels of zoonotic sporotrichosis, with increasing cases of disseminated disease, especially in people living with HIV (PLHIV). Involvement of the nasal mucosa is rare and occurs isolated or in disseminated cases, with a delayed resolution., Methodology/principal Findings: This study aimed to describe the epidemiological, clinical, and therapeutic profiles of 37 cases of sporotrichosis with involvement of the nasal mucosa treated at the ear, nose, and throat (ENT) outpatient clinic of the Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, from 1998 to 2020. Data were reviewed from the medical records and stored in a database. The Mann-Whitney test was used to compare the means of quantitative variables, and Pearson chi-square and Fisher's exact tests were used to verify the association between qualitative variables (p<0.05). Most patients were males, students or retirees, with a median age of 38 years, residents in the municipality of Rio de Janeiro, and infected through zoonotic transmission. Disseminated sporotrichosis forms in patients with comorbidities (mostly PLHIV) were more common than the isolated involvement of the mucosa. The main characteristics of lesions in the nasal mucosa were the presence/elimination of crusts, involvement of various structures, mixed appearance, and severe intensity. Due to therapeutic difficulty, itraconazole was combined with amphotericin B and/or terbinafine in most cases. Of the 37 patients, 24 (64.9%) healed, with a median of 61 weeks of treatment, 9 lost follow-up, 2 were still treating and 2 died., Conclusions: Immunosuppression was determinant to the outcome, with worse prognosis and lower probability of cure. Notably in this group, the systematization of the ENT examination for early identification of lesions is recommended to optimize the treatment and outcome of the disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Izoton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: To describe 120 cases of ocular sporotrichosis., Methods: Review of medical records of patients with culture-proven (from eye specimen) ocular sporotrichosis, in Rio de Janeiro, from 2007 to 2017., Results: Women were more affected (61.7%) and median age was 24 years. The isolated ocular form was more frequent (75.8%). Fixed cutaneous sporotrichosis was the most commonly associated form (48.3%). Hypersensitivity reactions were observed in 10% of patients. Ocular involvement was unilateral in 98.3% of the cases, and the most frequent clinical presentation was granulomatous conjunctivitis (86.7%), followed by eyelid lesion (25%). Dacryocystitis represented 7.5% of the cases, predominantly in children (55.6%). Itraconazole was the first choice treatment (95.8%). Sequelae were observed in 23 patients (22.5%), and surgical treatment was required for most of them., Conclusion: Ocular sporotrichosis can be considered a characteristic form of the zoonotic transmission, with high morbidity. Delay in initiating specific treatment is likely to increase the risk of progression to more severe forms of the disease, and development of ocular sequelae.

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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The zoonotic transmission of sporotrichosis due to Sporothrix brasiliensis occurs largely in Rio de Janeiro state, Brazil since the 1990´s. Most patients infected with S. brasiliensis respond well to itraconazole or terbinafine. However, a few patients have a slow response or do not respond to the treatment and develop a chronic infection. The aim of this study was to analyze strains of S. brasiliensis against five different drugs to determine minimal inhibitory concentration distributions, to identify non-wild type strains to any drug evaluated and the clinical aspects of infections caused by them. This study evaluated 100 Sporothrix spp. strains obtained from 1999 to 2018 from the Evandro Chagas National Institute of Infectious Diseases, Fiocruz, which were identified through a polymerase chain reaction using specific primers for species identification. Two-fold serial dilutions of stock solutions of amphotericin B, itraconazole, posaconazole, ketoconazole and terbinafine prepared in dimethyl sulfoxide were performed to obtain working concentrations of antifungal drugs ranging from 0.015 to 8.0 mg/L. The broth microdilution reference method was performed according the M38-A2 CLSI guideline. All strains were identified as S. brasiliensis and thirteen were classified as non-wild type, two of them against different drugs. Non-wild type strains were identified throughout the entire study period. Patients infected by non-wild type strains presented prolonged treatment times, needed increased antifungal doses than those described in the literature and one of them presented a permanent sequel. In addition, three of them, with immunosuppression, died from sporotrichosis. Despite the broad use of antifungal drugs in hyperendemic areas of sporotrichosis, an emergence of non-wild type strains did not occur. The results of in vitro antifungal susceptibility tests should guide sporotrichosis therapy, especially in immunosuppressed patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bernardes-Engemann, Tomki, Rabello, Almeida-Silva, Freitas, Gutierrez-Galhardo, Almeida-Paes and Zancopé-Oliveira.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Bone sporotrichosis is rare. The metropolitan region of Rio de Janeiro is hyperendemic for zoonotic sporotrichosis and the bone presentations are increasing., Methods: We studied a retrospective cohort of 41 cases of bone sporotrichosis, diagnosed from 1999-2016. The inclusion criteria was fungal culture isolation from any clinical specimen associated to bone involvement (radiography and/or computed tomography) compatible with fungal osteomyelitis or histopathological findings of bone material compatible with sporotrichosis. Molecular identification was performed when possible., Results: Male patients represented 58.5% of the cases, with a cohort median age of 43 years. Immunosuppressive conditions were present in 68.3% of the patients, mostly HIV coinfection (51.2%). Multifocal bone involvement (more than one anatomical segment) was diagnosed in 61% of the patients, while 39% presented unifocal involvement. The bones of the hands were the most affected (58.5%), followed by the feet (41.5%) and tibia (26.8%). Multifocal group was characterized by a higher proportion of males (p = 0.0045) with immunosuppressive conditions (p = 0.0014). Amphotericin B followed by oral itraconazole was the main treatment, with a median time of 16.7 months (1.5 to 99.2 months), and cure of 53.7% of the patients (84.6% of immunocompetent and 39.3% of immunocompromised patients). Sequelae occurred in 12.2% of the patients-amputations (7.3%) and ankylosis (4.9%), while 22% died in the course of the disease. Sporothrix brasiliensis was the causative agent in all the 9 (22%) performed cases., Conclusions: Bone sporotrichosis is a chronic, challenging condition with prolonged treatment, often with poor results and sequelae., Competing Interests: The authors have declared that no competing interests exist.

