Dayvison Francis Saraiva Freitas

Zoonotic Sporotrichosis in Rio de Janeiro, Brazil: A Protracted Epidemic yet to Be Curbed

514 used in 184 (23%) patients. Amphotericin B was very seldom used (6 patients). Al- most 2% of clinically cured patients had clinical relapses (reemergence of their le- sions), whereas 11% ( ) of the pa- n p 90 tients did not need to be treated, because of spontaneous cure. Patients were fol- lowed from 3-6 months after the end of therapy. Nine percent of the patients were lost to follow-up. Six patients were hos- pitalized, with 2 deaths. Irrespective of the drug regimens, 89% of the cases were cured. It is still not certain how the infectious agent has been disseminated throughout the Rio de Janeiro municipality and its outskirts, but it is beyond reasonable doubt that the close interaction with cats represents a key form of transmission of the fungus. Felines have very close contact with contaminated soil and organic matter and constitute a reservoir of this agent (4, 5). An improper destination given to ill or dead cats was mentioned by 71% of their current/former owners (most cats were just abandoned or died without receiving a proper burial or cremation). Such non- hygienic practices most likely foster the sustained dissemination of the mycosis, contributing to its current epidemic (en route to endemization?) status, which has yet to be curbed in Rio de Janeiros met- ropolitan area.

Sporotrichosis in Rio de Janeiro, Brazil: Sporothrix brasiliensis is associated with atypical clinical presentations.

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: an emerging neglected opportunistic infection in HIV-infected patients in Rio de Janeiro, Brazil.

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.

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.

Sporotrichosis in the Central Nervous System caused by Sporothrix brasiliensis

TO THE EDITOR—The metropolitan region of Rio de Janeiro is hyperendemic for catassociated sporotrichosis, and Sporothrix brasiliensis has been implicated in the majority of cases in this region. A unique clinical profile has been characterized by disseminated cases in nonimmunosuppressed patients, hypersensitivity reactions, and an increase in the number of patients with human immunodeficiency virus (HIV), with a higher incidence of severe disseminated cases, hospitalizations, and deaths [1, 2]. From January 1999 through March 2013, 3618 adult patients were diagnosed with sporotrichosis at the Instituto Nacional de Infectologia Evandro Chagas/ Fundação Oswaldo Cruz, the main referral center for the treatment of this mycosis in Rio de Janeiro State. Among these patients, 48 were coinfected with HIV, and the disseminated or disseminated cutaneous forms were present in the majority of these patients (58.3%), in contrast with the localized forms (lymphocutaneous or fixed cutaneous [41.7%]) [2]. The first patient with sporotrichosis and HIV coinfection had meningitis; since that first diagnosis, all patients with disseminated sporotrichosis have undergone a lumbar puncture to exclude central nervous system (CNS) invasion. Furthermore, the remaining 3 patients had fungus present in the cerebrospinal fluid (CSF). All but 1 patient was male, and the median CD4 cell count was 104/μL. Sporothrix brasiliensis was identified using T3B polymerase chain reaction fingerprinting [3]. Patients had skin lesions and developed subacute meningoencephalitis during the infection. Two patients died due to hydrocephalus complications. One patient presented with Cryptococcus neoformans coinfection of the CNS and died of complications that were not related to sporotrichosis. The first diagnosed patient is still alive 16 years after the onset of sporotrichosis. Three of these cases have been previously reported [4, 5]. CNS involvement in sporotrichosis, although rare, has been previously described in immunosuppressed patients, particularly within recent decades due to the HIV pandemic. When we analyzed this cohort of HIV-infected sporotrichosis patients, we found a considerable number of patients with disseminated forms of the disease, in whom S. brasiliensis was found in the CSF (14.3%). In a murine model, S. brasiliensis was the most virulent member of the Sporothrix schenckii complex, with dissemination to different organs including the CNS [6]. Sporothrix brasiliensis produces large amounts of urease and melanin, which are virulence factors that can promote penetration into tissues and evasion from the immune system [7]. We propose that S. brasiliensis, similar to what has been observed in C. neoformans infection, is neurotropic in humans, although the mechanisms implicated in CNS invasion and persistence are not yet completely understood [8, 9]. These findings highlight the potential aggressiveness of S. brasiliensis in immunosuppressed patients, particularly patients with HIV and advanced disease. CNS involvement is challenging to treat and is associated with a worse prognosis because its sterilization is difficult. In areas where HIV and sporotrichosis overlap, physicians should be aware of this potentially disastrous association and should perform an early lumbar puncture to aggressively treat CNS disease. Close follow-up of patients is necessary in order to document CSF sterilization, and alternative treatment strategies, such as novel azoles and combination therapy, may be considered.

