Extra-pulmonary manifestations of paracoccidioidomycosis; Manifestacoes extrapulmonares da paracoccidioidomicose

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Costa, Marlos Augusto Bittencourt; Carvalho, Tarcisio Nunes; Araujo Junior, Cyrillo Rodrigues de; Borba, Ana Olivia Cardoso; Veloso, Gerson Augusto; Teixeira, Kim-Ir-Sem Santos [Goias Univ., Goiania, GO (Brazil). Hospital das Clinicas. Dept. de Diagnostico por Imagem]. E-mail: radiologia@brturbo.com

2001-02-01

The authors present a review and iconographic study of patients with disseminated paracoccidioidomycosis, including the main radiographic findings seen in the central nervous system, adrenal glands, osteoarticular system, lymph nodes and digestive tract. Imaging diagnostic methods have allowed a more precise approach of these patients due to their high sensitivity in detecting lesions, even in asymptomatic patients. In most cases these abnormalities are unspecific, simulating either neoplasic or chronic infectious lesions, and sometimes difficult to distinguish from tuberculosis. Although these findings are nonspecific and only the mycologic and histologic fungus demonstration can confirm the diagnosis, they may suggest a presumptive one, when these imaging findings are considered in an appropriate clinical and epidemiological setting. (author)

Pulmonary paracoccidioidomycosis: A case report with high-resolution computed tomography findings

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M. Armas

2012-07-01

Full Text Available Paracoccidioidomycosis is a systemic mycosis which is endemic in rural areas of Latin America, an important European source of immigrants and a growing European touristic destination as well, with most cases occurring in Brazil, Argentina, Venezuela and Colombia. The authors report a case of a 43-year-old man who previously worked in Venezuela and is living in Portugal for 8 years, presenting with a single cutaneous lesion. Despite the absence of valuable respiratory complaints, severe lung damage was found with high-resolution computed tomography (HRCT. Biopsy of the cutaneous lesion and mycologic sputum examination were performed revealing Paracoccidioides brasiliensis infection. Resumo: A Paracoccidioidomicose é uma micose sistémica endémica nas áreas rurais da América Latina, uma fonte importante de imigrantes e destino de emigração e turismo europeu, a maioria dos casos ocorrendo no Brasil, Argentina, Venezuela e Colômbia. Os autores descrevem o caso clínico de um paciente com 43 anos, anteriormente emigrado na Venezuela e residente em Portugal há 8 anos, que se apresenta com lesão cutânea isolada. Embora sem queixas relevantes do foro respiratório, apresentava extensas lesões do parênquima pulmonar caracterizadas por tomografia computorizada de alta resolução (TCAR. Foi realizada biópsia da lesão cutânea e exame micológico da expetoração que revelaram infeção por Paracoccidioides brasiliensis (PB. Keywords: Paracoccidioidomycosis, Paracoccidioides brasiliensis, Pulmonary fibrosis, High-resolution computed tomography, Palavras-chave: Paracoccidioidomicose, Paracoccidioides brasiliensis, Fibrose pulmonar, Tomografia computorizada de alta resolução

Inapparent lung involvement in patients with the subacute juvenile type of paracoccidioidomycosis

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A. Restrepo

1989-02-01

Full Text Available Three patients with the diagnosis of subacute juvenile paracoccidioidomycosis who, at the time of their first visit, had no signs or symptoms of lung involvement, were studied. Initially the diagnosis was confirmed by the observation of P. brasiliensis in biopsy material obtained from clinically involved lymphadenopathies. The lung X-rays done in all patients, did not reveal pathologic changes, although it was possible to observe and isolate the fungus from sputum samples obtained from the three patients. This fact reinforces the pulmonary genesis of the mycosis and proofs the existence of a pulmonary primary infection, even in patients with the juvenile manifestations, in whom the lung component is obscured by the predominant lymph node involvement.

Diagnosis and Treatment of Paracoccidioidomycosis in the Maxillofacial Region: A Report of 5 Cases

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Antonio Dionízio De Albuquerque Neto

2018-01-01

Full Text Available Paracoccidioidomycosis is a fungal infection initially described in Brazil in 1908 by Adolfo Lutz. Manifestation of this disease depends on numerous factors, such as microorganism virulence, hormonal profile, genetic predisposition, nutrition, and immune system. It is characterized classically by cutaneous lesions, lymphadenopathy, and pulmonary involvement. It presents male predilection, which can be explained by the protective effect of female hormones. Classic presentation within oral cavity is a superficial ulcer characterized by hemorrhagic dots of moriform aspect. Treatment should be established individually and closely monitored. This manuscript aims at reporting five cases of this pathology.

Paracoccidioidomycosis mortality in the State of Paraná, Brazil, 1980/1998 Mortalidade por paracoccidiodomicose no Estado do Paraná, Brasil, 1980/1998

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Jeanine Izabel Margraf Bittencourt

2005-12-01

Full Text Available The paracoccidioidomycosis mortality rate in the State of Paraná, Brazil (1980/1998 was analyzed using the death registry data from the Brazilian Mortality Information System and the estimated population from the Brazilian Institute of Geography and Statistics. To qualify the deaths, we deployed ICD-9 for 1980/1995 and ICD-10 for the more recent years. During this period there were 551 deaths from paracoccidioidomycosis in the State of Paraná. Most of the deaths were in male in the 30-59-year age group. The average annual mortality rate was 3.48 per million inhabitants, showing a tendency to stabilize during the study period. Paracoccidioidomycosis was the fifth cause of mortality among the predominantly chronic infectious diseases and had the highest mortality rate among the systemic mycoses. Paracoccidioidomycosis was observed in 184 counties in the State of Paraná. Most deaths were recorded in the North-Central meso-region, and the highest mortality rate occurred in the West meso-region.Foi conduzido um estudo de mortalidade por paracoccidioidomicose no Estado do Paraná, Brasil, no período de 1980 a 1998, utilizando-se como fonte de dados os registros de óbitos do Sistema de Informação sobre Mortalidade e a população estimada pelo Instituto Brasileiro de Geografia e Estatística. Para classificação dos óbitos, empregou-se a CID-9 para os anos de 1980 a 1995 e a CID-10 para os anos mais recentes. Nesse período, no Paraná, ocorreram 551 óbitos por paracoccidioidomicose, com prevalência do sexo masculino, na faixa etária compreendida ente 30 a 59 anos. A taxa de mortalidade média anual foi de 3,48 por milhão de habitantes, demonstrando estabilidade no período de estudo. Destacou-se como a quinta causa de mortalidade entre as doenças infecciosas e parasitárias redominantemente crônicas, apresentando a mais alta taxa de mortalidade entre as micoses sistêmicas. Foi observada em 184 municípios, verificando-se, no estudo por

Paracoccidioidomycosis in the state of Maranhão, Brazil: geographical and clinical aspects

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Wilma Batista de Matos

2012-06-01

Full Text Available INTRODUCTION: The study aimed to show the situation of paracoccidioidomycosis in the state of Maranhão, Brazil. METHODS: This study is a descriptive case series developed in two stages. First, a survey of cases originating from the state of Maranhão at the Instituto de Doenças Tropicais Natan Portela, Piauí (IDTNP from 1997 to 2007, and second, the clinical description of 29 cases diagnosed in the Centro de Referências em Doenças Infecciosas e Parasitárias, Maranhão (CREDIP from 2004 to 2010. RESULTS: Two hundred and sixteen cases have been cataloged at the IDTNP. West, east, and central regions of the state of Maranhão recorded 90.3% of cases proving to be important areas for study. The western region, with a prevalence of 10.8/100,000 inhabitants, has a significantly higher proportion of cases than the northern, southern, and eastern regions (p < 0.05. The occurrence was higher in men with 89.3% of cases, and the male-to-female ratio was 8.4:1. The majority of patients were older than 20 years, lived in rural areas, and had farming or soil management as main occupation (73.8%. At CREDIP, 29 cases were diagnosed, of which 26 (89.6% had multifocal manifestations. Mucous tissues were involved more (75.8% frequently, followed by lymph nodes, skin, and lungs with 65.5%, 39% and 37.9 %, respectively. The diagnosis was made by combining direct examination, culture, and histopathology. CONCLUSIONS: The study shows the geographical distribution and the epidemiological and clinical aspects of paracoccidioidomycosis, revealing the significance of the disease to the state of Maranhão.

Paracoccidioidomycosis of the central nervous system: CT findings

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Rodacki, M.A. [Section of Neuroradiology, Service of Radiology, Sta Isabel Hospital, Sta Catarina (Brazil); Toni, G. de [University Hospital, Medical School of Curitiba, Parana (Brazil); Borba, L.A. [Division of Neurosurgery, Sta Isabel Hospital, Blumenau, Sta Catarina (Brazil); Oliveira, G.G. [Division of Pathology, Sta Isabel Hospital, Blumenau, Sta Catarina (Brazil)

1995-11-01

A retrospective analisis of six cases of central nervous system paracoccidioidomycosis, all but one proven by biopsy and surgery, was carried out to study the CT and clinical data and pathological correlation. Most of the patients were from the country. Headache, vomiting, seizures and hemiparesis were the most frequent symptoms. Papilloedema was present in four patients with raised intracranial pressure. Five patients had chronic lung disease and two with advanced systemic disease, skin and mucous membrane lesions were also observed. The neurological disturbance was sometimes the presenting features and the diagnosis was discovered incidentally after surgery. Both solitary and multiple parenchymal lesions were observed and the cerebral hemispheres were more commonly involved in four patients. Local meningeal involvement was observed in one with a single cortical granuloma. We enphasise the usefulness of CT, showing a rounded or lobulated mass with an isodense or radiolucent centre after contrast enhancement, surrounded by an irregular wall of varying thickness. There was always moderate oedema, extending peripherally. Other infections or neoplastic diseases may present similar findings. Preoperative diagnosis should rest on integration of clinical data, chest films, laboratory and neuroimaging studies. (orig.). With 4 figs., 2 tabs.

Seroepidemiological survey of paracoccidioidomycosis infection among urban and rural dogs from Uberaba, Minas Gerais, Brazil.

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Fontana, Fabricio Fernandes; dos Santos, Celso Tadeu Barbosa; Esteves, Flavia Maria; Rocha, Ademir; Fernandes, Geisa Ferreira; do Amaral, Cristiane Candida; Domingues, Marcos Abel; De Camargo, Zoilo Pires; Silva-Vergara, Mario León

2010-03-01

There is some evidence that dogs can be naturally infected by Paracoccidioides brasiliensis in endemic areas of paracoccidioidomycosis. In order to evaluate canine infection with this fungus, a survey with 149 urban and 126 rural dogs was carried out using ELISA and intradermal tests with the gp43 antigen of P. brasiliensis in Uberaba, Minas Gerais state of Brazil. Forty-one out of 149 urban dogs were euthanatized and had their lungs, liver and spleen removed. One slice from each viscera was processed for histopathological examination and the remaining was homogenized and then cultivated on mycobiotic agar at room temperature and Fava-Netto medium at 35 degrees C and observed for 12 weeks. Of urban dogs, 75 (50.3%) were small adult females, 56 (36%) were strays, while 93 (64%) had been donated to the municipal zoonosis control center. Nine (6.2%) had a positive intradermal test without statistical differences regarding gender, race, nutritional status or origin. No colonies with microscopic or morphology appearances resembling P. brasiliensis were isolated, nor granulomatous process or fungal structures were observed from histopathological examination. Eighty (53.6%) of the urban dogs presented seroreactivity, without statistical differences regarding gender, race, nutritional state, origin, or positive intradermal test. Of 126 rural dogs, 102 (80.5%) presented antibodies against gp43 antigen, and this was statistically significant in relation to the reactivity detected in urban dogs (P = 0.0001). Thus, dogs are commonly infected with P. brasiliensis, but they probably present natural resistance to develop paracoccidioidomycosis.

Tendência da mortalidade relacionada à paracoccidioidomicose, Estado de São Paulo, Brasil, 1985 a 2005: estudo usando causas múltiplas de morte Paracoccidioidomycosis-related mortality trend, state of São Paulo, Brazil: a study using multiple causes of death

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Augusto Hasiak Santo

2008-05-01

Full Text Available OBJETIVO: Estudar a mortalidade relacionada à paracoccidioidomicose informada em qualquer linha ou parte do atestado médico da declaração de óbito. MÉTODOS: Os dados provieram dos bancos de causas múltiplas de morte da Fundação Sistema Estadual de Análise de Dados (SEADE de São Paulo entre 1985 e 2005. Foram calculados os coeficientes padronizados de mortalidade relacionada à paracoccidioidomicose como causa básica, como causa associada e pelo total de suas menções. RESULTADOS: No período de 21 anos ocorreram 1 950 óbitos, sendo a paracoccidioidomicose a causa básica de morte em 1 164 (59,7% e uma causa associada de morte em 786 (40,3%. Entre 1985 e 2005 observou-se um declínio do coeficiente de mortalidade pela causa básica de 59,8% e pela causa associada, de 53,0%. O maior número de óbitos ocorreu entre os homens, nas idades mais avançadas, entre lavradores, com tendência de aumento nos meses de inverno. As principais causas associadas da paracoccidioidomicose como causa básica foram a fibrose pulmonar, as doenças crônicas das vias aéreas inferiores e as pneumonias. As neoplasias malignas e a AIDS foram as principais causas básicas estando a paracoccidioidomicose como causa associada. Verificou-se a necessidade de adequar as tabelas de decisão para o processamento automático de causas de morte nos atestados de óbito com a menção de paracoccidioidomicose. CONCLUSÕES: A metodologia das causas múltiplas de morte, conjugada com a metodologia tradicional da causa básica, abre novas perspectivas para a pesquisa que visa a ampliar o conhecimento sobre a história natural da paracoccidioidomicose.OBJECTIVE: To investigate mortality in which paracoccidioidomycosis appears on any line or part of the death certificate. METHODS: Mortality data for 1985-2005 were obtained from the multiple cause-of-death database maintained by the São Paulo State Data Analysis System (SEADE. Standardized mortality coefficients were

Paracoccidioidomycosis: high-resolution computed tomography - anatomo-pathological correlation; Paracoccidioidomicose: correlacao da tomografia computadorizada de alta resolucao com a anatomopatologia

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Marchiori, Edson; Muniz, Maria Angelica Soares; Santos, Maria Lucia de Oliveira [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Inst. de Radiologia; Moraes, Heleno Pinto de [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Inst. de Patologia; Capone, Domenico [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Pneumologia

2000-12-01

We reviewed the high-resolution computed tomography scans of 13 patients with paracoccidioidomycosis and correlated the findings with the anatomo-pathological findings of 5 patients. The most frequent findings observed were thickening of the interlobular septa, emphysema, ground glass areas, thickening of bronchial walls, tracheal dilatation, nodules, cavities and evidence of fibrosing disease such as architectural distortion, parenchymatous bands, spicular pleural thickening, intralobular reticulate and thickening with distortion off the axial interstitium. (author)

Spontaneous pneumothorax in paracoccidioidomycosis patients from an endemic area in Midwestern Brazil.

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Cabrera, Lucas G G; Santos, Aline F; Andrade, Ursulla V; Guedes, Carlos Ivan A; Oliveira, Sandra M V L; Chang, Marilene R; Mendes, Rinaldo P; Paniago, Anamaria M M

2017-02-01

Paracoccidioidomycosis (PCM) is the most important systemic mycosis in Latin America. About 80% of PCM patients are present with its chronic form. The lungs are affected in most patients with the chronic form; however, pleural involvement has rarely been reported. We describe nine cases of PCM that presented with lung involvement and spontaneous pneumothorax. All patients, except one whose condition was not investigated, were smokers. PCM was diagnosed during the pneumothorax episode in three patients, and from 3 to 16 years before the pneumothorax episode in six patients. A total of six patients underwent chest drainage and one died as a direct result of the pneumothorax. We suggest that pneumothorax, although rare, should be considered in PCM patients who present with suddenly worsening dyspnoea. PCM should also be investigated in cases of pneumothorax in adult men from mycosis-endemic areas. © 2016 Blackwell Verlag GmbH.

Paracoccidioidomicose sistêmica com envolvimento do sistema nervoso central Systemic paracoccidioidomycosis with central nervous system involvement

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Antônio Luiz Wiener Pureza Duarte

1999-08-01

Full Text Available É relatado o caso de um paciente portador de paracoccidioidomicose sistêmica, com comprometimento oral e ganglionar regional e posterior envolvimento pulmonar. O paciente, tratado com drogas específicas(anfotericina B, itraconazol, sulfametoxazol + trimetoprim e acompanhado durante seis anos, foi ao óbito com extenso comprometimento do sistema nervoso centralA clinical case of a patient bearing systemic paracoccidioidomycosis with regional ganglionic and oral exposure and later pulmonary envolvement is presented. The patient was treated with especific drugs (amphotericin B, itraconazole, sulfamethoxazole-trimethoprim and followed throughout a 6-year period and eventually died showing an extensive envolvement of the central nervous system.

Oral paracoccidioidomycosis: Retrospective analysis of 55 Brazilian patients.

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Trindade, Aline Heloísa; Meira, Henrique Côrtes; Pereira, Igor Figueiredo; de Lacerda, Julio César Tanos; de Mesquita, Ricardo Alves; Santos, Vagner Rodrigues

2017-08-01

Paracoccidioidomycosis (PCM) is a rare fungal infection in the world, but endemic and acquired exclusively in Latin America, with the highest prevalence in South America and Brazil, particularly. Changes in oral cavity are common and constitute the first clinical manifestation in many patients. The aim of this study was to describe the prevalence of oral PCM and analyse the profile of the disease and patients. Retrospective research, consisting of information present in the medical records in the period 1998-2015, whose histopathological diagnosis was oral PCM. Fifty-five oral PCM cases were confirmed. Of these patients, 90.9% were males and 9.1% were females. The average age was 49.66 years and the most reported occupation was rural workers. The painful symptomatology was present in 61.82% of patients. Erythematous lesions were predominant in 73% of them. In single lesions (22 cases), the most common locations were jugal mucosa and tongue. In multiple involvement (30 cases), the most affected regions were lips, jugal mucosa and alveolar ridge. Epidemiology of PCM, was similar to several other studies, especially in Brazil. This is the most important fungal infection in Latin America and the recognition of oral lesions is extremely important, as is often the first and in many cases the only manifestation of the disease. © 2017 Blackwell Verlag GmbH.

Amphotericin B: an antifungal drug in nanoformulations for the treatment of paracoccidioidomycosis

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Mônica Pereira Garcia

2013-12-01

Full Text Available The use of magnetic nanoparticles (MNPs in drug delivery vehicles must address issues such as drugloading capacity, desired release profile, aqueous dispersion stability, biocompatibility with cells and tissue, and retention of magnetic properties after interaction with macromolecules or modification via chemical reactions. Amphotericin B (AmB is still the first choice for the treatment of severe paracoccidioidomycosis, an important systemic fungal infection caused by Paracoccidoides brasiliensis. Unfortunately, AmB causes acute side effects (mainly urinary problems following intravenous administration, which limits its clinical use. The use of magnetic nanoparticles stabilized with biocompatible substances, together with the possibility of their conjugation with drugs has become a new nanotechnological strategy in the treatment of diseases for drug delivery to specific locations, such as the lungs in paracoccidoidiodomycosis. This review provides an overview of the disease, its etiologic agent and treatment with emphasis on the main strategies to improve the use of AmB in nanoformulations.

Use of immunoblotting assay improves the sensitivity of paracoccidioidomycosis diagnosis

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D. F. Silva

2008-01-01

Full Text Available The purpose of this work was to evaluate two serological assays: double immunodiffusion (DI and immunoblotting (IB in immunodiagnosis of paracoccidioidomycosis (PCM. We evaluated by IB assay 23 sera samples from patients with clinical confirmation of PCM, all of them with negative DI results against culture filtrate from Paracoccidioides brasiliensis isolate 113. For IB, as well as for comparative DI assay, we employed soluble components of the cell wall outer surface (SCCWOS from P. brasiliensis isolate 113 cultivated at 36°C in Fava-Neto's agar medium for 5 and 10 days. Among the 20 sera samples analyzed by DI, 13 (65% were negative and 7 (35% were positive against SCCWOS obtained on the 5th and 10th days. By IB assay, 95.4% and 100% of sera reacted against gp43 and gp70 present in SCCWOS from the 5th day and 95.6% recognized these fractions when evaluated against SCCWOS from the 10th day. Our results demonstrated that the use of an immunoenzymatic assay significantly improves the sensitivity of PCM immunodiagnosis and also suggests that at least two serological tests for antibody detection should be adopted in cases of questionable diagnosis.

Comprometimento da medula óssea e eosinofilia na paracoccidioidomicose Bone marrow involvement associated with eosinophilia in paracoccidioidomycosis

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M.A. Shikanai-Yasuda

1992-04-01

Full Text Available São descritos 3 casos de paracoccidioidomicose com a forma aguda da doença, nos quais formas leveduriformes de Paracoccidioides brasiliensis foram visualizadas ao exame direto de medula óssea, sendo a cultura também positiva em um caso. Salienta-se o acometimento do sistema fagocítico-mononuclear e a ausência de resposta às provas cutâneas de hipersensibilidade tardia a antígenos microbianos e de P. brasiliensis em todos, bem como a gravidade do quadro clínico e lesões ósseas generalizadas em um caso, com 20.260 eosinófilos/mm³ no sangue periférico. Os autores discutem o possível papel do eosinófilo na interação hospedeiro-parasita na paracoccidioidomicose, sugerindo que a ativação de subpopulação TH 2 e o aumento de secreção de IL 5 e de GM-CSF possam estar relacionados à grande eosinofilia presente no caso mais graveThe authors described three acute paracoccidioidomycosis patients with bone marrow involvement. P. brasiliensis yeast forms were observed in bone marrow smears of all them, and in one case, culture also revealed fungus growth. The mononuclear phagocytic sistem involvement, the blood eosinophilia and the negative skin hipersensibility responses were emphasized in all of them, as well as the severity of the disease in one case, with disseminated bone lesions and 20.260 eosinophils/mm³ in peripheral blood. The authors discuss the possible role of eosinophil in the host-parasite interaction in paracoccidioidomycosis, suggesting that TH 2 subpopulation activation and increased IL 5 and GM-CSF secretions may be responsible by eosinophilia in the most severe case

Registro de um caso de paracoccidioidomicose no Japão Paracoccidioidomycosis in Japan report of a case

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Taishiro Chikamori

1984-10-01

Full Text Available Os Autores descrevem um caso de paracoccidioidomicose em Tóquio, o segundo observado no Japão. A paciente residiu cerca de cinco anos na zona urbana de São Paulo, onde provavelmente adquiriu a primo-infecção. Não tomou corticóides, nem teve história de outras afecções que justificassem a paracoccidioidomicose. Após três anos do retorno ao Japão apresentou linfadenopatia, comprometimento hepatesplênico e ausência de lesões pulmonares. O presente caso, com exame histopatoló-gico e cultivo positivos para Paracoccidioides brasiliensis também apresentou quadro soroló-gico compatível. O aspecto blástico das lesões ósseas, raro em arcos costáis nesta micose, bem como a linfadenopatia generalizada são discutidos. Tratamento à base de anfotericina B e ketoconazol ofereceu resultados favoráveis. Neste trabalho os Autores discutem o problema de "patologia de importação", com suas implicações.The Authors report a non-autochthonous case of paracoccidioidomycosis in Tokyo, the second related in Japan. The patient lived for nearly five years in the urban area of São Paulo, where probably she acquired the primary infection. There was no history of corticoid therapy or other diseases that could explain paracoccidioidomycosis. Three years after her return to Japan, she presented lymphadenopathy, hepatosplenic involvement and absence of pulmonary lesions. The present case, with histopathological examination and culture positive to Paracoccidioides brasiliensis also showed compatible serological results. The blastic feature of bone lesions, rare in ribs in this mycosis, as well as the generalized lymphadenopathy are discussed. Treatment with amphotericin B and ketoconazole offered good results. In this paper the Authors discuss the problem of the "pathology of importation" with its implications.

Avaliação do exame citopatológico como método para diagnosticar a paracoccidioidomicose crônica oral Evaluation of cytopathologic exam for diagnosis of oral chronic paracoccidioidomycosis

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Marcelo Sivieri de Araújo

2003-06-01

Full Text Available Com o objetivo de avaliar o exame citológico esfoliativo no diagnóstico das lesões orais da paracoccidioidomicose, foram estudados oito portadores desta doença. Em todos os casos, demonstrou-se o fungo através de esfregaços citológicos corados com impregnação pela prata Gomori-Grocott. Conclui-se que a citologia esfoliativa oral é um método diagnóstico útil e válido na paracoccidioidomicose, podendo auxiliar no controle terapêutico das formas orais desta micose.With the aim of evaluating exfoliative cytology for the diagnosis of paracoccidioidomycosis oral lesions, eight patients that presented the disease were studied. The presence of fungi was demonstrated in all these cases. It was concluded that the oral exfoliative cytology exam can be effectively used in the diagnosis of paracoccidioidomycosis and contribute to the therapeutic control of oral forms of this mycosis.

Paracoccidioidomicose: freqüência, morfologia e patogênese de lesões tegumentares Paracoccidioidomycosis: frequency, morphology, and pathogenesis of tegumentary lesions

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Silvio Alencar Marques

2007-10-01

Full Text Available FUNDAMENTOS: Paracoccidioidomicose é micose sistêmica de alta prevalência no Brasil. As lesões orocutâneas são de importância para o diagnóstico e acompanhamento clínico. OBJETIVO: Quantificar e qualificar a presença de lesões cutâneas em pacientes com paracoccidioidomicose e correlacionar com forma clínica e gravidade dos casos. MÉTODOS: Realizou-se estudo clínico observacional de série de casos, classificados segundo a forma clínica, localização topográfica e morfologia da lesão quando presente. RESULTADOS: Foram estudados 152 pacientes classificados como forma crônica do adulto (87,5% ou como forma aguda-subaguda, tipo juvenil (12,5%. Lesão cutânea foi identificada em 61,2% dos pacientes. Não houve correlação estatística entre presença de lesão e forma clínica (p=1,000 ou entre presença de lesão e gravidade clínica (p= 0,5607. Houve correlação entre presença de lesão mucosa e a forma clínica crônica do adulto (pBACKGROUND: Paracoccidioidomycosis is a highly prevalent systemic mycosis in Brazil. The oral and cutaneous lesions are useful for diagnostic proposals and clinical follow-up. OBJECTIVE: To quantify and qualify skin lesions associated to active paracoccidioidomycosis and to correlate them with the clinical form and severity of cases. METHODS: An observational clinical study of cases was performed. Patients were classified according to the clinical form, topographic distribution and morphology of skin lesions. RESULTS: A total of 152 patients classified as chronic form (adult type (87.5% or acute-subacute form (juvenile type (12.5% were studied. Skin lesion was diagnosed in 61.2% of patients. There was no statistical correlation between presence of skin lesion and clinical form (p=1.000, nor between skin lesion and severity of disease (p=0.5607. There was statistical correlation between mucosal lesion and adult patients (p <0.001. The lesions were on the cephalic segment (47.6%, trunk (14

Revisão radiológica de 173 casos consecutivos de paracoccidioidomicose Radiological review of 173 consecutive cases of paracoccidioidomycosis

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Henrique Simão Trad

2006-06-01

Full Text Available OBJETIVO: Revisar e determinar a incidência dos achados radiológicos mais importantes da paracoccidioidomicose, e verificar as possíveis variantes de suas apresentações. MATERIAIS E MÉTODOS: Foram revistos 173 casos consecutivos de paracoccidioidomicose, atendidos no período de 1970 a 1980. Os estudos radiológicos direcionados a cada caso foram reanalisados por no mínimo dois radiologistas experientes. RESULTADOS: Foram encontrados 94 casos de acometimento pulmonar isolado e 38 de acometimento pulmonar associado a lesões ganglionares, viscerais, ósseas e à tuberculose. Sem envolvimento pulmonar foram encontrados 41 casos, com lesões intestinais, viscerais, ósseas ou combinadas. Os principais achados radiológicos da forma pulmonar foram opacidade intersticial reticular e nodular bilateral, seguida por consolidação, também bilateral. As formas visceral e intestinal apresentaram lesões predominantes no fígado, jejuno e íleo. Na forma ganglionar houve predominância do comprometimento difuso abdominal e periférico, e no ósseo, áreas de lise principalmente em ossos longos e clavícula. CONCLUSÃO: A paracoccidioidomicose é doença granulomatosa comum no Brasil, acometendo principalmente o pulmão, tendo como porta de entrada a inalação dos esporos do fungo. Outras formas desta doença, menos freqüentes ou raras, devem ser permanentemente lembradas no diagnóstico diferencial.OBJECTIVE: To determine the incidence of most significant radiological findings of paracoccidioidomycosis and to verify its possible variants. MATERIALS AND METHODS: One hundred and seventy-three cases of paracoccidioidomycosis presented between 1970 and 1980 were reviewed, including their radiological workup reanalysis by at least two experienced radiologists. RESULTS: Ninety-four cases were pulmonary only and 38 were pulmonary associated with ganglial, visceral and osseous lesions or in association with tuberculosis. There was no pulmonary

Paracoccidioidomicose sistêmica multifocal: desafio diagnóstico por manifestação cutânea tardia Multifocal paracoccidioidomycosis: a diagnostic challenge due to late cutaneous manifestation

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Priscilla Maria Rodrigues Pereira

2011-02-01

Full Text Available No Brasil, a paracoccidioidomicose é uma micose sistêmica endêmica frequente na zona rural e em homens adultos. É relatado caso em agricultor, usuário de drogas ilícitas, com manifestações insidiosas, atingindo rins, pulmões, gânglios, ossos e tardiamente pele, com atraso no diagnóstico e na terapêutica eficaz em mais de um ano. É importante incluir a paracoccidioidomicose como diagnóstico diferencial frente a um quadro sugestivo, mesmo na ausência de lesões cutâneas, para reconhecimento e tratamento precoce, em vista da elevada morbimortalidade desta entidade.Paracoccidioidomycosis is an endemic systemic mycosis in Brazil, frequent in the rural areas and often in adult men. It is reported the case of a farmer, who is an illicit drugs' user, with insidious manifestations affecting kidneys, lungs, lymphonodes, bones and lately, the skin, with a delay of more than one year in the diagnosis and effective therapy It is important to include paracoccidioidomycosis as differential diagnosis, even in the absence of cutaneous lesions, for early recognition and treatment, given the high mortality of this entity.

