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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.)

Over the past two decades, zoonotic sporotrichosis transmitted by naturally infected cats has become hyperendemic in Rio de Janeiro, Brazil. Sporothrix brasiliensis is the main agent involved. However, there are other forms of transmission of sporotrichosis. The aim of this study was to evaluate and associate the epidemiological, clinical and therapeutic data and the susceptibility of Sporothrix spp. to antifungal drugs in 43 non-zoonotic sporotrichosis cases. Forty-three clinical strains of Sporothrix were identified by partial sequencing of the calmodulin gene. An antifungal susceptibility test of amphotericin B, terbinafine, itraconazole, posaconazole and isavuconazole was performed according to the broth microdilution method. Most patients were male (55.8%). Regarding the source of infection, 21 patients (48.8%) reported trauma involving plants and/or contact with soil. Sporothrix brasiliensis was the predominant species (n = 39), followed by S. globosa (n = 3) and S. schenckii (n = 1). Sporothrix brasiliensis was associated with all the sources of infection, reinforcing previous data showing the presence of this species in environmental sources, as well as with all the clinical forms, including severe cases. One clinical strain of Sporothrix brasiliensis was classified as a non-wild-type strain for amphotericin B and another for itraconazole. S. schenckii was classified as non-WT for all the antifungals tested. In this context, it is important to emphasize that non-zoonotic sporotrichosis still occurs in the state of Rio de Janeiro, with S. brasiliensis as the main etiological agent, primarily associated with infections acquired after traumatic inoculation with plants and/or soil contact, followed by S. globosa and S. schenckii . In addition, non-WT strains were found, indicating the need to monitor the antifungal susceptibility profile of these species. It is crucial to investigate other natural sources of S. brasiliensis to better understand this fungal pathogen and its environment and host cycle.

Zoonotic sporotrichosis, a subcutaneous mycosis caused by Sporothrix brasiliensis , has become hyperendemic and a serious public health issue in Brazil and an emerging disease throughout the world. Typical sporotrichosis is defined as fixed or lymphocutaneous lesion development, however, reports of atypical presentations have been described in hyperendemic areas, which may result in a worse prognosis. Thus, considering an increase in atypical cases and in more severe extracutaneous cases and hospitalizations reported in Brazil, we aimed to perform a systematic review to search for hypersensitivity reactions (HRs) and extracutaneous presentations associated with zoonotic sporotrichosis. A systematic review was performed, following the PRISMA guidelines to search for atypical/extracutaneous cases (mucosal, osteoarthritis, HRs, pulmonary, meningeal) of zoonotic sporotrichosis. A total of 791 published cases over 26 years (1998-2023) in eleven Brazilian states were reviewed. Most cases corresponded to a HR (47%; n = 370), followed by mucosal (32%; n = 256), multifocal (8%; n = 60), osteoarthritis (7%; n = 59), meningeal (4%; n = 32), and pulmonary (2%; n = 14) infections. When available (n = 607), the outcome was death in 7% (n = 43) of cases. Here, we show a frequent and worrisome scenario of zoonotic sporotrichosis in Brazil, with a high and dispersed incidence of atypical/extracutaneous cases throughout the Brazilian territory. Therefore, educational measures are necessary to make health professionals and the overall population aware of this fungal pathogen in Brazil as well as in other countries in the Americas.

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.

Paracoccidioidomycosis (PCM) is a neglected endemic mycosis in Latin America. Most cases occur in Brazil. It is classified as PCM infection and PCM disease and is subdivided into chronic (adult type) or acute (juvenile type) disease, with the latter being less frequent and more severe. In 2016, we reported an increase in the numbers of patients diagnosed with acute PCM after a highway's construction. We conducted a study at INI-Fiocruz, a reference center for infectious diseases, including endemic mycoses, in Rio de Janeiro, Brazil, aiming to deepen the analysis of this new clinical and epidemiological profile of PCM. The authors developed a retrospective study including 170 patients diagnosed with PCM between 2010 and 2019. There was an increase in the number of atypical and severe forms, starting in 2014. In subsequent years, we detected a higher incidence of adverse outcomes with patients requiring more hospitalizations and an increased mortality rate. We estimate that PCM has become more severe throughout the Rio de Janeiro state, affecting a greater number of young individuals and leading to a greater number of and longer hospitalizations. Surveillance measures and close monitoring of future notification data in the state, with emphasis on children, adolescents, and young adults are necessary for a better understanding of the perpetuation of this public health challenge.