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.

Pregnancy during a sporotrichosis epidemic in Rio de Janeiro, Brazil

Sporotrichosis is a subacute or chronic disease that affects animals and humans. It is caused by the dimorphic fungus Sporothrix schenckii and is the primary subcutaneous mycosis in Latin America [1,2]. Zoonotic transmission of sporotrichosis appears to be rare worldwide. An epidemic of sporotrichosis occurred in Rio de Janeiro, Brazil, from 1998 onward. Cats were found to be the main link in the epidemiological chain [1]. From 2005 through 2010, about 1000 patients were diagnosed with sporotrichosis at IPEC–Fiocruz, including 12 pregnant women. The mean age of the 12 patients was 28.3 years (range, 18–40 years). Two clinical forms of the infection, lymphocutaneous sporotrichosis (10 cases) and fixed sporotrichosis (2 cases), were recorded. Fungal culture was positive in all cases (Fig. 1). The patients underwent monthly outpatient assessments and the time of evolution ranged from 4–12 weeks. The upper limbs were the most commonly affected body area and cat scratch or bites were cited in 11 cases, suggesting that the lesions were the putative means of transmission of the fungus. All patients were instructed to perform thermotherapy with warm compresses 3 times a day. Eight patients were cured with thermotherapy, 2 patients had to use itraconazole after delivery, and 2 patients were lost to follow up. The causative fungus can be found in decaying vegetation, soil, moss, and wood and can infect a diversity of animals. The usual mode of transmission is traumatic cutaneous inoculation of the

Sweet syndrome associated with sporotrichosis

MADAM, Sweet syndrome (SS) is characterized by fever, acute onset of painful erythematous papules, plaques or nodules, peripheral neutrophil leucocytosis, and histological findings of a dense neutrophilic infiltrate without evidence of primary vasculitis. It usually affects middle-aged women and has been associated with infection and an underlying disease. Regarding fungal infections, SS has been described in coccidioidomycosis. Here we report three cases of SS in patients with sporotrichosis. Diagnosis of sporotrichosis was based on isolation in culture of Sporothrix schenckii from the initial lesion and diagnosis of SS was based on clinical and histopathological findings. The first patient was a 47-year-old woman with a cutaneous ulcerated lesion on her right thigh followed by fever, osteoarticular pain, and disseminated cutaneous plaque lesions (Fig. 1). She reported the absence of local trauma and had not taken any medication before the diagnosis. She also reported that she took care of a diseased cat. Her white blood cell count reached 20Æ3 · 10 L and culture of the ulcerated lesion evidenced S. schenckii. She improved after 8 weeks of itraconazole 100 mg daily and 2 weeks of oral prednisone. The second patient was a 47-year-old woman with an ulcerated lesion on the knee and disseminated cutaneous erythematous plaques. She remembered taking diclofenac-cholestyramine for back pain for 5 days prior to the appearance of the lesions, and denied any contact with cats. Her white blood cell count was 11Æ0 · 10 L. Culture of her ulcerated lesion showed S. schenckii. She improved after 12 weeks of itraconazole 100 mg daily and 8 weeks of oral prednisone. The third patient was a 78-year-old woman who had a knee injury 40 days before the onset of diffuse pruriginous cutaneous papules and plaques. She also had fever and headache. She had contact with a diseased cat at home but reported no injuries caused by the animal. She had systemic arterial hypertension that was under control with the use of hydrochlorothiazide and enalapril. Her white blood cell count was 7Æ9 · 10 L and S. schenckii was isolated from ulcerated knee lesion. The patient improved after 8 weeks of itraconazole 100 mg daily and a 1-week course of oral potassium diclofenac and oral dexchlorpheniramine. Histopathological findings of one erythematous plaque from each patient were very similar (Fig. 2). There was marked oedema of the papillary dermis mimicking a subepidermal vesiculation. The underlying upper dermis contained an intense perivascular and interstitial infiltrate of neutrophils with leukocytoclasis and macrophages, some with epithelioid differentiation. In patients 1 and 2 there were dilated vessels and extravasated red blood cells while in patients 1 and 3 focal spongiosis with small spongiotic vesicles was seen. A few eosinophils were seen in patient 2. Sporotrichosis is a subcutaneous infection caused by the dimorphic fungus S. schenckii. Hypersensitivity reactions such as erythema nodosum and erythema multiforme have been described in cat-transmitted endemic sporotrichosis in Rio de Janeiro. The patients presented here were from an endemic area of sporotrichosis and two had contact with cats. They presented localized forms of sporotrichosis and developed clinical and histopathological characteristics of SS. Patient 1 had no other factor that could explain the onset of the SS. The drugs used by patients 2 and 3 are not known to be associated with SS. In all cases, patients were successfully treated for the mycosis and for the SS. BJD British Journal of Dermatology