Humoral response of paracoccidioidomycosis sera in hamsters with different Venezuelan isolates

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Lilian M Spencer

2009-09-01

Full Text Available Humoral response of paracoccidioidomycosis sera in hamsters with different Venezuelan isolates. Paracoccidioidomycosis (PCM is a progressive systemic mycosis caused by the fungus Paraccocidioides brasiliensis (Pb, endemic to Venezuela and Latin America. In this study, eight different Venezuelan isolates obtained from patients with PCM, were inoculated intraperitoneally in Syrian hamsters (Cricetus auratus and studied by immune-serum. Each strain was collected by gently scraping the surface of the culture medium (Sabouraud Dextrose Agar and suspended in 3ml of 0.15 M phosphate-buffered saline. The antigen obtained was called Paraccocidioides brasiliensis Crude Antigen (CAP. Immunoblotting results showed that the immune-sera from hamsters recognized at least 3 bands: one over 200 kDa, and two of 80 and 15-20 kDa. This study suggests that IgG anti-CAP can reveal a significant variability in the eight Venezuelan isolates. Sera from 88 infected hamsters were evaluated by ELISA with eight different CAPs and Western blot with CAP 37383. ELISA results showed that, the antigen of the virulent isolate 37383 had the highest percentage (38% of positivity, while the non-virulent isolate 1458 had the lowest one (13.6%. Furthermore, scanning densitometry revealed that the isolate 37383 had less bands than the non-virulent isolates. These results suggest that the ELISA test with CAP 37383 can detect circulating antibodies, and that this virulent isolate may be useful for the diagnosis of PCM, and to monitor disease responses to treatments. Rev. Biol. Trop. 57 (3: 505-513. Epub 2009 September 30.La Paracoccidioidomicosis (PCM, es una micosis sistémica causada por el hongo Paraccocidioides brasiliensis (Pb, endémica en Venezuela y Latino América. En este estudio ocho diferentes aislados venezolanos, obtenidos de pacientes con PCM, fueron inoculados intraperitonealmente en hámsteres y fueron estudiados por ELISA e inmunoblotting. Los antígenos obtenidos de P

Paracoccidioidomicose crônica multifocal tendo como primeira manifestação o envolvimento palpebral: relato de caso Chronical and multifocal paracoccidioidomycosis having the lid involvement as the first sign: case report

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Tiago Nelson de Oliveira Rassi

2009-12-01

Full Text Available O acometimento ocular da paracoccidioidomicose é raro e quando ocorre é geralmente secundário à disseminação hematogênica. Descrição de um caso de paracococcidioidomicose multifocal em homem de 73 anos com história de trauma contuso no olho direito por pedaço de madeira e que teve como primeira manifestação clínica lesão palpebro-conjuntival. Interroga-se possível infecção primária ocular por contiguidade e alerta-se para a manifestação da doença em idade mais avançada.Ocular involvement of paracoccidioidomycosis is rare and when it occurs it is usually secondary to hematogenic dissemination. A case of multifocal paracoccidioidomycosis in a 73 year-old male after history of blunt trauma in the right eye with a stick of wood that presented as the first clinical sign a lid-conjunctival lesion is described. The possible primary ocular infection spreading by contiguity is argued and the disease manifestation in an advanced age is highlighted.

PARACOCCIDIOIDOMYCOSIS: CHALLENGES IN THE DEVELOPMENT OF A VACCINE AGAINST AN ENDEMIC MYCOSIS IN THE AMERICAS

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Carlos. P. TABORDA

2015-09-01

Full Text Available SUMMARYParacoccidioidomycosis (PCM, caused by Paracoccidioides spp, is an important endemic mycosis in Latin America. There are two recognized Paracoccidioides species, P. brasiliensis and P. lutzii, based on phylogenetic differences; however, the pathogenesis and disease manifestations of both are indistinguishable at present. Approximately 1,853 (~51,2% of 3,583 confirmed deaths in Brazil due to systemic mycoses from 1996-2006 were caused by PCM. Antifungal treatment is required for patients with PCM. The initial treatment lasts from two to six months and sulfa derivatives, amphotericin B, azoles and terbinafine are used in clinical practice; however, despite prolonged therapy, relapses are still a problem. An effective Th1-biased cellular immune response is essential to control the disease, which can be induced by exogenous antigens or modulated by prophylactic or therapeutic vaccines. Stimulation of B cells or passive transference of monoclonal antibodies are also important means that may be used to improve the efficacy of paracoccidioidomycosis treatment in the future. This review critically details major challenges facing the development of a vaccine to combat PCM.

Natural antibodies in paracoccidioidomycosis Anticorpos naturais na paracoccidioidomicose

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Carmelinda S. Unterkircher

2004-06-01

Full Text Available Recent attention has been focused on the natural antibodies as a component of natural immunity and as integral part of the idiotypic network. However, their functional role in different infections has rarely been studied. This work was undertaken to investigate the presence of natural antibodies in paracoccidioidomycosis (PCM. In addition, we analyzed anti-P. brasiliensis antibodies and their distribution in IgG subclasses in order to acquire better knowledge about the humoral immune response in this mycosis. Our findings show that the natural antibody response is not very much increased in PCM when compared with other parasite infections and this response is restricted to a few specificities, suggesting that P. brasiliensis moderately triggers CD5+ B cells. The anti-actin antibody was the main antibody specificity found in PCM. Specific antibodies to P. brasiliensis were mainly found in the IgG1 subclass in chronic patients of PCM.Recente atenção tem sido dada aos anticorpos naturais como componentes da imunidade natural e como parte integrante da rede idiotípica. Todavia, seu papel funcional em diferentes infecções tem, raramente, sido estudado. O objetivo deste trabalho foi investigar a presença de anticorpos naturais na paracoccidioidomicose (PCM. Em adição, analisamos os anticorpos específicos anti-P. brasiliensis e sua distribuição em subclasses a fim de adquirir mais conhecimento sobre a resposta imune humoral nesta micose. Nossos achados mostram que a resposta de anticorpos naturais não é acentuada na PCM quando comparada com outras infecções por parasitas e, é restrita a poucas especificidades, sugerindo que o P. brasiliensis estimula moderadamente as células B CD5+. O anticorpo anti-actina foi a principal especificidade encontrada na PCM. Os anticorpos especificos para P. brasiliensis, nos pacientes crônicos, eram, principalmente, da subclasse IgG1.

Gallium-67 scintigraphy for monitoring therapy response and follow-up of paracoccidioidomycosis

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Yamaga, L.Y.; Watanabe, T.; Hironaka, F.; Buchpiguel, C.; Cerri, G.; Benard, G.; Shikanai-Yasuda, M.A.

2002-01-01

Objectives: The current tools to evaluate patients' therapy response in paracoccidioidomycosis (PCM) are based on clinical, immunological and radiological data. However, these criteria may be of limited value in the follow-up of asymptomatic lesions, negative pre-treatment serological tests and in severe pulmonary involvement whose chest radiography usually doesn't differentiate active from fibrotic lesions. The purpose of this study was to determine the value of Ga imaging for monitoring therapy response and follow-up of PCM patients. Methods: We studied 45 patients with confirmed PCM. Each patient underwent 2 to 7 Ga scintigraphies (total:147 scans) during a follow-up period of 4 months to 8,5 years. The Ga findings were compared to the clinical outcome and serum specific antibody levels. Results: Most patients showed improvement in the sequential Ga scans during the treatment with progressive decrease in number and intensity of sites with active infectious process. Ga scan was performed in nine patients with clinical cure and negative or persistently low levels of serum antibody following prolonged treatment. The scintigraphy confirmed the absence of inflammatory disease in all of these cases. Three patients with clinically suspected recurrence after irregular treatment showed positive Ga scans, confirming disease reactivation. Conclusion: Ga imaging is helpful in monitoring therapy response of PCM patients. Moreover, this method may be used to evaluate disease activity by confirming apparent cure and clinical recurrence

Protective effect of the LevRad on treat of paracoccidioidomycosis

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Martins, Estefania M.N.; Andrade, Antero S.R.; Fernandes, Viviane Cristina; Morais, Elis Araujo; Goes, Alfredo M.; Resende, Maria Aparecida de

2011-01-01

Paracoccidioides brasiliensis is the agent of Paracoccidioidomycosis (PCM), the most prevalent deep mycosis of Latin America. The period of treat depend on the chemotherapeutic and the severity of disease and its administration not ensure the complete destruction of the fungus. The search for new alternatives is necessary. The aim of this study was to evaluate the protective effect of yeast cells of P. brasiliensis attenuated by gamma irradiation (LevRad) on therapeutic vaccination of BALB/c. The therapeutic potential of LevRad with or without fluconazole was assessed for the first time, intraperitoneally, in BALB/c, 60 days after intratracheal infection with a highly virulent non-irradiated P.brasiliensis isolate. The animals were divided in five experimental groups: uninfected (C-), infected (C+), infected treated with fluconazole (Inmed), infected treated with LevRad (InRad) and infected treated with fluconazole + LevRad (InRadMed). The organs (lungs, spleen and liver) were collected to analyze CFU (colony forming units) and histology. The sera were used to evaluate the immunization efficacy, and to assess IgG subtypes (IgG1, IgG2a, IgG2b, IgG3) and total IgG levels. There was significant decrease in the CFU counts of the lungs of InMed, InRadMed and InRad. No were visualized histopathological alterations in the organs of these groups, except in InRad there was granulomatous lesions unifocal, little and discrete. The levels of IgG and its subtypes IgG2a, IgG2b increased, probably due to the increase of cytokines that promote switching to these isotypes. These preliminary results can provide new prospect for immunotherapy of PCM, but it will be necessary new studies to evaluate administration dose and period treatment. (author)

Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis.

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Christopher A Desjardins

2011-10-01

Full Text Available Paracoccidioides is a fungal pathogen and the cause of paracoccidioidomycosis, a health-threatening human systemic mycosis endemic to Latin America. Infection by Paracoccidioides, a dimorphic fungus in the order Onygenales, is coupled with a thermally regulated transition from a soil-dwelling filamentous form to a yeast-like pathogenic form. To better understand the genetic basis of growth and pathogenicity in Paracoccidioides, we sequenced the genomes of two strains of Paracoccidioides brasiliensis (Pb03 and Pb18 and one strain of Paracoccidioides lutzii (Pb01. These genomes range in size from 29.1 Mb to 32.9 Mb and encode 7,610 to 8,130 genes. To enable genetic studies, we mapped 94% of the P. brasiliensis Pb18 assembly onto five chromosomes. We characterized gene family content across Onygenales and related fungi, and within Paracoccidioides we found expansions of the fungal-specific kinase family FunK1. Additionally, the Onygenales have lost many genes involved in carbohydrate metabolism and fewer genes involved in protein metabolism, resulting in a higher ratio of proteases to carbohydrate active enzymes in the Onygenales than their relatives. To determine if gene content correlated with growth on different substrates, we screened the non-pathogenic onygenale Uncinocarpus reesii, which has orthologs for 91% of Paracoccidioides metabolic genes, for growth on 190 carbon sources. U. reesii showed growth on a limited range of carbohydrates, primarily basic plant sugars and cell wall components; this suggests that Onygenales, including dimorphic fungi, can degrade cellulosic plant material in the soil. In addition, U. reesii grew on gelatin and a wide range of dipeptides and amino acids, indicating a preference for proteinaceous growth substrates over carbohydrates, which may enable these fungi to also degrade animal biomass. These capabilities for degrading plant and animal substrates suggest a duality in lifestyle that could enable pathogenic

Paracoccidioidomicose: centenário do primeiro relato de caso Paracoccidioidomycosis: a century from the first case report

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Silvio Alencar Marques

2008-06-01

Full Text Available Há 100 anos Adolpho Lutz publicava relato pioneiro de enfermidade descrita como mycose pseudococcidica, hoje paracoccidioidomicose, em que discorria sobre suas manifestações clínico-histopatológicas e micológicas. Com precisão, em abril de 1908, descreveu que "O agrupamento de corpúsculos kysticos é bastante característico. Geralmente há um maior no centro e outros pequenos em redor, o que sempre me produziu a impressão de resultar de um processo de gemmação". Inaugurava-se novo campo para investigações científicas.One hundred years ago Adolpho Lutz published published the frist report of a patient with paracoccidioidomycosis, then referred as mycosis pseudococcidica. in his original article published in April 1908, he accurately informed that "The arrangement of cystic corpuscles is highly characteristic. Generally one finds a large central corpuscle surrounded by small ones, and this feature has always left me under the impression that it is the results of a gemulation process" A new field of scientific research was then opened.

Paracoccidioidomicosis perianal asociada a lepra lepromatosa: Presentación de un caso clínico Perianal paracoccidioidomycosis associated with lepromatous leprosy: A clinical case report

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M A Reyes

2008-06-01

Full Text Available Se presenta el caso de un paciente alcoholista con una ulceración perianal y manifestaciones cutáneas de enfermedad de Hansen. La biopsia de la lesión perianal y otros estudios arribaron al diagnóstico de una forma diseminada de paracoccidioidomicosis, así como también las biopsias cutáneas y los estudios baciloscópicos fueron diagnósticos de lepra lepromatosa. La respuesta a la terapéutica fue satisfactoria con desaparición de las lesiones cutáneas. La disminución de la respuesta inmunológica celular genera un terreno propicio para la infección de estos gérmenes y al compartir área endémica la asociación entre ambas patologías puede ocurrir.Lepra and Paracoccidioidomycosis are endemic diseases in Argentina. We report a case of a patient with an unusual perianal ulceration and cutaneous manifestations of Hansen's disease. The biopsy of perianal lesion and subsequent studies revealed a disseminated form of paracoccidioidomycosis, as well as skin biopsy and baciloscopic finding diagnostic of Lepromatous Leprosy. The main portal of entry of paracoccidioides is the lung. Hematogenous dissemination of the fungus may occur at this time, with the establishment of metastatic foci in any organ. Anal and perianal lesions are present only in 1.3 to 2.4% of the patients. The pathogenesis of anal lesions remains unclear, it may be secondary from a systemic or a local disease. The patient response to the therapeutic was notable, with disappearance of lesions up to the third month of started itraconazole orally 400 mg/day leading just atrophy scars in perianal areas. The treatment of Hansen's disease was made according to OMS guidelines for multibacillary disease.

Retrospective seroepidemiological analysis of patients with suspicion of paracoccidioidomycosis in São Paulo State, Brazil

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CM Kamikawa

2012-01-01

Full Text Available The geographic distribution of paracoccidioidomycosis (PCM in the Brazilian state of São Paulo was evaluated in a retrospective study using secondary data from serological analyses, carried out by double immunodiffusion assay of patients with PCM suspicion, from January 1999 to May 2010. Sixty percent of 10,176 patients, from 239 cities, were serologically reactive to P. brasiliensis. The cities that showed the most serological reactivity among patients were São João da Boa Vista (85%, Piracicaba (75%, Sorocaba (73%, Campinas (72% and São Paulo (62%. São Paulo state has an area of 248,209.4 km²; the climate is tropical and sub-tropical with annual temperatures between 18 and 24ºC, high rainfall (900 to 1800 mm/year, rainy summers and mild winters. It also features large areas composed of acidic soils, and is one of the greatest contributors to Brazilian agricultural production and, separately, the largest producer of orange juice and, the ninth greatest producer of soy and sugar cane and the fourth largest coffee producer. We suggest that the climatic characteristics associated with soil type and development of primary activities can contribute to the endemic potential of PCM in São Paulo state.

Voice disorders in residual paracoccidioidomycosis in upper airways and digestive tract.

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da Costa, Ananda Dutra; Vargas, Amanda Pereira; Lucena, Marcia Mendonça; Ruas, Ana Cristina Nunes; Braga, Fernanda da Silva Santos; Bom-Braga, Mateus Pereira; Bom-Braga, Frederico Pereira; do Valle, Antonio Carlos Francesconi; Igreja, Ricardo Pereira; Valete-Rosalino, Cláudia Maria

Paracoccidioidomycosis (PCM) is a systemic mycosis of acute and chronic evolution, caused by species belonging to the genus Paracoccidioides. It is considered the most prevalent systemic endemic mycosis in Latin America, with cases in the tropical and subtropical regions. Residual PCM refers to the fibrotic scar sequelae resulting from the disease treatment which, when associated with collagen accumulation, leads to functional and anatomic alterations in the organs. The aim of this study was to evaluate the vocal function of patients with residual PCM in upper airways and digestive tract. We performed a cross-sectional study in 2010 in a cohort of 21 patients with residual PCM in upper airways and digestive tract. The average age was 49.48±9.1 years, and only two (9.5%) patients were female. The study was performed in the 1-113 month-period (median 27) after the end of drug treatment. Five (23.8%) patients had alterations in the larynx as a sequela of the disease. However, all patients had vocal changes in vocal auditory perceptual analysis by GRBASI scale. The computerized acoustic analysis using the software Vox Metria, showed that 11 patients (52.4%) presented alterations in jitter, 15 (71.4%) in shimmer, 8 (38.1%) in F0, 4 (19%) in glottal to noise excitation (GNE), 7 (33.3%) in the presence of noise and 12 (57.1%) in the presence of vibratory irregularity. The great frequency of alterations in residual PCM suggests that the patients in such phase could benefit from a multidisciplinary treatment, offering them integral monitoring of the disease, including speech rehabilitation after the PCM is healed. Copyright © 2017 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.

Dendritic Cells Primed with Paracoccidioides brasiliensis Peptide P10 Are Therapeutic in Immunosuppressed Mice with Paracoccidioidomycosis

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Leandro B. R. Silva

2017-06-01

Full Text Available Paracoccidioidomycosis (PCM is an endemic systemic mycosis in Latin America, with the highest prevalence in Brazil, Colombia, and Venezuela. Fungi of the Paracoccidioides genus are etiologic agents of the disease. The 15 amino acid peptide P10 is derived from gp43, the main diagnostic antigen of Paracoccidioides brasiliensis. We previously reported that P10-pulsed dendritic cells (DCs induce a protective response against P. brasiliensis. Presently, dexamethasone-treated BALB/c mice were intratracheally infected with P. brasiliensis Pb18 to establish the therapeutic efficacy of P10-pulsed DCs. Immunosuppressed and infected animals that received DCs had a reduction in their fungal burden, and this result was most pronounced in mice receiving DCs primed with P10. The efficacy of therapeutic DCs was significantly augmented by concomitant treatment with trimethoprim-sulfamethoxazole. Additionally, primed-DCs with or without the antifungal drug induced a beneficial Th1-biased immune response and significantly reduced tissue damage. In conclusion, these studies with immunocompromised mice demonstrate that P10-pulsed DCs with or without concomitant antifungal drugs are potently effective in combating invasive PCM. These findings support further translational studies to validate the use of P10-primed DCs for PCM in immunocompetent and immunosuppressed hosts.

Paracoccidioidomycosis in southern Rio Grande do Sul: a retrospective study of histopathologically diagnosed cases

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Silvana Pereira de Souza

2014-01-01

Full Text Available Paracoccidioidomycosis (PCM is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis and is endemic to Brazil. The aim of this study was to perform a retrospective analysis of the PCM cases in the countryside south of Rio Grande do Sul, Brazil. The files from four histopathology laboratories located in the city of Pelotas were obtained, and all of the epidemiological and clinical data from the PCM diagnosed cases were collected for analysis. A total of 123 PCM cases diagnosed between 1966 and 2009 were selected. Of these patients, 104 (84.5% were male, and 17 were female. The patients ranged from 02 to 92 years of age. Fifty-two cases (41.9% were obtained from the oral pathology laboratory, and the remaining 71 cases (58.1% were obtained from the three general pathology laboratories. Of all of the patients studied, 65.2% lived in rural zones and worked in agriculture or other related fields. Data on the evolution of this disease was available for 43 cases, and the time frame ranged from 20 to 2920 days (mean = 572.3 days. An accurate diagnosis performed in less than 30 days only occurred in 21% of the cases. PCM is endemic to the countryside of Rio Grande do Sul. Therefore, it is recommended that PCM be included as a differential diagnosis, mainly for individuals between 30 and 60 years of age, living in rural zones and who have respiratory signs and associated-oropharyngeal lesions.

Functional and phenotypic evaluation of eosinophils from patients with the acute form of paracoccidioidomycosis.

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Braga, Fernanda Gambogi; Ruas, Luciana Pereira; Pereira, Ricardo Mendes; Lima, Xinaida Taligare; Antunes, Edson; Mamoni, Ronei Luciano; Blotta, Maria Heloisa Souza Lima

2017-05-01

Eosinophilia is a typical finding of the acute/juvenile form of paracoccidioidomycosis (PCM), a systemic mycosis endemic in Latin America. This clinical form is characterized by depressed cellular immune response and production of Th2 cytokines. Moreover, it has been shown that the increased number of eosinophils in peripheral blood of patients returns to normal values after antifungal treatment. However, the role of eosinophils in PCM has never been evaluated. This study aimed to assess the phenotypic and functional characteristics of eosinophils in PCM. In 15 patients with the acute form of the disease, we detected expression of MBP, CCL5 (RANTES) and CCL11 (eotaxin) in biopsies of lymph nodes and liver. In addition, there were higher levels of chemokines and granule proteins in the peripheral blood of patients compared to controls. Isolation of eosinophils from blood revealed a higher frequency of CD69+ and TLR2+ eosinophils in patients compared to controls, and a lower population of CD80+ cells. We also evaluated the fungicidal capacity of eosinophils in vitro. Our results revealed that eosinophils from PCM patients and controls exhibit similar ability to kill P. brasiliensis yeast cells, although eosinophils of patients were less responsive to IL-5 stimulation than controls. In conclusion, we suggest that eosinophils might play a role in the host response to fungi and in the pathophysiology of PCM by inducing an intense and systemic inflammatory response in the initial phase of the infection.

The contribution of ultrasonography and computed tomography in the evaluation of abdominal involvement in paracoccidioidomycosis

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Paula, Ivie Braga de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Radiologia; Pedroso, Enio Roberto Pietra; Ferreira, Cid Sergio, E-mail: enio@medicina.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Fac. de Medicina

2014-01-15

Introduction: paracoccidioidomycosis (PCM) is a polymorphic systemic granulomatous inflammatory disease determined by Paracoccidioides brasiliensis, one of the 10 leading causes of morbidity and mortality among the parasitic diseases endemic in Brazil. Objective: To identify the following aspects of PCM by ultrasound (US) and computed tomography (CT): abdominal changes, intensity and characteristics of the observed images, frequency of changes depending on clinical presentation, differences from other nosological entities. Patients and methods: This was a retrospective, observational, cross-sectional study carried out with 35 patients with PCM treated at the Hospital das Clinicas (HC) at the Universidade Federal de Minas Gerais (UFMG). Patients with tuberculosis, bronchial asthma, generalized chronic obstructive pulmonary disease, or in contact with silica or mines, as well as those with granulomatous diseases at any point in their current or past clinical history and detected through serology, anatomopathology or microbiological exams were excluded. Collected data were transcribed into SPSS for Windows® for statistical analysis. The study was approved by the UFMG Ethics Committee (082/00). Results and conclusion: CT and U.S. showed involvement of abdominal organs in all forms of PCM, including lymphadenopathy (40%), hepatomegaly (37%), splenomegaly (37%) and adrenal involvement (17%). Gallbladder and retroperitoneal musculature involvement were also observed, along with ascites and pleural effusion. Lymph node calcification, adrenal involvement and ascites constituted evidence of high probability of PCM even though these findings are not enough to differentiate PCM from tuberculosis. Chronic and sequelae forms, abdominal involvement is more frequent than indicated by the clinical manifestations. (author)

The function of the adrenal cortex in patients with paracoccidioidomycosis: a study by radioimmunoassay of plasma ACTH

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Tendrich, M.; Vaisman, M.; Pedrosa, P.N.; Guimaraes, M.M.; Cordeiro, J.G.H.

1987-01-01

Fifteen patients with paracoccidioidomycosis were studied: ten with the chronic disseminated form (adult types), 4 with the acute or subacute disseminated form (juvenile type) and 1 with the progressive pulmonary form. Ten patients reported no previous treatment and 5 had relapse of the disease. In all cases P. brasiliensis was demonstrated in specimens obtained from the lesions by direct microscopy (KOH), histopathology and/or culture. The adrenocortical function was evaluated by means of basal plasma determination of ACTH and cortisol, and 24 hour urine determination of 17 hydroxisteroids (17 OHCS); after stimulation by ACTH determinations were repeated. Patients were classified in 3 groups: 1) plasma ACTH 58 pg/ml. According to the correlation between ACTH and cortisol level after simulation test 8 patients were classified in group 1, 2 of them with cortisol response lower than twice the basal levels; four patients were classified in group 3. All them had ACTH levels definitely above the normal, 2 of them had no cortisol response after stimulation in addition to signs and symptoms of Addison's disease, thus fulfilling the criteria of primary adrenal insufficiency. The correlation between ACTH and 17 OHCS after stimulation test demonstrated that in 7 out of 8 patientes from group 1 response was lower than twice the basal and that in 3 out of 4 patientes from group 3 proven primary adrenal insufficiency was present. (The other patient showed a 17 OHCS response three times higher than the basal levels). (author) [pt

Paracoctidioidomicose: atendimento a nível de assistência primária a saúde The treatment of paracoccidioidomycosis at primary health level

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Sérgio Pripas

1988-06-01

Full Text Available Discute-se o tratamento de pacientes com paracoccidioidomicose a nível de assistência primária a saúde. Foram tratados 8 pacientes no Centro de Saúde I, de São Carlos, SP (Brasil, empregando-se o cetoconazol, durante um ano, na dose de 400 mg diários, em uma única tomada. Em todos os pacientes tratados, houve remissão do quadro clínico e melhora dos exames laboratoriais. Não houve relato de efeitos colaterais. Conclui com proposta de tratamento da paracoccidioidomicose, a nível de rede básica de saúde.The treatment of paracoccidioidomycosis, with ketoconazole, at public health level is discussed. Eight patients were treated with single daily doses of 400 mg of ketoconazole for one year. The patients were treated at Health Center I in S. Carlos, Brazil. All patients treated showed clinical remission and an improvement in radiological findings. No side-effects were reported. The benefits of this treatment at Health Centers, under the administrative, social and economic aspects are stressed.

Paracoccidioidomycosis in a western Brazilian Amazon State: Clinical-epidemiologic profile and spatial distribution of the disease

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Gabriel de Deus Vieira

2014-01-01

Full Text Available Introduction: Paracoccidioidomycosis (PCM is a systemic infection caused by the fungus Paracoccidioides brasiliensis. PCM is considered one of the most important systemic mycoses in Latin America. Methods: This is a clinical, epidemiological, retrospective, quantitative study of PCM cases in patients attending the National Health Service in the State of Rondônia in 1997-2012. The examined variables included sex, age group, year of diagnosis, education level, profession, place of residence, diagnostic test, prior treatment, medication used, comorbidities and case progress. Results: During the study period, 2,163 PCM cases were registered in Rondônia, and the mean annual incidence was 9.4/100,000 people. The municipalities with the highest rates were located in the southeastern region of Rondônia, and the towns of Pimenteiras do Oeste and Espigão do Oeste had the highest rates in the state, which were 39.1/100,000 and 37.4/100,000 people, respectively. Among all cases, 90.2% and 9.8% were observed in men and women, respectively, and most cases (58.2% were observed in patients aged between 40 and 59 years. Itraconazole was used to treat 91.6% (1,771 of cases, followed by sulfamethoxazole in combination with trimethoprim (4.4% [85] of cases. One hundred thirty-one (6% patients died. Conclusions: The State of Rondônia has a high incidence of PCM, and the municipalities in the southeastern region of the state were found to have the highest incidence rates of this disease. Our findings suggest that Rondônia is the state in the northern region with the highest mortality rate for PCM.

Production of TNF-α, nitric oxide and hydrogen peroxide by macrophages from mice with paracoccidioidomycosis that were fed a linseed oil-enriched diet.

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Sargi, Sheisa Cyléia; Dalalio, Márcia Machado de Oliveira; Visentainer, Jesuí Vergílio; Bezerra, Rafael Campos; Perini, João Ângelo de Lima; Stevanato, Flávia Braidotti; Visentainer, Jeane Eliete Laguila

2012-05-01

Omega-3 polyunsaturated fatty acids (n-3 PUFA) can modulate the immune system and their primary effect is on macrophage function. Paracoccidioidomycosis (PCM) is an endemic systemic mycosis in Latin America that is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb). Macrophages are the main defence against this pathogen and have microbicidal activity that is dependent on interferon-Γ and tumour necrosis factor (TNF)-α. These cytokines stimulate the synthesis of nitric oxide (NO) and hydrogen peroxide (H₂O₂), leading to the death of the fungus. To study the effect of n-3 PUFA on the host immune response during experimental PCM, macrophages that were obtained from animals infected with Pb18 and fed a diet enriched by linseed (LIN) oil were cultured and challenged with the fungus in vitro. The macrophage function was analysed based on the concentrations of TNF-α, NO and H₂O₂. LIN oil seems to influence the production of TNF-α during the development of disease. A diet enriched with LIN oil influences the microbicidal activity of the macrophages by inducing the production of cytokines and metabolites such as NO and H₂O₂, predominantly in the chronic phase of infection.

