The present and future research agenda of sporotrichosis on the silver anniversary of zoonotic sporotrichosis in Rio de Janeiro, Brazil

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 and pregnancy: A 40-year single-center cohort study in the endemic area of Rio de Janeiro, Brazil.

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.

Sporotrichosis in Older Adults: A Cohort Study of 911 Patients from a Hyperendemic Area of Zoonotic Transmission in Rio de Janeiro, Brazil.

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.

Human sporotrichosis: recommendations from the Brazilian Society of Dermatology for the clinical, diagnostic and therapeutic management

Abstract 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. Conclusions: 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.

Paracoccidioidomycosis in people living with HIV/AIDS: A historical retrospective cohort study in a national reference center for infectious diseases, Rio de Janeiro, Brazil.

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.

In vitro activity of Schinus terebinthifolius extract and fractions against Sporothrix brasiliensis

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.

Neuroparacoccidioidomycosis: A 13-Year Cohort Study, Rio de Janeiro, Brazil.

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.

Ocular Sporotrichosis: 26 Cases with Bulbar Involvement in a Hyperendemic Area of Zoonotic Transmission.

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.

Hospitalizações e óbitos relacionados à esporotricose no Brasil (1992-2015) / Hospitalizations and deaths related to sporotrichosis in Brazil (1992-2015) / Hospitalizaciones y óbitos relacionados con la esporotricosis en Brasil (1992-2015)

Resumo: A esporotricose é uma micose subcutânea de distribuição global e, em geral, os pacientes são tratados ambulatorialmente. Desde 1998, observa-se aumento dos casos no Estado do Rio de Janeiro, Brasil, especialmente por transmissão zoonótica envolvendo gatos. Os pacientes coinfectados pelo vírus da imunodeficiência humana (HIV), muitas vezes, necessitam de hospitalizações e evoluem a óbito. Este estudo analisa e descreve dados de 1992 a 2015, provenientes de bancos de dados do Sistema Único de Saúde. No Brasil, ocorreram 782 hospitalizações e 65 óbitos. Em 6% das hospitalizações e 40% dos óbitos, havia coinfecção pelo HIV. No Rio de Janeiro, foram 250 hospitalizações e 36 óbitos, com aumento progressivo, ao longo do período. Destacaram-se, ainda, São Paulo e Goiás. Homens, não brancos, com baixa escolaridade evoluíram mais frequentemente a óbito. Conclui-se que a esporotricose está associada a hospitalizações e óbitos em todo o Brasil, com destaque para o Rio de Janeiro.

Abstract: 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.

Resumen: La esporotricosis es una micosis subcutánea de distribución global y, en general, los pacientes son tratados ambulatoriamente. Desde 1998, se observa un aumento de los casos en el estado de Río de Janeiro, Brasil, principalmente por transmisión zoonótica implicando gatos. Los pacientes coinfectados por el virus de la inmunodeficiencia humana (VIH), muchas veces, necesitan de hospitalizaciones y evolucionan a óbito. Este estudio analiza y describe datos de 1992 a 2015, provenientes de bancos de datos del Sistema Único de Salud (SUS). En Brasil, se produjeron 782 hospitalizaciones y 65 óbitos. En un 6% de las hospitalizaciones y 40% de los óbitos, había coinfección por el VIH. En Río de Janeiro, fueron 250 hospitalizaciones y 36 óbitos, con un aumento progresivo a lo largo del período. Se destacaron, incluso, São Paulo y Goiás. Hombres, no blancos, con baja escolaridad evolucionaron más frecuentemente a óbito. Se concluye que la esporotricosis está asociada a hospitalizaciones y óbitos en todo Brasil, destacando Río de Janeiro.

Cryosurgery for the treatment of cutaneous sporotrichosis in four pregnant women.

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.

Cutaneous tuberculosis and HIV infection at a referral centre in Rio de Janeiro, Brazil

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.

Hepatic Disease with Portal Hypertension and Acute Juvenile Paracoccidioidomycosis: A Report of Two Cases and Literature Review.

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.

Acute juvenile Paracoccidioidomycosis: A 9-year cohort study in the endemic area of Rio de Janeiro, Brazil.

BACKGROUND: Paracoccidioidomycosis (PCM) is a systemic mycosis caused by pathogenic dimorphic fungi of the genus Paracoccidioides. It is the most important systemic mycosis in Latin America and the leading cause of hospitalizations and death among them in Brazil. Acute PCM is less frequent but relevant because vulnerable young patients are affected and the severity is usually higher than that of the chronic type. METHODS: The authors performed a retrospective cohort study from 2001 to 2009 including acute juvenile PCM patients from a reference center in Rio de Janeiro, Brazil. Clinical, epidemiological, diagnostic, therapeutic, and prognostic data were reported. RESULTS: Twenty-nine patients were included. The average age was 23 years old and the male to female ratio was 1:1.07. All cases were referred from 3 of 9 existing health areas in the state of Rio de Janeiro, predominantly from urban areas (96.5%). Lymph nodes were the most affected organs (100%), followed by the skin and the spleen (31% each). Twenty-eight patients completed treatment (median 25 months) and progressed to clinical and serological cure; 1 death occurred. Twenty-four patients completed 48-month median follow-up. Four patients abandoned follow-up after the end of treatment. The most frequent sequela was low adrenal reserve. Paracoccidioides brasiliensis S1 was identified by partial sequencing of the arf and gp43 genes from 4 patients who presented a viable fungal culture. CONCLUSION: Acute juvenile PCM is a severe disease with a high rate of complications. There are few cohort clinical studies of acute PCM in the literature. More studies should be developed to promote improvement in patients' healthcare.

Acute dacryocystitis: another clinical manifestation of sporotrichosis.

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.