Sporotrichosis in immunocompromised patients has a high morbidity and may cause deaths. Particularly, patients with acquired immunodeficiency syndrome (AIDS) with low T CD4 counts develop a chronic disease, with severe and widespread forms. Recently, the ability of Sporothrix brasiliensis, the main agent of zoonotic sporotrichosis, to increase its virulence in a diabetic patient without HIV infection was described. Since it was a unique finding, it is not known how often this occurs in patients with chronic and refractory sporotrichosis. The aim of this study is to compare sequential Sporothrix isolates obtained from patients with sporotrichosis and AIDS in order to detect changes in virulence-related phenotypes and acquisition of antifungal resistance during the evolution of the disease. Fungal growth in different substrates, antifungal susceptibility, thermotolerance, resistance to oxidative stress, and production of hydrolytic enzymes were evaluated. Correlations were assessed between clinical and phenotypic variables. Sixteen isolates, all identified as S. brasiliensis, obtained from five patients were studied. They grew well on glucose and N-acetyl-D-glucosamine, but poorly on lactate. Except from isolates collected from two patients, which were non-wild type for terbinafine, they were considered wild type for the antifungal drugs tested. Thermotolerance of the isolates was moderate to high. Except for phytase and phospholipase, isolates were able to produce virulence-related enzymes on different levels. Changes in all studied phenotypes were observed during the course of the disease in some patients. The results show that the HIV-driven immunosuppression is more relevant than fungal phenotypes on the unfavorable outcomes of disseminated sporotrichosis.

Competing Interests: The authors have declared that no competing interests exist.

Purpose: To describe 26 cases of bulbar conjunctival sporotrichosis., Methods: Review of clinical records of patients with bulbar conjunctivitis due to culture-proven Sporothrix spp. infection, in Rio de Janeiro, from 2007 to 2017., Results: Twenty-six patients were identified. Median age was 25 years. Adults were more affected (53.8%), followed by adolescents (26.9%). There was a predominance of women (73.1%). Twenty-four patients (96%) reported contact with cats with sporotrichosis. Twenty-one patients (80.8%) presented a primary ocular sporotrichosis. Five patients presented associated eyelid lesions, and 21 (80.8%) tarsal conjunctivitis. Parinaud oculoglandular syndrome was observed in 17 (81%) patients. Eight patients (36.4%) reported the use of steroid drops before diagnosis was made. All patients but one were treated with oral itraconazole. Twenty-three patients (88.5%) were completely cured and three (11.5%) were lost to follow-up. Eight patients (34.8%) developed ocular sequelae., Conclusion: Bulbar conjunctivitis is an important clinical presentation of ocular sporotrichosis. It can lead to ocular sequelae. Sporotrichosis should be considered in the differential diagnosis of ophthalmic external diseases, especially in patients with cat contact history.