In this study, samples of bromeliad Tillandsia usneoides (n = 70) were transplanted and exposed for 15 and 45 days in 35 outdoor residential areas in Brumadinho (Minas Gerais state, Brazil) after one of the most severe mining dam collapses in the world. Trace elements aluminum (Al), arsenic (As), chromium (Cr), copper (Cu), iron (Fe), mercury (Hg), manganese (Mn), nickel (Ni) and zinc (Zn) were quantified by atomic absorption spectrometry. Scanning electron microscope generated surface images of T. usneoides fragments and particulate matter (PM 2.5 , PM 10 and PM  > 10 ). Aluminum, Fe and Mn stood out from the other elements reflecting the regional geological background. Median concentrations in mg kg -1 increased (p < 0.05) between 15 and 45 days for Cr (0.75), Cu (1.23), Fe (474) and Mn (38.1), while Hg (0.18) was higher at 15 days. The exposed-to-control ratio revealed that As and Hg increased 18.1 and 9.4-fold, respectively, not showing a pattern associated only with the most impacted sites. The PM analysis points to a possible influence of the prevailing west wind on the increase of total particles, PM 2.5 and PM 10 in transplant sites located to the east. Brazilian public health dataset revealed increase in cases of some cardiovascular and respiratory diseases/symptoms in Brumadinho in the year of the dam collapse (1.38 cases per 1000 inhabitants), while Belo Horizonte capital and its metropolitan region recorded 0.97 and 0.37 cases, respectively. Although many studies have been carried out to assess the consequences of the tailings dam failure, until now atmospheric pollution had not yet been evaluated. Furthermore, based on our exploratory analysis of human health dataset, epidemiological studies are required to verify possible risk factors associated with the increase in hospital admissions in the study area., 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 © 2023 Elsevier Inc. All rights reserved.)

The occurrence of acute paracoccidioidomycosis (PCM) in urban areas of the Rio de Janeiro state, Brazil, has emerged in recent years. Therefore, young populations, including pregnant women, are at a higher risk of infection. Furthermore, young women undergoing itraconazole treatment for PCM have increased chances to get pregnant because this medication may reduce the effectiveness of contraceptives. Acute PCM is invasive, reaching abdominal organs, posing a maternal-fetal risk. PCM treatment in pregnant women is also challenging due to the teratogenicity associated with the currently available oral drugs. There are scarce studies on PCM and pregnancy, mainly consisting of case reports and experimental murine models that highlight the severity of this association. We conducted a database research at a PCM reference center in Rio de Janeiro state from 1980 to 2020. We included patients diagnosed with PCM who were pregnant shortly before, at admission, or at any moment of their PCM follow-up care. Data related to pregnancy, childbirth, and the newborn were obtained from the Brazilian official public databases. We also reviewed the epidemiological and clinical features of these patients. During the study period, we identified 18 pregnant patients, with a median age of 26 years (range: 16-38). Among these cases, six (33.3%) were detected in the last 5 years, and 14 (77.8%) presented acute PCM, supporting the recent shift in the epidemiological profile towards acute PCM. Most pregnancies occurred during PCM treatment (n = 11, 61.1%), which led to challenges in the therapeutic management. Maternal-fetal complications occurred in some of these cases, including vaginal bleeding (n = 1), preeclampsia (n = 1), prematurity (n = 2), low birth weight (n = 4), and fetal deaths (n = 2). PCM during pregnancy presents a significant public health concern in the context of the emergence of acute PCM in urban areas., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Benko 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.)

