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.

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.

A case of sporotrichosis caused by different Sporothrix brasiliensis strains: mycological, molecular, and virulence analyses

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.

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.

Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis

BACKGROUND Sporothrix brasiliensis is the most virulent sporotrichosis agent. This species usually responds to antifungal drugs, but therapeutic failure can occur in some patients. Antifungal susceptibility tests have been performed on this species, but no clinical breakpoints (CBPs) are available. In this situation, minimal inhibitory concentration (MIC) distributions and epidemiological cutoff values (ECVs) support the detection of identification of resistant strains. OBJECTIVES To study the MIC distributions of five antifungal drugs against S. brasiliensis and to propose tentative ECVs. METHODS MICs of amphotericin B (AMB), itraconazole (ITR), ketoconazole (KET), posaconazole (POS), and terbinafine (TRB) against 335 S. brasiliensis strains were determined by the Clinical and Laboratory Standards Institute broth microdilution method. FINDINGS The proposed ECV, in µg/mL, for AMB, ITR, KET, POS, and TRB were 4.0, 2.0, 1.0, 2.0, and 0.25, respectively. Percentages of wild-type strains in our population for the above antifungal drugs were 98.48, 95.22, 95.33, 100, and 97.67%, respectively. MAIN CONCLUSIONS These ECVs will be useful to detect strains with resistance, to define CBPs, and to elaborate specific therapeutic guidelines for S. brasiliensis. Rational use of antifungals is strongly recommended to avoid the emergence of resistant strains and ensure the therapeutic effectiveness of sporotrichosis.

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.

Eumycetoma by Madurella mycetomatis with 30 years of evolution: therapeutic challenge / Eumicetoma por Madurella mycetomatis com 30 anos de evolução: desafio terapêutico

We report a case of eumycetoma by Madurella mycetomatis on the buttocks and thighs in an adult immunocompetent patient, diagnosed after 30 years of clinical development. He was treated over four years with fluconazol and itraconazol associated with five times surgical excisions of subcutaneous nodules. At the eighth year of follow-up, one nodule recurred on the right infragluteal region, which was excised surgically and has remained asymptomatic ever since.

Relatamos o caso de um paciente adulto, imunocompetente, com eumicetoma por Madurella mycetomatis, localizado nos glúteos e coxas, diagnosticado após 30 anos de evolução clínica. Tratado no decorrer de quatro anos com fluconazol e itraconazol, associado a cinco tempos cirúrgicos de exérese dos nódulos subcutâneos. No oitavo ano de follow-up ocorreu recidiva de apenas um nódulo na região infraglútea, o qual foi excisado cirurgicamente, mantendo-se assintomático desde então.

Use of the bilobed flap in the pubic region after tumoral lesion excision / Utilizacao do retalho bilobado na regiao pubiana apos exerese de lesao tumoral

Reconstruction of surgical defects in the pubic region is a challenge to any surgeon. Our goal was to demonstrate the use of the bilobed flap to reconstruct the pubic region skin after the excision of a recurrent HPV lesion, resistant to conventional treatments. In spite of its classical use in nasal reconstructions, the bilobed flap has applications in extranasal defects, with excellent functional and aesthetic results.

A reconstrução de defeitos cirúrgicos na região pubiana é um desafio para qualquer cirurgião. Objetivamos demonstrar a aplicação do retalho bilobado na reconstrução da região pubiana, após excisão de HPV recidivante aos tratamentos convencionais. Apesar da utilização clássica deste retalho ser na região nasal, aplicações em áreas distintas também se mostraram com excelentes resultados funcionais e estéticos.

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.

Immunohistochemical detection of the latent nuclear antigen-1 of the human herpesvirus type 8 to differentiate cutaneous epidemic Kaposi sarcoma and its histological simulators / Detecção imuno-histoquímica do antígeno nuclear latente-1 do herpesvirus tipo 8 para diferenciar o sarcoma de Kaposi epidêmico cutâneo de seus simuladores histológicos

Kaposi's sarcoma is the most common neoplasia diagnosed in AIDS patients and the expression of the human herpesvirus-8 (HHV-8) latent nuclear antigen-1 has been useful for its histological diagnosis. The aim of this study is to confirm that immunohistochemistry is a valuable tool for differentiating KS from its simulators in skin biopsies of HIV patients. Immunohistochemical and histological analyses were performed in 49 Kaposi's sarcoma skin biopsies and 60 of its histological simulators. Positivity was present in the 49 Kaposi's sarcoma skin biopsies and no staining was observed in the 60 simulators analyzed, resulting in sensibility and specificity of 100%. HHV-8 immunohistochemical detection is an effective tool for diagnosing Kaposi's sarcoma, especially in early lesions in which neoplastic features are not evident. It also contributes to its histological differential diagnosis.