The most common otorhinolaryngologic manifestations of granulomatous diseases

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Heshiki, Rosana Emiko

2008-09-01

Full Text Available Introduction: Granulomatous diseases result from immunopathologic processes in which there is a failure in the fagocitosis of intracellular organisms. They can cause oral, nasal and pharyngeal mucosa ulcers, vocal cords lesions, otorrhoea and oropharyngeal vegetant lesions. Objective: Describing the most frequent otorhinolaryngologic manifestations in common granulomatous diseases: hanseniasis, paracoccidioidomycosis, leishmaniasis. Method: A retrospective study has been carried out from records of patients diagnosed with the abovementioned diseases between January 1, 2005 and October 31, 2007 in an infectology ambulatory of a tertiary hospital. Results: 142 patients were evaluated; 93 with leishmaniasis, 39 with paracoccidioidomycosis and 10 with hanseniasis. In 93 cases of leishmaniasis, 16 (17.2% had mucosal affection, and the most common signs were septum perforation and nasal mucosal ulcers, both with 8 cases. In paracoccidioidomycosis, oropharyngeal ulcer was the most frequent, with 15 cases (38,4%. Conclusion: Head and neck signs and symptoms are common in patients with leishmaniasis and paracoccidioidomycosis. Nasal manifestations prevail in leishmaniasis and oropharyngeal ones in paracoccidioidomycosis.

Incubation Period and Early Natural History Events of the Acute Form of Paracoccidioidomycosis: Lessons from Patients with a Single Paracoccidioides spp. Exposure.

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Buccheri, Renata; Khoury, Zarifa; Barata, Luis Carlos Barradas; Benard, Gil

2016-06-01

Several aspects of the natural history of paracoccidioidomycosis are still poorly understood. Different from the most prevalent, chronic form of the disease, the acute form represents a continuum from the initial respiratory infection to the full-blown disease, thus providing an opportunity to elucidate the pathogenesis of the early phase of this mycosis. We describe, for the first time, two patients with a single time point exposure to Paracoccidioides spp., for whom we were able to determine the time lapsed between exposure to the fungus Paracoccidioides spp. and the onset of signs and symptoms. In case 1, the pulmonary infection was unapparent, and the first manifestations of the acute/subacute form of the disease presented 4 months after Paracoccidioides spp. In case 2, self-limited, non-specific respiratory and systemic symptoms presented 45 days after infection. Thus, our patients confirm that, within a few weeks of infection, Paracoccidioides spp. affects the pulmonary lymphatic system and initially causes no or mild-to-moderate self-limited symptoms, eventually causing abnormalities on a chest X-ray, all of which spontaneously subside. These cases provide some insight into the natural history of this mycosis, the extent of the host exposure to the fungus, and the determination of its incubation period.

Emergence of acute/subacute infant-juvenile paracoccidioidomycosis in Northeast Argentina: Effect of climatic and anthropogenic changes?

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Giusiano, Gustavo; Aguirre, Clarisa; Vratnica, Claudia; Rojas, Florencia; Corallo, Teresa; Cattana, María Emilia; Fernández, Mariana; Mussin, Javier; de Los Angeles Sosa, María

2018-01-13

Argentina has two endemic areas of paracoccidioidomycosis (PCM). Bordering Paraguay and Brazil, Northeast Argentina (NEA) comprises the area with the highest incidence where the chronic adult clinical form has historically been reported. Juvenile form in children and adolescents is rare in this area since only one case was reported in the last 10 years. Despite this, between 2010 and 2012, several cases of acute/subacute clinical forms in children aged 10 to 16 (median 12) were detected. In the last decade, the NEA region has been exposed to ecological variations as consequences of certain climatic and anthropogenic changes, including El Niño-Southern Oscillation phenomenon during 2009, and deforestation. The region has also suffered from the significant ecological effects of the construction of one of the biggest hydroelectric dams of South America. This study aims to describe clinical and epidemiological aspects of acute/subacute PCM cases detected in children from NEA and to discuss climatic and anthropogenic changes as possible contributing factors in the emergence of this disease in children. This acute/subacute PCM cluster was characterized by severe disseminated and aggressive presentations to localized form, with a high spectrum of clinical manifestations uncommonly observed. Due to the lack of experience in acute/subacute PCM in children in the studied area and the atypical clinical manifestations observed, the diagnosis was delayed. In order to avoid misdiagnosis, a higher level of suspicion is now required in NEA and countries bordering the southern part of the endemic area, which are affected by the changes discussed in this article. © The Author(s) 2018. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Production of TNF-α, nitric oxide and hydrogen peroxide by macrophages from mice with paracoccidioidomycosis that were fed a linseed oil-enriched diet

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Sheisa Cyléia Sargi

2012-05-01

Full Text Available Omega-3 polyunsaturated fatty acids (n-3 PUFA can modulate the immune system and their primary effect is on macrophage function. Paracoccidioidomycosis (PCM is an endemic systemic mycosis in Latin America that is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb. Macrophages are the main defence against this pathogen and have microbicidal activity that is dependent on interferon-Γ and tumour necrosis factor (TNF-α. These cytokines stimulate the synthesis of nitric oxide (NO and hydrogen peroxide (H2O2, leading to the death of the fungus. To study the effect of n-3 PUFA on the host immune response during experimental PCM, macrophages that were obtained from animals infected with Pb18 and fed a diet enriched by linseed (LIN oil were cultured and challenged with the fungus in vitro. The macrophage function was analysed based on the concentrations of TNF-α, NO and H2O2. LIN oil seems to influence the production of TNF-α during the development of disease. A diet enriched with LIN oil influences the microbicidal activity of the macrophages by inducing the production of cytokines and metabolites such as NO and H2O2, predominantly in the chronic phase of infection.

Hipercalcemia e lesões osteolíticas múltiplas em criança com paracoccidioidomicose disseminada e tuberculose pulmonar Hypercalcemia and multiple osteolytic lesions in a child with disseminated paracoccidioidomycosis and pulmonary tuberculosis

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Antonia T. Tresoldi

2005-08-01

Full Text Available OBJETIVO: Descrever o caso de uma criança com paracoccidioidomicose, que apresentou hipercalcemia associada a múltiplas lesões osteolíticas. DESCRIÇÃO: Menino de 6 anos, internado com história de febre e hepatoesplenomegalia há 1 mês. À internação, apresentava-se em regular estado geral, descorado, com linfonodomegalia generalizada e hepatoesplenomegalia. Os exames laboratoriais identificaram anemia (hemoglobina = 6,8 g/dl, eosinofilia (1.222/mm³, plaquetopenia (102.000/mm³ e hipoalbuminemia (albumina = 2,2 g/dl. Paracoccidioides brasiliensis foi identificado no mielograma. A partir da segunda semana de internação, apresentou artralgia, hipoatividade e dificuldade à deambulação, sendo constatada hipercalcemia (dosagem máxima de 14,9 mg% e redução da função renal, que duraram pouco mais de 2 semanas. No 42º dia de internação, foram vistas, na radiografia de tórax, múltiplas lesões líticas em clavículas, escápulas, costelas e úmeros, com escorregamento epifisário de úmero bilateral. Apresentou nefrocalcinose e nefrolitíase, com redução no clearance de creatinina e evidências de lesão tubular. No final do segundo mês de internação, na cultura do lavado gástrico, foi identificado Mycobacterium tuberculosis. Recebeu tratamento para paracoccidioidomicose e tuberculose e está há mais de 3 anos em acompanhamento, sem nenhuma seqüela. COMENTÁRIOS: O desenvolvimento da hipercalcemia sintomática, levando à lesão renal e associada a lesões ósseas múltiplas e disseminadas, nunca foi descrito em paracoccidioidomicose. Embora tenha sido diagnosticada tuberculose pulmonar, que pode estar relacionada à hipercalcemia, a forma abrupta como se instalou e como se normalizou sem o tratamento específico para tuberculose sugere que a lise óssea foi o fator mais importante na gênese da hipercalcemia.OBJECTIVE: To describe the case of a child with paracoccidioidomycosis who presented hypercalcemia with multiple

Fungal infections of the mucous membrane.

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Marques, Silvio Alencar

2010-01-01

A clinical review of three potentially severe fungal diseases, which are characterized in many cases by mucosal involvement, is presented. They are paracoccidioidomycosis, histoplasmosis, and mucormycosis. Mucosal involvement for paracoccidioidomycosis and rhinocerebral mucormycosis is frequent. Thus, oral involvement may provide early clue for diagnosis. In paracoccidioidomycosis, the mucosal lesion classically shows superficial ulcers with granular appearance and hemorrhagic points, usually on lips, palate, and jugal mucosa. In mucormycosis, necrosis of the palate followed for purulent discharge is a hallmark of rhinocerebral disease. Treatment with amphotericin B desoxycholate or the new second-generation triazoles is highly efficacious.

In pulmonary paracoccidioidomycosis IL-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology.

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Tânia A Costa

Full Text Available BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM, the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and IL-10(-/- C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb infection. We verified that Pb-infected peritoneal macrophages from IL-10(-/- mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO and MCP-1. For in vivo studies, IL-10(-/- and WT mice were i.t. infected with 1×10(6 Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(-/- mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(-/- mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+ and CD8(+ T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a

Paracoccidioidomycosis in children in the state of Rio de Janeiro (Brazil: Geographic distribution and the study of a "reservarea"

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A. J. RIOS GONÇALVES

1998-01-01

Full Text Available Thirty six cases of acute disseminated paracoccidioidomycosis in 3 to 12 year-old children, natives of the state of Rio de Janeiro, were seen in the period 1981-1996. All patients were residents in the rural region of 15 counties, scattered on the Southwestern part of this state. The rural region of two neighboring counties, where 16 cases (44.4% occurred, was visited. It exhibited the environmental conditions that are considered favorable to the survival of P. brasiliensis. The most important of these conditions, abundant watercourses and autochthonous forest, are distributed on well defined and limited areas, in which the dwellings are also localized. Probably, a careful epidemiological study of forthcoming cases of the disease in children may facilitate the search for the micro-niche of the fungus.No período 1981-1996 foram observados 36 casos de paracoccidioidomicose aguda disseminada em crianças, entre 3 e 12 anos de idade, nativas do estado do Rio de Janeiro. Todos os pacientes residiam em região rural, distribuída por 15 municípios localizados na parte sudoeste do estado. Dois municípios vizinhos, onde haviam ocorrido 16 (44,4% dos casos, foram visitados. Na região rural de ambos, existem as condições climáticas e ambientais favoráveis à sobrevivência do P. brasiliensis. Dentre essas condições, as mais importantes, abundantes cursos de água e vegetação nativa, distribuem-se em áreas limitadas e bem definidas. Nessas áreas localizam-se, também, as casas dos rurículas. Provavelmente, um cuidadoso estudo epidemiológico de novos casos, que venham a ocorrer na região, facilitará a busca do nicho do fungo

Un caso excepcional de paracoccidioidomicosis e histoplasmosis pulmonares de presentación concomitante Concomitant pulmonary paracoccidioidomycosis and pulmonary histoplasmosis: a rare case

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Veronica Torres Esteche

2012-04-01

Full Text Available La incidencia de las micosis pulmonares en Uruguay es muy baja, y estas usualmente aparecen en pacientes inmunocomprometidos. Se discute el caso de un paciente inmunocompetente proveniente de área rural, que presenta tos, disnea y fiebre de dos meses de evolución. La imagenología mostró una neumonitis extensa y fibrosis pulmonar. Los test micológicos directos, cultivo y serológicos muestran histoplasmosis y paraccocidioidomicosis en forma concomitante. El paciente presentó hipotensión arterial diagnosticándose una insuficiencia suprarrenal. A pesar de que la extensa fibrosis pulmonar y la neumonitis no fueron reversibles, el paciente mejoró clínicamente con el tratamiento antifúngico. Se trata de un caso excepcional de dos micosis pulmonares en un mismo paciente.The incidence of pulmonary fungal infections is very low in Uruguay, and such infections typically affect immunocompromised patients. We report the case of an immunocompetent patient presenting with a two-month history of cough, dyspnea, and fever. The patient resided in a rural area. Imaging tests revealed extensive pneumonitis and pulmonary fibrosis. On the basis of direct mycological examination, culture, and serological testing, we made a diagnosis of concomitant histoplasmosis and paracoccidioidomycosis. The patient presented arterial hypotension that was diagnostic of adrenocortical insufficiency. Although the pulmonary fibrosis and pneumonia were irreversible, the clinical condition of the patient improved after antifungal treatment. This was an exceptional case of two pulmonary fungal infections occurring simultaneously in the same patient.

DISSEMINATED FUNGAL INFECTION WITH ADRENAL INVOLVEMENT: REPORT OF TWO HIV NEGATIVE BRAZILIAN PATIENTS

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Graziella Hanna PEREIRA

2015-12-01

Full Text Available Paracoccidioidomycosis and histoplasmosis are systemic fungal infections endemic in Brazil. Disseminated clinical forms are uncommon in immunocompetent individuals. We describe two HIV-negative patients with disseminated fungal infections, paracoccidioidomycosis and histoplasmosis, who were diagnosed by biopsies of suprarenal lesions. Both were treated for a prolonged period with oral antifungal agents, and both showed favorable outcomes.

Avaliação Do Tratamento Da Paracoccidioidomicose Com O Ketoconazol Evaluation of ketoconazole in the treatment of paracoccidioidomycosis

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Jussara Marcondes

1984-04-01

Full Text Available Foram, tratados 12 doentes atendidos na Disciplina de Moléstias Infecciosas e Parasitárias da Faculdade de Medicina de Botucatu com diagnóstico etiológico de paracoccidioidomicose que apresentavam lesões orgânicas múltiplas e evolução prolongada. O tratamento foi realizado por 18 meses, com o ketoconazol, pela via oral, nas doses diárias de 400 mg no primeiro mês e de 200 mg nos meses seguintes. Todos os doentes foram acompanhados durante o tratamento e, em média 4 meses e meio após o mesmo, clínica, radiológica e sorologicamente pelas reações de imunofluorescência indireta, precipitinas e imunodifusão em gel. A competência imunitária foi avaliada em todos os doentes antes do tratamento e repetida em quatro, no final do mesmo. Os resultados mostraram que houve recaída em 5 doentes. A droga foi bem tolerada e a imunodifusão em gel e a hemossedimentação foram as provas que mostraram maior paralelismo com a evolução clínica.Twelve patients with chronical and sistemic lesions due to paracoccidioidomycosis were treated with Ketoconazole. The treatment lasted for 18 months and the Ketoconazole was ad ministered by oral route, in a once a day do sage of 400 mg during the first month and of 200 mg in the next 17 months. All patients were evaluated in the course of the treatment as well as for 135 days after the end of it, by means of clinical picture, chest X-Ray and serological tests. The immune response was observed in all patients before the treatment and in 4 of them at the end of it. Results showed that there was recrudescence in 5 patients and side effect was observed in only one patient (pruritus. The agar-gel difusion and the sedimentation rate were the laboratorial findings which paralleled the best the clinical picture.

Paracoccidioidomicose em hemisfério cerebral e tronco encefálico: relato de caso Paracoccidioidomycosis in cerebral hemisphere and brainstem: case report

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Manoel Baldoino Leal Filho

2006-09-01

Full Text Available Relata-se sobre um homem de 36 anos com passagem quatro anos antes pela selva amazônica. Admitido após seis meses do aparecimento progressivo de tetraparesia, ataxia de marcha, disfagia, disartria, dispnéia e soluço. A ressonância magnética revelou lesão parietoccipital à direita e no bulbo, sendo esta última maior. Investigações para tuberculose e síndrome da imunodeficiência adquirida tiveram resultados negativos. Foi submetido a microcirurgia da lesão do bulbo. O estudo anatomopatológico revelou paracoccidioidomicose. Recebeu tratamento com anfotericina B até 2100 mg, e sulfametoxazol-trimetoprim por três meses, e fisioterapia. Voltou às atividades após seis meses do término do tratamento. Comenta-se sobre a participação do sistema imunológico e das citocinas (interleucinas.We report on a 36 years-old man that had been at the Amazon forest four years before. Six months before the admission he had developed a progressive quadriparesis, gait ataxia, dysphagia, dysarthria, difficulty in breathing and hiccup. The gadolinium-enhanced T1-weighted MRI showed a lesion into the right parietoccipital area and another into the medulla, that was the largest. There was any evidence of tuberculosis or AIDS. The patient was submitted to microsurgical approach to the medulla. Pathological examination revealed paracoccidioidomycosis. Treatment with anphotericin B till 2100mg was administered followed by sulfamethoxazole-trimetoprim for three months plus physical therapy. The patient went back to his activities six months after the end of the treatment. Comments are presented about the participation of the immunological system and of the cytokines (interleukines.

Tracheoesophageal fistula associated with paracoccidioidomicosis

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Antonio Carlos Nogueira

2011-09-01

Full Text Available Paracoccidioidomycosis is a systemic fungal disease caused byParacoccidioides brasiliensis, agent geographically distributed to certainareas of Central and South America. The infection by P. brasiliensis hasbeen reported from north Mexico to south Argentina. Paracoccidioidomycosispresents similar clinical findings of many other diseases whatever in acute or chronic scenarios. Chronic pulmonary paracoccidioidomycosis is frequentlymisdiagnosed as malignancy or tuberculosis. The authors present a caseof a 57 year-old man admitted to the hospital due to a chronic consumptivesyndrome. He underwent anti-tuberculous treatment with rifampin, isoniazid andpyrazinamide 1 year ago without resolution of the simptoms. During the clinicalinvestigation, pulmonary paracoccidioidomycosis with tracheoesophagealfistula was diagnosed. The systemic infection was treated with deoxicolate Bamphotericin followed by sulfametoxazole and trimetoprin due to acute renalfunction impairment. The fistula was endoscopically treated; inittialy with theprotection of left main bronchus with a tracheal prosthesis followed by theesophageal fistula’s ostium clipping.

Computed tomography findings of paracoccidiodomycosis in musculoskeletal system

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Lima Junior, Francisco Valtenor Araujo; Savarese, Leonor Garbin; Monsignore, Lucas Moretti; Martinez, Roberto; Nogueira-Barbosa, Marcello Henrique, E-mail: fvaltenor@gmail.com [Universidade de Sao Paulo (FM/USP), Ribeirao Preto, SP (Brazil). Fac. de Medicina

2015-01-15

Objective: to evaluate musculoskeletal involvement in paracoccidioidomycosis at computed tomography. Materials and methods: development of a retrospective study based on a review of radiologic and pathologic reports in the institution database. Patients with histopathologically confirmed musculoskeletal paracoccidioidomycosis and submitted to computed tomography were included in the present study. The imaging findings were consensually described by two radiologists. In order to avoid bias in the analysis, one patient with uncountable bone lesions was excluded from the study. Results: a total of seven patients were included in the present study. A total of 18 bone lesions were counted. The study group consisted of 7 patients. A total number of 18 bone lesions were counted. Osteoarticular lesions were the first manifestation of the disease in four patients (57.14%). Bone lesions were multiple in 42.85% of patients. Appendicular and axial skeleton were affected in 85.71% and 42.85% of cases, respectively. Bone involvement was characterized by well-demarcated osteolytic lesions. Marginal osteosclerosis was identified in 72.22% of the lesions, while lamellar periosteal reaction and soft tissue component were present in 5.55% of them. One patient showed multiple small lesions with bone sequestra. Conclusion: paracoccidioidomycosis can be included in the differential diagnosis of either single or multiple osteolytic lesions in young patients even in the absence of a previous diagnosis of pulmonary or visceral paracoccidioidomycosis. (author)

Isoniazid acetylating phenotype in patients with paracoccidioidomycosis and its relationship with serum sulfadoxin levels, glucose-6-phosphate dehydrogenase and glutathione reductase activities

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Benedito Barraviera

1991-06-01

Full Text Available The authors evaluated the isoniazid acetylating phenotype and measured hematocrit, hemoglobin, glucose-6-phosphate dehydrogenase and glutathione reductase activities plus serum sulfadoxin levels in 39 patients with paracoccidioidomycosis (33 males and 6 females aged 17 to 58 years. Twenty one (53.84% of the patients presented a slow acetylatingphenotype and 18(46.16% a fast acetylating phenotype. Glucose-6-phosphate- dehydrogenase (G6PD acti vity was decreased in 5(23.80% slow acetylators and in 4(22.22% fast acetylators. Glutathione reductase activity was decreased in 14 (66.66% slow acetylators and in 12 (66.66% fast acetylators. Serum levels of free and total sulfadoxin Were higher in slow acetylator (p Os autores avaliaram o fenótipo acetilador da isoniazida, hematócrito, hemoglobina, atividade da glicose-6- fosfato desidrogenase, glutationa redutase e os níveis séricos de sulfadoxina de 39 doentes com paracoccidíoidomicose, senão 33 do sexo masculino e 6 do feminino, com idades compreendidas entre 17 e 58 anos. Vinte e um (53,84% doentes apresentaram fenótipo acetilador lento e 18 (46,16% rápido. A atividade da glicose-6-fosfato desidrogenase (G6PD esteve diminuída em 5 (23,80% acetiladores lentos e 4 (22,22% rápidos. A atividade da glutationa redutase esteve diminuída em 14 (66,66% acetiladores lentos e 12 (66,66% rápidos. Os níveis séricos de sulfadoxina livre e total foram maiores nos acetiladores lentos (p < 0,02. A análise dos resultados permite concluir que os níveis séricos de sulfadoxina relaciona-se com o fenótipo acetilador. Além disso, os níveis estiveram sempre acima de 50 µg/ml, níveis estes considerados terapêuticos. Por outro lado, a deficiência de glutationa redutase pode estar relacionada com a má absorção intestinal de nutrientes, entre eles riboflavina, vitamina precursora de FAD.

In Vitro Comparison of Activities of Terbinafine and Itraconazole against Paracoccidioides brasiliensis

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Hahn, R. C.; Fontes, C. J. F.; Batista, R. D.; Hamdan, J. S.

2002-01-01

In vitro, terbinafine is highly active against a broad spectrum of pathogenic fungi. We evaluated the activities of terbinafine and itraconazole against 31 isolates of Paracoccidioides brasiliensis. The tests were conducted by using a broth macrodilution procedure. MICs, in micrograms per milliliter, were as follows: terbinafine, 0.015 to 1.0 (geometric mean, 0.1188); itraconazole, 0.007 to 0.5 (geometric mean, 0.03165). The usual therapy for paracoccidioidomycosis is sulfonamides, amphotericin B, and azole derivatives (ketoconazole, itraconazole, and fluconazole). In comparison to amphotericin B, azole derivatives allow shorter treatment courses, can be administered orally, and are equally effective. Itraconazole has as high efficacy as ketoconazole, but with superior tolerance. It is the current drug of choice for treatment of paracoccidioidomycosis. The data obtained in this study indicate that terbinafine is active against P. brasiliensis in vitro and suggest that this allylamine can be considered a new option as drug therapy for paracoccidioidomycosis. PMID:12149337

A semi-nested PCR assay for molecular detection of Paracoccidioides brasiliensis in tissue samples Semi-nested PCR para a detecção molecular de Paracoccidioides brasiliensis em amostras de tecido

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Andrea Cristine Koishi

2010-12-01

Full Text Available INTRODUCTION: Paracoccidioidomycosis is a systemic infection caused by Paracoccidioides brasiliensis. METHODS: In this study, a semi-nested PCR for paracoccidioidomycosis diagnosis was developed. The primers ITS1 and ITS4 were used in the first reaction, while the primers MJ03 and ITS1 primer were used in the second reaction. The semi-nested PCR was used to investigate biopsies of five patients with oral lesions that resembled paracoccidioidomycosis. RESULTS: The semi-nested PCR was positive for four samples and negative for a sample from a patient later diagnosed with leishmaniasis. CONCLUSIONS: The new semi-nested PCR describe is useful for paracoccidioidomycosis diagnosis.INTRODUÇÃO: A paracoccidioidomicose é uma infecção sistêmica causada pelo Paracoccidioides brasiliensis. MÉTODOS: Neste estudo, uma semi-nested PCR foi desenvolvida para o diagnóstico da paracoccidioidomicose. Os oligonucleotídeos iniciadores ITS1 e ITS4 foram usados na primeira reação, enquanto os oligonucleotídeos iniciadores MJ03 e ITS1 foram usados na segunda reação. A semi-nested PCR foi usada para investigar biopsias de cinco pacientes com lesões orais que se assemelhavam a paracoccidioidomicose. RESULTADOS: A semi-nested PCR foi positiva para quatro amostras e negativa para a amostra de um paciente, posteriormente diagnosticado com leishmaniose. CONCLUSÕES: A semi-nested PCR descrita aqui é útil para o diagnóstico da paracoccidioidomicose.

Immunodiagnosis of paracoccidioidomycosis due to Paracoccidioides brasiliensis using a latex test: detection of specific antibody anti-gp43 and specific antigen gp43.

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Priscila Oliveira Dos Santos

2015-02-01

Full Text Available Paracoccidioidomycosis (PCM is a life-threatening systemic disease and is a neglected public health problem in many endemic regions of Latin America. Though several diagnostic methods are available, almost all of them present with some limitations.A latex immunoassay using sensitized latex particles (SLPs with gp43 antigen, the immunodominant antigen of Paracoccidioides brasiliensis, or the monoclonal antibody mAb17c (anti-gp43 was evaluated for antibody or antigen detection in sera, cerebrospinal fluid (CSF, and bronchoalveolar lavage (BAL from patients with PCM due to P. brasiliensis. The gp43-SLPs performed optimally to detect specific antibodies with high levels of sensitivity (98.46%, 95% CI 91.7-100.0, specificity (93.94%, 95% CI 87.3-97.7, and positive (91.4% and negative (98.9% predictive values. In addition, we propose the use of mAb17c-SLPs to detect circulating gp43, which would be particularly important in patients with immune deficiencies who fail to produce normal levels of immunoglobulins, achieving good levels of sensitivity (96.92%, 95% CI 89.3-99.6, specificity (88.89%, 95% CI 81.0-94.3, and positive (85.1% and negative (97.8% predictive values. Very good agreement between latex tests and double immune diffusion was observed for gp43-SLPs (k = 0.924 and mAb17c-SLPs (k = 0.850, which reinforces the usefulness of our tests for the rapid diagnosis of PCM in less than 10 minutes. Minor cross-reactivity occurred with sera from patients with other fungal infections. We successfully detected antigens and antibodies from CSF and BAL samples. In addition, the latex test was useful for monitoring PCM patients receiving therapy.The high diagnostic accuracy, low cost, reduced assay time, and simplicity of this new latex test offer the potential to be commercialized and makes it an attractive diagnostic assay for use not only in clinics and medical mycology laboratories, but mainly in remote locations with limited laboratory infrastructure

Cyclophosphamide effect on paracoccidioidomycosis in the rat Efecto de la ciclofosfamida en ratas con paracoccidioidomicosis

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J. L. Blejer

1995-06-01

Full Text Available Paracoccidioidomycosis is an endemic fungal disease widely distributed throughout Latin America. The potent immunosuppressor cyclophosphamide (CY has been used to modulate host immune response to Paracoccidioides brasiliensis in an experimental model. Inbred male Buffalo/Sim rats weighing 250-300 g were inoculated with 5 x 10(6 P. brasiliensis cells of the yeast phase form by intracardiac route. One group of animals was treated with 20 mg/kg body weight at days +4, +5, +6, +7, +11 and +12 post-infection (pi., while a control group was infected alone. No mortality was recorded in either group. Treated rats presented: a a decrease in granuloma size, which contained less fungal cells; b a lack of specific antibodies up to 35 days pi., and c a significant increase in the footpad swelling test (DTH against paracoccidioidin. Splenic cell transfer from CY-treated P. brasiliensis-infected donors to recipients infected alone led to a significant increase in DTH response in the latter versus untreated infected controls. Likewise, in treated infected recipients transferred with untreated infected donor spleen cells, footpad swelling proved greater than in controls. Thus, it would seem that each successive suppressor T lymphocyte subset belonging to the respective cascade may be sensitive to repeated CY doses administered up to 12 days pi.. Alternatively, such CY schedule may induce the appearance of a T cell population capable of amplifying DTH response.La paracoccidioidomicosis es una enfermedad endémica fúngica ampliamente distribuida en Latino-América. La ciclofosfamida ha sido usada como potente inmunosupresor para modular la respuesta inmune, en un modelo experimental infectado con Paracoccidioides brasiliensis. Ratas machos Buffalo/Sim endocriadas de 250-300 gr. de peso, fueron inoculadas por via intracardiaca con 5.10 6 células de P. brasiliensis en fase levaduriforme. Un grupo de animales fue tratado con 20 mg/kg de peso de ciclofosfamida en

Associação da rifampicina à anfotericina B no tratamento da paracoccidioidomicose: resultados em três pacientes tratados Association of Amphotericin B and Rifampicin in the treatment of paracoccidioidomycosis. Report of efficacy in three cases

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Bodo Wanke

1984-08-01

Full Text Available Trabalhos experimentais demonstraram que a anfotericina B, desorganizando funcionalmente a membrana celular fúngica, permite a penetração da rifampicina no citoplasma e sua conseqüente ação contra Histoplasma capsulatum, Blastomyces dermatitidis e Candida albicans. Com metade das doses habituais' de anfotericina B associada à rifampicina conseguem-se melhores resultados do que com a anfotericina B isoladamente em doses plenas. Os Autores discutem as possíveis aplicações desta associação no tratamento da paracoccidioidomi-cose e apresentam 3 casos desta micose em que a inatividade clínica e micológica só foi obtida após o emprego combinado destas drogas.Experimental data have shown that low concentration of amphotericin B disrupts of the fungal cellular membranes, enhancing entrance of rifampicin into citoplasm, where it acts specifically as an antifungal agent against Histoplasma capsulatum, Blastomyces dermatitidis and Candida albicans. Amphotericin B in half dosage combined with rifampicin is more effective than when used alone in full dosage. The Authors discuss the possible indications of this association in the therapy of paracoccidioidomycosis, and report its efficacy in three cases of this disease only controlled after its use.

Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006.

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Prado, Marli; Silva, Marcelo Barbosa da; Laurenti, Ruy; Travassos, Luiz R; Taborda, Carlos P

2009-05-01

Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (approximately 51.2%). When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9%) appeared at the top of the list, followed by candidiasis (30.2%), histoplasmosis (10.1%) and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

Mortality due to systemic mycoses as a primary cause of death or in association with AIDS in Brazil: a review from 1996 to 2006

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Marli Prado

2009-05-01

Full Text Available Deaths caused by systemic mycoses such as paracoccidioidomycosis, cryptococcosis, histoplasmosis, candidiasis, aspergillosis, coccidioidomycosis and zygomycosis amounted to 3,583 between 1996-2006 in Brazil. When analysed as the underlying cause of death, paracoccidioidomycosis represented the most important cause of deaths among systemic mycoses (~ 51.2%. When considering AIDS as the underlying cause of death and the systemic mycoses as associated conditions, cryptococcosis (50.9% appeared at the top of the list, followed by candidiasis (30.2%, histoplasmosis (10.1% and others. This mortality analysis is useful in understanding the real situation of systemic mycoses in Brazil, since there is no mandatory notification of patients diagnosed with systemic mycoses in the official health system.

Aspectos incomuns da paracoccidioidomicose infantil

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Achiléa Lisboa Bittencourt

1987-12-01

Full Text Available São relatados dois casos de paracoccidioidomicose (PCM infantil. Em um deles, a principal manifestação da doença foi tumoração abdominal, simulando linfoma maligno não Hodgkin. O outro apresentou acentuado envolvimento articular, com ruptura da cápsula. Representam o segundo e terceiro casos de PCM infantil observados na Bahia, ambos procedentes de áreas urbanas.The authors present two cases of infantil para-coccidioidomycosis. In one case the main presentation was an abdominal mass that mimicked non- Hodgkin lymphoma. In the other case the child had a joint swelling with rupture of the capsule and the clinical diagnosis was piogenic arthritis. They represent the second and third cases of infantile paracoccidioidomycosis observed in the state of Bahia, all coming from urban areas.

Paracoccidioidomicosis asociada a otras patologías respiratorias en un hospital de Corrientes, Argentina Association of paracoccidioidomycosis with different pulmonary pathologies in a hospital in Corrientes province, Argentina

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A. M. Pato

2007-09-01

Full Text Available Se realizó la búsqueda sistemática de paracoccidioidomicosis (PCM en un conjunto de pacientes que fueron atendidos en un hospital de la ciudad de Corrientes dentro de un período de dos años. El criterio de inclusión fue: pacientes con tuberculosis (TBC, pacientes con diagnóstico presuntivo o confirmado de cáncer de pulmón (CA, pacientes con enfermedad pulmonar obstructiva crónica (EPOC y pacientes con imagen radiológica compatible con micosis pulmonar (IRXC. Se estudiaron 84 pacientes: 57 con TBC, 1 con CA, 5 con EPOC, 3 con TBC+CA, 4 con TBC+EPOC, 4 con EPOC+CA y 10 con IRXC. A todos se les realizó serología por inmunodifusión en gel de agar (IDGA y, en los casos en que se pudo obtener una muestra clínica, también se efectuaron estudios microbiológicos. Por IDGA se diagnosticaron 10 casos de PCM: 4 asociados a TBC, 1 a TBC+CA, 3 a EPOC y 2 a IRXC; 9 de ellos se corroboraron por el hallazgo del hongo. La búsqueda sistemática de PCM en habitantes del área endémica que presentan patología pulmonar favorecería el diagnóstico precoz y, por lo tanto, las posibilidades de un tratamiento eficaz.For 2 years, a systematic research of paracoccidioidomycosis (PCM had been conducted in a hospital in the city of Corrientes. The inclusion criterium used was: tuberculosis patients (TBC, presumptive or confirmed diagnosis of pulmonary cancer (CA, chronic obstructive pulmonary disease (COPD and/or X-ray images compatible with pulmonary mycosis (XRC. Eighty four patients were studied: 57 (TBC, 1 (CA, 5 (COPD, 3 (TBC+CA, 4 (TBC+COPD, 4 (COPD+CA and 10 (XRC. Serology tests by agar gel immunodiffusion (IDGA were performed on all patients, whereas microbiological studies were performed on those cases in which clinical samples could be obtained. Ten PCM were diagnosed by IDGA; 4 associated to TBC, 1 to TBC+CA, 3 to COPD and only 2 to XRC. PCM was mycologically proven in 9 of these cases. Systematic research of PCM would lead to an early

Caso para diagnóstico Case for diagnosis

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Silvio Alencar Marques

2007-12-01

Full Text Available A paracoccidioidomicose é enfermidade potencialmente grave podendo levar ao óbito. Lesões cutâneas específicas são freqüentes e propícias ao diagnóstico precoce. A disseminação para órgãos do sistema monocítico-macrofágico corresponde à forma aguda-subaguda da enfermidade. Derrame pleural e ascite, raros na paracoccidioidomicose, no presente caso foram conseqüentes à pancreatite aguda hemorrágica. Nos casos graves a anfotericina B e o suporte hospitalar adequado são decisivos na recuperação.Paracoccidioidomycosis is a potentially severe disease that may lead to death. Specific skin lesions are common and suitable for early diagnosis. Dissemination to the reticuloendothelial system is the main characteristic of the acute and subacute clinical forms. Pleural exudate and ascitis are rare in paracoccidioidomycosis. In the present case, these followed an acute hemorrhagic pancreatitis. Amphotericin B and proper hospital care are crucial for the recovery of severe cases.

Matrix metalloproteinases with gelatinolytic activity induced by Paracoccidioides brasiliensis infection

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Nishikaku, Angela Satie; Ribeiro, Luciana Cristina; Molina, Raphael Fagnani Sanchez; Albe, Bernardo Paulo; Cunha, Cláudia da Silva; Burger, Eva

2009-01-01

Matrix metalloproteinases (MMPs) modulate extracellular matrix turnover, inflammation and immunity. We studied MMP-9 and MMP-2 in experimental paracoccidioidomycosis. At 15 and 120 days after infection (DAI) with virulent Paracoccidioides brasiliensis, MMP-9 was positive by immunohistochemistry in multinucleated giant cells, in mononuclear cells with macrophage and lymphocyte morphologies and also in fungal cells in the lesions of susceptible and resistant mice. Using gelatin zymography, pro- and active MMP-9 and active MMP-2 were detected in all infected mice, but not in controls. Gelatinolytic activity was not observed in P. brasiliensis extracts. Semiquantitative analysis of gelatinolytic activities revealed weak or absent MMP-2 and strong MMP-9 activity in both mouse strains at 15 DAI, declining at 120 DAI. Avirulent P. brasiliensis-infected mice had residual lesions with MMP-9-positive pseudoxantomatous macrophages, but no gelatinase activity at 120 DAI. Our findings demonstrate the induction of MMPs, particularly MMP-9, in experimental paracoccidioidomycosis, suggesting a possible influence in the pattern of granulomas and in fungal dissemination. PMID:19765107

Bilateral paracoccidioidomycotic iliopsoas abscess associated with ileo-colonic lesion

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Helena Duani

2012-10-01

Full Text Available This case report shows the clinical development of a patient with systemic paracoccidioidomycosis presenting with lymphatic-intestinalmanifestation. The patient initially had a substantial clinical improvement but had a recrudescence after six months of sulfamethoxazoletrimethoprim oral treatment, with the emergence of feverish syndrome, lumbar pain, and intermittent claudication, characterizing a bilateral iliopsoas muscle abscess, necessitating clinicosurgical therapeutics.

Failure of nitric oxide production by macrophages and decrease in CD4+ T cells in oral paracoccidioidomycosis: possible mechanisms that permit local fungal multiplication Falha na produção de óxido nítrico pelos macrófagos e diminuição de células T CD4+ na paracoccidioidomicose bucal: possíveis mecanismos que permitem a multiplicação fúngica local

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Aline Carvalho Batista

2005-10-01

Full Text Available Paracoccidioidomycosis is a chronic granulomatous disease that induces a specific inflammatory and immune response. The participation of nitric oxide (NO, a product of the inducible nitric oxide synthase enzyme (iNOS, as an important fungicidal molecule against Paracoccidioides brasiliensis has been demonstrated. In order to further characterize the Oral Paracoccidioidomycosis (OP, we undertook an immunohistochemical study of iNOS+, CD45RO+, CD3+, CD8+, CD20+, CD68+ cells and mast cells. The samples were distributed in groups according to the number of viable fungi per mm². Our results showed weak immunolabeling for iNOS in the multinucleated giant cells (MNGC and in most of the mononuclear (MN cells, and the proportion of iNOS+ MN/MNGC cells in the OP were comparable to Control (clinically healthy oral tissues. Additionally, our analysis revealed a similarity in the number of CD4+ cells between the Control and the OP groups with higher numbers of fungi. These findings suggest that a low expression of iNOS and a decrease in the CD4+ T cells in OP may represent possible mechanisms that permit the local fungal multiplication and maintenance of active oral lesions.A paracoccidioidomicose é uma doença granulomatosa crônica que induz resposta inflamatória e imune específica. A participação do óxido nítrico (NO, produto da enzima óxido nítrico sintase induzível (iNOS, como uma importante molécula fungicida contra o fungo Paracoccidioides brasiliensis tem sido demonstrada. Com o objetivo de melhor caracterizar as lesões orais da paracoccidioidomicose (OP, propusemos estudo imunohistoquímico das células iNOS+ e das células CD45RO+, CD3+, CD8+, CD20+, CD68+ e mastócitos. As amostras foram distribuídas em grupos de acordo com o número de fungos viáveis por mm². Nossos resultados demonstraram leve imunomarcação para iNOS nas células gigantes multinucleadas (MNGC e na maioria das células mononucleares (MN, e a proporção de c

The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia

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Muñoz, José F.; Gauthier, Gregory M.; Desjardins, Christopher A.; Gallo, Juan E.; Holder, Jason; Sullivan, Thomas D.; Marty, Amber J.; Carmen, John C.; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret

2015-01-01

Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated...

Paracoccidioidomicose: estudo clínico e epidemiológico de 422 casos observados no Estado de Mato Grosso do Sul Paracoccidioidomycosis: a clinical and epidemiological study of 422 cases observed in Mato Grosso do Sul

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Anamaria Mello Miranda Paniago

2003-07-01

Full Text Available São descritas as características clínicas e epidemiológicas de 422 casos de paracoccidioidomicose atendidos no Hospital Universitário da Universidade Federal do Mato Grosso do Sul (Campo Grande, Mato Grosso do Sul, Brasil no período de Janeiro de 1980 a Agosto de 1999. A média de idade foi de 43,4 anos e a proporção homem: mulher foi de 10:1. Quase metade (45,5% dos doentes era trabalhadora rural no momento do diagnóstico. A forma aguda/subaguda (tipo juvenil(15,4% dos casos revelou-se com importante comprometimento do sistema fagocítico-monocitário, manifestado principalmente por adenomegalia (95,4%; hepatomegalia (40%; esplenomegalia (23,1%. A forma crônica (tipo adulto(84,6% dos casos apresentou-se com maiores proporções de lesões em orofaringe (66,4%; rouquidão (31,4% e tosse (50,7%. Para o diagnóstico, foram utilizados o exame micológico direto em 365 pacientes e o histopatológico em 302, com positividade de 50,7% e 97,3%, respectivamente. O tratamento antifúngico preferencial foi a associação de sulfametoxazol e trimetoprim (co-trimoxazol, utilizado em 90,3% dos doentes. Seqüelas foram observadas em 30,3% e óbito em 7,6% dos casos.Clinical and epidemiological features of 422 cases of paracoccidioidomycosis attended at University Hospital of Universidade Federal de Mato Grosso do Sul (Campo Grande, Mato Grosso do Sul, Brazil from January 1980 to August 1999, were analysed. The mean age was 43.4 years old and the male: female ratio was 10:1. Nearly half (45.5% of the patients were agricultural workers at the moment of diagnosis. In the acute/subacute form (juvenile type the phagocytic-monocytic system was very much impaired and mainly marked by lymphadenopathy (95.4%, hepatomegaly (40%, splenomegaly (23.1%. The chronic form (adult type presents more lesions in oropharynx (66.4%, dysphonia (31.4% and cough (50.7%. Mycological diagnosis was obtained by direct microscopy of wet mounts in 185/365 (50.7% patients and by

[Immunohistochemistry diagnosis of fungal infections].

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Rocha, D C; Duarte, M I; Pagliari, C; de Oliveira, M S

1998-01-01

Because the mycosis incidence has increased a lot with the appearing of AIDS, the Immunohistochemistry study among fungus shows the importance of fast methods for their identification that have advantage of been a durable method in comparison with immunofluorescence and the possibility of making retrospective studies in material embedded in paraffin. The Immunohistochemistry reaction with Histoplasma capsulatum, Pneumocystis carinii; and Criptococcus neoformans antibodies were sensitive, specifics, and intensely positive in all the cases previously diagnosed as Histoplasmosis, Pneumocystosis and Cryptococcosis, without cross-reaction with other fungus; while the anti-Candida albicans antibody showed weak positiveness in four Histoplasmosis cases, in one of Paracoccidioidomycosis cases and Sporotrichosis case; and the reactions with the antibody anti-P. brasiliensis were intensely positive in all the Paracoccidioidomycosis cases and weakly positive in two Histoplasmosis and two of the four Candidiasis cases. The previous identification of each fungi on tissue sample was made by Grocott method. This preliminary study showed that it is necessary to use other kinds of antibody and fungus, in order to get more details about the possible occurrence of cross-reactions. We suggest the use of new antibodies, with new standardizations in order to find the best titles for each reaction and eliminate the cross-reactions.

Lipoxin Inhibits Fungal Uptake by Macrophages and Reduces the Severity of Acute Pulmonary Infection Caused by Paracoccidioides brasiliensis

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Laura R. R. Ribeiro

2015-01-01

Full Text Available Cysteinyl leukotrienes (CysLTs and lipoxins (LXs are lipid mediators that control inflammation, with the former inducing and the latter inhibiting this process. Because the role played by these mediators in paracoccidioidomycosis was not investigated, we aimed to characterize the role of CysLT in the pulmonary infection developed by resistant (A/J and susceptible (B10.A mice. 48 h after infection, elevated levels of pulmonary LTC4 and LXA4 were produced by both mouse strains, but higher levels were found in the lungs of susceptible mice. Blocking the CysLTs receptor by MTL reduced fungal loads in B10.A, but not in A/J mice. In susceptible mice, MLT treatment led to reduced influx of PMN leukocytes, increased recruitment of monocytes, predominant synthesis of anti-inflammatory cytokines, and augmented expression of 5- and 15-lipoxygenase mRNA, suggesting a prevalent LXA4 activity. In agreement, MTL-treated macrophages showed reduced fungal burdens associated with decreased ingestion of fungal cells. Furthermore, the addition of exogenous LX reduced, and the specific blockade of the LX receptor increased the fungal loads of B10.A macrophages. This study showed for the first time that inhibition of CysLTs signaling results in less severe pulmonary paracoccidioidomycosis that occurs in parallel with elevated LX activity and reduced infection of macrophages.

Central nervous system paracoccidioidomycosis. Report of a case successfully treated with Itraconazol Paracoccidioidomicose do sistema nervoso central. Apresentação de um caso tratado com êxito com itraconazole

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Luis A. VILLA

2000-08-01

Full Text Available Paracoccidioidomycosis (PCM is a primary pulmonary infection that often disseminates to other organs and systems. Involvement of the central nervous system (CNS is rare and due to the fact that both clinical alertness and establishment of the diagnosis are delayed, the disease progresses causing serious problems. We report here a case of neuroparacoccidioidomycosis (NPCM, observed in a 55 year-old male, who consulted due to neurological symptoms (left hemiparesis, paresthesias, right palpebral ptosis, headache, vomiting and tonic clonic seizures of a month duration. Upon physical examination, an ulcerated granulomatous lesion was observed in the abdomen. To confirm the diagnosis a stereotactic biopsy was taken; additionally, mycological tests from the ulcerated lesion and a bronchoalveolar lavage were performed. In the latter specimens, P. brasiliensis yeast cells were visualized and later on, the brain biopsy revealed the presence of the fungus. Treatment with itraconazole (ITZ was initiated but clinical improvement was unremarkable; due to the fact that the patient was taking sodium valproate for seizure control, drug interactions were suspected and confirmed by absence of ITZ plasma levels. The latter medication was changed to clonazepam and after several weeks, clinical improvement began to be noticed and was accompanied by diminishing P. brasiliensis antigen and antibody titers. In the PCM endemic areas, CNS involvement should be considered more often and the efficacy of itraconazole therapy should also be taken into consideration.A paracoccidioidomicose (PCM é infecção pulmonar primária que algumas vezes pode se disseminar a outros órgãos e sistemas. O envolvimento do sistema nervoso central (SNC é raro e devido ao fato que a alerta clínica e o estabelecimento do diagnóstico são tardios, a doença progride e o paciente piora. Aquí apresentamos caso de neuroparacoccidioidomicose (NPCM observada em homem de 55 anos de idade que

Data in support of quantitative proteomics to identify potential virulence regulators in Paracoccidioides brasiliensis isolates

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Alexandre Keiji Tashima

2015-12-01

Full Text Available Paracoccidioides genus are the etiologic agents of paracoccidioidomycosis (PCM, a systemic mycosis endemic in Latin America. Few virulence factors have been identified in these fungi. This paper describes support data from the quantitative proteomics of Paracoccidioides brasiliensis attenuated and virulent isolates [1]. The protein compositions of two isolates of the Pb18 strain showing distinct infection profiles were quantitatively assessed by stable isotopic dimethyl labeling and proteomic analysis. The mass spectrometry and the analysis dataset have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with identifier PXD000804.

Paracoccidioidomicose: revisão de literatura = Paracoccidioidomycosis: iterature Review

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Palmeiro, Mariana Reuter

2005-01-01

Full Text Available Objetivo: Apresentar uma revisão da literatura sobre a paracoccidioidomicose, abordando aspectos clínicos importantes da doença. Fonte de dados: Foram consultados artigos indexados no Medline e livros-texto sobre o tema, ambos publicados no período de 1990 a 2004. Síntese de dados: A paracoccidioidomicose é uma doença sistêmica, endêmica, causada pelo fungo dimórfico Paracoccidioides brasiliensis. Embora a via primária de infecção seja a pulmonar, pela inalação de esporos ou partículas do fungo, vários sítios anatômicos podem ser acometidos pela disseminação linfoematogênica, inclusive a mucosa oral. Conclusão: A via primária de infecção da paracoccidioidomicose é pulmonar, mas a doença é, freqüentemente, diagnosticada a partir de manifesta- ções orais. A abordagem clínica de pacientes portadores de lesões ulceradas crônicas de mucosa oral deve, portanto, considerar a paracoccidioidomicose como possibilidade diagnóstica

Connective matrix organization in chronic granulomas of experimental paracoccidioidomycosis.

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Kerr, I B; de Oliveira, P C; Lenzi, H L

1988-07-01

The histological and ultrastructural aspects of chronic granulomas from rats infected intraperitoneally with Paracoccidioides brasiliensis are described with special emphasis on the composition of the extracellular matrix. The granulomas were structurally arranged in two zones, one central containing fungi, and the other peripheral. The extracellular matrix was composed of collagen types I and III, proteoglycans, glycoprotein, and an undefined amorphous substance. The main cellular population was represented by macrophages, epithelioid cells, and giant cells in the central zone, and fibroblasts in the peripheral zone. The fibrotic process was a critical event in this stage of the infection, and showed a centrifugal direction. This might be provoked by direct stimulus from the fungi or by macrophage-fibroblastic interaction.

[Mycoses in Venezuela: Working Groups in Mycology reported cases (1984-2010)].

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Martínez Méndez, Dilia; Hernández Valles, Rosaura; Alvarado, Primavera; Mendoza, Mireya

2013-01-03

In 1984 the Venezuelan Work Groups in Mycology (VWGM) were created introducing an innovative approach to the study of the mycoses in Venezuela. To study the occurrence of the mycoses in Venezuela. Review the reported cases of mycoses by the newsletter Boletín Informativo Las Micosis en Venezuela (VWGM) from 1984 to 2010. The data collected showed 36,968 reported cases of superficial mycoses, 1,989 of deep systemic cases, and 822 of localized mycoses. Pityriasis dermatophytosis was the most common superficial infection, and paracoccidioidomycosis and histoplasmosis the most frequent deep systemic infection. Chromoblastomycosis was the most frequently diagnosed subcutaneous infection. The data provided showed the distribution by geographical area for each of the fungal infections studied, which may help to establish the endemic areas. Superficial mycosis is a public health problem due to its high morbidity and is probably responsible for some of the outbreaks in high-risk groups. Paracoccidioidomycosis and histoplasmosis were reported more often, which agrees with earlier reports prior to the formation of the VWGM. Cases of sporotrichosis and chromoblastomycosis in Venezuela can be considered unique due to the high number of cases. This study highlights the contribution of the VWGM to the behavior of the mycoses in Venezuela, its incidence, prevalence, and the recognition of these infections as a problem of public health importance. The VWGM should keep working in this endeavor, not only reporting new cases, but also unifying the clinical and epidemiological criteria, in order to properly monitor the evolving epidemiological changes reported in these types of infections. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier España, S.L. All rights reserved.

Paracoccidioidomicose pulmonar: relato de caso clínico com aspetos em tomografia computorizada de alta resolução

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M. Armas

2012-07-01

Full Text Available Resumo: A Paracoccidioidomicose é uma micose sistémica endémica nas áreas rurais da América Latina, uma fonte importante de imigrantes e destino de emigração e turismo europeu, a maioria dos casos ocorrendo no Brasil, Argentina, Venezuela e Colômbia. Os autores descrevem o caso clínico de um paciente com 43 anos, anteriormente emigrado na Venezuela e residente em Portugal há 8 anos, que se apresenta com lesão cutânea isolada. Embora sem queixas relevantes do foro respiratório, apresentava extensas lesões do parênquima pulmonar caracterizadas por tomografia computorizada de alta resolução (TCAR. Foi realizada biópsia da lesão cutânea e exame micológico da expetoração que revelaram infeção por Paracoccidioides brasiliensis (PB. Abstract: Paracoccidioidomycosis is a systemic mycosis which is endemic in rural areas of Latin America, an important European source of immigrants and a growing European touristic destination as well, with most cases occurring in Brazil, Argentina, Venezuela and Colombia. The authors report a case of a 43 year old man who previously worked in Venezuela and is living in Portugal for 8 years, presenting with a single cutaneous lesion. Despite the absence of valuable respiratory complaints, severe lung damage was found with high-resolution computed tomography (HRCT. Biopsy of the cutaneous lesion and mycologic sputum examination were performed revealing Paracoccidioides brasiliensis infection. Palavras-chave: Paracoccidioidomicose, Paracoccidioides brasiliensis, Fibrose pulmonar, Tomografia computorizada de alta resolução, Keywords: Paracoccidioidomycosis, Paracoccidioides brasiliensis, Pulmonary fibrosis, High-resolution computed tomography

Diffuse abnormalities of the trachea: computed tomography findings

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Marchiori, Edson; Araujo Neto, Cesar de

2008-01-01

The aim of this pictorial essay was to present the main computed tomography findings seen in diffuse diseases of the trachea. The diseases studied included amyloidosis, tracheobronchopathia osteochondroplastica, tracheobronchomegaly, laryngotracheobronchial papillomatosis, lymphoma, neurofibromatosis, relapsing polychondritis, Wegener's granulomatosis, tuberculosis, paracoccidioidomycosis, and tracheobronchomalacia. The most common computed tomography finding was thickening of the walls of the trachea, with or without nodules, parietal calcifications, or involvement of the posterior wall. Although computed tomography allows the detection and characterization of diseases of the central airways, and the correlation with clinical data reduces the diagnostic possibilities, bronchoscopy with biopsy remains the most useful procedure for the diagnosis of diffuse lesions of the trachea. (author)

Deep mycoses in Amazon region.

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Talhari, S; Cunha, M G; Schettini, A P; Talhari, A C

1988-09-01

Patients with deep mycoses diagnosed in dermatologic clinics of Manaus (state of Amazonas, Brazil) were studied from November 1973 to December 1983. They came from the Brazilian states of Amazonas, Pará, Acre, and Rondônia and the Federal Territory of Roraima. All of these regions, with the exception of Pará, are situated in the western part of the Amazon Basin. The climatic conditions in this region are almost the same: tropical forest, high rainfall, and mean annual temperature of 26C. The deep mycoses diagnosed, in order of frequency, were Jorge Lobo's disease, paracoccidioidomycosis, chromomycosis, sporotrichosis, mycetoma, cryptococcosis, zygomycosis, and histoplasmosis.

Neutrophils in oral paracoccidioidomycosis and the involvement of Nrf2.

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Vera Cavalcanti Araújo

Full Text Available Neutrophils have been implicated in granuloma formation in several infectious diseases, in addition to their main phagocytic and pathogen destruction role. It has been demonstrated that Nrf2 regulates antioxidant protection in neutrophils, attenuating inflammation without compromising the hosts bacterial defense. In this study, we analyzed the presence of neutrophils in Paracoccidioides brasiliensis mycosis (PCM, as well as the immunoexpression of Nrf2. Thirty-nine cases of oral PCM were classified according to quantity of fungi and to the presence of loose or well-organized granulomas and microabscesses. An Nrf2 antibody was used for immunohistochemical analysis. The results showed that neutrophils are present in microabscesses and loose granulomas, but were absent in structured granulomas. A greater quantity of fungi was shown in cases with only loose granulomas when compared to loose and well organized granulomas. Nrf2 was observed in the nuclei of neutrophils of loose granulomas and abscesses, with its expression in loose granulomas maintained despite the additional presence of well organized granulomas in the same specimen. This study suggests that neutrophils participate in P. brasiliensis granuloma formation and that Nrf2 has a possible role in neutrophil survival, via modulation of the inflammatory response.

Perfil clínico-epidemiológico dos pacientes portadores de paracoccidioidomicose no Serviço de Estomatologia do Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul Clinical-epidemiologic profile of paracoccidioidomycosis at the Stomatology Department of São Lucas Hospital, Pontificia Universidade Católica of Rio Grande do Sul

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Flaviana Dornela Verli

2005-05-01

Full Text Available No presente estudo, são descritas as características clínicas e epidemiológicas de 61 casos de paracoccidioidomicose, atendidos no Serviço de Estomatologia do Hospital São Lucas da PUCRS, no período de junho de 1976 a junho de 2004. O Rio Grande do Sul é considerado uma região endêmica da doença devido às condições eco-epidemiológicas para o desenvolvimento do fungo. Observou-se que a doença ocorreu em 58 (95% homens e 3 (5% mulheres, predominando a faixa etária de 40 a 59 anos (70,5%, e a profissão vinculada à agricultura em 27 (44,3% pacientes. O hábito de fumar foi prevalente em 52 (85,3% pacientes da amostra e muitos eram, também, etilistas. Todos os casos apresentavam manifestações estomatológicas, sendo que as lesões orais ocorreram predominantemente com aspecto ulcerado e moriforme, observadas em vários sítios anatômicos. As evidências radiográficas de lesões pulmonares estavam presentes em 32 (65,3% radiografias avaliadas.The aim of the article was to describe clinical and epidemiological features of 61 oral paracoccidioidomycosis cases from the Stomatology Department of São Lucas Hospital, analyzed from July 1976 to June 2004. The State of Rio Grande do Sul is an endemic region due to ecoepidemiologic conditions, that are favorable for the development of the yeast. Men are the most affected gender, with 58 (95% affected compared to 3 (5% women. Ii is most prevalent (70.5% between 40 and 59 years of age. Agricultural labor was the most common occupation with 27/61 (44.3% patients. Tobacco smoking was prevalent in 52 (85.3% of the sample, and alcoholism was a frequent finding. All the patients showed stomatologic manifestations, with ulcers and mulberry-like stomatitis the most prevalent, these oral lesions were also observed in many anatomical sites. Alterations were present in 32 (65.3% of the pulmonary radiographs.