Generally, older people tend to suffer from more severe infections than younger adults. In addition, there are accumulations of comorbidities and immune senescence in some cases. This cohort study evaluated the clinical and epidemiological characteristics of older adults (≥60 years old) with sporotrichosis. The cohort consisted of 911 patients with a median age of 67 years, most of whom were female (72.6%), white (62.1%), and afflicted with comorbidities (64.5%). The lymphocutaneous form occurred in 62% of the patients, followed by the fixed form (25.7%), cutaneous disseminated form (8.9%), and extracutaneous/disseminated forms (3.3%). In this study, we draw attention to the frequency of osteoarticular involvement (2.1%) secondary to skin lesions such as osteomyelitis and/or tenosynovitis. A clinical cure was achieved in 87.3% of cases. Itraconazole was used in 81.1% of cases, while terbinafine was used in 22.7% of cases, usually in low doses. Survival analysis showed that the median treatment time was 119 days, and the multiple Cox model demonstrated that the presentation of a black coloration and diabetes was associated with a longer treatment time required to establish a cure. Therefore, these subgroups should be monitored more closely to reduce possible difficulties during treatment. It would be interesting to conduct more studies analyzing older adults with sporotrichosis from different geographic areas to better comprehend the disease in this group.

Proteomics provide a robust approach to profile and quantify proteins within cells, organs, or tissues, providing comprehensive insights about the dynamics of cellular processes, modifications, and interactions. Similarly, understanding the transcriptome is essential to decipher functional elements of the genome, unraveling the mechanisms of disease development and the molecular constituents of cells and tissues. Some thermodimorphic fungi of the genus Sporothrix cause sporotrichosis, a subcutaneous mycosis of worldwide relevance. The transcriptome and proteome of the main Sporothrix species of clinical interest can elucidate the mechanisms underlying pathogenesis and host interactions. Studies of these techniques can contribute to the advancement of novel diagnostic and therapeutic strategies. A literature review was carried out, addressing all articles based on proteomics using mass spectrometry and transcriptomics of Sporothrix spp. Twenty-one studies were eligible for this review. The main findings include proteins and genes involved in dimorphism, cell differentiation, thermotolerance, virulence, immune evasion, metabolism, cell adhesion, cell transport, and biosynthesis. With the spread and emergence of sporotrichosis in different countries, ongoing research efforts and new discoveries are welcome to advance knowledge about this mycosis and its agents.

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.)

Sporotrichosis is the main subcutaneous mycosis worldwide. Several complications, including meningeal forms, can be observed in immunocompromised individuals. The sporotrichosis diagnosis is time-consuming due to the culture's limitations. The low fungal burden in cerebrospinal fluid (CSF) samples is another important drawback in the diagnosis of meningeal sporotrichosis. Molecular and immunological tests can improve the detection of Sporothrix spp. in clinical specimens. Therefore, the following five non-culture-based methods were evaluated for the detection of Sporothrix spp. in 30 CSF samples: (i) species-specific polymerase chain reaction (PCR); (ii) nested PCR; (iii) quantitative PCR; (iv) enzyme-linked immunosorbent assay (ELISA) for IgG detection; and (v) ELISA for IgM detection. The species-specific PCR was unsuccessful in the diagnosis of the meningeal sporotrichosis. The other four methods presented substantial levels of sensitivity (78.6% to 92.9%) and specificity (75% to 100%) for the indirect detection of Sporothrix spp. Both DNA-based methods presented similar accuracy (84.6%). Both ELISA methods were concomitantly positive only for patients with sporotrichosis and clinical signs of meningitis. We suggest that these methods should be implemented in clinical practice to detect Sporothrix spp. in CSF early, which may optimize treatment, augment the chances of a cure, and improve the prognosis of affected individuals.

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.

Meningeal sporotrichosis is rare and occurs predominantly in immunosuppressed individuals. This retrospective study explored clinical and laboratory characteristics, treatment, and prognosis of patients with disseminated sporotrichosis who underwent lumbar puncture (LP) at a Brazilian reference center from 1999 to 2020. Kaplan-Meier and Cox regression models were used to estimate overall survival and hazard ratios. Among 57 enrolled patients, 17 had meningitis. Fifteen (88.2%) had HIV infection, and in 6 of them, neurological manifestations occurred because of the immune reconstitution inflammatory syndrome (IRIS). The most frequent symptom was headache (88.2%). Meningeal symptoms at first LP were absent in 7/17 (41.2%) patients. Sporothrix was diagnosed in cerebrospinal fluid either by culture or by polymerase chain reaction in seven and four patients, respectively. All but one patient received prolonged courses of amphotericin B formulations, and seven received posaconazole, but relapses were frequent. Lethality among patients with meningitis was 64.7%, with a higher chance of death compared to those without meningitis (HR = 3.87; IC95% = 1.23;12.17). Meningeal sporotrichosis occurs mostly in people with HIV and can be associated with IRIS. Screening LP is indicated in patients with disseminated disease despite the absence of neurological complaints. Meningitis is associated with poor prognosis, and better treatment strategies are needed.