O sarcoma de Kaposi é a neoplasia mais diagnosticada em pacientes com SIDA e a expressão do antígeno nuclear latente-1 do herpesvírus humano tipo-8 (HHV-8) tem se mostrado útil no seu diagnóstico histológico. O objetivo deste estudo é confirmar que o método imuno-histoquímico é uma ferramenta útil para diferenciar o sarcoma de Kaposi cutâneo de seus simuladores histológicos em pacientes HIV positivos. Análise histológica e imuno-histoquímica foram realizadas em 49 casos de sarcoma de Kaposi cutâneo e 60 casos de seus simuladores histológicos. Positividade à imuno-histoquímica para o antígeno nuclear latente 1 do HHV-8 foi observada nos 49 casos de sarcoma de Kaposi e nenhuma reação foi detectada nos 60 simuladores analisados, resultando em 100% de sensibilidade e especificidade. A detecção do HHV-8 por imuno-histoquímica é uma ferramenta útil para o diagnóstico de sarcoma de Kaposi, especialmente na lesão inicial cujo caráter neoplásico não é evidente, e contribui para seu diagnóstico diferencial histológico.

Esporotricose urbana: epidemia negligenciada no Rio de Janeiro, Brasil / Urban sporotrichosis: a neglected epidemic in Rio de Janeiro, Brazil

Na literatura científica, a esporotricose esteve associada por anos a profissionais que lidam com a terra, local onde o fungo causador habita. Recentemente, numa área urbana tem sido registrada a ocorrência relacionada à transmissão zoonótica. Este trabalho objetivou contribuir para o conhecimento sobre a esporotricose em área urbana, por intermédio da analise exploratória de sua distribuição socioespacial no Rio de Janeiro, Brasil, entre 1997 e 2007, identificando os espaços de transmissão mais intensos. Utilizando-se base de dados do Serviço de Vigilância em Saúde, Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, foram realizadas análises de frequência da doença e sua distribuição espacial. No período estudado, foram registrados 1.848 casos de esporotricose, com predomínio em mulheres adultas fora do mercado de trabalho. A fonte de contaminação predominante foi ferimento causado pelo gato doméstico, o que contribuiu para a disseminação da esporotricose em área urbana. O georreferenciamento de 1.681 casos evidenciou um cinturão de transmissão ao longo da divisa entre a capital e os municípios da região metropolitana.

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

Molecular characterisation of Sporothrix schenckii isolates from humans and cats involved in the sporotrichosis epidemic in Rio de Janeiro, Brazil

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

Cladophialophora carrionii: a rare agent of chromoblastomycosis in Rio de Janeiro State, Brazil / Cladophialophora carrionii: agente raro de cromoblastomicose no estado do Rio de Janeiro, Brasil

A 73 year-old male farm laborer from a rural area presented a 15 year history of extensive tumoral lesions over his left leg. Histological studies of skin biopsy showed pseudoepitheliomatous hyperplasia and granulomatous chronic inflammatory process with muriform cells, confirming chromoblastomycosis (CBM). Cladophialophora carrionii was isolated in culture. Treatment with itraconazole 400 mg/day for 12 months resulted in complete remission of lesions. As far we aware, this is the first case report of CBM caused by Cladophialophora carrionii in Rio de Janeiro State, Brazil.

Lavrador, com 73 anos, residente em área rural apresentava há 15 anos lesões tumorais disseminadas na perna esquerda. Exame histopatológico de biópsia de pele mostrou hiperplasia pseudo-epiteliomatosa e processo inflamatório crônico granulomatoso com células muriformes, confirmando o diagnóstico de cromoblastomicose (CBM). Cladophialophora carrionii foi isolado na cultura. Tratamento com itraconazol 400 mg/dia durante 12 meses resultou na completa remissão das lesões. Este é o primeiro relato de CBM causado por C. carrionii no estado do Rio de Janeiro, Brasil.

Criptococose associada à Aids: a importância do cultivo da urina no seu diagnóstico / Importance of culture of urine in the diagnosis of AIDS associated cryptococcosis

Neste estudo retrospectivo analisamos 70 pacientes HIV positivos com criptococose em um período de 16 anos. Os espécimes com melhor rendimento diagnóstico foram o LCR (97,8 por cento), seguido do cultivo do sedimento urinário (86,7 por cento) e sangue (58,8 por cento). Concluímos que a urina pode ser uma ferramenta útil para o diagnostico da criptococose.