Background: Sporotrichosis is a subcutaneous mycosis caused by dimorphic pathogenic fungi belonging to the Sporothrix genus. Pathogenic Sporothrix species typically produce melanin, which is known to be a virulence factor., Objectives: The aim of this study was to perform phenotypic, genotypic, and virulence analyses of two distinct Sporothrix brasiliensis strains isolated from the same lesion on a patient from Rio de Janeiro., Methods and Findings: Genotypic analyses by partial sequencing of the calmodulin, β-tubulin, and chitin synthase genes, as well as polymerase chain reaction (PCR)-fingerprinting by T3B, M13, and GACA, showed that the isolates were very similar but not identical. Both isolates had similar phenotypic characteristics and effectively produced melanin in their yeast forms, accounting for their ability of causing disease in a murine sporotrichosis model. Remarkably, isolate B was albino in its environmental form but caused more severe disease than the pigmented A isolate., Conclusions: These findings indicate that the patient was infected by two genetically and biologically distinct S. brasiliensis that vary in their production of melanin in their environmental forms. The results underscore the importance of characterizing phenotypically different isolates found in the same clinical specimen or patient.

Sporotrichosis is a subcutaneous mycosis with global distribution, and patients generally receive outpatient treatment. Since 1998 there has been an increase in cases in the state of Rio de Janeiro, Brazil, mainly via zoonotic transmission involving cats. Patients coinfected with the human immunodeficiency virus (HIV) often require hospitalization and evolve to death. This study analyzes and describes data from 1992 to 2015 obtained from the database of the Brazilian Unified National Health System (SUS). There were 782 hospitalizations and 65 deaths in Brazil. Six percent of the hospitalizations and 40% of the deaths involved coinfection with HIV. There were 250 hospitalizations and 36 deaths in Rio de Janeiro, with a progressive increase over the course of the period. The states of São Paulo and Goiás also showed high numbers. Men, non-whites, and individuals with low schooling evolved more frequently to death. In conclusion, sporotrichosis is associated with hospitalizations and deaths throughout Brazil, especially in the state of Rio de Janeiro.

Background: The 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., Aims: To correlate the results of culture and serology of patients with suspected sporotrichosis., Methods: A 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., Results: Positive 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., Conclusions: These two techniques are complementary in the diagnosis of sporotrichosis, making diagnosis and clinical decision more precise., (Copyright © 2019 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Pregnant women with sporotrichosis should not receive systemic antifungal therapy except in severe cases when amphotericin B is recommended. Thermotherapy is the most reported treatment described in this group of patients. It entails weeks of daily self-application of heat to the lesions, requires that the patient faithfully apply it, and it could cause skin burns. Cryosurgery is a useful therapeutic tool for many cutaneous infectious diseases, safe for pregnant women, but not well evaluated for sporotrichosis treatment in this group., Methodology: The authors conducted a retrospective study describing epidemiological, clinical, and therapeutic data related to four pregnant patients with sporotrichosis treated with cryosurgery. The authors reviewed the clinical records of four pregnant patients diagnosed with cutaneous sporotrichosis and treated with cryosurgery. The sessions were carried out monthly up to clinical cure. Molecular identification of the Sporothrix species was performed in two cases using T3B PCR fingerprinting assays., Principal Findings: All patients were in the second trimester of pregnancy and their age ranged from 18 to 34 years. With regard to clinical presentation, two patients had lymphocutaneous and two had the fixed form. S. brasiliensis was identified in two cases as the causative agent. Cryosurgery was well tolerated and the number of sessions ranged from 1 to 3. All the patients reached a complete clinical cure., Conclusions: Cryosurgery was a safe, easy to perform and well tolerated method, and therefore it is suggested to be a suitable option for the treatment of cutaneous sporotrichosis in pregnant women.