Background: The increase in the zoonotic epidemic of sporotrichosis caused by Sporothrix brasiliensis, which started in the late 1990s in Rio de Janeiro and is now found in almost all Brazilian states, has been equally advancing in neighboring countries of Brazil. Changes in the clinical-epidemiological profile, advances in the laboratory diagnosis of the disease, and therapeutic difficulties have been observed throughout these almost 25 years of the epidemic, although there is no national consensus. The last international guideline dates from 2007., Objectives: Update the clinical classification, diagnostic methods and recommendations on the therapeutic management of patients with sporotrichosis., Methods: Twelve experts in human sporotrichosis were selected from different Brazilian regions, and divided into three work groups: clinical, diagnosis and treatment. The bibliographic research was carried out on the EBSCOHost platform. Meetings took place via electronic mail and remote/face-to-face and hybrid settings, resulting in a questionnaire which pointed out 13 divergences, resolved based on the opinion of the majority of the participants., Results: The clinical classification and laboratory diagnosis were updated. Therapeutic recommendations were made for the different clinical forms., Conclusion: Publication of the first national recommendation, carried out by the Brazilian Society of Dermatology, aimed at the Brazilian scientific community, especially dermatologists, infectologists, pediatricians, family medicine personnel, and laboratory professionals who work in the management of human sporotrichosis., (Copyright © 2022 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

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.)

A 47-year-old woman who lived in the metropolitan area of Rio de Janeiro and had abandoned her Acquired Immune Deficiency Syndrome (AIDS) therapy 3 years prior, was admitted to our hospital due to weight loss, cough, and fever for 2 weeks. The dermatologic examination established normochromic papules with molluscum-like central umbilication on the face (Figure 1) and hands, erythema and infiltration in the oral cavity (Figure 2), desquamative patches on the legs, and ulceration on right calcaneus (Figure 3). Her CD4 (T-cells) count was 47 cells/ mm. 3 Direct mycology examination and cultures for several agents were performed. The mycology culture done from her skin and sputum grew Sporothrix 1 week after admission (Figure 4).

Background: Sporothrix brasiliensis is the causative agent of zoonotic cases of sporotrichosis in Brazil and is associated with atypical and severe presentations in cats, dogs, and humans. Sporotrichosis treatment is usually time- and cost-consuming, sometimes with poor response and host toxicity. Schinus terebinthifolius has proven efficacy against bacteria and fungi of clinical interest., Objective: To determine the in vitro activity of S. terebinthifolius against S. brasiliensis., Methods: Five S. brasiliensis isolates and three reference strains were subjected to a hydroethanol extract derived from the leaves of S. terebinthifolius and its fractions. The minimal inhibitory concentration (MIC) was determined using the broth microdilution method according to the M38-A2 CLSI guidelines. Also, the fungicidal/fungistatic activity of the extract and fractions was studied., Findings: The crude extract of S. terebinthifolius inhibited the growth of S. brasiliensis (MIC: 0.5-1.0 µg/mL), while the partitioned extracts dichloromethane, ethyl acetate, and butanol demonstrated growth inhibition at 8 µg/mL due to a fungistatic activity., Main Conclusions: Due to its in vitro efficacy against S. brasiliensis and its known pharmacological safety, S. terebinthifolius is a candidate to be tested using in vivo models of sporotrichosis.

