Paciente infectado com paracoccidioidomicose adquirida em ambiente urbano: relato de caso / Patient infected with paracoccidioidomycosis acquired in urban environment: case report / Paciente infectado con paracoccidioidomicosis adquirida en ambiente urbano: reporte de caso

Introdução: A paracoccidioidomicose é uma doença fúngica e sistêmica frequente no Brasil, presente, principalmente, entre trabalhadores das zonas rurais. Na maioria dos casos, o contágio ocorre pela inalação de esporos e a infecção primária regride de maneira espontânea, podendo haver recidiva da doença por conta da reativação de focos fúngicos latentes ou nova exposição. Objetivo: Relatar o caso de uma paciente com paracoccidioidomicose de forma crônica como forma de mostrar a importância do diagnóstico e tratamento no prognóstico. Resultado: Paciente do sexo feminino, vinte e seis anos, apresentou lesões cutâneas indolores em face e pescoço, com aspecto irregular, eritematoso, com fundo granuloso e secretivo purulento 4 meses antes da internação hospitalar que foram tratadas com antimicrobianos e corticoide tópico, além de estado febril e astenia cerca de uma semana antes da hospitalização. Ficou internada por 19 dias e durante esse período administrou-se anfotericina B, bem como, loratadina, dipirona e ondansetrona. Conclusão: O diagnóstico é fundamental para instalação do tratamento e, consequente, prognóstico, e apesar de haver um vasto arsenal terapêutico contra esta afecção, o tratamento é longo, podendo chegar até 18 meses, e, em seguida, o paciente, rotineiramente, deve ser reavaliado por critérios de cura, como clínicos, imunológicos e radiológicos.(AU)

Introduction: Paracoccidioidomycosis is a fungal and systemic disease common in Brazil, present mainly among workers in rural areas. In most cases, contagion occurs by inhaling spores and the primary infection regresses spontaneously, and the disease may recur due to reactivation of latent fungal foci or new exposure. Objective: To report the case of a patient with chronic paracoccidioidomycosis as a way to show the importance of diagnosis and treatment in the prognosis. Result: A twenty-six-year-old female patient presented with painless skin lesions on the face and neck, with an irregular, erythematous appearance, with a granular background and purulent secretion 4 months before hospital admission, which were treated with antimicrobials and topical corticosteroids, in addition to febrile state and asthenia about one week before hospitalization. She was hospitalized for 19 days and during this period amphotericin B was administered, as well as loratadine, dipyrone and ondansetron. Conclusion: The diagnosis is essential for the installation of the treatment and, consequently, the prognosis, and although there is a vast therapeutic arsenal against this condition, the treatment is long, reaching up to 18 months, and then the patient, routinely, must be reassessed by cure criteria, such as clinical, immunological and radiological.(AU)

Introducción: La paracoccidioidomicosis es una enfermedad fúngica y sistémica común en Brasil, presente principalmente entre los trabajadores de las áreas rurales. En la mayoría de los casos, el contagio se produce por inhalación de esporas y la infección primaria remite espontáneamente, pudiendo reaparecer la enfermedad por reactivación de focos fúngicos latentes o por nueva exposición. Objetivo: Reportar el caso de un paciente con paracoccidioidomicosis crónica como una forma de mostrar la importancia del diagnóstico y tratamiento en el pronóstico. Resultado: Paciente femenina de 26 años de edad que presenta lesiones cutáneas indoloras en cara y cuello, de aspecto irregular, eritematoso, de fondo granular y secreción purulenta 4 meses antes del ingreso hospitalario, las cuales fueron tratadas con antimicrobianos y tratamiento tópico. corticoides, además de estado febril y astenia aproximadamente una semana antes de la hospitalización. Estuvo hospitalizada durante 19 días y durante este período se le administró anfotericina B, así como loratadina, dipirona y ondansetrón. Conclusión: El diagnóstico es fundamental para la instalación del tratamiento y, en consecuencia, el pronóstico, y aunque existe un vasto arsenal terapéutico contra esta condición, el tratamiento es largo, llegando hasta los 18 meses, y luego el paciente, de forma rutinaria, debe ser reevaluado por criterios de curación, tales como clínicos, inmunológicos y radiológicos.(AU)

Paracoccidioides brasiliensis infection increases regulatory T cell counts in female C57BL/6 mice infected via two distinct routes.