Sporotrichosis is a subacute to chronic infection caused by members of the Sporothrix schenckii complex. Itraconazole is the first choice antifungal drug for treating this infection, with terbinafine and potassium iodide as alternatives and amphotericin B used in cases of severe infections. Correlation of antifungal susceptibility data with the clinical outcome of the patients is scarce. The aim of this study was to correlate clinical and mycological data in patients with refractory sporotrichosis. In this work, antifungal susceptibilities, determined according to the reference M38-A2 CLSI protocol, of 25 Sporothrix strains, isolated from seven human cases of sporotrichosis with adversities in the treatment, are presented. Tested drugs included itraconazole, ketoconazole, posaconazole, voriconazole, terbinafine, and amphotericin B. Fungi were identified using the T3B PCR fingerprinting. This method identified all strains as Sporothrix brasiliensis and also demonstrated a high degree of similarity between the strains. In general, voriconazole was ineffective against all strains, and elevated minimal inhibitory concentrations (MICs) were observed for amphotericin B. High itraconazole and terbinafine MICs were not observed in S. brasiliensis isolates from patients of this study. Moreover, a significant increase in itraconazole and terbinafine MIC values from strains isolated from the same patient in different periods was not observed. The results suggest that the antifungal susceptibility to terbinafine and itraconazole determined by the reference method does not play an important role in therapeutic failure of sporotrichosis and that acquisition of resistance during prolonged antifungal treatment is not likely to occur in S. brasiliensis., (© The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: In this article, the authors describe multifocal choroiditis related to disseminated sporotrichosis in patients with HIV/AIDS., Methods: We conducted a retrospective observational study of three patients infected with HIV who presented with disseminated sporotrichosis characterized by cutaneous lesions, multifocal choroiditis, and other manifestations, including osteomyelitis and involvement of the bone marrow, larynx, pharynx, and nasal and oral mucosa., Results: Five eyes of three patients with HIV/AIDS showed multifocal choroiditis related to disseminated sporotrichosis. The CD4 counts ranged from 25 to 53 mm. All patients were asymptomatic visually. The ocular disease was bilateral in two patients. The lesion size ranged from 1/3 to 2 disc diameters. None of the patients had vitritis. Of the 12 lesions, 9 were localized in the posterior pole (Zone 1) and 3 were localized in the mild periphery (Zone 2)., Conclusion: Multifocal choroiditis due to disseminated sporotrichosis can occur in profoundly immunosuppressed patients with HIV/AIDS.

The Sporothrix complex members cause sporotrichosis, a subcutaneous mycosis with a wide spectrum of clinical manifestations. Several specific phenotypic characteristics are associated with virulence in many fungi, but studies in this field involving the Sporothrix complex species are scarce. Melanization, thermotolerance, and production of proteases, catalase, and urease were investigated in 61 S. brasiliensis, one S. globosa, and 10 S. schenckii strains. The S. brasiliensis strains showed a higher expression of melanin and urease compared with S. schenckii. These two species, however, presented similar thermotolerances. Our S. globosa strain had low expression of all studied virulence factors. The relationship between these phenotypes and clinical aspects of sporotrichosis was also evaluated. Strains isolated from patients with spontaneous regression of infection were heavily melanized and produced high urease levels. Melanin was also related to dissemination of internal organs and protease production was associated with HIV-coinfection. A murine sporotrichosis model showed that a S. brasiliensis strain with high expression of virulence factors was able to disseminate and yield a high fungal burden in comparison with a control S. schenckii strain. Our results show that virulence-related phenotypes are variably expressed within the Sporothrix complex species and might be involved in clinical aspects of sporotrichosis.

Sporotrichosis is an endemic mycosis caused by the dimorphic fungus Sporothrix schenckii sensu lato. It has gained importance in recent years due to its worldwide prevalence, recognition of multiple cryptic species within the originally described species, and its distinctive ecology, distribution, and epidemiology across the globe. In this review, we describe the current knowledge of the taxonomy, ecology, prevalence, molecular epidemiology, and outbreaks due to S. schenckii sensu lato. Despite its omnipresence in the environment, this fungus has remarkably diverse modes of infection and distribution patterns across the world. We have delved into the nuances of how sporotrichosis is intimately linked to different forms of human activities, habitats, lifestyles, and environmental and zoonotic interactions. The purpose of this review is to stimulate discussion about the peculiarities of this unique fungal pathogen and increase the awareness of clinicians and microbiologists, especially in regions of high endemicity, to its emergence and evolving presentations and to kindle further research into understanding the unorthodox mechanisms by which this fungus afflicts different human populations., (© The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