Paracoccidioidomycosis (PCM) is one of the main endemic systemic mycoses in Latin America, usually occurring in rural areas. When PCM occurs simultaneously with underlying immunosuppressive conditions, it can present as an opportunistic disease. Between 2000 and 2017, literature reported around 200 PCM cases in people living with HIV/AIDS (PLWHA). To address research gaps on this co-infection and to study its possible temporal changes in the last decade, we performed an active co-infection case search on the HIV/AIDS and PCM cohorts from a Brazilian reference center database from 1989 to 2019. We found 20 PLWHA among 684 PCM patients (2.92%), predominantly male (70.0%) and urban workers (80.0%). The median age of patients was higher in the 2010-2019 decade (p = 0.006). The occurrence of PCM in PLWHA was lower when compared with other fungal diseases. Although 50.0% of the patients had already been diagnosed with HIV infection and presented CD4+ T cell counts greater than 200/mm3 at the time of PCM diagnosis, the suspicion of immunosuppression in the context of atypical and more severe clinical forms of PCM revealed the diagnosis of HIV infection in 35.0% of the patients. Two (10.0%) patients had an evolution compatible with immune reconstitution inflammatory syndrome (IRIS) after starting antiretroviral therapy (ART).We highlight the importance of considering a PCM diagnosis in PLWHA to prevent a late-onset treatment and progression to severe manifestations and unfavorable outcomes. In addition, HIV investigation is recommended in PCM patients, especially those with atypical and more severe clinical presentations., Competing Interests: The authors have declared that no competing interests exist

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.)

Pulmonary sporotrichosis is a rare condition. It can present as a primary pulmonary disease, resulting from direct Sporothrix species (spp). conidia inhalation, or as part of multifocal sporotrichosis with multiple organ involvement, mainly in immunocompromised patients. This study aimed to describe the sociodemographic and epidemiological characteristics and clinical course of patients with positive cultures for Sporothrix spp. from pulmonary specimens (sputum and/or bronchoalveolar lavage) at a reference center in an area hyperendemic for zoonotic sporotrichosis. The clinical records of these patients were reviewed. Fourteen patients were included, and Sporothrix brasiliensis was identified in all cases. Disseminated sporotrichosis was the clinical presentation in 92.9% of cases, and primary pulmonary sporotrichosis accounted for 7.1%. Comorbidities included human immunodeficiency virus infection (78.6%), alcoholism (71.4%), and chronic obstructive pulmonary disease (14.3%). Treatment with amphotericin B followed by itraconazole was the preferred regimen and was prescribed in 92.9% of cases. Sporotrichosis-related death occurred in 42.9% while 35.7% of patients were cured. In five cases there was a probable contamination from upper airway lesions. Despite the significant increase in sporotrichosis cases, pulmonary sporotrichosis remains rare. The treatment of disseminated sporotrichosis is typically difficult. Prompt diagnosis and identification of all affected organs are crucial for better prognosis.

Although rare, disseminated sporotrichosis is increasing in several countries. Despite its limiting toxic potential, amphotericin B is the only intravenous antifungal available to treat severe sporotrichosis. We aimed to describe the effectiveness and safety of amphotericin B treatment for severe sporotrichosis. Clinical records of patients with disseminated sporotrichosis at a reference center were reviewed. This study included 73 patients. Most (53.4%) were men and non-white. HIV coinfection was the main comorbidity (52.1%). Most reported contact with cats (76.7%). Sporothrix brasiliensis was the causative species. Affected sites were skin (98.6%), osteoarticular system (64.4%), upper airway (42.5%), central nervous system (20.5%), eyes (12.3%), and lungs (8.2%). Median doses of amphotericin B used were 750 mg and 4500 mg for deoxycholate and lipid complex formulations, respectively. Amphotericin B discontinuation occurred in 20.5% due to adverse events, mainly azotemia. The outcomes included cure (52.1%), death due to sporotrichosis (21.9%), death due to other causes (9.6%), and loss to follow-up (8.2%). Survival analysis showed an association between cure and the absence of bone, upper airway, and central nervous system involvement. Amphotericin B is the first-choice treatment for disseminated sporotrichosis; however, the severity of systemic dissemination might predict its response. Favorable clinical results depend on prompt diagnosis, investigation of fungal dissemination, and early therapy initiation.