Fungal Colitis by Paracoccidioides brasiliensis: a case report

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Carlos José Galeazzi

2011-12-01

Full Text Available Paracoccidioidomycosis (PBM is an infection caused by a dimorphic fungus called Paracoccidioides brasiliensis. It occurs in Latin America, with incidence of 1 to 3 per 100,000 inhabitants in endemic areas. The digestive tract is usually not affected, but when it occurs, it may lead to events similar to colorectal neoplasm and inflammatory bowel disease (IBD. This is a case report of a 68-year-old female patient, with diarrhea without blood or mucus for 6 months, weight loss of 8 kg over the period. Abdominal ultrasonography showed some mass in the right colon, suggestive of cancer and liver perihilar lymph node. Colonoscopy showed lesions suggestive of Crohn's disease. Biopsy showed chronic granulomatous colitis of fungal etiology: Paracoccidioidomycosis. The patient did not tolerate oral treatment with itraconazole and subsequently sulfadiazine, requiring hospital admission for the treatment with amphotericin B. The presence of Paracoccidioidomycosis in the digestive tract may be associated with bloody diarrhea, mucus, rectal hemorrhage, abdominal pain, malabsorption syndrome. Histopathological studies show the fungus and a chronic inflammatory infiltrate and granulation tissue. The differential diagnoses are tuberculosis, colorectal cancer and inflammatory bowel disease. The treatment is oral antifungal (itraconazole, sulfadiazine or intravenous (amphotericin B based. The case has caused diagnostic confusion between colon cancer (clinical and US and Crohn's disease (colonoscopy.Paracoccidioidomicose (PBM é uma infecção causada por um fungo dimórfico: Paracoccidioides brasiliensis. Ocorre na América Latina, com incidência de 1 a 3 por 100.000 habitantes em áreas endêmicas. O acometimento do trato digestivo é infrequente, sendo que pode levar a manifestações semelhantes à neoplasia colorretal e doença inflamatória intestinal (DII. Relatamos o caso da paciente feminina, 68 anos, com diarreia sem sangue ou muco há seis meses, com

The Paracoccidioides cell wall: past and present layers towards understanding interaction with the host

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Rosana ePuccia

2011-12-01

Full Text Available The cell wall of pathogenic fungi plays import roles in interaction with the host, so that its composition and structure may determine the course of infection. Here we present an overview of the current and past knowledge on the cell wall constituents of Paracoccidioides brasiliensis and P. lutzii. These are temperature-dependent dimorphic fungi that cause paracoccidioidomycosis, a systemic granulomatous and debilitating disease. Focus is given on cell wall carbohydrate and protein contents, their immune-stimulatory features, adhesion properties, drug target characteristics, and morphological phase specificity. We offer a journey towards the future understanding of the dynamic life that takes place in the cell wall and of the changes that it may suffer when living in the human host.

Estudo de 26 casos de Paracoccidioidomicose avaliados no Serviço de Otorrinolaringologia da Fundação Oswaldo Cruz (FIOCRUZ A study of 26 cases of Paracoccidioidomycosis evaluated at the Oswaldo Cruz Foundation (FIOCRUZ Otorhinolaryngology Service

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Francisco X. Palheta-Neto

2003-10-01

Full Text Available A Paracoccidioidomicose (PCM é uma micose profunda sistêmica causada por um fungo dimorfo, de aspecto microscópico similar a roda de leme de navio, o Paracoccidioides brasiliensis (Pb. A PCM apresenta distribuição geográfica restrita ao continente americano, acomete sobretudo indivíduos do sexo masculino, sem predileção por raça. Seu quadro clínico é bastante variado. OBJETIVO: Realizar análise epidemiológica de 26 casos de PCM avaliados no Setor de Otorrinolaringologia da Fundação Oswaldo Cruz - FIOCRUZ. FORMA DE ESTUDO: Clínico retrospectivo. MATERIAL E MÉTODO: Estudou-se retrospectivamente 26 prontuários de pacientes com manifestações otorrinolaringológicas da PCM atendidos no período de outubro de 1998 a setembro de 2001. Avaliou-se: sexo, idade, profissão, grau de escolaridade, se etilistas e/ou tabagistas, sintomatologia, local das lesões, presença de co-infecção, exames complementares realizados e opção terapêutica. RESULTADOS: 23 (88,5% pacientes eram do sexo masculino e 3 (11,5% do sexo feminino, com idade entre 32 e 72 anos. 11 (42,3% pacientes eram agricultores e 21 (80,8% tabagistas e/ou etilistas. Os locais mais comumente atingidos foram a epiglote e a parede nasal lateral. Utilizaram-se derivados sulfamídicos para o tratamento de 14 (53,9% pacientes e imidazólicos em 12 (46,1% casos. DISCUSSÃO: Lesões pulmonares podem ser confundidas com tuberculose, devido a suas semelhanças clínicas e radiográficas. A desnutrição pode predispor quadros clínicos de extrema gravidade. CONCLUSÃO: A anamnese detalhada dos pacientes portadores de PCM revela importantes aspectos, como procedência e hábitos pessoais. A atuação interdisciplinar, sobretudo de médicos e dentistas, colabora para um precoce diagnóstico e adequado acompanhamento do doente.Paracoccidioidomycosis (PCM is an acute systemic mycosis caused by a dimorphous fungus, Paracoccidioides brasiliensis (Pb, whose appearance under the

Manifestações estomatológicas da paracoccidioidomicose Stomatological manifestations of paracoccidioidomycosis

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Júlio C. Bisinelli

2001-09-01

Full Text Available Forma de estudo: Retrospectivo clínico. Material e método: Para elaboração da presente pesquisa, foi realizada a revisão de 187 prontuários médicos de pacientes provenientes do Serviço de Infectologia do Ambulatório de Micoses Profundas do Hospital de Clínicas da Universidade Federal do Paraná em Curitiba-PR, no período de maio de 1985 a março de 1998. Os objetivos foram traçar o perfil epidemiológico, descrevendo as manifestações estomatológicas encontradas na amostra, discutir sobre os achados encontrados estabelecendo comparações com a literatura pertinente, observar possíveis mudanças e se estas são significativas, bem como observar a sensibilidade dos corantes que foram usados na histopatologia (HE, PAS e GROCOTT em 20 lâminas. Foi estabelecido um protocolo prévio, para obtenção de dados, referentes à epidemiologia da doença, como as manifestações orais, descrevendo o tipo e localização destas lesões. Nos resultados encontrados, o sexo, a idade, a naturalidade, a procedência e a profissão dos pacientes foram fatores determinantes na descrição do perfil epidemiológico e demográfico da amostra estudada (187 casos, comparada com a literatura pertinente. Resultado: A avaliação dos resultados evidenciou mudanças pouco significativas em relação à epidemiologia da doença. E ficou bem evidenciada, também, a exuberância nas manifestações orais da doença, que são muito comuns e com freqüência levam à piora do estado geral do paciente ou mesmo à manutenção da doença, pela dificuldade de alimentação que aumenta a imunossupressão. Da amostragem dos 187 pacientes revista por este estudo, 167 (89,3% eram do sexo masculino e 20 (10,7% do feminino. Em relação à idade, 75 (40,1% estão entre 41 e 50 anos, destacando-se alguns aspectos: 81 pacientes (43,3% eram agricultores, sendo que 93 (49,7% eram oriundos do interior do Paraná. A perda de peso foi relatada em 72 (17,22% das 418 queixas, seguidas de dispnéia. Em relação à forma da lesão, 85 (41,46% dos pacientes não apresentavam lesões visíveis. Naqueles em que as lesões eram visíveis, as mais comuns foram a ulcerada e a granulomatosa, seguida esta da moriforme. O local com maior incidência de lesões foi a região de lábios, seguida de orofaringe e de palato duro; foi também observado o aparecimento de mais de um tipo de lesão em um mesmo paciente. Dos 187 pacientes, cinco (2,65% apresentavam tuberculose concomitantemente, e 140 (72,54% não apresentavam linfonodos palpáveis. Dos pacientes 127 (67,92% negaram fazer uso de bebida alcoólica, e 117 (62,57% eram tabagistas. O envolvimento pulmonar foi predominante em 160 (51,78% dos casos analisados. Na histopatologia, a técnica da coloração pela prata (GROCOTT mostrou-se mais sensível, comparada às colorações HE e o PAS, para a visualização na demonstração do agente etiológico P. brasiliensis.Study design: Clinical retrospective. Material and method: develop this research it had been realized a retrospective in reference book of 187 patients proceeding from the Infectology Service at the Deep Mycosis Ambulatory at Federal University of Paraná, in Curitiba, between may 1985 and march 1998. The purpose of this paper was to delineate the epidemic outline describing the stomatologicals manifestations found in the sample, to discuss about the data found and to establish comparison with the pertinent literature, to observe possible changes and if they were significant as well as to notice the dyes sensibility that were used in the histopathology (HE, PAS and GROCOTT, in 20 microscopic slides. It had been settled a previous protocol to get the data concerning to the desease epidemiology such as oral manifestations, describing the kind and localization of the lesions. In the results that were found, references like sex, age, naturalness, origien and profession of the patients were determinant factors in the epidemiologic and demographic outline of the sample studied (187 cases compared with the pertinent literature. Results: The evaluation of the results showed changes that were not to much significant in relation to the desease epidemiology. On the other hand, it was evidenced the exuberance in oral manifestations of the desease that is very commom and frequently leads the patient to a worse condition or even to a maintenance of the desease by the difficulty of nutrition that increases the immunesuppression. In the sample of these 187 patients studied, 167 (89,3% were male and 20 (10,7% female. In relation to the age, 75 (40,1 % were between 40 and 50 years, with some relevant aspects:81 patients (43,3 % were agricultural workers, 93 (49,7 % were from inland areas of Paraná. The loss of weight was related in 72 (17,22% of the 187 complaints, followed dyspnea. In relation to the shape of the lesions, 85 (41,46% of the patients did not show visible, the most commom were the ulcerated ones, the granulomatuos ones, followed by moriform one. The place with major incidence of lesions were lips, followed by oropharynx and hard palate, it was also noticed more than one kind of lesion in the same patient, between these 187 patients, five (2,65% showed also tuberculosis, 140 (72,54% did not palpable lymphonodes, 127 (67,91% of the patients denied to use alcoholic drinks, 117 (62,57% were smokers. The pulmonary envelopment was predominant in 166 (51,78% of the analized cases. In the histopathology, the technique of dyeing by silver (GROCOTT showed it self more sensitive than HE and PAS for visualization in demonstration of the etiologic agent P. brasiliensis.

Antibodies against glycolipids enhance antifungal activity of macrophages and reduce fungal burden after infection with Paracoccidioides brasiliensis

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Renata Amelia eBueno

2016-02-01

Full Text Available Paracoccidioidomycosis is a fungal disease endemic in Latin America. Polyclonal antibodies to acidic glycosphingolipids (GSLs from Paracoccidioides brasiliensis opsonized yeast forms in vitro increasing phagocytosis and reduced the fungal burden of infected animals. Antibodies to GSL were active in both prophylactic and therapeutic protocols using a murine intratracheal infection model. Pathological examination of the lungs of animals treated with antibodies to GSL showed well-organized granulomas and minimally damaged parenchyma compared to the untreated control. Murine peritoneal macrophages activated by IFN-γ and incubated with antibodies against acidic GSLs more effectively phagocytosed and killed P. brasiliensis yeast cells as well as produced more nitric oxide compared to controls. The present work discloses a novel target of protective antibodies against P. brasiliensis adding to other well-studied mediators of the immune response to this fungus.

Clinical and endoscopic findings in the mucosae of the upper respiratory and digestive tracts in post-treatment follow-up of paracoccidioidomycosis patients Achados clínicos e endoscópicos na mucosa das vias aéreas e digestivas superiores no segmento pós-terapêutico de pacientes com paracoccidioidomicose

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Antonio Carlos Francesconi do Valle

1995-10-01

Full Text Available Systematic examination of the upper respiratory and digestive tracts (URDT was performed in a group of 80 paracoccidioidomycosis (PCM patients submitted to post-treatment follow-up ranging from 8 months to 17 years. Mucosae of the URDT had been involved prior to specific treatment in 74 patients, distributed as follows: oropharynx, 50 (41 alone, 7 in association with the larynx, and 2 with the nasal mucosa; larynx, 30 (23 alone and 7 in association; and nasal mucosa, 3(1 alone and 2 in association. Inactive lesions were observed in all the 50 patients with lesions of the oropharynx, 3 of whom with deforming scars (1 with retraction of the tongue and 2 with narrowing of the oral orifice. One case presented a destructive lesion, with perfuration of the palate. Of the other 46 cases, examination showed nacreous white striated scars which were nearly imperceptible in some cases and in others displayed partial retraction of anatomical structures without any alteration of their features. Patients presented a high rate of missing teeth. In 3 patients with involvement of the nasal mucosa, none of whom presented active PCM lesions, 2 still had nasal voices. In 30 patients with lesions of the larynx, 1 suffered a relapse of PCM and 2 developed epidermoid carcinoma. Of the other 27 cases, none of whom had active PCM lesions, 15 presented dysphonia, 3 were tracheotomized, and 9 were asymptomatic.Foi realizado sistematicamente o exame das vias aero-digestivas superiores (VADS em grupo de 80 pacientes de paracoccidioidomicose (PCM acompanhados após o tratamento específico por período que variou de 8 meses a 17 anos. A mucosa das VADS estava comprometida antes do tratamento específico em 74 pacientes, assim distribuídos: orofaringe, 50 (41 isoladamente, 7 em associação com o laringe e 2 com a mucosa nasal; laringe, 30 (23 isoladamente e 7 em associação e nasal, 3 (1 isoladamente e 2 em associação. Em todos os 50 que apresentavam lesões no

[Serological diagnosis of sporotrichosis using an antigen of Sporothrix schenckii sensu stricto mycelium].

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Alvarado, Primavera; Ostos, Ana; Franquiz, Nohelys; Roschman-González, Antonio; Zambrano, Edgar A; Mendoza, Mireya

2015-06-01

We developed and analyzed an Enzyme-Linked Immunosorbent Assay (ELISA) in order to detect antibodies in sera from sporotrichosis patients. We used a crude antigen of Sporothrix schenckii sensu stricto, obtained from the mycelial phase of the fungi. Positive sera were analyzed by other serological techniques such as double immunodiffusion (IGG) and counterimmunoelectrophoresis (CIE). The assay was validated by using sera from patients with other pathologies such as: histoplasmosis, paracoccidioidomycosis, tuberculosis, leishmaniasis, lupus and healthy individuals as negative controls. For the Sporothrix schenckii sensu stricto antigen, we found a 100% of specificity by every technique and sensitivity higher than 98% with IDD, CIE and ELISA. Our results show a high sensitivity and specificity for the Sporothrix schenckii sensu stricto antigen, so it can be used for IDD, CIE and ELISA. The results suggest that this antigen could be used in conjunction with other conventional tests for differential diagnosis and may be useful for monitoring the disease progression and response to treatment.

Development of computational algorithms for quantification of pulmonary structures; Desenvolvimento de algoritmos computacionais para quantificacao de estruturas pulmonares

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Oliveira, Marcela de; Alvarez, Matheus; Alves, Allan F.F.; Miranda, Jose R.A., E-mail: marceladeoliveira@ig.com.br [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Instituto de Biociencias. Departamento de Fisica e Biofisica; Pina, Diana R. [Universidade Estadual Paulista Julio de Mesquita Filho (UNESP), Botucatu, SP (Brazil). Hospital das Clinicas. Departamento de Doencas Tropicais e Diagnostico por Imagem

2012-12-15

The high-resolution computed tomography has become the imaging diagnostic exam most commonly used for the evaluation of the squeals of Paracoccidioidomycosis. The subjective evaluations the radiological abnormalities found on HRCT images do not provide an accurate quantification. The computer-aided diagnosis systems produce a more objective assessment of the abnormal patterns found in HRCT images. Thus, this research proposes the development of algorithms in MATLAB® computing environment can quantify semi-automatically pathologies such as pulmonary fibrosis and emphysema. The algorithm consists in selecting a region of interest (ROI), and by the use of masks, filter densities and morphological operators, to obtain a quantification of the injured area to the area of a healthy lung. The proposed method was tested on ten HRCT scans of patients with confirmed PCM. The results of semi-automatic measurements were compared with subjective evaluations performed by a specialist in radiology, falling to a coincidence of 80% for emphysema and 58% for fibrosis. (author)

Development of computational algorithms for quantification of pulmonary structures

International Nuclear Information System (INIS)

Oliveira, Marcela de; Alvarez, Matheus; Alves, Allan F.F.; Miranda, Jose R.A.; Pina, Diana R.

2012-01-01

The high-resolution computed tomography has become the imaging diagnostic exam most commonly used for the evaluation of the squeals of Paracoccidioidomycosis. The subjective evaluations the radiological abnormalities found on HRCT images do not provide an accurate quantification. The computer-aided diagnosis systems produce a more objective assessment of the abnormal patterns found in HRCT images. Thus, this research proposes the development of algorithms in MATLAB® computing environment can quantify semi-automatically pathologies such as pulmonary fibrosis and emphysema. The algorithm consists in selecting a region of interest (ROI), and by the use of masks, filter densities and morphological operators, to obtain a quantification of the injured area to the area of a healthy lung. The proposed method was tested on ten HRCT scans of patients with confirmed PCM. The results of semi-automatic measurements were compared with subjective evaluations performed by a specialist in radiology, falling to a coincidence of 80% for emphysema and 58% for fibrosis. (author)

Linfonodo pulmonar na paracoccidioidomicose aguda infantil (relato de um caso

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Evanil Pires de Campos

1992-09-01

; hyperglobulinemia; anemia; leukocytosis with eosinophilia. Immunodiffusion with exoantigen 43 kd of P. brasiliensis was 1/32. Primary complex like Ghon was observed in interstitial pneumonia followed by mediastinic and mesogastric mass (35 to 40 days. Clavicular osteolythic lesions (45 to 60 days appeared during paracoccidioidomycosis therapy. Recovery was observed 2 months after treatment of acute infantile paracoccidioidomycosis.

Serological diagnosis of paracoccidioidomycosis: high rate of inter-laboratorial variability among medical mycology reference centers.

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Monica Scarpelli Martinelli Vidal

2014-09-01

Full Text Available Serological tests have long been established as rapid, simple and inexpensive tools for the diagnosis and follow-up of PCM. However, different protocols and antigen preparations are used and the few attempts to standardize the routine serological methods have not succeeded.We compared the performance of six Brazilian reference centers for serological diagnosis of PCM. Each center provided 30 sera of PCM patients, with positive high, intermediate and low titers, which were defined as the "reference" titers. Each center then applied its own antigen preparation and serological routine test, either semiquantitative double immunodifusion or counterimmmunoelectrophoresis, in the 150 sera from the other five centers blindly as regard to the "reference" titers. Titers were transformed into scores: 0 (negative, 1 (healing titers, 2 (active disease, low titers and 3 (active disease, high titers according to each center's criteria. Major discordances were considered between scores indicating active disease and scores indicating negative or healing titers; such discordance when associated with proper clinical and other laboratorial data, may correspond to different approaches to the patient's treatment. Surprisingly, all centers exhibited a high rate of "major" discordances with a mean of 31 (20% discordant scores. Alternatively, when the scores given by one center to their own sera were compared with the scores given to their sera by the remaining five other centers, a high rate of major discordances was also found, with a mean number of 14.8 sera in 30 presenting a discordance with at least one other center. The data also suggest that centers that used CIE and pool of isolates for antigen preparation performed better.There are inconsistencies among the laboratories that are strong enough to result in conflicting information regarding the patients' treatment. Renewed efforts should be promoted to improve standardization of the serological diagnosis of PCM.

Long-term outcome of neuroparacoccidioidomycosis treatment

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Fabio Francesconi

2011-02-01

Full Text Available INTRODUCTION: Neuroparacoccidioidomycosis (NPCM is a term used to describe the invasion of the central nervous system by the pathogenic fungus Paracoccidioides brasiliensis. NPCM has been described sporadically in some case reports and small case series, with little or no focus on treatment outcome and long-term follow-up. METHODS: All patients with NPCM from January 1991 to December 2006 were analyzed and were followed until December 2009. RESULTS: Fourteen (3.8% cases of NPCM were identified out of 367 patients with paracoccidioidomycosis (PCM. A combination of oral fluconazole and sulfamethoxazole/trimethoprim (SMZ/TMP was the regimen of choice, with no documented death due to Paracoccidioides brasiliensis infection. Residual neurological deficits were observed in 8 patients. Residual calcification was a common finding in neuroimaging follow-up. CONCLUSIONS: All the patients in this study responded positively to the association of oral fluconazole and sulfamethoxazole/trimethoprim, a regimen that should be considered a treatment option in cases of NPCM. Neurological sequela was a relatively common finding. For proper management of these patients, anticonvulsant treatment and physical therapy support were also needed.

Clinical aspects and relevance of molecular diagnosis in late mucocutaneous leishmaniasis patients in Paraná, Brazil

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Andréa Thomaz-Soccol

2011-06-01

Full Text Available The aim of the present work was to study the clinical aspects and relevance of molecular diagnosis in late mucocutaneous leishmaniasis patients in Parana, Brazil. Twenty one suspected cases of mucocutaneous leishmaniasis (MCL in patients from the endemic areas of leishmaniasis were assessed. Different methods used in diagnosing the disease and the polymerase chain reaction (PCR technique were compared in order to establish the sensitivity of each method. Out of the 21 patients analyzed, 14.3% presented other etiologies such as vasculitis, syphilis, and paracoccidioidomycosis, with all tests negative for leishmaniasis. Out of the remaining 15 patients, 6.7% cases were confirmed for leishmaniasis by direct examination; 46.67% were positive for culture, which allowed isolating and identifying the parasite and - with the PCR technique - it was possible to diagnose 100% MCL patients for all the three repetitions of exams. The PCR optimized for the present work proved to be an auxiliary method for diagnosing leishmaniasis applicable in the patients carrying MCL due to Leishmania (Viannia braziliensis and did not need culture to be performed, resulting in a faster diagnosis.

The Cell Wall-Associated Proteins in the Dimorphic Pathogenic Species of Paracoccidioides.

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Puccia, Rosana; Vallejo, Milene C; Longo, Larissa V G

2017-01-01

Paracoccidioides brasiliensis and P. lutzii cause human paracoccidioidomycosis (PCM). They are dimorphic ascomycetes that grow as filaments at mild temperatures up to 28oC and as multibudding pathogenic yeast cells at 37oC. Components of the fungal cell wall have an important role in the interaction with the host because they compose the cell outermost layer. The Paracoccidioides cell wall is composed mainly of polysaccharides, but it also contains proportionally smaller rates of proteins, lipids, and melanin. The polysaccharide cell wall composition and structure of Paracoccidioides yeast cells, filamentous and transition phases were studied in detail in the past. Other cell wall components have been better analyzed in the last decades. The present work gives to the readers a detailed updated view of cell wall-associated proteins. Proteins that have been localized at the cell wall compartment using antibodies are individually addressed. We also make an overview about PCM, the Paracoccidioides cell wall structure, secretion mechanisms, and fungal extracellular vesicles. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Proteomic profile response of Paracoccidioides lutzii to the antifungal argentilactone

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Renata Silva Do Prado

2015-06-01

Full Text Available The dimorphic fungi Paracoccidioides spp. are the etiological agents of paracoccidioidomycosis (PCM, a mycosis of high incidence in Brazil. The toxicity of drug treatment and the emergence of resistant organisms have led to research for new candidates for drugs. In this study, we demonstrate that the natural product argentilactone was not cytotoxic or genotoxic to MRC5 cells at the IC50 concentration to the fungus. We also verified the proteomic profile of Paracoccidioides lutzii after incubation with argentilactone using a label free quantitative proteome nanoUPLC-MSE. The results of this study indicated that the fungus has a global metabolic adaptation in the presence of argentilactone. Enzymes of important pathways, such as glycolysis, the Krebs cycle and the glyoxylate cycle, were repressed, which drove the metabolism to the methylcytrate cycle and beta-oxidation. Proteins involved in cell rescue, defense and stress response were induced. In this study, alternative metabolic pathways adopted by the fungi were elucidated, helping to elucidate the course of action of the compound studied.

Situación de las micosis en la República Argentina Epidemiological status of mycoses in the Argentine Republic

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G. Davel

2007-03-01

conducted by the National Network of Mycology Laboratories and National Quality Control Program (NNML and NQCP in 1999 and 2002. The most frequent deep mycoses were yeast fungaemia (34 %, cryptococcosis (20%, broncho-pulmonary aspergillosis (13%, histoplasmosis (11%, paracoccidioidomycosis (7% and pneumocystosis (5%. In contrast with results of four previous nationwide studies on broncho-pulmonary mycoses including a survey performed by NNML and NQCP in 2002, our study revealed that histoplasmosis prevailed over paracoccidioidomycosis, thus ranking for the first time as the most frequent endemic mycosis in Argentina.

ArtinM offers new perspectives in the development of antifungal therapy

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Luciana Pereira Ruas

2012-06-01

Full Text Available The thermally dimorphic fungus Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis (PCM, the most frequent systemic mycosis that affects the rural populations in Latin America. Despite significant developments in antifungal chemotherapy, its efficacy remains limited since drug therapy is prolonged and associated with toxic side effects and relapses. In response to these challenges, it is now recognized that several aspects of antifungal immunity can be modulated to better deal with fungal infections. A common idea for halting fungal infections has been the need to activate a cell-based, pro-inflammatory Th1 immune response to improve the fungal elimination. ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has the property of modulating immunity against several intracellular pathogens. Here, we review the immunomodulatory activity of ArtinM during experimental PCM in mice. Both prophylactic and therapeutic protocols of ArtinM administration promotes a Th1 immune response balanced by IL-10, which outstandingly reduces the fungal load in organs of the treated mice while maintaining a controlled inflammation at the site of infection. A carbohydrate recognition based interaction of ArtinM

Identification of Paracoccidioides brasiliensis by gold nanoprobes

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Martins, Jaciara F. S.; Castilho, Maiara L.; Cardoso, Maria A. G.; Carreiro, Andrea P.; Martin, Airton A.; Raniero, Leandro

2012-01-01

Paracoccidioides brasiliensis (P. brasiliensis) is a thermal dimorphic fungus and causal agent of paracoccidioidomycosis. Epidemiological data shows that it is mainly concentrated in Central and South America countries, with most registered cases in Colombia, Brazil, and Venezuela. The histopathological similarity with others fungal infection makes the diagnosis of P. brasiliensis more complicated. Therefore, the aim of this work was to find a positive and negative test for P. brasiliensis using gold nanoprobes as a new tool for P. brasiliensis detection. Gold nanoparticles were synthesized by reduction of gold chloride with sodium citrate. The results of this procedure is a wine-red solution with a maximum absorption in the range of ~520-530nm. A specific P. brasiliensis sequence of oligonucleotide was bonded to the nanoparticles, which maintained the wine-red color. The color changes from red to blue for negative diagnostic and is unchanged for a positive test. The H-bond interaction of DNA with the complementary DNA keeps strands together and forms double helical structure, maintaining the colloid stability. However, for non-complimentary DNA sequence the nanoprobes merge into a cluster, changing the light absorption.

Gamma irradiation induced ultrastructural changes in Paracoccidioides brasiliensis yeast cells

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Demicheli, Marina C.; Andrade, Antero S.R.; Goes, Alfredo Miranda

2007-01-01

Paracoccidioides brasiliensis is a thermally dimorphic fungus agent of paracoccidioidomycosis, a deep-seated systemic infection of humans with high prevalence in Latin America. Up to the moment no vaccine has still been reported. Ionizing radiation can be used to attenuate pathogens for vaccine development and we have successfully attenuated yeast cells of P. brasiliensis by gamma irradiation. The aim of the present study was to examine at ultrastructural level the effects of gamma irradiation attenuation on the morphology of P. brasiliensis yeast cells. P. brasiliensis (strain Pb-18) cultures were irradiated with a dose of 6.5 kGy. The irradiated cells were examined by scanning and also transmission electron microscopy. When examined two hours after the irradiation by scanning electron microscopy the 6.5 kGy irradiated cells presented deep folds or were collapsed. These lesions were reversible since examined 48 hours after irradiation the yeast have recovered the usual morphology. The transmission electron microscopy showed that the irradiated cells plasma membrane and cell wall were intact and preserved. Remarkable changes were found in the nucleus that was frequently in a very electrodense form. A extensive DNA fragmentation was produced by the gamma irradiation treatment. (author)

The reversed halo sign: update and differential diagnosis

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Godoy, M C B; Viswanathan, C; Marchiori, E; Truong, M T; Benveniste, M F; Rossi, S; Marom, E M

2012-01-01

The reversed halo sign is characterised by a central ground-glass opacity surrounded by denser air–space consolidation in the shape of a crescent or a ring. It was first described on high-resolution CT as being specific for cryptogenic organising pneumonia. Since then, the reversed halo sign has been reported in association with a wide range of pulmonary diseases, including invasive pulmonary fungal infections, paracoccidioidomycosis, pneumocystis pneumonia, tuberculosis, community-acquired pneumonia, lymphomatoid granulomatosis, Wegener granulomatosis, lipoid pneumonia and sarcoidosis. It is also seen in pulmonary neoplasms and infarction, and following radiation therapy and radiofrequency ablation of pulmonary malignancies. In this article, we present the spectrum of neoplastic and non-neoplastic diseases that may show the reversed halo sign and offer helpful clues for assisting in the differential diagnosis. By integrating the patient's clinical history with the presence of the reversed halo sign and other accompanying radiological findings, the radiologist should be able to narrow the differential diagnosis substantially, and may be able to provide a presumptive final diagnosis, which may obviate the need for biopsy in selected cases, especially in the immunosuppressed population. PMID:22553298

Obtenção de exoantígenos de Histoplasma capsulatum em meio de neopeptona, glicose, tiamina e asparagina (NGTA Histoplasma capsulatum exocellular antigens. Obtention in neopeptone, glucose, thiamine and asparagine medium (NGTA

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Nilma Maciel Garcia

1990-10-01

Full Text Available O presente trabalho teve como objetivo a produção de exoantígenos H e M das amostras 58, B-679, A-811 e O187 de Histoplasma capsulatum, utilizando o meio NGTA (neopeptona, glicose, tiamina e asparagina em períodos de cultivo de 1, 2 e 3 meses, a 36ºC, sob agitação constante (50 v.p.m.. Os antígenos brutos foram avaliados contra anti-soro e antígeno de Histoplasma capsulatum de referência (Center for Disease Control, 4 soros de pacientes portadores de paracoccidioidomicose, 7 de histoplasmose e soro hiperimune anti-H. capsulatum produzido em coelhos, através da reação de imunodifusão dupla. Verificou-se que, com exceção de B-679 com 1 mês de crescimento, todos os demais exoantígenos apresentaram as frações H e M de precipitação. Os exoantígenos obtidos de A-811 apresentaram só a banda H. Excetuando-se os exoantígenos 58 e B-679 com 1 mês de crescimento, todos os demais exoantígenos reagiram contra soros de pacientes com histoplasmose. Em relação aos soros de pacientes com paracoccidioidomicose, somente os exoantígenos 58 e O187 não apresentaram reação cruzada. Todos os exoantígenos reagiram frente ao soro hiperimune de coelho anti-H. capsulatum. Para obtenção de exoantígenos de H. capsulatum, sugerimos que as amostras sejam cultivadas sob as condições anteriormente descritas, adotando-se o período de 3 meses de crescimento, utilizando-se exoantígenos de referência como controles da reação.The purpose of this work is obtaining exocellular antigens H and M from 4 H. capsulatum strains using NGTA medium (neopeptone, glucose, thiamine and asparagine for periods of 1,2 and 3 months, at 36ºC and continuously shaken. The exocellular antigens were evaluated by double immunodiffusion test against H. capsulatum rabbit antiserum, 7 histoplasmosis sera, 4 paracoccidioidomycosis sera and a reference antigen and antibody furnished by C.D.C. (Atlanta - USA. Except for the exocellular antigen from strain B.679 with 1

Lobomycosis-like disease in common bottlenose dolphins Tursiops truncatus from Belize and Mexico: bridging the gap between the Americas.