Sporotrichosis associated with zoonotic transmission remains a relevant public health problem in Rio de Janeiro, Brazil, affecting a large at-risk population, which includes HIV-infected individuals. We assessed patients co-infected by Sporothrix spp. and HIV over time in the context of an unabated sporotrichosis epidemic. A retrospective cohort retrieved information from a National reference institute for infectious diseases regarding 48 patients with sporotrichosis-HIV co-infection (group 1) as well as 3,570 patients with sporotrichosis (group 2), from 1987 through March 2013. Most patients from group 1 were male (68.8%), whereas women were predominant in group 2 (69.1%; p<0.0001). Patients from group 1 were younger than those from group 2 (μ = 38.38±10.17 vs. 46.34±15.85; p<0.001) and differed from group 2 in terms of their race/ethnic background, with 70.8% non-white patients in group 1 vs. 38.6% from group 2 (p<0.0001). Close to half (∼44%) of the patients from group 1 were hospitalized due to sporotrichosis over time, whereas hospitalization was very unlikely in group 2, among whom approximately 1% were hospitalized over time. Dissemination of sporotrichosis was the main cause of hospitalization in both groups, although it was more common among hospitalized patients from group 1 (19/21 [90.5%] vs. 16/37 [43.2%]; p<0.001). Over the period under analysis, eight patients died due to sporotrichosis (3/48 vs. 5/3,570). The diagnosis of sporotrichosis elicited HIV testing and subsequent diagnosis in 19/48 patients, whereas 23/48 patients were simultaneously diagnosed with the two infections. HIV infection aggravates sporotrichosis, with a higher incidence of severe disseminated cases and a higher number of hospitalizations and deaths. Underserved populations, among whom sporotrichosis has been propagated, have been affected by different transmissible (e.g., HIV) and non-transmissible diseases. These populations should be targeted by community development programs and entitled to integrated management and care of their superimposed burdens.

Sporotrichosis associated with exposure to domestic cats is hyperendemic in Rio de Janeiro, Brazil. A review of the clinical records at our institute revealed four patients with clinical signs of dacryocystitis and a positive conjunctival culture for Sporothrix who were diagnosed with Sporothrix dacryocystitis. Three patients were children (< 13 years of age) and one patient was an adult. Two patients reported contact with a cat that had sporotrichosis. Dacryocystitis was associated with nodular, ulcerated lesions on the face of one patient and with granulomatous conjunctivitis in two patients; however, this condition manifested as an isolated disease in another patient. All of the patients were cured of the fungal infections, but three patients had chronic dacryocystitis and one patient developed a cutaneous fistula. Sporotrichosis is usually a benign disease, but may cause severe complications when the eye and the adnexa are affected. Physicians, especially ophthalmologists in endemic areas, should be aware of the ophthalmological manifestations and complications of sporotrichosis.

Sporothrix schenckii, an ascomycetous dimorphic organism that for over a century was recognized as the sole agent of sporotrichosis, a subcutaneous mycosis with a worldwide distribution. However, it has been proposed, based on physiologic and molecular aspects, that S. schenckii is a complex of distinct species: Sporothrix brasiliensis, Sporothrix mexicana, Sporothrix globosa, S. schenckii sensu strictu, Sporothrix luriei, and Sporothrix albicans (formerly Sporothrix pallida). Human disease has a broad range of clinical manifestations and can be classified into fixed cutaneous, lymphocutaneous, disseminated cutaneous, and extracutaneous sporotrichosis. The gold standard for the diagnosis of sporotrichosis is the culture; however, serologic, histopathologic and molecular approaches have been recently adopted for the diagnosis of this mycosis. Few molecular methods have been applied to the diagnosis of sporotrichosis to detect S. schenckii DNA from clinical specimens, and to identify Sporothrix spp. in culture. Until now, Sporothrix is the unique clinically relevant dimorphic fungus without an elucidated genome sequence, thus limiting molecular knowledge about the cryptic species of this complex, and the sexual form of all S. schenckii complex species. In this review we shall focus on the current diagnosis of the sporotrichosis, and discuss the current molecular tools applied to the diagnosis and identification of the Sporothrix complex species. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012)., (Copyright © 2013 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.)

This is a report on eight non-HIV infected leprosy patients presenting unusual co-infection with other, often neglected, tropical diseases, namely: American tegumentary leishmaniasis (ATL), sporotrichosis, and cryptococcosis. To the best of our knowledge, there have been very few ATL-leprosy co-infection reports in the literature to date and only one previous description of the coexistence of leprosy-cryptococcosis and leprosy-sporotricosis.

Sporotrichosis is a subcutaneous mycosis diagnosed by isolation of the fungus in culture. Serological tests for help in diagnosis in general do not use purified or recombinant antigens, because there is a paucity of described immunoreactive proteins, especially for the new described Sporothrix species, such as Sporothrix brasiliensis. This study aims to characterise antigens from S. brasiliensis and verify their application in serodiagnosis of sporotrichosis. An immunoblot assay allied with computer-based analysis was used to identify putative antigenic molecules in a cell-free extracts of both morphological phases of this fungus, and to delineate antigenic polymorphism among seven S. brasiliensis isolates and one S. schenckii Brazilian strain. The mycelial and yeast phase of the fungus originated 14 and 23 reactive bands, respectively, which were variable in intensity. An 85 kDa antigen, verified in the yeast phase of the fungus, was observed in all strains used and the immunodominant protein was identified. This protein, however, cross-react with serum samples from patients infected with other pathogens. The results show that the S. brasiliensis cell-free antigen extract is a single and inexpensive source of antigens, and can be applied on the sporotrichosis serodiagnosis., (© 2012 Blackwell Verlag GmbH.)