Sporotrichosis is a subacute/chronic subcutaneous mycosis. Since the late 1990s, there has been a hyperendemic zoonotic transmission in the state of Rio de Janeiro, involving Sporothrix brasiliensis , the most virulent causative species, and a "belt" was described along the limits between the capital and its outskirts ("Baixada Fluminense"). This study analyzes the distribution of sporotrichosis using secondary data from the Notifiable Diseases Information System (Sinan) of the Rio de Janeiro State Health Department (SES/RJ) from 2011 to 2015 and from the INI Electronic Patient Record System (Sipec) from 2008 to 2015. Cases diagnosed since the onset of the hyperendemic exceed all previously reported case series of the disease and there is a progressive expansion in the state of Rio de Janeiro. The study suggests the spread of the mycosis to all regions of the state and the expansion of the previously described "belt", despite public health measures and changes in its profile over the years, with great social impact.

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.)

Competing Interests: None disclosed.

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.

Neuroparacoccidioidomycosis (NPCM) is a rare and severe clinical presentation of paracoccidioidomycosis (PCM). We performed a retrospective cohort study at the Evandro Chagas National Institute of Infectious Diseases (INI/Fiocruz), a reference center for PCM in the state of Rio de Janeiro, Brazil. All cases of PCM admitted to the INI/Fiocruz from January 2007 to December 2019 were reviewed. Eight (3.9%) among 207 patients met the diagnostic criteria for NPCM. The mean age was 44.6 years and the male:female ratio was 7:1. All cases presented multifocal disease, 5 (62.5%) the chronic form and 3 (37.5%) the acute/subacute form. All patients presented the pseudotumoral pattern and 6 (75.0%) had multiple lesions in the cerebral hemispheres. Seizures and motor symptoms were the most frequent clinical manifestations (50.0%, each). The treatment of choice was sulfamethoxazole/trimethoprim (SMZ-TMP) and fluconazole, in association (87.5%). Most patients responded well to the treatment. Sequela and death occurred in one (12.5%) patient, each.

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

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 usually caused by the traumatic inoculation of pathogenic species of fungi of the genus Sporothrix. The most prevalent species in Brazil is Sporothrix brasiliensis, which is generally associated with transmission involving infected cats. Sporotrichosis is hyperendemic in the state of Rio de Janeiro and Duque de Caxias is one of the most affected municipalities., Methods: This was a cross-sectional, geo-epidemiological and socioeconomic study of human sporotrichosis in the municipality of Duque de Caxias using geoprocessing information for the construction of thematic maps., Results: Eight hundred and twenty-seven cases of sporotrichosis from Duque de Caxias were reported between 2007 and 2016, most of them in women from 25-59 years. The most affected areas had low per capita income and scarce supply of treated water. Human sporotrichosis expanded throughout the territory of the municipality over time., Conclusions: An increase in both the number of reported cases and their spatial distribution occurred throughout the studied decade. The concentration of the disease was more intense in areas with greater vulnerability of the population, expressed by low per capita income and deficient provision of basic sanitation services. Sporotrichosis requires measures to better control the disease in Duque de Caxias and in the state of Rio de Janeiro., (© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Brazil is one of the highest tuberculosis (TB) burden countries of the world. Cutaneous tuberculosis (CTB) is a rare form of extrapulmonary manifestation of tuberculosis. This study aimed to describe the clinico-evolutive, laboratory and therapeutic aspects of CTB cases among patients from a cohort with TB in Rio de Janeiro, Brazil., Methods: Cases of diagnosed CTB with microbiologic confirmation or clinical response to anti-tuberculous treatment associated with positive smear or histopathological findings between the years 2000 and 2016 were selected., Results: Seventy-five patients with CTB were included, most were women (58.7%) with a median age of 42 years. CTB diagnosis was based on culture in only 42.7% of the cases. Scrofuloderma represented 50.7% of the cases, followed by erythema induratum of Bazin (EIB) (18.7%), tuberculous gumma (13.3%), lupus vulgaris (8%), TB verrucosa cutis (4%), orificial TB (2.7%) and associated forms (2.7%). Other TB presentations were pulmonary (22.7%), mammary (6.6%) and osteoarticular (4%). All patients who completed the treatment (97.3%) had their lesions healed. Only two patients (2.6%) needed to change the therapy due to adverse reactions. Fifty percent of EIB patients presented recurrence., Conclusions: These data highlight the diversity of CTB presentations and the importance of the skin to assist in early identification and treatment of TB. More studies are necessary to improve the knowledge on EIB for a better approach towards these patients, mainly in cases of recurrence., (© 2019 The International Society of Dermatology.)