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Ramos, Eric A; Castelblanco-Martínez, Delma N; Garcia, Jazmin; Rojas Arias, Jorge; Foley, James R; Audley, Katherina; Van Waerebeek, Koen; Van Bressem, Marie-Françoise

2018-03-22

Lobomycosis and lobomycosis-like diseases (LLD) (also: paracoccidioidomycosis) are chronic cutaneous infections that affect Delphinidae in tropical and subtropical regions worldwide. In the Americas, these diseases have been relatively well-described, but gaps still exist in our understanding of their distribution across the continent. Here we report on LLD affecting inshore bottlenose dolphins Tursiops truncatus from the Caribbean waters of Belize and from the eastern tropical Pacific Ocean off the southwestern coast of Mexico. Photo-identification and catalog data gathered between 1992 and 2017 for 371 and 41 individuals, respectively from Belize and Mexico, were examined for the presence of LLD. In Belize, 5 free-ranging and 1 stranded dolphin were found positive in at least 3 communities with the highest prevalence in the south. In Guerrero, Mexico, 4 inshore bottlenose dolphins sighted in 2014-2017 were affected by LLD. These data highlight the need for histological and molecular studies to confirm the etiological agent. Additionally, we document a single case of LLD in an adult Atlantic spotted dolphin Stenella frontalis in southern Belize, the first report in this species. The role of environmental and anthropogenic factors in the occurrence, severity, and epidemiology of LLD in South and Central America requires further investigation.

Antifungal Activity of Maytenin and Pristimerin

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Fernanda P. Gullo

2012-01-01

Full Text Available Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa. It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents.

Immunoglobulins and C3 in the P. brasiliensis granuloma

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Lilian M. V. Biagioni

1987-04-01

Full Text Available The experimental model of paracoccidioidomycosis induced in mice by the intravenous injection of yeast-forms of P. brasiliensis (Bt2 strain; 1 x 10(6 viable fungi/animal was used to evaluate sequentially 2, 4, 8, 16 and 20 weeks after inoculation: 1. The presence of immunoglobulins and C3 in the pulmonary granuloma-ta, by direct immunofluorescence; 2. The humoral (immunodiffusion test and the cellular (footpad sweeling test immune response; 3. The histopathology of lesions. The cell-immune response was positive since week 2, showing a transitory depression at week 16. Specific antibodies were first detected at week 4 and peaked at week 16. At histology, epithelioid granulomas with numerous fungi and polymorphonuclear agreggates were seen. The lungs showed progressive involvement up to week 16, with little decrease at week 20. From week 2 on, there were deposits of IgG and C3 around fungal walls within the granulomas and IgG stained cells among the mononuclear cell peripheral halo. Interstitital immunoglobulins and C3 deposits in the granulomas were not letected. IgG and C3 seen to play an early an important role in. the host defenses against P. brasiliensis by possibly cooperating in the killing of parasites and blocking the antigenic diffusion.

Oenothein B inhibits the expression of PbFKS1 transcript and induces morphological changes in Paracoccidioides brasiliensis.

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Santos, Glaciane D; Ferri, Pedro H; Santos, Suzana C; Bao, Sônia N; Soares, Célia M A; Pereira, Maristela

2007-11-01

The fungus Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis (PCM), the most prevalent human systemic mycosis in Latin America. Drug toxicity and the appearance of resistant strains have created the need to search for new therapeutic approaches. Plants with reputed antimicrobial properties represent a rich screening source of potential antifungal compounds. In this work, the growth of P. brasiliensis yeast cells was evaluated in the presence of oenothein B extracted from Eugenia uniflora. The oenothein B dosage that most effectively inhibited the development (74%) of P. brasiliensis yeast cells in vitro was 500 microg/ml. To verify if oenothein B interferes with cell morphology, we observed oenothein B-treated yeast cells by electron microscopy. The micrographs showed characteristic cell changes noted with glucan synthesis inhibition, including squashing, rough surface, cell wall rupture and cell membrane recess. The expression of P. brasiliensis genes was evaluated in order to investigate the action of oenothein B. Here we report that oenothein B inhibits 1,3-beta-glucan synthase (PbFKS1) transcript accumulation. The results indicate that oenothein B interferes with the cell morphology of P. brasiliensis, probably by inhibiting the transcription of 1,3-beta-glucan synthase gene, which is involved in the cell wall synthesis.

The burden of serious human fungal infections in Brazil.

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Giacomazzi, Juliana; Baethgen, Ludmila; Carneiro, Lilian C; Millington, Maria Adelaide; Denning, David W; Colombo, Arnaldo L; Pasqualotto, Alessandro C

2016-03-01

In Brazil, human fungal infections are prevalent, however, these conditions are not officially reportable diseases. To estimate the burden of serious fungal diseases in 1 year in Brazil, based on available data and published literature. Historical official data from fungal diseases were collected from Brazilian Unified Health System Informatics Department (DATASUS). For fungal diseases for which no official data were available, assumptions of frequencies were made by estimating based on published literature. The incidence (/1000) of hospital admissions for coccidioidomycosis was 7.12; for histoplasmosis, 2.19; and for paracoccidioidomycosis, 7.99. The estimated number of cryptococcal meningoencephalitis cases was 6832. Also, there were 4115 cases of Pneumocystis pneumonia in AIDS patients per year, 1 010 465 aspergillosis and 2 981 416 cases of serious Candida infections, including invasive and non-invasive diseases. In this study, we demonstrate that more than 3.8 million individuals in Brazil may be suffering from serious fungal infections, mostly patients with malignant cancers, transplant recipients, asthma, previous tuberculosis, HIV infection and those living in endemic areas for truly pathogenic fungi. The scientific community and the governmental agencies should work in close collaboration in order to reduce the burden of such complex, difficult-to-diagnose and hard to treat diseases. © 2015 Blackwell Verlag GmbH.

Antifungal Activity of Maytenin and Pristimerin

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Gullo, Fernanda P.; Sardi, Janaina C. O.; Santos, Vânia A. F. F. M.; Sangalli-Leite, Fernanda; Pitangui, Nayla S.; Rossi, Suélen A.; de Paula e Silva, Ana C. A.; Soares, Luciana A.; Silva, Julhiany F.; Oliveira, Haroldo C.; Furlan, Maysa; Silva, Dulce H. S.; Bolzani, Vanderlan S.; Mendes-Giannini, Maria José S.; Fusco-Almeida, Ana Marisa

2012-01-01

Fungal infections in humans have increased alarmingly in recent years, particularly in immunocompromised individuals. Among the infections systemic candidiasis, aspergillosis, cryptococcosis, paracoccidioidomycosis, and histoplasmosis mortality are more prevalent and more severe in humans. The current high incidence of dermatophytosis is in humans, especially as the main etiologic agents Trichophyton rubrum and Trichophyton mentagrophytes. Molecules pristimerin and maytenin obtained from the plant Maytenus ilicifolia (Celastraceae) are known to show various pharmacological activities. This study aimed to evaluate the spectrum of antifungal activity of maytenin and pristimerin and their cytotoxicity in human keratinocytes (NOK cells of the oral mucosa). It was concluded that the best spectrum of antifungal activity has been shown to maytenin with MIC varying from 0.12 to 125 mg/L, although it is also active with pristimerin MIC ranging between 0.12 and 250 mg/L. Regarding the toxicity, both showed to have high IC50. The SI showed high pristimerin against some species of fungi, but SI maytenin was above 1.0 for all fungi tested, showing a selective action of fungi. However, when comparing the two substances, maytenin also showed better results. The two molecules can be a possible prototype with a broad spectrum of action for the development of new antifungal agents. PMID:22675379

The malate synthase of Paracoccidioides brasiliensis is a linked surface protein that behaves as an anchorless adhesin

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Pereira Maristela

2009-12-01

Full Text Available Abstract Background The pathogenic fungus Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis (PCM. This is a pulmonary mycosis acquired by inhalation of fungal airborne propagules that can disseminate to several organs and tissues leading to a severe form of the disease. Adhesion and invasion to host cells are essential steps involved in the internalization and dissemination of pathogens. Inside the host, P. brasiliensis may use the glyoxylate cycle for intracellular survival. Results Here, we provide evidence that the malate synthase of P. brasiliensis (PbMLS is located on the fungal cell surface, and is secreted. PbMLS was overexpressed in Escherichia coli, and polyclonal antibody was obtained against this protein. By using Confocal Laser Scanning Microscopy, PbMLS was detected in the cytoplasm and in the cell wall of the mother, but mainly of budding cells of the P. brasiliensis yeast phase. PbMLSr and its respective polyclonal antibody produced against this protein inhibited the interaction of P. brasiliensis with in vitro cultured epithelial cells A549. Conclusion These observations indicated that cell wall-associated PbMLS could be mediating the binding of fungal cells to the host, thus contributing to the adhesion of fungus to host tissues and to the dissemination of infection, behaving as an anchorless adhesin.

Multifaceted roles of metabolic enzymes of the Paracoccidioides species complex

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Caroline Maria Marcos

2014-12-01

Full Text Available Paracoccidioides species are dimorphic fungi, and are the etiologic agents of paracoccidioidomycosis (PCM, a serious disease of multiple organs. The large number of tissues colonized by this fungus suggests the presence of a variety of surface molecules involved in adhesion. A surprising finding is that the majority of enzymes in the glycolytic pathway, tricarboxylic acid (TCA cycle and glyoxylate cycle in Paracoccidioides spp. has adhesive properties that aid in the interaction with the host extracellular matrix, and so act as ‘moonlighting’ proteins. Moonlighting proteins have multiple functions and add another dimension to cellular complexity, while benefiting cells in several ways. This phenomenon occurs in both eukaryotes and prokaryotes. For example, moonlighting proteins from the glycolytic pathway or TCA cycle can play roles in bacterial pathogens, either by acting as proteins secreted in a conventional pathway or not and/or as cell surface component that facilitate adhesion or adherence . This review outlines the multifuncionality exposed by a variety of Paracoccidioides spp. enzymes including aconitase, aldolase, glyceraldehyde-3-phosphate dehydrogenase, isocitrate lyase, malate synthase, triose phosphate isomerase, fumarase and enolase. The roles that moonlighting activities play in the virulence characteristics of this fungus and several other human pathogens during their interactions with the host are discussed.

Evidence for positive selection in putative virulence factors within the Paracoccidioides brasiliensis species complex.

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Daniel R Matute

Full Text Available Paracoccidioides brasiliensis is a dimorphic fungus that is the causative agent of paracoccidioidomycosis, the most important prevalent systemic mycosis in Latin America. Recently, the existence of three genetically isolated groups in P. brasiliensis was demonstrated, enabling comparative studies of molecular evolution among P. brasiliensis lineages. Thirty-two gene sequences coding for putative virulence factors were analyzed to determine whether they were under positive selection. Our maximum likelihood-based approach yielded evidence for selection in 12 genes that are involved in different cellular processes. An in-depth analysis of four of these genes showed them to be either antigenic or involved in pathogenesis. Here, we present evidence indicating that several replacement mutations in gp43 are under positive balancing selection. The other three genes (fks, cdc42 and p27 show very little variation among the P. brasiliensis lineages and appear to be under positive directional selection. Our results are consistent with the more general observations that selective constraints are variable across the genome, and that even in the genes under positive selection, only a few sites are altered. We present our results within an evolutionary framework that may be applicable for studying adaptation and pathogenesis in P. brasiliensis and other pathogenic fungi.

[Immunodiagnosis of endemic mycoses and bronchopulmonary aspergillosis: a multicenter study in Argentina].

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Canteros, C E; Rivas, M C; Soria, M; Lee, W; Perrotta, D; Rodero, L; Davel, G

2004-01-01

In order to contribute to the knowledge of the relative frequency of chronic fungal diseases and assess the performance of diagnostic laboratories in Argentina, a multicenter study was performed with the participation of 25 medical centers located in 12 different provinces and Buenos Aires City. Between 04-01-2000 and 03-30-2001, 965 serum specimens from patients clinically suspected of having histoplasmosis (HP), paracoccidioidomycosis (PCM), coccidioidomycosis (CM) or aspergilosis were analyzed. Agar immunodiffusion tests (IDD) were done locally. All positive and 35% of negative sera were retested in the reference center. Results of laboratories of origin showed 98.8% concordance with those of reference center. Antibodies against any of the etiological agents were detected in 120 specimens from 98 patients. Endemic mycoses (HP, PCM and CM) were diagnosed in 70 patients (71.4%) and aspergilosis in 28 (28.6%). The frequencies of the different mycoses in decreasing order were PCM 47 patients (47.9%), aspergilosis 28 patients (28.6%), HP 13 patients (13.3%) and CM 10 patients (10.2%). The study was carried out on a voluntary basis and some areas of the country were not represented. However, the frequencies were in range with the expected rates in the population under study.

Histoplasmosis and Paracoccidioidomycosis in northwestern Argentina III. Epidemiological survey in Vipos, La Toma, and Choromoro - Trancas, Tucuman, Argentina

International Nuclear Information System (INIS)

Komaid, Aida van Gelderen de; Duran, Estela; Kestelman, Isabel Borges de

1999-01-01

The present work was undertaken to obtain epidemiological data on the extent and distribution of Histoplasma capsulatum var. capsulatum and Paracoccidiodes brasiliensis diseases in the Vipos, La Toma and Choromoro areas. Skin test surveys with histoplasmin and paracoccidioidin were carried out in the permanent human population of those localities. Mycological sputum studies and serological tests were performed to skin test reactors to determine if there were signs or symptoms of active mycotic disease. La Toma and Choromoro are highly prevalent areas of histoplasmosis ( > 30% the histoplasmin positive individuals) whereas Vipos can be relatively considered a highly prevalent area (between 20-30% the histoplasmin reactors) according to the normally accepted range used to define an endemic disease [2]. Early Histoplasma capsulatum infection ( < 10 years old) is reported for Vipos and Choromoro. La Toma has the highest rate of previous exposure to P. brasiliensis detected in the studied area (10.2%). Vipos residents are not infected with P. brasiliensis

PARACOCCCIDIOIDOMICOSE COM MANIFESTAÇÃO BUCAL -CASUÍSTICA EM VOLTA REDONDA-RJ NOS ANOS DE 2005 A 2008

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Oriental Luiz de Noronha Filho

2011-01-01

Full Text Available Paracoccidioidomycosis, formerly known as South American Blastomycosis, can be installed by inhalation or by skin lesions or mucous membranes. Poor hygiene and oral diseases are theports of entry most common for this fungus, once in the bloodstream becomes systemic to infect the lungs, spleen, liver, kidneys, pancreas, bones and lymph nodes. The fungus grows on plants and soils in geographical and climatic conditions common areas of the valley of the Paraíba do Sul. The disease has preferences for males, for white and aged between 41 and 50. The primary lesion compromises the oral tongue, gums, lips and other mucous, isolated or associated. The oral lesions appear as lesions located andbulky appearance of micro granules, resembling a blackberry. This study examined medical records of the Municipal Health Department of Volta Redonda, whose primary lesion was in the mouth. We selected 11patient records that corroborated with the literary data, emphasizing the language as the most affected andthe association with bad oral hygiene and oral habits such as smoking and alcohol consumption. All evaluated had pulmonary infection and were treated clinically by the administration of sulfa drugs, outpatient and six to twelve months. It was concluded this could be an endemic area and the importance of the role of the Dental Surgeon in the diagnosis of the disease.

ArtinM offers new perspectives in the development of antifungal therapy

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Ruas, Luciana P.; Carvalho, Fernanda C.; Roque-Barreira, Maria-Cristina

2012-01-01

The thermally dimorphic fungus Paracoccidioides brasiliensis is the causative agent of paracoccidioidomycosis (PCM), the most frequent systemic mycosis that affects the rural populations in Latin America. Despite significant developments in antifungal chemotherapy, its efficacy remains limited since drug therapy is prolonged and associated with toxic side effects and relapses. In response to these challenges, it is now recognized that several aspects of antifungal immunity can be modulated to better deal with fungal infections. A common idea for halting fungal infections has been the need to activate a cell-based, pro-inflammatory Th1 immune response to improve the fungal elimination. ArtinM, a D-mannose binding lectin from Artocarpus heterophyllus, has the property of modulating immunity against several intracellular pathogens. Here, we review the immunomodulatory activity of ArtinM during experimental PCM in mice. Both prophylactic and therapeutic protocols of ArtinM administration promotes a Th1 immune response balanced by IL-10, which outstandingly reduces the fungal load in organs of the treated mice while maintaining a controlled inflammation at the site of infection. A carbohydrate recognition-based interaction of ArtinM with Toll-like receptor 2 (TLR2) accounts for initiating the immunomodulatory effect of the lectin. The precise identification of the TLR2 N-glycan(s) targeted by ArtinM may support novel basis for the development of antifungal therapy. PMID:22715337

Ground-glass opacity in diffuse lung diseases: high-resolution computed tomography-pathology correlation

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Santos, Maria Lucia de Oliveira; Vianna, Alberto Domingues; Marchiori, Edson; Souza Junior, Arthur Soares; Moraes, Heleno Pinto de

2003-01-01

Ground-glass opacity is a finding frequently seen in high-resolution computed tomography examinations of the chest and is characterized by hazy increased attenuation of lung, however without blurring of bronchial and vascular margins. Due to its un specificity, association with other radiological, clinical and pathological findings must be considered for an accurate diagnostic interpretation. In this paper were reviewed 62 computed tomography examinations of patients with diffuse pulmonary diseases of 14 different etiologies in which ground-glass opacity was the only or the most remarkable finding, and correlated this findings with pathology abnormalities seen on specimens obtained from biopsies or necropsies. In pneumocystosis, ground-glass opacities correlated histologically with alveolar occupation by a foaming material containing parasites, in bronchiole alveolar cell carcinoma with thickening of the alveolar septa and occupation of the lumen by mucus and tumoral cells, in paracoccidioidomycosis with thickening of the alveolar septa, areas of fibrosis and alveolar bronchopneumonia exudate, in sarcoidosis with fibrosis or clustering of granulomas and in idiopathic pulmonary fibrosis with alveolar septa thickening due to fibrosis. Alveolar occupation by blood was found in cases of leptospirosis, idiopathic hemo siderosis, metastatic kidney tumor and invasive aspergillosis whereas oily vacuole were seen in lipoid pneumonia, proteinaceous and lipo proteinaceous material in silico proteinosis and pulmonary alveolar proteinosis, and edematous fluid in cardiac failure. (author)

Exploring potential virulence regulators in Paracoccidioides brasiliensis isolates of varying virulence through quantitative proteomics.

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Castilho, Daniele G; Chaves, Alison F A; Xander, Patricia; Zelanis, André; Kitano, Eduardo S; Serrano, Solange M T; Tashima, Alexandre K; Batista, Wagner L

2014-10-03

Few virulence factors have been identified for Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis. In this study, we quantitatively evaluated the protein composition of P. brasiliensis in the yeast phase using minimal and rich media to obtain a better understanding of its virulence and to gain new insights into pathogen adaptation strategies. This analysis was performed on two isolates of the Pb18 strain showing distinct infection profiles in B10.A mice. Using liquid chromatography/tandem mass spectrometry (LC-MS/MS) analysis, we identified and quantified 316 proteins in minimal medium, 29 of which were overexpressed in virulent Pb18. In rich medium, 29 out of 295 proteins were overexpressed in the virulent fungus. Three proteins were found to be up-regulated in both media, suggesting the potential roles of these proteins in virulence regulation in P. brasiliensis. Moreover, genes up-regulated in virulent Pb18 showed an increase in its expression after the recovery of virulence of attenuated Pb18. Proteins up-regulated in both isolates were grouped according to their functional categories. Virulent Pb18 undergoes metabolic reorganization and increased expression of proteins involved in fermentative respiration. This approach allowed us to identify potential virulence regulators and provided a foundation for achieving a molecular understanding of how Paracoccidioides modulates the host-pathogen interaction to its advantage.

Ground-glass opacity in diffuse lung diseases: high-resolution computed tomography-pathology correlation; Opacidades em vidro fosco nas doencas pulmonares difusas: correlacao da tomografia computadorizada de alta resolucao com a anatomopatologia

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Santos, Maria Lucia de Oliveira; Vianna, Alberto Domingues; Marchiori, Edson [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Radiologia; Souza Junior, Arthur Soares [Faculdade de Medicina de Sao Jose do Rio Preto (FAMERP), SP (Brazil). Disciplina de Radiologia; Moraes, Heleno Pinto de [Universidade Federal Fluminense, Niteroi, RJ (Brazil). Dept. de Patologia]. E-mail: edmarchiori@zipmail.com.br

2003-12-01

Ground-glass opacity is a finding frequently seen in high-resolution computed tomography examinations of the chest and is characterized by hazy increased attenuation of lung, however without blurring of bronchial and vascular margins. Due to its un specificity, association with other radiological, clinical and pathological findings must be considered for an accurate diagnostic interpretation. In this paper were reviewed 62 computed tomography examinations of patients with diffuse pulmonary diseases of 14 different etiologies in which ground-glass opacity was the only or the most remarkable finding, and correlated this findings with pathology abnormalities seen on specimens obtained from biopsies or necropsies. In pneumocystosis, ground-glass opacities correlated histologically with alveolar occupation by a foaming material containing parasites, in bronchiole alveolar cell carcinoma with thickening of the alveolar septa and occupation of the lumen by mucus and tumoral cells, in paracoccidioidomycosis with thickening of the alveolar septa, areas of fibrosis and alveolar bronchopneumonia exudate, in sarcoidosis with fibrosis or clustering of granulomas and in idiopathic pulmonary fibrosis with alveolar septa thickening due to fibrosis. Alveolar occupation by blood was found in cases of leptospirosis, idiopathic hemo siderosis, metastatic kidney tumor and invasive aspergillosis whereas oily vacuole were seen in lipoid pneumonia, proteinaceous and lipo proteinaceous material in silico proteinosis and pulmonary alveolar proteinosis, and edematous fluid in cardiac failure. (author)

Pediatric allergy and immunology in Brazil.

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Rosario-Filho, Nelson A; Jacob, Cristina M; Sole, Dirceu; Condino-Neto, Antonio; Arruda, Luisa K; Costa-Carvalho, Beatriz; Cocco, Renata R; Camelo-Nunes, Inês; Chong-Neto, Herberto J; Wandalsen, Gustavo F; Castro, Ana P M; Yang, Ariana C; Pastorino, Antonio C; Sarinho, Emanuel S

2013-06-01

The subspecialty of pediatric allergy and immunology in Brazil is in its early years and progressing steadily. This review highlights the research developed in the past years aiming to show the characteristics of allergic and immunologic diseases in this vast country. Epidemiologic studies demonstrated the high prevalence of asthma in infants, children, and adolescents. Mortality rates and average annual variation of asthma hospitalization have reduced in all pediatric age groups. Indoor aeroallergen exposure is excessively high and contributes to the high rates of allergy sensitization. Prevalence of food allergy has increased to epidemic levels. Foods (35%), insect stings (30%), and drugs (23%) are the main etiological agents of anaphylaxis in children and adolescents. Molecular diagnosis of primary immunodeficiencies (PID) showed a high incidence of fungal infections including paracoccidioidomycosis in X-linked hyper-IgM syndrome, and the occurrence of BCG adverse reactions or other mycobacterial infections in patients with chronic granulomatous disease. Education in pediatric allergy and immunology is deficient for medical students, but residency programs are effective in training internists and pediatricians for the practice of allergy. The field of PID requires further training. Last, this review is a tribute to Prof. Dr. Charles Naspitz, one of the pioneers of our specialty in Brazil. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections.

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Monteiro, Paulo Henrique Silva; de Souza, Thiago Ferreira; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Mengatti, Jair; de Lima, Mariana da Cunha Lopes; Santos, Allan Oliveira; Ramos, Celso Darío

2017-01-01

To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ( 67 Ga) citrate scintigraphy. We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99m Tc-EDDA-HYNIC-TOC, and 21 after injection of 111 In-DTPA-octreotide. All patients also underwent 67 Ga citrate imaging, except for one patient who died before the 67 Ga was available. In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67 Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67 Ga uptake in 11 of the 20 patients with positive images and similar to 67 Ga uptake in the other 9 patients. The only patient who did not undergo 67 Ga scintigraphy underwent 99m Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. SPECT/CT with 99m Tc-EDDA-HYNIC-TOC or 111 In-DTPA-octreotide seems to be a good alternative to 67 Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

Estimating the Burden of Serious Fungal Infections in Uruguay

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Marina Macedo-Viñas

2018-03-01

Full Text Available We aimed to estimate for the first time the burden of fungal infections in Uruguay. Data on population characteristics and underlying conditions were extracted from the National Statistics Institute, the World Bank, national registries, and published articles. When no data existed, risk populations were used to estimate frequencies extrapolating from the literature. Population structure (inhabitants: total 3,444,006; 73% adults; 35% women younger than 50 years. Size of populations at risk (total cases per year: HIV infected 12,000; acute myeloid leukemia 126; hematopoietic stem cell transplantation 30; solid organ transplants 134; COPD 272,006; asthma in adults 223,431; cystic fibrosis in adults 48; tuberculosis 613; lung cancer 1400. Annual incidence estimations per 100,000: invasive aspergillosis, 22.4; candidemia, 16.4; Candida peritonitis, 3.7; Pneumocystis jirovecii pneumonia, 1.62; cryptococcosis, 0.75; severe asthma with fungal sensitization, 217; allergic bronchopulmonary aspergillosis, 165; recurrent Candida vaginitis, 6323; oral candidiasis, 74.5; and esophageal candidiasis, 25.7. Although some under and overestimations could have been made, we expect that at least 127,525 people suffer from serious fungal infections each year. Sporothrichosis, histoplasmosis, paracoccidioidomycosis, and dermatophytosis are known to be frequent but no data are available to make accurate estimations. Given the magnitude of the burden of fungal infections in Uruguay, efforts should be made to improve surveillance, strengthen laboratory diagnosis, and warrant access to first line antifungals.

Prevalência da Paracoccidioidomicose em pacientes diagnosticados no Hospital Araújo Jorge em Goiânia-Goiás, Brasil

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Sara de Paula FERREIRA

2012-01-01

Full Text Available The fungus Paracoccidioides brasiliensis is a human pathogen widely distributed in Latin America. It isa deep mycosis and severe and may present associated with other diseases such as tuberculosis, AIDS and cancer. Thepresent study analyzed the clinical and pathological aspects of patients diagnosed with PCM in the Service of PathologyAnatomy (SAP of Araújo Jorge Hospital, Goiânia-Goiás, in the period 2000 to 2006. The cases analyzed werecollected from the registration books of the SAP and the clinical and pathological data obtained from their medicalrecords. We diagnosed 77 cases of PCM, of which 94.8% were male patients and 5.2% female. The age of highestincidence is identified between 40 and 60 years of age. As for the location of the lesions, the highest percentages ofcases were found in the oral cavity (25.97%, larynx (12.98%, lymphnodes (10.38%, tongue (7.79%, the skin (6.49%and the lip (5.19%. Regarding the distribution annual the largest number of cases (18 was detected in 2000. The PCMis not subject to routine surveillance, and cases diagnosed at the Hospital Araújo Jorge are not properly informed, fornot having preventive tool and preferably be specialized in cancer treatment. In Brazil, has records of more than 50cases of PCM associated with AIDS infection which puts this as another indicator of the syndrome. 100 years after its description, paracoccidioidomycosis is still a disease that requires consideration, continuous interest andmultidisciplinary approach.