Clinical characteristics and evolution of syphilis in 24 HIV+ individuals in Rio de Janeiro, Brazil

Foram tratados 24 indivíduos com sífilis e infecção pelo HIV, de Março de 1997 a Janeiro de 2003, no ambulatório de Dermatologia Infecciosa do Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brasil. Foram 20 homens (83,3%) e quatro mulheres (16,7%) com idade média de 38,04 anos e contagem média de linfócitos T CD4 de 389,5 céls/mm3. A sífilis foi classificada como secundária em 16 pacientes (62,5%), latente tardia em oito (33,3%) e terciária em uma paciente (4,2%). As manifestações de sífilis secundária foram de lesões cutâneas eritematopapulosas em regiões palmar e plantar em nove (37,5%), exantema papuloso em quatro (16,7%), alopecia em clareira em três (12,5%) e osteocondrite em um paciente (4,2%). A sífilis terciária apresentou-se como lesão verrucosa. Cinco pacientes (20,8%) apresentavam neurossífilis, sendo a cefaléia a única manifestação presente em dois pacientes. As drogas utilizadas foram penicilina benzatina, ceftriaxone, eritromicina e penicilina. A cura ocorreu em 18 pacientes (75%). Seis pacientes (25%) foram retratados, sendo que três apresentavam história de re-exposição. Este estudo confirmou a importância de se estabelecer o diagnóstico de neurossífilis em pacientes com infecção pelo HIV, assim como de se realizar seguimento clínico e laboratorial após o tratamento da sífilis.

Morbidity and survival in advanced AIDS in Rio de Janeiro, Brazil

Opportunistic diseases (OD) are the most common cause of death in AIDS patients. To access the incidence of OD and survival in advanced immunodeficiency, we included 79 patients with AIDS treated at Hospital Evandro Chagas (FIOCRUZ) from September 1997 to December 1999 with at least one CD4 count <=100 cells/mm³. The incidence of OD was analyzed by Poisson's regression, and survival by Kaplan Meier and Cox analysis, considering a retrospective (before CD4 <=100 cells/mm³) and a prospective (after CD4 <=100 cells/mm³) period, and controlling for demographic, clinical and laboratory characteristics. The confidence interval estipulated was 95 percent. Mean follow-up period was 733 days (CI = 683-782). During the study 9 (11.4 percent) patients died. Survival from AIDS diagnosis was a mean of 2589 days (CI = 2363-2816) and from the date of the CD4 count CD4 <=100 cells/mm³ was a mean of 1376 (CI = 1181-1572) days. Incidence of OD was 0.51 pp/y before CD4 <= 100 cells/mm³ and 0.29 pp/y after CD4 <= 100 cells/mm³. A lower number of ODs before CD4 < 100 cells/mm³ was associated with lower incidence rates after CD4 <= 100 cells/mm³. AIDS diagnosis based on CD4+ counts <= 200 cells/mm³ was associated with lower incidence rates after CD4 <= 100 cells/mm³. Baseline CD4 counts above 50 cells/mm³ (HR = 0.13) and restoration of baseline CD4+ counts above 100 cells/mm³ (HR = 0.16) were associated with a lower risk of death. Controling both variables, only restoration of baseline counts was statistically significant (HR = 0.22, p = 0.04). We found a very low incidence of OD and long survival after CD4 < 100 cells/mm³. Survival was significantly associated with restoration of baseline CD4 counts above 100 cells/mm³

Adult T-cell leukemia/lymphoma associated with HTLV-1 infection in a Brazilian adolescent

We present the case of a 15-year-old patient infected with HTLV-1 who developed a cutaneous T-cell lymphoma, confirmed by histopathological and immunohistochemical examination, as well as clinically and hematologically confirmed leukemia. The patient died 3 months after initial presentation of the disease. The rarity of the disease in this age group justifies the present report

Sporotrichosis: an emergent zoonosis in Rio de Janeiro

During the period from 1987 to 1998, 13 cases of human sporotrichosis were recorded at the Research Center Evandro Chagas Hospital (CPqHEC) in Rio de Janeiro. Two of these patients related scratch by a sick cat. During the subsequent period from July 1998 to July 2000, 66 human, 117 cats and 7 dogs with sporotrichosis were diagnosed at the CPqHEC. Fifty-two humans (78.8 percent) reported contact with cats with sporotrichosis, and 31 (47 percent) of them reporting a history of a scratch or bite. This epidemic, unprecedented in the literature, involving cats, dogs and human beings may have started insidiously before 1998

Reativaçäo da infecçäo por Trypanosoma cruzi em paciente com síndrome de imunodeficiência adquirida / Reactivation of Trypanosoma cruzi ifection in a patient with acquired immunodeficiency syndrome

Uma paciente com síndrome de imunodeficiência adquirida (SIDA) e doença de Chagas, com xenodiagnóstico positivo, estava em uso prolongado de cetoconazol com o objetivo de suprimir a parasitemia e prevenir a reativaçäo da doença de Chagas. O cetoconazol foi suspenso inadvertidamente após 6 meses de uso. Um mês após, a paciente foi internada com febre, cefaléia, vomitos, taquicardia e hepatoesplenomegalia. Tanto o xenodiagnóstico como o exame de sangue a fresco demonstraram a presença de Trypanosoma cruzi. O tratamento com benzonidarol foi instituído, com supressäo da parasitemia. A paciente desenvolveu concomitantemente uma provável neurotoxopiasmose, evoluindo para o óbito em septcemia. A necropsia, näo foram encontrados parasitas