In the scientific literature, sporotrichosis has traditionally been associated with agricultural work, since the causative agent is found naturally in the soil. However, cases have been reported recently in an urban area, related to zoonotic transmission. The current study aimed to contribute to knowledge on sporotrichosis in an urban area through an exploratory analysis of its socio-spatial distribution in Rio de Janeiro, Brazil, from 1997 to 2007, identifying the areas with the heaviest transmission. The database from the Health Surveillance Service at the Evandro Chagas Institute for Clinical Research, Oswaldo Cruz Foundation, was used to estimate incidence rates and spatial distribution. During the study period, 1,848 cases of sporotrichosis were reported, predominantly in adult women not currently in the labor market. The leading source of infection was wounds caused by domestic cats, which contributed to the spread of sporotrichosis in this urban area. Georeferencing of 1,681 cases showed a transmission belt along the border between the city of Rio de Janeiro and the adjacent municipalities in the Greater Metropolitan Area.

Background: American tegumentary leishmaniasis (ATL) and sporotrichosis exhibit similar histopathology and low frequencies of microorganism detection., Objectives: This study seeks to identify microscopic alterations that can distinguish between these diseases., Methods: Haematoxylin and eosin stained slides of 171 ATL and 97 sporotrichosis samples from active cutaneous lesions were examined for histopathological alterations. The lesions were diagnosed by isolating the agent (which was not visible) in culture. An intuitive diagnosis was assigned to each slide. The strength of the association between the histopathological findings and the diagnosis was estimated by an odds ratio, and each finding was graded according to a regression model. A score was assigned to each sample based on the histopathological findings. A study of the interobserver reliability was performed by calculating kappa coefficients of the histopathological findings and intuitive diagnoses., Results: The markers 'macrophage concentration', 'tuberculoid granuloma' and 'extracellular matrix degeneration' were associated with ATL. 'Suppurative granuloma', 'stellate granuloma', 'different types of giant cells', 'granulomas in granulation tissue' and 'abscess outside the granuloma' were associated with a diagnosis of sporotrichosis. 'Macrophage concentration' and 'suppurative granuloma' had the highest (substantial and almost perfect, respectively) reliability. The regression model score indicated 92.0% accuracy. The intuitive diagnosis had 82.5% diagnostic accuracy and substantial reliability., Conclusions: Taking into account the clinical and epidemiological context, some histopathological alterations might be useful for the differential diagnosis between ATL and sporotrichosis cutaneous lesions in cases in which the aetiological agent is not visible., (© 2012 The Authors. BJD © 2012 British Association of Dermatologists.)

Sporotrichosis is endemic in Rio de Janeiro, Brazil, and cases have been reported to be associated with HIV. This article describes the clinical manifestations and evolution of sporotrichosis in HIV-positive patients and constitutes the largest case series reported to date. There were 21 HIV-positive patients with sporotrichosis diagnosed by the recovery of the etiologic agent from 1999-2009. Sixteen patients (76.2%) were men and five (23.8%) were women, with a mean age of 41.2 years. Seven of these individuals were previously unaware of their HIV infection. Mean CD4 count was 346.4 cells/μl. The most frequent clinical presentations of sporotrichosis in these patients were the lymphocutaneous and disseminated form (seven patients each, 33.3%), followed by the widespread cutaneous form in five (23.8%), and fixed form in the remaining two (9.5%). In patients with the disseminated forms, clinical manifestations involved the skin in six, mucosa (nasal, oral, or conjunctival) in four, bone in two, and meninges in two. Eleven (52.4%) patients received itraconazole and eight (38.1%) amphotericin B contributing to an overall cure rate of 81%. Spontaneous cure was observed in one patient. The clinical forms of sporotrichosis varied according to the patients' immune status. The results demonstrate the importance of sporotrichosis as an opportunistic infection associated with AIDS in countries where the mycosis occurs.