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: Cutaneous tuberculosis (CTB) is a rare extrapulmonary form of tuberculosis (TB). Despite the increase in the number of cases of TB and HIV, few cases of CTB have been reported., Objective: To describe CTB cases among patients with HIV infection from a cohort with tuberculosis., Methods: We describe a series of 15 CTB and HIV cases, based on secondary data from 2000 to 2016. Diagnosis was based on isolation of Mycobacterium tuberculosis in culture or clinical response to anti-tuberculous treatment associated with positive smear or histopathologic findings from affected skin or an adjacent lymph node., Findings: Scrofuloderma was present in 12 (80%) patients and solitary gumma in three (20%) patients. One case of scrofuloderma was associated with papulonecrotic tuberculid. Seven (46.6%) patients had pulmonary TB. Diagnosis was based on culture in nine patients (60%). The median CD4 cell count was 262 cells/µL. All patients were cured at the end of treatment (median time 6 months). Three patients presented with immune reconstitution inflammatory syndrome., Conclusions: In this study, CTB associated with HIV infection presented as localised forms or in association with pulmonary TB. In patients with HIV who have subacute and chronic skin lesions, CTB should be considered in differential diagnosis, which may represent a good opportunity for early diagnosis of active TB.

Background: Chromoblastomycosis (CBM) is a difficult-to-treat chronic subcutaneous mycosis. In Brazil, the main agent of this disease is Fonsecaea pedrosoi, which is phenotypically very similar to other Fonsecaea species, differing only genetically. The correct species identification is relevant since different species may differ in their epidemiologic aspects, clinical presentation, and treatment response., Methodology/principal Findings: Partial sequencing of the internal transcribed spacer (ITS) was used to identify twenty clinical isolates of Fonsecaea spp. Their in vitro antifungal susceptibility was determined using the broth microdilution method, according to the M38-A2 protocol. Amphotericin B (AMB), flucytosine (5FC), terbinafine (TRB), fluconazole (FLC), itraconazole (ITC), ketoconazole (KTC), posaconazole (POS), voriconazole (VRC), ravuconazole (RVC), caspofungin (CAS), and micafungin (MFG) were tested. The association between ITC/TRB, AMB/5FC, and ITC/CAS was studied by the checkerboard method to check synergism. The available patients' data were correlated with the obtained laboratory results. Fonsecaea monophora (n = 10), F. pedrosoi (n = 5), and F. nubica (n = 5) were identified as CBM' agents in the study. TRB and VRC were the drugs with the best in vitro activity with minimal inhibitory concentrations (MIC) lower than 0.25 mg/L. On the other hand, FLC, 5FC, AMB, and MFG showed high MICs. The AMB/5FC combination was synergistic for three F. monophora strains while the others were indifferent. Patients had moderate or severe CBM, and ITC therapy was not sufficient for complete cure in most of the cases, requiring adjuvant surgical approaches., Conclusions/significance: F. monophora, the second most frequent Fonsecaea species in South America, predominated in patients raised and born in Rio de Janeiro, Brazil, without cerebral involvement in these cases. TRB, VRC, and the AMB/5FC combination should be further investigated as a treatment option for CBM., Competing Interests: The authors have declared that no competing interests exist.

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.

Paracoccidioidomycosis (PCM) is a neglected systemic mycosis endemic to Latin America caused by dimorphic fungi of the genus Paracoccidioides. The acute juvenile PCM is a severe type of presentation that usually affects young vulnerable patients and rarely progresses to portal hypertension. Here, two cases of liver disease and portal hypertension as complications of acute juvenile PCM are reported. Diagnosis of PCM was performed by isolation of the fungus and molecular identification of the strains provided through partial sequencing of two protein encoding genes, arf and gp43. Genotypic analysis revealed that Paracoccidioides brasiliensis S1 was the phylogenic species involved in both cases. Patients presented a good clinical response to amphotericin B and sulfamethoxazole-trimethoprim. These results highlight the importance of the interdisciplinary approach in patients with severe forms of PCM to avoid and treat complications, and the necessity of further investigations focusing on host-pathogen interaction in order to explain the broad clinical spectrum in PCM as well as the severity and poor outcome in some clinical cases.