Studies that show an overview of the peripheral immune response in a model of Paracoccidioides brasiliensis (Pb) infection in females are scarce in the literature. We sought to characterize the innate and adaptive immune responses in female C57BL/6 mice infected with Pb through two distinct routes of administration, intranasal and intravenous. In addition to the lung, P. brasiliensis yeast cells were observed in liver and brain tissues of females infected intravenously. To our knowledge, our study is the first to prove the presence of this pathogenic fungus in the cerebral cortex of female mice. During the initial stages of infection, augmented expression of both MHCII and CD86 was observed on the surface of CD11c+ pulmonary antigen-presenting cells (APCs) in intranasally and intravenously infected females. However, CD40 expression was downregulated in these cells. Concomitantly with increasing serum IL-10 levels, we noted that splenic dendritic cells (DCs) from both intravenously- and intranasally-infected female mice had acquired an immature phenotype. Further, increased T regulatory cell counts were observed in female mice infected via both routes, along with an increase in the infiltration of IL-10-producing CD8+ T cells into the lungs. Moreover, we noted that P. brasiliensis infection resulted in enhanced IL-10 production - by CD11c+ APCs in the lung tissue - and induction of Th17 polarization. Taken together, our results suggest that P. brasiliensis could modulates the immune response in female mice by influencing the balance between regulatory T cells (Tregs) and Th17 polarization.

Diagnóstico de la paracoccidioidomicosis / Diagnosis of paracoccidioidomycosis

La paracoccidioidomicosis es una micosis sistemática, endémica de amplias regiones de América Latina, causada por un hongo termodimorfo, Paracoccidioides brasiliensis. Afecta de manera predominante a individuos de mediana edad y sexo masculino, en particular aquellos que cumplen tareas rurales. la infección se adquiere por vía inhalatoria, y puede diseminarse por vía hemática a diversos órganos y tejidos. La enfermedad puede evolucionar en forma aguda, subaguda o crónica. El diagnóstico presuntivo de la paracoccidioidomicosis se sustenta en los antecedentes epidemiológicos del paciente y en las manifestaciones clínicas. El diagnóstico etiológico clásico consiste en la visualización, el aislamiento y la identificación del agente causal, o bien el empleo de pruebas serológicas para determinar la presencia de anticuerpos específicos en sangre. Se presentan tres casos de paracoccidioidomicosis en pacientes varones, dos con formas agudas de la enfermedad y el restante con una forma crónica. En todos los casos, el diagnóstico se efectuó por los hallazgos de la microscopia, los cultivos y las pruebas serológicas

Paracoccidioidomycosis is a systemic mycosis, endemic to large regions of Latin America, caused by a thermodimorphic fungus, Paracoccidioides brasiliensis. It predominantly affects middle-aged and male individuals, particularly those who perform rural tasks. The infection is acquired by inhalation, and it can spread by blod to various organs and tissues. The disease can evolve in acute, subacute or chronic form. The presumptive diagnosis of paracoccidiodomycosis is based on the patient's epidemiological history and clinical manifestations. The classic etiological diagnosis consists of visualization, isolation and identification of the causative agent, or the use of serological tests to determine the presence of specific antibodies in the blood. There are threee cases of paracoccidioidomycosis in male patients, two with acute forms of the disease and the remaining with a chronic form. In all cases, the diagnosis was made by the findings of microscopy, cultures and serological tests

Imported endemic mycoses in Spain: Evolution of hospitalized cases, clinical characteristics and correlation with migratory movements, 1997-2014.

Endemic mycoses are systemic fungal infections. Histoplasmosis is endemic in all temperate areas of the world; coccidioidomycosis and paracoccidioidomycosis are only present in the American continent. These pathogens are not present in Spain, but in the last years there has been an increase of reported cases due to migration and temporary movements. We obtained from the Spanish hospitals records clinical and demographic data of all hospitalized cases between 1997 and 2014. There were 286 cases of histoplasmosis, 94 of Coccidioidomycosis and 25 of paracoccidioidomycosis. Overall, histoplasmosis was strongly related to HIV infection, as well as with greater morbidity and mortality. For the other mycoses, we did not find any immunosuppressive condition in most of the cases. Although we were not able to obtain data about clinical presentation of all the cases, the most frequently found was pulmonary involvement. We also found a temporal correlation between the Spanish population born in endemic countries and the number of hospitalized cases along this period. This study reflects the importance of imported diseases in non-endemic countries due to migratory movements.