Sporotrichosis has significantly increased in Brazil in the last decade, particularly in the state of Rio de Janeiro, with the occurrence of an epidemic related to zoonotic transmission from cats to humans. Recently, four new phylogenetic species were incorporated into the Sporothrix species complex based on the phenotypic and molecular characteristics, and a new species name (Sporothrix brasiliensis) was proposed for some of the Sporothrix isolates from this epidemic. This study describes the characterization of 246 isolates obtained from patients attending the Laboratory of Infectious Dermatology, IPEC-FIOCRUZ, between 1998 and 2008, together with one environmental sample. Two hundred and six of the isolates (83.4%) were characterized as S. brasiliensis, 15 (6.0%) as S. schenckii, and one (0.5%) as S. mexicana. Twenty-five isolates (10.1%) could not be identified according to their phenotype and were classified as Sporothrix spp. The calmodulin gene was sequenced to confirm the identity of these isolates. The molecular analysis demonstrated that 24 of the isolates were S. brasiliensis, with the remainder being a S. globosa isolate. The isolate characterized phenotypically as S. mexicana was clustered on the S. schenckii clade. The correlation between molecular data and phenotypic characteristics described in this study is fundamental to the identification of the Sporothrix complex.

Unlabelled: Itraconazole is currently used for the treatment of cutaneous sporotrichosis. Terbinafine at a daily dose of 250 mg has been successfully applied to the treatment of cutaneous sporotrichosis., Objective: To compare the efficacy of 250 mg/day terbinafine and 100 mg/day itraconazole for the treatment of cutaneous sporotrichosis., Materials and Methods: A bidirectional cohort study was conducted on 55 patients receiving 250 mg/day terbinafine and 249 patients receiving 100 mg/day itraconazole. The latter patients were matched for age and clinical form to the terbinafine group at a ratio of 5:1. Sporothrix schenckii was isolated by culture from all patients (age range: 18-70 years), who were submitted to the standard care protocol consisting of clinical and laboratory evaluation and periodic visits., Results: Cure was observed in 51 (92.7%) patients of the terbinafine group and 229 (92%) of the itraconazole group within a similar mean period of time (11.5 and 11.8 weeks, respectively). An increase in the terbinafine dose to 500 mg was necessary in two patients due to the lack of a response, and one patient presented recurrence. In the itraconazole group, two patients required a dose increase and three presented recurrence. Adverse events were equally frequent among patients receiving terbinafine (n = 4, 7.3%) and itraconazole (n = 19, 7.6%) and were generally mild without the need for drug discontinuation, except for two patients of the itraconazole group., Conclusion: Terbinafine administered at a daily dose of 250 mg is an effective and well-tolerated option for the treatment of cutaneous sporotrichosis.

Background: Sporotrichosis is the most common subcutaneous mycosis in Rio de Janeiro. Histopathological examination reveals diffuse granulomatous and suppurative dermatitis, and the fungus is rarely identifiable in tissue. We describe the histopathological features of cutaneous sporotrichosis, and investigate the association between them and the lack of visualization of the fungus., Methods: A total of 119 samples of confirmed sporotrichosis cases were studied. The characteristics of the inflammatory infiltrate, the presence of epidermal changes, necrosis and fibrosis, and the parasite burden were analyzed. The association between histopathological changes and the lack of visualization of the fungus was evaluated using prevalence ratios., Results: Granulomas were observed in all samples, suppurative granulomas in 100 (84%) and diffuse dermatitis in 114 (95.8%). Liquefaction and caseous necrosis were present in 78 (65.5%) and 52 (43.7%) samples, respectively. The fungus was not seen in 77 (64.7%) samples. Epithelioid, tuberculoid or foreign-body-type granulomas, caseous, fibrinoid or absent necrosis, predominance of lymphocytes among nonphagocytic cells and fibrosis were associated with the lack of visualization of the fungus., Conclusion: The histopathological characteristics of sporotrichosis were variable when the causative fungus was not seen. In a proper context, the diagnosis of sporotrichosis remains a potential consideration even in the absence of demonstrable yeast., (Copyright © 2010 John Wiley & Sons A/S.)

Sporotrichosis is a fungal disease usually restricted to the cutaneous and lymphatic systems. Visceral involvement is unusual. To date, only 21 cases of sporotrichosis meningitis have been reported, some of these associated with immunosuppression. According to the reported cases, difficulty establishing the correct diagnosis is almost the rule which, undoubtedly, is associated with a worse prognosis. In this report, two HIV infected patients are described who developed meningitis due to Sporothrix schenckii associated with immune reconstitution inflammatory syndrome. This is the first report of sporotrichosis meningitis associated with immune reconstitution inflammatory syndrome in AIDS patients.