Epidemiological Aspects of Sporotrichosis Epidemic in Brazil

Generally, in Brazil, the transmission of sporotrichosis is by traumatic inoculation of fungi with the handling of organic matter. However, since the late 1990s, sporotrichosis in the great metropolitan area of Rio de Janeiro has become an urban endemic/epidemic zoonotic phenomenon, with transmission from infected cats to humans. Middle-aged housewives are the most affected population, particularly from deprived social strata. With the consolidation of the epidemic, vulnerable groups have been affected and the most striking group is people with HIV infection because of the superimposed burdens of both infections. Other states in Brazil have also presented zoonotic cases, however, with smaller dimensions. Sporothrix brasiliensis is the primary species involved in this hyperendemic. We believe that the combination of susceptible hosts, a virulent infecting species, and the absence of an effective public health structure are some of the possible associated factors that resulted in this catastrophe.

Review of 21 cases of mycetoma from 1991 to 2014 in Rio de Janeiro, Brazil

Mycetoma is caused by the subcutaneous inoculation of filamentous fungi or aerobic filamentous bacteria that form grains in the tissue. The purpose of this study is to describe the epidemiologic, clinic, laboratory, and therapeutic characteristics of patients with mycetoma at the Oswaldo Cruz Foundation in Rio de Janeiro, Brazil, between 1991 and 2014. Twenty-one cases of mycetoma were included in the study. There was a predominance of male patients (1.3:1) and the average patient age was 46 years. The majority of the cases were from the Southeast region of Brazil and the feet were the most affected anatomical region (80.95%). Eumycetoma prevailed over actinomycetoma (61.9% and 38.1% respectively). Eumycetoma patients had positive cultures in 8 of 13 cases, with isolation of Scedosporium apiospermum species complex (n = 3), Madurella mycetomatis (n = 2) and Acremonium spp. (n = 1). Two cases presented sterile mycelium and five were negative. Six of 8 actinomycetoma cases had cultures that were identified as Nocardia spp. (n = 3), Nocardia brasiliensis (n = 2), and Nocardia asteroides (n = 1). Imaging tests were performed on all but one patients, and bone destruction was identified in 9 cases (42.68%). All eumycetoma cases were treated with itraconazole monotherapy or combined with fluconazole, terbinafine, or amphotericin B. Actinomycetoma cases were treated with sulfamethoxazole plus trimethoprim or combined with cycles of amikacin sulphate. Surgical procedures were performed in 9 (69.2%) eumycetoma and in 3 (37.5%) actinomycetoma cases, with one amputation case in each group. Clinical cure occurred in 11 cases (7 for eumycetoma and 4 for actinomycetoma), and recurrence was documented in 4 of 21 cases. No deaths were recorded during the study. Despite of the scarcity of mycetoma in our institution the cases presented reflect the wide clinical spectrum and difficulties to take care of this neglected disease.