Recipient of kidney from donor with asymptomatic infection by Paracoccidioides brasiliensis.

The increase in solid organ transplantations may soon create a rise in the occurrence of endemic fungal diseases, such as paracoccidioidomycosis, due to the lack of rigorous screening of donors from endemic areas. Here we present the first case of an immunocompetent and asymptomatic kidney donor who had Paracoccidioides brasiliensis infected-adrenal tissue but no glandular dysfunction.

Histological and serological evidence of experimental paracoccidioidomycosis in Calomys callosus (Rodentia: Cricetidae).

The responses of animal experimental models related to the infectivity, virulence and pathogenicity of Paracoccidioides brasiliensis is constantly used to develop new perspectives of investigation. The rodent Calomys callosus, Rengger 1830 (Rodentia: Cricetidae) is an indigenous inhabitant of the savannah environment found in the central regions of Brazil. The aim of the present work was to evaluate the histopathological and serological features of C. callosus after inoculation with the Pb18 strain of P. brasiliensis. Furthermore, A/Sn and B10.A mice strains were also tested to compare the results obtained in C. callosus to these well-established experimental models of resistance and susceptibility respectively. In every instance, survival analysis was performed, and histopathological study of the lungs, liver and spleen was employed to investigate tissue involvement, degree of inflammation and fungal presence. Levels of antibodies to P. brasiliensis were measured by using an enzyme-linked immunosorbent assay after 4 weeks and at the advanced stage of infection. The mortality rate was proportional to inoculation dose in all groups, but overall it was much superior in C. callosus than in the B10.A-susceptible mice. Macroscopical and microscopical pathological alterations were also more extensive and remarkable for C. callosus, once again proportional to inoculation dose, but more noticeable differences among the studied groups were found with 0.6x10(5) inoculum. In addition, the serological profile of C. callosus was similar to that found for B10.A-susceptible mice. Infection of C. callosus with 0.6x10(8) Pb18 inoculum resulted in more serious illness, and it decreased in severity in proportion to the inoculum dose. This difference was more pronounced in C. callosus, and the clinical, serological and pathological findings in this animal were more intense and precocious compared with the B10.A-susceptible mice. The present results suggest that C. callosus is a potentially alternative experimental animal model for paracoccidioidomycosis infection.

Distribution of paracoccidioidomycosis: determination of ecologic correlates through spatial analyses.

Paracoccidioidomycosis (PCM) is endemic in Latin America and in countries like Brazil it carries a high mortality rate. The fungus' habitat has not been precisely determined. The present study aims to identify ecologic correlates based on PCM distribution in a hyper-endemic area in southeastern Brazil. The Geographic Information System (GIS) and spatial statistics were used to associate environmental attributes, human population density and, PCM distribution. By means of the Pearson r correlation coefficient, the highest statistically significant associations with prevalence density were the percent area (by county) of: basaltic rocks (r=0.63; P <0.0001), Podzolic soils (r= -0.48; P <0.001), Latosol soils (r=0.40; P <0.01), mean annual precipitation between 1500 and 1600 mm (r = 0.46; P < 0.001) and, mean precipitation during the wet season between 940 and 1040 mm (r= -0.44; P <0.01). Soil texture and precipitation analyzed together reached r=0.61 (P <0.000002) for fine-textured soils with annual precipitation above 1400 mm. Environmental correlates indicate that moisture availability plays an important role in PCM distribution.

The habitat of Paracoccidioides brasiliensis: how far from solving the riddle?