Isolation of fungi from nature in the region of Botucatu, state of São Paulo, Brazil, an endemic area of paracoccidioidomycosis

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MR Montenegro

1996-12-01

Full Text Available In an attempt to isolate Paracoccidioides brasiliensis from nature 887 samples of soil from Botucatu, SP, Brazil, were collected cultured in brain heart infusion agar supplemented with dextrose, in potato dextrose agar and in yeast extract starch dextrose agar, all with antibiotics, at 25º and 37ºC. Five thermo-dependent dimorphic fungi morphologically resembling P. brasiliensis were isolated; two from armadillo holes; further studies of the biology, antigenicity and genetic features of the five dimorphic fungi are necessary to clarify their taxonomy and their possible relation to P. brasiliensis. In addition, 98 dematiaceous fungi and 581 different species of Aspergillus spp. were also isolated. Our findings emphasize that armadillos and their environment are associated with thermo-dimorphic fungi and confirm the ubiquity of pathogenic dematiaceous fungi and Aspergillus spp.

SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

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Monteiro, Paulo Henrique Silva; Souza, Thiago Ferreira de; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Lima, Mariana da Cunha Lopes de; Santos, Allan Oliveira; Ramos, Celso Darío

2017-01-01

Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ( 67 Ga) citrate scintigraphy. Materials And Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99m Tc-EDDA-HYNIC-TOC, and 21 after injection of 111 In-DTPA-octreotide. All patients also underwent 67 Ga citrate imaging, except for one patient who died before the 67 Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67 Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67 Ga uptake in 11 of the 20 patients with positive images and similar to 67 Ga uptake in the other 9 patients. The only patient who did not undergo 67 Ga scintigraphy underwent 99m Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with 99m Tc-EDDA-HYNIC-TOC or 111 In-DTPA-octreotide seems to be a good alternative to 67 Ga citrate imaging for the evaluation of patients with systemic granulomatous disease. (author)

SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

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Paulo Henrique Silva Monteiro

2017-10-01

Full Text Available Abstract Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs in systemic granulomatous infections in comparison with gallium-67 (67Ga citrate scintigraphy. Materials and Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of 99mTc-EDDA-HYNIC-TOC, and 21 after injection of 111In-DTPA-octreotide. All patients also underwent 67Ga citrate imaging, except for one patient who died before the 67Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by 67Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than 67Ga uptake in 11 of the 20 patients with positive images and similar to 67Ga uptake in the other 9 patients. The only patient who did not undergo 67Ga scintigraphy underwent 99mTc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with 99mTc-EDDA-HYNIC-TOC or 111In-DTPA-octreotide seems to be a good alternative to 67Ga citrate imaging for the evaluation of patients with systemic granulomatous disease.

Dynamics evaluation of total IgG, IgG1 and IgG2a in the serum of mice immunized with radioattenuated paracoccidioides brasiliensis yeast cells

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Martins, Estefania M.N.; Andrade, Antero S.R.; Reis, Bernardo S.; Goes, Alfredo M.

2007-01-01

Paracoccidioides brasiliensis is the fungus agent of paracoccidioidomycosis, a deep-seated systemic infection of humans. Up to the moment no vaccine has still been reported. The potential of gamma radiation for pathogens attenuation and vaccine development was explored in this work. In our laboratory we developed radioattenuated yeast cells of P. brasiliensis and the aim of the present work was to evaluate the antibody production dynamics in mice immunized with this cells. Were analyzed the IgG antibodies titers as well as the type of response by analyzing the IgG1 and IgG2a antibody pattern in the course of infection. The mice were divided in two groups that were immunized one time and two times respectively. The mice infected with the virulent P. brasiliensis showed a high level of antibody production while the infection with the radioattenuated yeast did not significantly change the antibody level. The level of IgG raised in both immunized groups after the challenge. In the group immunized one time was not observed a significant difference between the levels of both subclasses when compared with the control. After the challenge of the group immunized two times the IgG2a levels increased significantly when analyzed 90 days post challenge. We concluded that a pattern related to the disease control was apparent in the group submitted to two immunizations. The mice had not developed a totally polarized pattern of TH1/TH2 response but a trend to a TH1 response was evident. (author)

Effects of Argentilactone on the Transcriptional Profile, Cell Wall and Oxidative Stress of Paracoccidioides spp.

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Araújo, Felipe Souto; Coelho, Luciene Melo; Silva, Lívia do Carmo; da Silva Neto, Benedito Rodrigues; Parente-Rocha, Juliana Alves; Bailão, Alexandre Melo; de Oliveira, Cecília Maria Alves; Fernandes, Gabriel da Rocha; Hernández, Orville; Ochoa, Juan Guillermo McEwen; Soares, Célia Maria de Almeida; Pereira, Maristela

2016-01-01

Paracoccidioides spp., a dimorphic pathogenic fungus, is the etiologic agent of paracoccidioidomycosis (PCM). PCM is an endemic disease that affects at least 10 million people in Latin America, causing severe public health problems. The drugs used against pathogenic fungi have various side effects and limited efficacy; therefore, there is an inevitable and urgent medical need for the development of new antifungal drugs. In the present study, we evaluated the transcriptional profile of Paracoccidioides lutzii exposed to argentilactone, a constituent of the essential oil of Hyptis ovalifolia. A total of 1,058 genes were identified, of which 208 were up-regulated and 850 were down-regulated. Cell rescue, defense and virulence, with a total of 26 genes, was a functional category with a large number of genes induced, including heat shock protein 90 (hsp90), cytochrome c peroxidase (ccp), the hemoglobin ligand RBT5 (rbt5) and superoxide dismutase (sod). Quantitative real-time PCR revealed an increase in the expression level of all of those genes. An enzymatic assay showed a significant increase in SOD activity. The reduced growth of Pbhsp90-aRNA, Pbccp-aRNA, Pbsod-aRNA and Pbrbt5-aRNA isolates in the presence of argentilactone indicates the importance of these genes in the response of Paracoccidioides spp. to argentilactone. The response of the P. lutzii cell wall to argentilactone treatment was also evaluated. The results showed that argentilactone caused a decrease in the levels of polymers in the cell wall. These results suggest that argentilactone is a potential candidate for antifungal therapy.

Effects of Argentilactone on the Transcriptional Profile, Cell Wall and Oxidative Stress of Paracoccidioides spp.

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Felipe Souto Araújo

2016-01-01

Full Text Available Paracoccidioides spp., a dimorphic pathogenic fungus, is the etiologic agent of paracoccidioidomycosis (PCM. PCM is an endemic disease that affects at least 10 million people in Latin America, causing severe public health problems. The drugs used against pathogenic fungi have various side effects and limited efficacy; therefore, there is an inevitable and urgent medical need for the development of new antifungal drugs. In the present study, we evaluated the transcriptional profile of Paracoccidioides lutzii exposed to argentilactone, a constituent of the essential oil of Hyptis ovalifolia. A total of 1,058 genes were identified, of which 208 were up-regulated and 850 were down-regulated. Cell rescue, defense and virulence, with a total of 26 genes, was a functional category with a large number of genes induced, including heat shock protein 90 (hsp90, cytochrome c peroxidase (ccp, the hemoglobin ligand RBT5 (rbt5 and superoxide dismutase (sod. Quantitative real-time PCR revealed an increase in the expression level of all of those genes. An enzymatic assay showed a significant increase in SOD activity. The reduced growth of Pbhsp90-aRNA, Pbccp-aRNA, Pbsod-aRNA and Pbrbt5-aRNA isolates in the presence of argentilactone indicates the importance of these genes in the response of Paracoccidioides spp. to argentilactone. The response of the P. lutzii cell wall to argentilactone treatment was also evaluated. The results showed that argentilactone caused a decrease in the levels of polymers in the cell wall. These results suggest that argentilactone is a potential candidate for antifungal therapy.

Importance of xenarthrans in the eco-epidemiology of Paracoccidioides brasiliensis

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Pedrini Silvia CB

2009-11-01

Full Text Available Abstract Background Several pathogens that cause important zoonotic diseases have been frequently associated with armadillos and other xenarthrans. This mammal group typically has evolved on the South American continent and many of its extant species are seriously threatened with extinction. Natural infection of armadillos with Paracoccidioides brasiliensis in hyperendemic areas has provided a valuable opportunity for understanding the role of this mammal in the eco-epidemiology of Paracoccidioidomycosis (PCM, one of the most important systemic mycoses in Latin America. Findings This study aimed to detect P. brasiliensis in different xenarthran species (Dasypus novemcinctus, Cabassous spp., Euphractus sexcinctus, Tamandua tetradactyla and Myrmecophaga tridactyla, by molecular and mycological approaches, in samples obtained by one of the following strategies: i from road-killed animals (n = 6; ii from naturally dead animals (n = 8; iii from animals that died in captivity (n = 9; and iv from living animals captured from the wild (n = 2. Specific P. brasiliensis DNA was detected in several organs among 7/20 nine-banded armadillos (D. novemcinctus and in 2/2 anteaters (M. tridactyla. The fungus was also cultured in tissue samples from one of two armadillos captured from the wild. Conclusion Members of the Xenarthra Order, especially armadillos, have some characteristics, including a weak cellular immune response and low body temperature, which make them suitable models for studying host-pathogen interaction. P. brasiliensis infection in wild animals, from PCM endemic areas, may be more common than initially postulated and reinforces the use of these animals as sentinels for the pathogen in the environment.

Importance of xenarthrans in the eco-epidemiology of Paracoccidioides brasiliensis.

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Richini-Pereira, Virgínia B; Bosco, Sandra M G; Theodoro, Raquel C; Barrozo, Lígia; Pedrini, Silvia C B; Rosa, Patrícia S; Bagagli, Eduardo

2009-11-17

Several pathogens that cause important zoonotic diseases have been frequently associated with armadillos and other xenarthrans. This mammal group typically has evolved on the South American continent and many of its extant species are seriously threatened with extinction. Natural infection of armadillos with Paracoccidioides brasiliensis in hyperendemic areas has provided a valuable opportunity for understanding the role of this mammal in the eco-epidemiology of Paracoccidioidomycosis (PCM), one of the most important systemic mycoses in Latin America. This study aimed to detect P. brasiliensis in different xenarthran species (Dasypus novemcinctus, Cabassous spp., Euphractus sexcinctus, Tamandua tetradactyla and Myrmecophaga tridactyla), by molecular and mycological approaches, in samples obtained by one of the following strategies: i) from road-killed animals (n = 6); ii) from naturally dead animals (n = 8); iii) from animals that died in captivity (n = 9); and iv) from living animals captured from the wild (n = 2). Specific P. brasiliensis DNA was detected in several organs among 7/20 nine-banded armadillos (D. novemcinctus) and in 2/2 anteaters (M. tridactyla). The fungus was also cultured in tissue samples from one of two armadillos captured from the wild. Members of the Xenarthra Order, especially armadillos, have some characteristics, including a weak cellular immune response and low body temperature, which make them suitable models for studying host-pathogen interaction. P. brasiliensis infection in wild animals, from PCM endemic areas, may be more common than initially postulated and reinforces the use of these animals as sentinels for the pathogen in the environment.

Detection of Antibodies against Paracoccidioides brasiliensis Melanin in In Vitro and In Vivo Studies during Infection ▿

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Urán, Martha E.; Nosanchuk, Joshua D.; Restrepo, Angela; Hamilton, Andrew J.; Gómez, Beatriz L.; Cano, Luz E.

2011-01-01

Several cell wall constituents, including melanins or melanin-like compounds, have been implicated in the pathogenesis of a wide variety of microbial diseases caused by diverse species of pathogenic bacteria, fungi, and helminthes. Among these microorganisms, the dimorphic fungal pathogen Paracoccidioides brasiliensis produces melanin in its conidial and yeast forms. In the present study, melanin particles from P. brasiliensis were injected into BALB/c mice in order to produce monoclonal antibodies (MAbs). We identified five immunoglobulin G1 (IgG1) κ-chain and four IgM melanin-binding MAbs. The five IgG1 κ-chain isotypes are the first melanin-binding IgG MAbs ever reported. The nine MAbs labeled P. brasiliensis conidia and yeast cells both in vitro and in pulmonary tissues. The MAbs cross-reacted with melanin-like purified particles from other fungi and also with commercial melanins, such as synthetic and Sepia officinalis melanin. Melanization during paracoccidioidomycosis (PCM) was also further supported by the detection of IgG antibodies reactive to melanin from P. brasiliensis conidia and yeast in sera and bronchoalveolar lavage fluids from P. brasiliensis-infected mice, as well as in sera from human patients with PCM. Serum specimens from patients with other mycoses were also tested for melanin-binding antibodies by enzyme-linked immunosorbent assay, and cross-reactivities were detected for melanin particles from different fungal sources. These results suggest that melanin from P. brasiliensis is an immunologically active fungal structure that activates a strong IgG humoral response in humans and mice. PMID:21813659

Detection of antibodies against Paracoccidioides brasiliensis melanin in in vitro and in vivo studies during infection.

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Urán, Martha E; Nosanchuk, Joshua D; Restrepo, Angela; Hamilton, Andrew J; Gómez, Beatriz L; Cano, Luz E

2011-10-01

Several cell wall constituents, including melanins or melanin-like compounds, have been implicated in the pathogenesis of a wide variety of microbial diseases caused by diverse species of pathogenic bacteria, fungi, and helminthes. Among these microorganisms, the dimorphic fungal pathogen Paracoccidioides brasiliensis produces melanin in its conidial and yeast forms. In the present study, melanin particles from P. brasiliensis were injected into BALB/c mice in order to produce monoclonal antibodies (MAbs). We identified five immunoglobulin G1 (IgG1) κ-chain and four IgM melanin-binding MAbs. The five IgG1 κ-chain isotypes are the first melanin-binding IgG MAbs ever reported. The nine MAbs labeled P. brasiliensis conidia and yeast cells both in vitro and in pulmonary tissues. The MAbs cross-reacted with melanin-like purified particles from other fungi and also with commercial melanins, such as synthetic and Sepia officinalis melanin. Melanization during paracoccidioidomycosis (PCM) was also further supported by the detection of IgG antibodies reactive to melanin from P. brasiliensis conidia and yeast in sera and bronchoalveolar lavage fluids from P. brasiliensis-infected mice, as well as in sera from human patients with PCM. Serum specimens from patients with other mycoses were also tested for melanin-binding antibodies by enzyme-linked immunosorbent assay, and cross-reactivities were detected for melanin particles from different fungal sources. These results suggest that melanin from P. brasiliensis is an immunologically active fungal structure that activates a strong IgG humoral response in humans and mice.

Burden of Serious Fungal Infections in Argentina

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Fernando O. Riera

2018-04-01

Full Text Available The number of fungal infections at any given time in Argentina is not known. Here we estimate the burden of serious fungal infections in Argentina for the first time. Specific population statistics were searched from multiple sources, local literature was identified, and estimates made. Some additional data were sourced from the Ministry of Health, the Global Initiative for Asthma (GINA program, and national haematology and transplant societies. Argentina has a population of 43.8 million, with 25% of this total being children under 15 years. The predicted candidemia annual incidence is 2193 cases, with 50% occurring in the ICU. At a 6% prevalence rate, an estimated 593,695 women suffer from recurrent vulvovaginal candidiasis. Invasive aspergillosis is relatively common because of high smoking and chronic obstructive pulmonary disease (COPD rates, with 268 cases in immunocompromised patients and another 1938 in the 168,000 COPD patients admitted to hospital. Asthma is also common, affecting 14% of adults, and so allergic bronchopulmonary aspergillosis (ABPA and severe asthma with fungal sensitization (SAFS are major problems. An estimated 432 cases of cryptococcal meningitis (CM—90% of them in AIDS patients—and 1177 cases of Pneumocystis pneumonia (PCP occur each year. The estimated annual case number of disseminated histoplasmosis is 404 in AIDS patients, almost as frequent as CM. Paracoccidioidomycosis annual incidence is estimated at 219, and coccidioidomycosis at 16 cases. At least 881,023 people (>2.01% in Argentina are affected by a serious fungal disease annually, with considerable morbidity and mortality.

Dynamics evaluation of total IgG, IgG1 and IgG2a in the serum of mice immunized with radioattenuated paracoccidioides brasiliensis yeast cells

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Martins, Estefania M.N.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)]. E-mail: estefaniabio@yahoo.com.br; antero@cdtn.br; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia]. E-mail: brsgarbi@mono.icb.ufmg.br; goes@mono.icb.ufmg.br

2007-07-01

Paracoccidioides brasiliensis is the fungus agent of paracoccidioidomycosis, a deep-seated systemic infection of humans. Up to the moment no vaccine has still been reported. The potential of gamma radiation for pathogens attenuation and vaccine development was explored in this work. In our laboratory we developed radioattenuated yeast cells of P. brasiliensis and the aim of the present work was to evaluate the antibody production dynamics in mice immunized with this cells. Were analyzed the IgG antibodies titers as well as the type of response by analyzing the IgG1 and IgG2a antibody pattern in the course of infection. The mice were divided in two groups that were immunized one time and two times respectively. The mice infected with the virulent P. brasiliensis showed a high level of antibody production while the infection with the radioattenuated yeast did not significantly change the antibody level. The level of IgG raised in both immunized groups after the challenge. In the group immunized one time was not observed a significant difference between the levels of both subclasses when compared with the control. After the challenge of the group immunized two times the IgG2a levels increased significantly when analyzed 90 days post challenge. We concluded that a pattern related to the disease control was apparent in the group submitted to two immunizations. The mice had not developed a totally polarized pattern of TH1/TH2 response but a trend to a TH1 response was evident. (author)

Nuclear medicine in tropical disease: an overview

International Nuclear Information System (INIS)

Braga, Francisco Jos H. N

2002-01-01

Leprosy is an infectious granulomatous disease. Incidence is again increasing and millions of people are affected in the world. Ga-67 scintigraphy is a good tool to identify active disease; bone scintigraphy is useful in the evaluation of mutilation and 99mTc-DTPA is good to evaluate kidney function. Paracoccidioidomycosis is a deep mycosis that affects nearly all organs. The following scintigraphic exams are useful to evaluate such patients: Ga-67, bone scintigraphy, liver / spleen / bone marrow scintigraphy, 99mTc-DISIDA scintigraphy, lymphoscintigraphy. Mycetoma is bone and soft tissue mycosis and gallium-67 and bone studies are very useful for the detection of active disease. Tuberculosis is the most well studied tropical disease and dozens of radiopharmaceuticals and techniques were described to evaluate such patients. Jorge Lobo's disease is a rare mycosis that affects mainly indians from the Amazon region and gallium-67 was shown to accumulate in active disease. Neurocysticercosis is spread worldwide and brain SPECT (99mTc-ECD or 99mTc-HMPAO) is a very good tool for the functional evaluation of the disease. Patients suffering from Cutaneous and mucous leishmaniosis may benefit from Gallium-67 scintigraphy. Chagas' disease may affect the heart and/or the digestive tract and several scintigraphic exams may be helpful in the evaluation of such cases (gated blood pool, heart perfusion tests, pharyngeal transit tests, gastric emptying tests, intestinal transit tests, hepato-biliary scintigraphy, among others). Scintigraphy should be more largely used in the functional evaluation of organs and systems of patients affected by topical diseases (Au)

Effect of ArtinM on Human Blood Cells During Infection With Paracoccidioides brasiliensis.

Science.gov (United States)

Ruas, Luciana P; Genaro, Livia M; Justo-Junior, Amauri S; Coser, Lilian O; de Castro, Lívia F; Trabasso, Plinio; Mamoni, Ronei L; Roque-Barreira, Maria-Cristina; Blotta, Maria-Heloisa S L

2018-01-01

Infections caused by fungi are prominent in our environment and can be potentially fatal. paracoccidioidomycosis (PCM), caused by fungi of the Paracoccidioides genus, is the most frequent systemic mycosis in Brazil and the main cause of death among immunocompetent individuals. The antifungal therapy for PCM is usually effective but side effects and relapses are often reported. The latter could be avoided with alternative or complementary therapies aimed at boosting the immune response to combat this pathogen. Recent reports have pointed at the importance of an effective cellular immune response, with the participation of Th1 cells, in the resistance to and control of Paracoccidioides infection. The ArtinM lectin, extracted from jackfruit ( Artocarpus heterophyllus ) seeds, exhibits immunomodulatory activity against several intracellular pathogens, including Paracoccidioides brasiliensis , by promoting the development of a Th1 immune response. The aim of this work was to characterize the effect of ArtinM on peripheral blood cells of patients with PCM and on those of control individuals infected with fungal yeasts cells in vitro . Our results demonstrate that ArtinM activates human neutrophils in vitro , leading to an increase in cytokine production and CD54 expression. ArtinM activated P. brasiliensis -infected neutrophils from both healthy individuals and patients with PCM. This activation was not dependent on the dectin-1 receptor, because pre-incubation with laminarin, a dectin-1 receptor blocker, did not reverse the activated state of the cells. ArtinM also stimulated human peripheral blood mononuclear cells to secrete pro-inflammatory Th1-related cytokines, which are protective against Paracoccidioides infection. These data support the immunostimulatory action of ArtinM and encourage new studies using the lectin for the immunotherapy of PCM.

In-silico gene co-expression network analysis in Paracoccidioides brasiliensis with reference to haloacid dehalogenase superfamily hydrolase gene

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Raghunath Satpathy

2015-01-01

Full Text Available Context: Paracoccidioides brasiliensis, a dimorphic fungus is the causative agent of paracoccidioidomycosis, a disease globally affecting millions of people. The haloacid dehalogenase (HAD superfamily hydrolases enzyme in the fungi, in particular, is known to be responsible in the pathogenesis by adhering to the tissue. Hence, identification of novel drug targets is essential. Aims: In-silico based identification of co-expressed genes along with HAD superfamily hydrolase in P. brasiliensis during the morphogenesis from mycelium to yeast to identify possible genes as drug targets. Materials and Methods: In total, four datasets were retrieved from the NCBI-gene expression omnibus (GEO database, each containing 4340 genes, followed by gene filtration expression of the data set. Further co-expression (CE study was performed individually and then a combination these genes were visualized in the Cytoscape 2. 8.3. Statistical Analysis Used: Mean and standard deviation value of the HAD superfamily hydrolase gene was obtained from the expression data and this value was subsequently used for the CE calculation purpose by selecting specific correlation power and filtering threshold. Results: The 23 genes that were thus obtained are common with respect to the HAD superfamily hydrolase gene. A significant network was selected from the Cytoscape network visualization that contains total 7 genes out of which 5 genes, which do not have significant protein hits, obtained from gene annotation of the expressed sequence tags by BLAST X. For all the protein PSI-BLAST was performed against human genome to find the homology. Conclusions: The gene co-expression network was obtained with respect to HAD superfamily dehalogenase gene in P. Brasiliensis.

Proteomic analysis reveals that iron availability alters the metabolic status of the pathogenic fungus Paracoccidioides brasiliensis.

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Ana F A Parente

Full Text Available Paracoccidioides brasiliensis is a thermodimorphic fungus and the causative agent of paracoccidioidomycosis (PCM. The ability of P. brasiliensis to uptake nutrients is fundamental for growth, but a reduction in the availability of iron and other nutrients is a host defense mechanism many pathogenic fungi must overcome. Thus, fungal mechanisms that scavenge iron from host may contribute to P. brasiliensis virulence. In order to better understand how P. brasiliensis adapts to iron starvation in the host we compared the two-dimensional (2D gel protein profile of yeast cells during iron starvation to that of iron rich condition. Protein spots were selected for comparative analysis based on the protein staining intensity as determined by image analysis. A total of 1752 protein spots were selected for comparison, and a total of 274 out of the 1752 protein spots were determined to have changed significantly in abundance due to iron depletion. Ninety six of the 274 proteins were grouped into the following functional categories; energy, metabolism, cell rescue, virulence, cell cycle, protein synthesis, protein fate, transcription, cellular communication, and cell fate. A correlation between protein and transcript levels was also discovered using quantitative RT-PCR analysis from RNA obtained from P. brasiliensis under iron restricting conditions and from yeast cells isolated from infected mouse spleens. In addition, western blot analysis and enzyme activity assays validated the differential regulation of proteins identified by 2-D gel analysis. We observed an increase in glycolytic pathway protein regulation while tricarboxylic acid cycle, glyoxylate and methylcitrate cycles, and electron transport chain proteins decreased in abundance under iron limiting conditions. These data suggest a remodeling of P. brasiliensis metabolism by prioritizing iron independent pathways.

Employing proteomic analysis to compare Paracoccidioides lutzii yeast and mycelium cell wall proteins.

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Araújo, Danielle Silva; de Sousa Lima, Patrícia; Baeza, Lilian Cristiane; Parente, Ana Flávia Alves; Melo Bailão, Alexandre; Borges, Clayton Luiz; de Almeida Soares, Célia Maria

2017-11-01

Paracoccidioidomycosis is an important systemic mycosis caused by thermodimorphic fungi of the Paracoccidioides genus. During the infective process, the cell wall acts at the interface between the fungus and the host. In this way, the cell wall has a key role in growth, environment sensing and interaction, as well as morphogenesis of the fungus. Since the cell wall is absent in mammals, it may present molecules that are described as target sites for new antifungal drugs. Despite its importance, up to now few studies have been conducted employing proteomics in for the identification of cell wall proteins in Paracoccidioides spp. Here, a detailed proteomic approach, including cell wall-fractionation coupled to NanoUPLC-MS E , was used to study and compare the cell wall fractions from Paracoccidioides lutzii mycelia and yeast cells. The analyzed samples consisted of cell wall proteins extracted by hot SDS followed by extraction by mild alkali. In summary, 512 proteins constituting different cell wall fractions were identified, including 7 predicted GPI-dependent cell wall proteins that are potentially involved in cell wall metabolism. Adhesins previously described in Paracoccidioides spp. such as enolase, glyceraldehyde-3-phosphate dehydrogenase were identified. Comparing the proteins in mycelium and yeast cells, we detected some that are common to both fungal phases, such as Ecm33, and some specific proteins, as glucanase Crf1. All of those proteins were described in the metabolism of cell wall. Our study provides an important elucidation of cell wall composition of fractions in Paracoccidioides, opening a way to understand the fungus cell wall architecture. Copyright © 2017 Elsevier B.V. All rights reserved.

SPECT/CT with radiolabeled somatostatin analogues in the evaluation of systemic granulomatous infections

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Monteiro, Paulo Henrique Silva; Souza, Thiago Ferreira de; Moretti, Maria Luiza; Resende, Mariangela Ribeiro; Lima, Mariana da Cunha Lopes de; Santos, Allan Oliveira; Ramos, Celso Darío, E-mail: paulohsm42@gmail.com [Universidade de Campinas (UNICAMP), SP (Brazil). Escola de Medicina; Mengatti Jair [Instituto de Pesquisas Energéticas e Nucleares (IPEN/CNEN-SP), São Paulo, SP (Brazil)

2017-11-15

Objective: To evaluate SPECT/CT with radiolabeled somatostatin analogues (RSAs) in systemic granulomatous infections in comparison with gallium-67 ({sup 67}Ga) citrate scintigraphy. Materials And Methods: We studied 28 patients with active systemic granulomatous infections, including tuberculosis, paracoccidioidomycosis, pneumocystosis, cryptococcosis, aspergillosis, leishmaniasis, infectious vasculitis, and an unspecified opportunistic infection. Of the 28 patients, 23 had started specific treatment before the study outset. All patients underwent whole-body SPECT/CT imaging: 7 after injection of {sup 99m}Tc-EDDA-HYNIC-TOC, and 21 after injection of {sup 111}In-DTPA-octreotide. All patients also underwent {sup 67}Ga citrate imaging, except for one patient who died before the {sup 67}Ga was available. Results: In 20 of the 27 patients who underwent imaging with both tracers, 27 sites of active disease were detected by {sup 67}Ga citrate imaging and by SPECT/CT with an RSA. Both tracers had negative results in the other 7 patients. RSA uptake was visually lower than {sup 67}Ga uptake in 11 of the 20 patients with positive images and similar to {sup 67}Ga uptake in the other 9 patients. The only patient who did not undergo {sup 67}Ga scintigraphy underwent {sup 99m}Tc-EDDA-HYNIC-TOC SPECT/CT-guided biopsy of a lung cavity with focal RSA uptake, which turned to be positive for aspergillosis. Conclusion: SPECT/CT with {sup 99m}Tc-EDDA-HYNIC-TOC or {sup 111}In-DTPA-octreotide seems to be a good alternative to {sup 67}Ga citrate imaging for the evaluation of patients with systemic granulomatous disease. (author)

Effect of ArtinM on Human Blood Cells During Infection With Paracoccidioides brasiliensis

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Luciana P. Ruas

2018-05-01

Full Text Available Infections caused by fungi are prominent in our environment and can be potentially fatal. paracoccidioidomycosis (PCM, caused by fungi of the Paracoccidioides genus, is the most frequent systemic mycosis in Brazil and the main cause of death among immunocompetent individuals. The antifungal therapy for PCM is usually effective but side effects and relapses are often reported. The latter could be avoided with alternative or complementary therapies aimed at boosting the immune response to combat this pathogen. Recent reports have pointed at the importance of an effective cellular immune response, with the participation of Th1 cells, in the resistance to and control of Paracoccidioides infection. The ArtinM lectin, extracted from jackfruit (Artocarpus heterophyllus seeds, exhibits immunomodulatory activity against several intracellular pathogens, including Paracoccidioides brasiliensis, by promoting the development of a Th1 immune response. The aim of this work was to characterize the effect of ArtinM on peripheral blood cells of patients with PCM and on those of control individuals infected with fungal yeasts cells in vitro. Our results demonstrate that ArtinM activates human neutrophils in vitro, leading to an increase in cytokine production and CD54 expression. ArtinM activated P. brasiliensis-infected neutrophils from both healthy individuals and patients with PCM. This activation was not dependent on the dectin-1 receptor, because pre-incubation with laminarin, a dectin-1 receptor blocker, did not reverse the activated state of the cells. ArtinM also stimulated human peripheral blood mononuclear cells to secrete pro-inflammatory Th1-related cytokines, which are protective against Paracoccidioides infection. These data support the immunostimulatory action of ArtinM and encourage new studies using the lectin for the immunotherapy of PCM.