This report describes the first isolation of Sporothrix globosa from a Brazilian patient. A 77-year-old woman was examined for sporotrichosis infection. Histopathological examination of skin biopsy revealed chronic granulomatous infiltrate with microabcess. Furthermore, S. schenckii-like yeasts were evident as demonstrated by PAS and Grocott stains. The fungus was identified based on colony morphology on Sabouraud Dextrose Agar slants, Potato Dextrose Agar, and Corn Meal Agar, microscopic morphology on slides cultures, and assimilation of different carbon sources. The species confirmation was made by molecular methodology.

Background: There are a few studies on the treatment of sporotrichosis. The standard drug used is itraconazole. However, the use of itraconazole is limited by its interaction with other drugs., Objective: To evaluate the effectiveness and safety of 250 mg terbinafine for the treatment of cutaneous sporotrichosis in patients in whom itraconazole use is not possible., Methods: We performed a descriptive study of cutaneous sporotrichosis cases treated with 250 mg terbinafine for which itraconazole was contraindicated or resulted in severe or moderate pharmacological interactions. Sporotrichosis was diagnosed based on the isolation of S. schenckii., Results: Fifty patients seen between July 2005 and September 2007 were included. Forty-five (92%) patients reported contact with a sick cat and 47 (94%) presented comorbidities (high blood pressure: 64.0%; diabetes mellitus: 30.0%; dyslipidemia: 16.7%; depression: 10.0%; migraine: 2.1%; Parkinsonís disease: 2.1%; peptic ulcer disease: 2.1%; heart failure: 2.1%, and arrhythmia: 2.1%). All patients used some medication interacting with itraconazole (psycholeptics: 36.0%; antidiabetic agents: 28.0%; hypolipemiant agents: 18.0%; calcium-channel blockers: 16.0%; anticonvulsants: 8.0%; cardiotropic drugs: 6.3%; antacids: 6.3%, and antiparkinsonian agent: 2.1%). Most patients (96%) were cured within a mean period of 14 weeks. The drug was discontinued due to a skin rash in one patient. There were no cases of recurrence of the mycosis within a mean follow-up period of 37 weeks., Conclusions: This study suggests that 250 mg/day terbinafine is an effective and well-tolerated alternative to drug therapy of cutaneous sporotrichosis in a population in which itraconazole use is not possible.

An epidemic of sporotrichosis, a subcutaneous mycosis caused by the fungus Sporothrix schenckii, is ongoing in Rio de Janeiro, Brazil, in which cases of human infection are related to exposure to cats. In an attempt to demonstrate the zoonotic character of this epidemic using molecular methodology, we characterised by DNA-based typing methods 19 human and 25 animal S. schenckii isolates from the epidemic, as well as two control strains. To analyse the isolates, the random amplified polymorphic DNA (RAPD) technique was performed using three different primers, together with DNA fingerprinting using the minisatellite derived from the wild-type phage M13 core-sequence. The analyses generated amplicons with considerable polymorphism. Although isolates exhibited high levels of genetic relatedness, they could be clustered into 5-10 genotypes. The RAPD profiles of epidemic S. schenckii isolates could be distinguished from that of the United States isolate, displaying 20% similarity to each primer and 60% when amplified with the M13 primer. DNA fingerprinting of S. schenckii isolated from the nails (42.8%) and the oral cavities (66%) of cats were identical to related human samples, suggesting that there is a common infection source for animals and humans in this epidemic. It is clear that cats act as a vehicle for dissemination of S. schenckii.

Since 1998 a cat-transmitted epidemic of sporotrichosis has been observed in Rio de Janeiro (RJ), Brazil. Besides the lymphocutaneous and fixed forms, other presentations, such as disseminated cutaneous and mucosal involvement, as well as for the first time, erythema nodosum and erythema multiforme have been reported associated with sporotrichosis. This study investigates the phenotypes and genotypes of Sporothrix schenckii isolates recovered from different clinical forms of the disease noted as part of this epidemic. A total of 88 isolates recovered from 59 cases associated with the epidemic and 29 controls (from cases in other Brazilian regions and Spain) were included in this study. In vitro susceptibility testing was conducted as part of the phenotypic analysis, while the genotypic analysis involved a DNA fingerprinting method with primer M13 and ribosomal DNA sequencing of the internal transcribed spacer (ITS). MIC values of amphotericin B, itraconazole, posaconazole, ravuconazole, and terbinafine were found to be significantly lower (P<0.01) for isolates associated with the epidemic than for control strains. No differences in MIC values were observed related to clinical forms of the infection. Fingerprinting analysis showed that RJ epidemic strains were genetically related. Although nine subtypes were found, they were not associated with specific clinical forms. Similar results were obtained with the ITS sequence analysis. These data suggest that the strains isolated from the epidemic cases of sporotrichosis in RJ all originated from a common source.