When trying to understand the pathophysiology of any infectious agent, one key piece of information is the determination of its habitat. In the case of Paracoccidioides brasiliensis, the precise location of the fungus' environmental niche remains undefined despite the efforts of various research groups. This review summarizes recent studies on the ecology of P. brasiliensis and certain facets of paracoccidioidomycosis. Studies on the juvenile form of paracoccidioidomycosis in children less than 13 years of age, the characterization of the ecological factors in the 'reservarea' where the infection is acquired and the presence of P. brasiliensis in the nine-banded armadillo (Dasypus novemcinctus), are all helping to pinpoint the microniche of this pathogen. The application of molecular biology techniques based on the amplification of nucleic acids will also hopefully help in establishing the precise habitat of P. brasiliensis.

Experimental paracoccidioidomycosis in hamsters (Mesocricetus auratus): gestational interactions.

Paracoccidioides brasiliensis is a dimorphic fungus presenting specific steroid hormone receptors, both in the yeast and mycelial forms and estrogen inhibits the transition from mycelium to yeast. In the acute phase, the disease occurs with equal frequency in both sexes but in adults, females are spared. Placental fungal infection has been reported, but references to fetal infection have not been confirmed. We used 78 Syrian female hamsters divided into 3 groups: GI consisted of 30 infected mated females, GII of 20 infected unmated females and GIII of 28 uninfected mated females. Animals of group I were mated 4 weeks after infection and half of them were submitted to cesarean section on day 15 after successful mating; the other half was maintained and submitted to cesarean section and sacrificed 14 weeks after infection. Half of the animals of group II were sacrificed seven weeks and the other half 14 weeks after infection. Uninfected animals of group III were treated the same as the animals of group I. The animals were infected with strain 18 of P. brasiliensis by the intracardiac route. We evaluated the disease by the volume of granulomas in different organs, number of fungi in liver and spleen and the immunologic responses [ELISA, Double Immunodifusion (DID), Delayed Hypersensitivity Skin Test (DHT) and Macrophage Migration Inhibition (MMI)]. We studied the infection through the gestation by evaluation of the abortions, morphologic and clinic examinations of the fetuses. Our results showed that the infection did not transfer to the fetus through the placenta, but the number of abortions was larger among infected females. The newborns of GI females were smaller, weighed less and showed little vitality. The disease was more severe and disseminated in infected mated females, especially in the second sacrifice 14 weeks after inoculation, when the total volume of granulomas in them (56.3 mm) was much greater than in the infected unmated females (12 mm).

Paracoccidioidomicosis. A propósito del primer caso uruguayo en un paciente de sexo femenino / Paracoccidioidomycosis. First case in Uruguay in a female patient

Se refiere el primer caso uruguayo autóctono de paracoccidioidomicosis en paciente de sexo femenino, habiendo correspondido los 77 previamente diagnosticados a pacientes del sexo masculino. Se destaca la presencia de lesiones granulomatosas orales ricas en células del agente etiológico que son interpretadas como de origen metastásico a punto de partida de lesiones pulmonares de larga data. La diseminación extrapulmonar del hongo pudo haber sido favorecida por un bajo tenor de estrógenos circulantes, propios del perfil hormonal climatérico comprobado en la paciente con una menopausia de corta duración. La infección primaria de la enferma probablemente tuvo lugar antes de los 14 años de edad, época en que vivió sobre costas del arroyo Sacra, afluente del Río Uruguay, plena área endémica

Manifestaçöes estomatológicas da Paracoccidioidomicose (Paracoccidioide Brasiliensis ou Enfermidade de Lutz-Splendore-Almeida): consideraçöes gerais e apresentaçäo de casos / Stomatological manifestations of the Paracoccidiodomycosis (Paracoccidioides Brasiliensis or Lutz-Splendore-Almeida disease): general considerations and cases presentation

Foram estudados 45 pacientes provenientes do Serviço de Doenças Infecto-Parasitárias e de Semiologia Aplicada da Universidade Federal do Paraná, que apresentavam manifestaçöes estomatológicas decorrentes da infecçäo fúngica causada pelo Paracoccidioides brasiliensis, no período compreendido entre 1992 a 1994. Da amostragem estudada, 39 pacientes do sexo masculino (86,67 por cento) e 6 do sexo feminino (13,33 por cento), com média de idade de 51 ñ 10 anos (faixa de 34 - 75), destacando-se alguns aspectos: 26 pacientes (57,80 por cento) eram agricultores, 19 (42,22 por cento) eram oriundos do interior do Paraná, 22 pacientes (48,89 por cento) eram tabagistas, sendo encontradas lesöes de orofaringe em 42 pacientes (93,33 por cento), sendo o local mais comumente o palato, bem como comum o aparecimento de vários tipos de lesöes num mesmo paciente. Näo houve comprometimento de linfonodos em 34 pacientes (75,56 por cento); 30 pacientes (66,67 por cento) apresentavam doença periodontal; 7 (15,56 por cento) exibiam dentes em péssimo estado de conservaçäo, e 10 pacientes (22,22 por cento) tinham comprometimento ósseo. Lesöes sistêmicas estavam ausentes em 35 pacientes (77,80 por cento), uma vez que já havia sido iniciada a terapêutica em muitos pacientes, e a lesäo mais comumente encontrada foi a fibrose pulpomar. Vinte e nove (29) pacientes (64,45 por cento) foram submetidos a tratamento com Sulfametoxazol + trimetropin, tendo sido também utilizado o Ketoconazol e o Itracoanazol nos casos resistentes ao tratamento convencional padronizado. Quarenta e dois (42) pacientes (93,33 por cento) mostraram remissäo das lesöes estomatológicas. Dois (02) pacientes (4,44 por cento) foram a óbito. Além da observaçäo clínica foram realizadas biópsias para o exame microscópico, micológico e sorologia para PCM, para acompanhar a evoluçäo do tratamento e proservaçäo

Paracoccidiodomicosis: casuistica de la consulta de micología del Servicio de Dermatología del Hospital Universitario de Caracas 1980-1990 / Paracoccidioidomycosis: casuistic of the micology consultation of the Dermatol Service from the University Hospital of Caracas 1980-1990

Se presenta la casuistica de la Consulta de Micología del Servicio de Dermatología del Hospital Universitario de Caracas, desde 1980 a 1990

Hipótesis sobre el nicho ecológico de paracoccidioides brasiliensis / Hypothesis on the ecologic niche of paracoccidioides brasiliensis

La ignorancia sobre el hábitat natural de Paracoccidioides brasiliensis, agente de la paracoccidioidomicosis, enfermedad propia de Latinoamérica, con alta incidencia y prevalencia, así como elevada mortalidad, justifica la elaboración de hipótesis que ayuden a resolver el apasionante enigma, posibilitando el control de la afección. La presente hipótesis se basa esencialmente en datos epidemiológicos de la enfermedad en Uruguay que revelan una íntima vinculación con nuestros bosques indígenas observandose aquella en leñadores en casi el 70 por ciento. En virtud de la probada labilidad del hongo a la desecación y a su sensibilidad a la competencia biológica, postulamos que el mismo viva en la naturaleza protegido por especies acuáticas heterotérmicas de agua dulce (¿peces?, ¿anfibios?, ¿moluscos?, ¿antrópodos?) integrando una biocenosis altamente eficiente con características propias. A partir de esos reservorios el parásito debería ser transportado a sitios y sustratos aptos para afectar al hombre y a los animales, previa transformación de la fase parasitaria, levaduriforme, en la fase miceliana, esporulante e infectante. Aves acuáticas podrían ingerir los animales reservorios y actuar, a través de fecas y regurgitaciones, como activos dispersantes del parásito sobre árboles, nidos masas de agua, vegetación etc., asegurando la reinfección de aquellos. El hombre adquiriría la enfermedad inhalando esporos (aleurias) liberadas por diversos mecanismos, de ramas, nidos, etc. durante el trabajo del monteador en el bosque indígena, actividad desarrollada generalmente durante años. En los restantes países del área endémica en los que la mayoría de los pacientes son agricultores, postulamos la infección de los mismos durante la cosecha de diferentes cultivos infectados a su vez por aguas contaminadas mediante los mecanismos expuestos. Animales domésticos como equipos, bovinos y ovinos en los que se ha comprobado la infección paracoccidióidica o armadillos, en los que se ha diagnosticado la enfermedad, se infectarían también por vía aérea durante su alimentación sobre las márgenes de ríos y arroyos contaminados