Characterization of Paracoccidioides brasiliensis by FT-IR spectroscopy and nanotechnology

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Ferreira, Isabelle; Ferreira-Strixino, Juliana; Castilho, Maiara L.; Campos, Claudia B. L.; Tellez, Claudio; Raniero, Leandro

2016-01-01

Paracoccidioides brasiliensis, the etiological agent of paracoccidioidomycosis, is a dimorphic fungus existing as mycelia in the environment (or at 25 °C in vitro) and as yeast cells in the human host (or at 37 °C in vitro). Because mycological examination of lesions in patients frequently is unable to show the presence of the fungus and serological tests can misdiagnose the disease with other mycosis, the development of new approach's for molecular identification of P. brasiliensis spurges is needed. This study describes the use of a gold nanoprobe of a known gene sequence of P. brasiliensis as a molecular tool to identify P. brasiliensis by regular polymerase chain reaction (PCR) associated with a colorimetric methods. This approach is suitable for testing in remote areas because it does not require any further step than gene amplification, being safer and cheaper than electrophoresis methods. The proposed test showed a color change of the PCR reaction mixture from red to blue in negative samples, whereas the solution remains red in positive samples. We also performed a Fourier Transform Infrared (FT-IR) Spectroscopy analysis to characterize and compare the chemical composition between yeast and mycelia forms, which revealed biochemical differences between these two forms. The analysis of the spectra showed that differences were distributed in chemical bonds of proteins, lipids and carbohydrates. The most prominent difference between both forms was vibration modes related to 1,3-β-glucan usually found in mycelia and 1,3-α-glucan found in yeasts and also chitin forms. In this work, we introduce FT-IR as a new method suitable to reveal overall differences that biochemically distinguish each form of P. brasiliensis that could be additionally used to discriminate biochemical differences among a single form under distinct environmental conditions.

From magic to science: a journey throughout Latin American medical mycology.

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San-Blas, G

2000-01-01

The start of Latin America's love story with fungi may be placed in pre-Hispanic times when the use of fungi in both ritual ceremonies and daily life were common to the native civilizations. But the medical mycology discipline in Latin America started at the end of the 19th Century. At that time, scholars such as A. Posadas, R. Seeber, A. Lutz and P. Almeida, discovered agents of fungal diseases, the study of which has influenced the regional research ever since. Heirs to them are the researchers that today thrive in regional Universities and Research Institutes. Two current initiatives improve cooperation among Latin American medical mycologists. First, the periodical organization of International Paracoccidioidomycosis Meetings (seven so far, from 1979 to 1999); second, the creation of the Latin American Association for Mycology in 1991 (three Congresses, from 1993 to 1999). Latin American publications have increased in international specialized journals such as that from our Society (ISHAM) (from 8% in 1967 to 19% in 1999), and the Iberoamerican Journal of Mycology (Revista Iberoamericana de Micologia; > 40% from 1997 to 1999). In addition, Latin American participation at ISHAM International Congresses has risen from 6.9% in 1975 to 21.3% in 1997, and 43.2% at the 14th ISHAM Congress, held for the first time in a Latin American country, Argentina. A significant contribution of women to the scientific establishment of Latin American medical mycology (e.g., 45% of Latin American papers vs. 18% of other regions published in Journal of Medical and Veterinary Mycology in 1987, had women as authors or coauthors) suggests a better academic consideration of Latin American women against their counterparts in the developed world. Taken together, all these figures reflect the enthusiasm of our Latin American colleagues in the field, despite the difficulties that afflict our region, and affect our work.

Low-level laser therapy to the mouse femur enhances the fungicidal response of neutrophils against Paracoccidioides brasiliensis.

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Eva Burger

2015-02-01

Full Text Available Neutrophils (PMN play a central role in host defense against the neglected fungal infection paracoccidioidomycosis (PCM, which is caused by the dimorphic fungus Paracoccidioides brasiliensis (Pb. PCM is of major importance, especially in Latin America, and its treatment relies on the use of antifungal drugs. However, the course of treatment is lengthy, leading to side effects and even development of fungal resistance. The goal of the study was to use low-level laser therapy (LLLT to stimulate PMN to fight Pb in vivo. Swiss mice with subcutaneous air pouches were inoculated with a virulent strain of Pb or fungal cell wall components (Zymosan, and then received LLLT (780 nm; 50 mW; 12.5 J/cm2; 30 seconds per point, giving a total energy of 0.5 J per point on alternate days at two points on each hind leg. The aim was to reach the bone marrow in the femur with light. Non-irradiated animals were used as controls. The number and viability of the PMN that migrated to the inoculation site was assessed, as well as their ability to synthesize proteins, produce reactive oxygen species (ROS and their fungicidal activity. The highly pure PMN populations obtained after 10 days of infection were also subsequently cultured in the presence of Pb for trials of protein production, evaluation of mitochondrial activity, ROS production and quantification of viable fungi growth. PMN from mice that received LLLT were more active metabolically, had higher fungicidal activity against Pb in vivo and also in vitro. The kinetics of neutrophil protein production also correlated with a more activated state. LLLT may be a safe and non-invasive approach to deal with PCM infection.

Transcriptome Profile of the Response of Paracoccidioides spp. to a Camphene Thiosemicarbazide Derivative.

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Lívia do Carmo Silva

Full Text Available Paracoccidioidomycosis (PCM is a systemic granulomatous human mycosis caused by fungi of the genus Paracoccidioides, which is geographically restricted to Latin America. Inhalation of spores, the infectious particles of the fungus, is a common route of infection. The PCM treatment of choice is azoles such as itraconazole, but sulfonamides and amphotericin B are used in some cases despite their toxicity to mammalian cells. The current availability of treatments highlights the need to identify and characterize novel targets for antifungal treatment of PCM as well as the need to search for new antifungal compounds obtained from natural sources or by chemical synthesis. To this end, we evaluated the antifungal activity of a camphene thiosemicarbazide derivative (TSC-C compound on Paracoccidioides yeast. To determine the response of Paracoccidioides spp. to TSC-C, we analyzed the transcriptional profile of the fungus after 8 h of contact with the compound. The results demonstrate that Paracoccidioides lutzii induced the expression of genes related to metabolism; cell cycle and DNA processing; biogenesis of cellular components; cell transduction/signal; cell rescue, defense and virulence; cellular transport, transport facilities and transport routes; energy; protein synthesis; protein fate; transcription; and other proteins without classification. Additionally, we observed intensely inhibited genes related to protein synthesis. Analysis by fluorescence microscopy and flow cytometry revealed that the compound induced the production of reactive oxygen species. Using an isolate with down-regulated SOD1 gene expression (SOD1-aRNA, we sought to determine the function of this gene in the defense of Paracoccidioides yeast cells against the compound. Mutant cells were more susceptible to TSC-C, demonstrating the importance of this gene in response to the compound. The results presented herein suggest that TSC-C is a promising candidate for PCM treatment.

The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

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José F Muñoz

2015-10-01

Full Text Available Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics

The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia.

Science.gov (United States)

Muñoz, José F; Gauthier, Gregory M; Desjardins, Christopher A; Gallo, Juan E; Holder, Jason; Sullivan, Thomas D; Marty, Amber J; Carmen, John C; Chen, Zehua; Ding, Li; Gujja, Sharvari; Magrini, Vincent; Misas, Elizabeth; Mitreva, Makedonka; Priest, Margaret; Saif, Sakina; Whiston, Emily A; Young, Sarah; Zeng, Qiandong; Goldman, William E; Mardis, Elaine R; Taylor, John W; McEwen, Juan G; Clay, Oliver K; Klein, Bruce S; Cuomo, Christina A

2015-10-01

Three closely related thermally dimorphic pathogens are causal agents of major fungal diseases affecting humans in the Americas: blastomycosis, histoplasmosis and paracoccidioidomycosis. Here we report the genome sequence and analysis of four strains of the etiological agent of blastomycosis, Blastomyces, and two species of the related genus Emmonsia, typically pathogens of small mammals. Compared to related species, Blastomyces genomes are highly expanded, with long, often sharply demarcated tracts of low GC-content sequence. These GC-poor isochore-like regions are enriched for gypsy elements, are variable in total size between isolates, and are least expanded in the avirulent B. dermatitidis strain ER-3 as compared with the virulent B. gilchristii strain SLH14081. The lack of similar regions in related species suggests these isochore-like regions originated recently in the ancestor of the Blastomyces lineage. While gene content is highly conserved between Blastomyces and related fungi, we identified changes in copy number of genes potentially involved in host interaction, including proteases and characterized antigens. In addition, we studied gene expression changes of B. dermatitidis during the interaction of the infectious yeast form with macrophages and in a mouse model. Both experiments highlight a strong antioxidant defense response in Blastomyces, and upregulation of dioxygenases in vivo suggests that dioxide produced by antioxidants may be further utilized for amino acid metabolism. We identify a number of functional categories upregulated exclusively in vivo, such as secreted proteins, zinc acquisition proteins, and cysteine and tryptophan metabolism, which may include critical virulence factors missed before in in vitro studies. Across the dimorphic fungi, loss of certain zinc acquisition genes and differences in amino acid metabolism suggest unique adaptations of Blastomyces to its host environment. These results reveal the dynamics of genome evolution

Immunogenic evaluation of Paracoccidioides brasiliensis radioattenuated yeast cells in murine model

International Nuclear Information System (INIS)

Martins, Estefania M.N.; Andrade, Antero S.R.; Fernandes, Viviane Cristina; Morais, Elis Araujo; Goes, Alfredo M.; Resende, Maria Aparecida de

2011-01-01

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis (PCM), a chronic systemic disease prevalent in Latin American, which is characterized by the formation of granulomatous lesions. To date, there is no effective vaccine to PCM or to any systemic mycosis. In an attempt to induce an efficient response to such agent in an animal model, gamma radiation attenuated P. brasiliensis yeast cells (LevRad) were developed at the Radiobiology Laboratory from CDTN/CNEN. A gamma radiation dose was defined in which the pathogen loses its ability to multiply, while retaining its viability, metabolic activity and antigenic profile. The prophylactic potential of LevRad was assessed after its intravenous administration in male Balb/C mice, challenged 45 days after immunization with intratracheal administration of 3x105 cells of a highly virulent non-radiated P.brasiliensis isolate. At 30 and 90 days post challenge (dpc), lungs, spleen and liver were collected to analyse CFU (colony forming units) recovery, histology, cell proliferation, cytokine (IFN-gamma, IL-4, IL-10, TNF-alpha and TGF-beta) and iNOS production. The sera were used to evaluate the immunization efficacy, and to assess IgG isotypes (IgG1, IgG2a, IgG2b, IgG3) and total IgG levels. The present data show that there was no significant decrease in the CFU counts of the lungs of immunized animals 30 dpc. Nevertheless, no CFU or histopathological alterations were visualized at the organs of immunized animals at 90 dpc. During the same period, IgG2a, IgG2b, IFN-alpha and iNOS levels raised while IL-10, TNF-alpha, TGF-beta and IL-4 maintained low levels, suggesting the prevalence of Th1 response profile. Our results confirmed the protective (author)

Nuclear medicine in tropical diseases

International Nuclear Information System (INIS)

Braga, Francisco Jose Hossri Nogueira

2002-01-01

Tropical diseases affect more people in the world than any other kind of disease, but scintigraphic data on that matter are not so frequent in the literature. Since the geographic regions where such diseases occur are normally very poor, scintillation cameras may not be available. We present a resumed summary of part of what has been done on this subject to-date. Leprosy affects circa 12 million people worldwide and has already been studied by means of the following scintigraphic exams: gallium-67, 99mTc-MDP or HMDP, 99mTc-colloid or Dextran, 99mTc-DTPA and 99mTc-WBC. Paracoccidioidomycosis is a deep mycosis and such cases may be evaluated by means of gallium-67, bone scintigraphy, lymphoscintigraphy, hepato-biliary, bone marrow and liver/spleen scintigraphies. Mycetoma is bone and soft tissue mycosis and gallium-67 and bone studies are very useful in the evaluation of such cases. Tuberculosis is the most well studied tropical disease and dozens of radiopharmaceuticals and techniques were described to evaluate such patients. Jorge Lobo disease is a rare mycosis that affects mainly indians from the Amazon region and gallium-67 was shown to accumulate in active disease. Neurocysticercosis is spread worldwide and brain SPECT (99mTc-ECD or 99mTc-HMPAO) is a very good tool for the functional evaluation of the disease. Patients suffering from cutaneous and mucous leishmaniasis may benefit from gallium-67 scintigraphy. Chagas disease may affect the heart and or the digestive tract and several scintigraphic exams may be helpful in the evaluation of such cases (gated blood pool, heart perfusions tests, pharyngeal transit tests, gastric emptying tests, intestinal transit tests, hepato-biliary scintigraphy, among others). Scintigraphy should be more largely used in the functional evaluation of organs and systems of patients affected y tropical diseases. It is a powerful tool to evaluate both the extent of disease and the efficacy of therapy. (author)

Attenuation of yeast form of Paracoccidioides Brasiliensis by gamma irradiation

International Nuclear Information System (INIS)

Demicheli, Marina Cortez

2006-01-01

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America, and currently there is no effective vaccine. The aim of this work was to attenuate the yeast form of P. brasiliensis by gamma irradiation for further studies on vaccine research. P. brasiliensis (strain Pb-18) cultures were irradiated at doses between 0.5 and 8.0 kGy. After each dose the fungal cells were plated and after 10 days the colony forming units (CFU) counted. The viability of the irradiated cells was measured using the dyes Janus green and methylene blue, and protein synthesis by incorporation of L 35 S methionine. The comparison between the antigenic profile of irradiated and control yeast was made by Western blot and the virulence evaluated by the inoculation in C 57 Bl/J6 and Balb/c mice. Morphological changes in irradiated yeast were evaluated by electronic microscopy and DNA integrity by electrophoresis in agarose gel. At 6.5 kGy the yeast lost the reproductive capacity. The viability and the incorporation of L- 35 S methionine were the same in control and up to 6.5 kGy irradiated cells, but 6.5 kGy irradiated yeast secreted 40% less proteins. The Western blot profile was clearly similar in control and 6.5 kGy irradiated yeast. No CFU could be recovered from the tissues of the mice infected with the radio attenuated yeast. At the dose of 6.5 kGy the DNA was degraded and this damage was not repaired. The transmission electronic microscopy showed significant alterations in the nucleus of the irradiated cells. The scanning electronic microscopy showed that two hours after the irradiation the cells were collapsed or presented deep folds in the surface, however these injury were reversible. We concluded that for P. brasiliensis yeast cells it was possible to find a dose in which the pathogen loses its reproductive ability and virulence, while retaining its viability, metabolic activity and the antigenic profile. (author)

Attenuation of yeast form of Paracoccidioides Brasiliensis by gamma irradiation; Atenuacao da forma leveduriforme do Paraccocidioides Brasiliensis por irradicao gama

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Demicheli, Marina Cortez

2006-07-01

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America, and currently there is no effective vaccine. The aim of this work was to attenuate the yeast form of P. brasiliensis by gamma irradiation for further studies on vaccine research. P. brasiliensis (strain Pb-18) cultures were irradiated at doses between 0.5 and 8.0 kGy. After each dose the fungal cells were plated and after 10 days the colony forming units (CFU) counted. The viability of the irradiated cells was measured using the dyes Janus green and methylene blue, and protein synthesis by incorporation of L {sup 35}S methionine. The comparison between the antigenic profile of irradiated and control yeast was made by Western blot and the virulence evaluated by the inoculation in C{sub 57}Bl/J6 and Balb/c mice. Morphological changes in irradiated yeast were evaluated by electronic microscopy and DNA integrity by electrophoresis in agarose gel. At 6.5 kGy the yeast lost the reproductive capacity. The viability and the incorporation of L- {sup 35}S methionine were the same in control and up to 6.5 kGy irradiated cells, but 6.5 kGy irradiated yeast secreted 40% less proteins. The Western blot profile was clearly similar in control and 6.5 kGy irradiated yeast. No CFU could be recovered from the tissues of the mice infected with the radio attenuated yeast. At the dose of 6.5 kGy the DNA was degraded and this damage was not repaired. The transmission electronic microscopy showed significant alterations in the nucleus of the irradiated cells. The scanning electronic microscopy showed that two hours after the irradiation the cells were collapsed or presented deep folds in the surface, however these injury were reversible. We concluded that for P. brasiliensis yeast cells it was possible to find a dose in which the pathogen loses its reproductive ability and virulence, while retaining its viability, metabolic activity and the antigenic profile. (author)

Nuclear medicine in tropical diseases

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Braga, Francisco Jose Hossri Nogueira [Centro Oncologico da Regiao de Araraquara, SP (Brazil). Servico de Medicina Nuclear]. E-mail: fjbraga@dfm.ffclrp.usp.br

2002-09-01

Tropical diseases affect more people in the world than any other kind of disease, but scintigraphic data on that matter are not so frequent in the literature. Since the geographic regions where such diseases occur are normally very poor, scintillation cameras may not be available. We present a resumed summary of part of what has been done on this subject to-date. Leprosy affects circa 12 million people worldwide and has already been studied by means of the following scintigraphic exams: gallium-67, 99mTc-MDP or HMDP, 99mTc-colloid or Dextran, 99mTc-DTPA and 99mTc-WBC. Paracoccidioidomycosis is a deep mycosis and such cases may be evaluated by means of gallium-67, bone scintigraphy, lymphoscintigraphy, hepato-biliary, bone marrow and liver/spleen scintigraphies. Mycetoma is bone and soft tissue mycosis and gallium-67 and bone studies are very useful in the evaluation of such cases. Tuberculosis is the most well studied tropical disease and dozens of radiopharmaceuticals and techniques were described to evaluate such patients. Jorge Lobo disease is a rare mycosis that affects mainly indians from the Amazon region and gallium-67 was shown to accumulate in active disease. Neurocysticercosis is spread worldwide and brain SPECT (99mTc-ECD or 99mTc-HMPAO) is a very good tool for the functional evaluation of the disease. Patients suffering from cutaneous and mucous leishmaniasis may benefit from gallium-67 scintigraphy. Chagas disease may affect the heart and or the digestive tract and several scintigraphic exams may be helpful in the evaluation of such cases (gated blood pool, heart perfusions tests, pharyngeal transit tests, gastric emptying tests, intestinal transit tests, hepato-biliary scintigraphy, among others). Scintigraphy should be more largely used in the functional evaluation of organs and systems of patients affected y tropical diseases. It is a powerful tool to evaluate both the extent of disease and the efficacy of therapy. (author)

Paracoccidioides brasilienses isolates obtained from patients with acute and chronic disease exhibit morphological differences after animal passage

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SVIDZINSKI Terezinha Inez Estivalet

1999-01-01

Full Text Available The basis for virulence in Paracoccidioides brasiliensis is not completely understood. There is a consensus that the sequencial in vitro subcultivation of P. brasiliensis leads to loss of its pathogenicity, which can be reverted by reisolation from animal passage. Attention to morphological and biochemical properties that are regained or demonstrated after animal passage may provide new insights into factors related to the pathogenicity and virulence of P. brasiliensis. We evaluated morphological characters: the percentage of budding cells, number of buds by cell and the diameter of 100 mother cells of yeast-like cells of 30 P. brasiliensis isolates, before and after animal passage. The isolates were obtained from patients with different clinical forms of paracoccidioidomycosis (PCM: acute form (group A, n=15 and chronic form (group C, n=15. The measurement of the yeast cell sizes was carried out with the aid of an Olympus CBB microscope coupled with a micrometer disc. We measured the major transverse and longitudinal axes of 100 viable cells of each preparation. The percentage of budding cells as also the number of buds by cell was not influenced by animal passage, regardless of the source of the strain (acute or chronic groups. The size values of P. brasiliensis isolates from groups A and C, measured before the animal passage exhibited the same behavior. After animal passage, there was a statistically significant difference between the cell sizes of P. brasiliensis isolates recovered from testicles inoculated with strains from groups A and C. The maximum diameter of mother cells from group A isolates exhibited a size of 42.1mm in contrast with 32.9mm exhibited by mother cells from group C (p<0.05. The diameter of 1500 mother cells from group A isolates exhibited a medium size of 16.0mm (SD ± 4.0, a value significantly higher than the 14.1mm (SD = ± 3.3 exhibited by 1500 mother cells from group C isolates (p<0.05. Our results reinforce the

Cell organisation, sulphur metabolism and ion transport-related genes are differentially expressed in Paracoccidioides brasiliensis mycelium and yeast cells

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Passos Geraldo AS

2006-08-01

Full Text Available Abstract Background Mycelium-to-yeast transition in the human host is essential for pathogenicity by the fungus Paracoccidioides brasiliensis and both cell types are therefore critical to the establishment of paracoccidioidomycosis (PCM, a systemic mycosis endemic to Latin America. The infected population is of about 10 million individuals, 2% of whom will eventually develop the disease. Previously, transcriptome analysis of mycelium and yeast cells resulted in the assembly of 6,022 sequence groups. Gene expression analysis, using both in silico EST subtraction and cDNA microarray, revealed genes that were differential to yeast or mycelium, and we discussed those involved in sugar metabolism. To advance our understanding of molecular mechanisms of dimorphic transition, we performed an extended analysis of gene expression profiles using the methods mentioned above. Results In this work, continuous data mining revealed 66 new differentially expressed sequences that were MIPS(Munich Information Center for Protein Sequences-categorised according to the cellular process in which they are presumably involved. Two well represented classes were chosen for further analysis: (i control of cell organisation – cell wall, membrane and cytoskeleton, whose representatives were hex (encoding for a hexagonal peroxisome protein, bgl (encoding for a 1,3-β-glucosidase in mycelium cells; and ags (an α-1,3-glucan synthase, cda (a chitin deacetylase and vrp (a verprolin in yeast cells; (ii ion metabolism and transport – two genes putatively implicated in ion transport were confirmed to be highly expressed in mycelium cells – isc and ktp, respectively an iron-sulphur cluster-like protein and a cation transporter; and a putative P-type cation pump (pct in yeast. Also, several enzymes from the cysteine de novo biosynthesis pathway were shown to be up regulated in the yeast form, including ATP sulphurylase, APS kinase and also PAPS reductase. Conclusion Taken

Correlação diagnóstica anatomoclínica. Aferição retrospectiva do diagnóstico clínico em necrópsias Correlation between anatomo-clinical diagnosis and retrospective assessment of clinical diagnosis in post mortms

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Marcos Célio de Almeida

1989-08-01

Full Text Available Analisaram-se retrospectivamente 200 necrópsias, correlacionando-se os diagnósticos clínicos e anatomopatológicos. Foram consideradas 20 entidades nosológicas para confronto. Os diagnósticos não formulados em vida, embora observados na necrópsia (falso negativo, e que apresentaram os maiores percentuais em relação aos respectivos totais de achados necroscópicos, foram: pielonefrite aguda (100%, embolia pulmonar (87,50%, aneurisma dissecante da aorta (66,66% e broncopneumonia (58,16%. Os diagnósticos formulados em vida que não tiveram confirmação pela necrópsia (falso positivo, e que apresentaram os maiores percentuais em relação aos respectivos totais dos diagnósticos clínicos, foram: tuberculose (69,50%, paracoccidioidomicose (57,14%, septicemia (53,13% e doença de Chagas (44,44%. Houve concordância diagnóstica em 97 (48,50% dos 200 casos. Em 19 (9,50% deles o desacordo diagnóstico, se antes verificado, poderia ter implicado alterações do prognóstico. Enfatiza-se a importância da necrópsia para uma adequada correlação anatomoclínica e discute-se os achados em relação a estudos prévios.The post mortem findings in 200 autopsies were compared with the clinical diagnoses. Twenty diseases were analysed with respect to clinico-pathological correlation. In relation to the respective totals the diseases most frequently missed clinically were (false negative pyelonephrites (100%, pulmonary embolus (87.50% and bronchopneumonia (58.16%. In relation to the respective totals the clinical diagnoses less frequently confirmed (false positive were tuberculosis (69.56%, paracoccidioidomycosis (57.14%, sepsis (53.13% and Chagas'disease (44.44%. There was clinico-pathological agreement in 97 autopsies (48.50%. In 19 cases (9.50% if the diagnostic error had been detected during life this probably would have changes the prognosis. The findings are discussed in the light of previous studies. The importance of routine post

Opportunistic infections in patients with aids admitted to an university hospital of the Southeast of Brazil Infecções oportunistas em pacientes com aids internados em um hospital universitário do sudeste do Brasil

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Vandack Nobre

2003-04-01

Full Text Available Opportunistic diseases in HIV-infected patients have changed since the introduction of highly active anti-retroviral therapy (HAART. This study aims at evaluating the frequency of associated diseases in patients with AIDS admitted to an university hospital of Brazil, before and after HAART. The medical records of 342 HIV-infected patients were reviewed and divided into two groups: group 1 comprised 247 patients before HAART and, group 2, 95 patients after HAART. The male-to-female rate dropped from 5:1 to 2:1for HIV infection. There was an increase in the prevalence of tuberculosis and toxoplasmosis, with a decrease in Kaposi's sarcoma, histoplasmosis and cryptococcosis. A reduction of in-hospital mortality (42.0% vs. 16.9%; p = 0.00002 has also occurred. An agreement between the main clinical diagnoses and autopsy findings was observed in 10 out of 20 cases (50%. Two patients with disseminated schistosomiasis and 2 with paracoccidioidomycosis are reported. Overall, except for cerebral toxoplasmosis, it has been noticed a smaller proportion of opportunistic conditions related to severe immunosuppression in the post HAART group. There was also a significant reduction in the in-hospital mortality, possibly reflecting improvement in the treatment of the HIV infection.O espectro das doenças oportunistas em pacientes com aids vem se modificando desde a introdução da terapia antiretroviral altamente eficaz (HAART. O objetivo deste estudo é o de avaliar o perfil das afecções oportunistas em pacientes com aids internados em um hospital universitário do Brasil, comparando os períodos pré e pós-utilização da terapia HAART. Para tanto, revisaram-se os prontuários médicos de 342 pacientes infectados pelo HIV, dividindo-os em dois grupos: grupo 1, composto de 247 pacientes pré-HAART e grupo 2, composto de 95 pacientes pós-HAART. A relação homem-mulher caiu de 5:1 para 2:1. Houve aumento da prevalência da tuberculose e da toxoplasmose, com

Influência do tempo e do meio de transporte no isolamento de fungos patogênicos de biópsias de pele Effects of time delay and transportation on isolation of pathogenic fungi from skin biopsies

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Rafael Taglialegna

2008-04-01

% chloramphenicol after a 48-72-hour (early or after 72-hour-7-day (late interval, comprising four groups of study. RESULTS: The medians of isolation rate of the four sporotrichosis groups were 100%. For paracoccidioidomycosis, the medians ranged from 50% to 84%, with no statistically significant difference among the groups (p=0.88. CONCLUSION: It was concluded that skin biopsies can be transported in Sabouraud medium or saline solution within a 7-day interval from specimen collection up to final inoculation, at room temperature, maintaining viability and growth rate of fungus in culture.

Rhinoscleroma: eight Peruvian cases Rinoscleroma: oito casos peruanos

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Ciro Maguiña

2006-10-01

Full Text Available Rhinoscleroma is a rare infection in developed countries; although, it is reported with some frequency in poorer regions such as Central Africa, Central and South America, Eastern and Central Europe, Middle East, India and Indonesia. Nowadays, rhinoscleroma may be erroneously diagnosed as mucocutaneos leishmaniasis, leprosy, paracoccidioidomycosis, rhinosporidiasis, late syphilis, neoplasic diseases or other upper airway diseases. From 1996 to 2003, we diagnosed rhinoscleroma in eight patients attended in the Dermatologic and Transmitted Diseases service of "Cayetano Heredia" National Hospital, in Lima, Peru. The patients presented airway structural alterations producing nasopharyngeal, oropharyngeal and, in one patient, laryngeal stenosis. Biopsy samples revealed large vacuolated macrophages (Mikulicz cells in all patients. Ciprofloxacin 500 mg bid for four to 12 weeks was used in seven patients and oxytetracycline 500 mg qid for six weeks in one patient. After follow-up for six to 12 months the patients did not show active infection or relapse, however, all of them presented some degree of upper airway stenosis. These cases are reported because of the difficulty diagnosing the disease and the success of antibiotic treatment.O rinoscleroma é uma infecção rara nos países desenvolvidos, no entanto, tem sido relatado com alguma freqüência nas regiões pobres da África Central, América Central e do Sul, Europa Central e Oriental, Oriente Médio, Índia e Indonésia. A doença pode ser erroneamente diagnosticada como leishmaniose mucocutânea, hanseníase, paracoccidioidomicose, rinosporidiose, sífilis tardia, neoplasias ou outras doenças que afetam a via respiratória superior. No período de 1996 a 2003, foram diagnosticados oito casos de rinoscleroma no serviço de Doenças Dermatológicas e Infecciosas do Hospital Nacional "Cayetano Heredia", em Lima, Peru. Os pacientes apresentaram alterações estruturais das vias respirat

Inmunodiagnóstico de micosis endémicas y aspergilosis broncopulmonar: Estudio multicéntrico en la República Argentina Immunodiagnosis of endemic mycoses and bronchopulmonary aspergilosis: A multicenter study in Argentina

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C.E. Canteros

2004-06-01

Full Text Available Se realizó entre 01-04-2000 y 30-03-2001, un estudio de corte transversal, para conocer la frecuencia relativa de las enfermedades por hongos dimorfos y Aspergillus spp. en la República Argentina y evaluar la certeza en el diagnóstico de los laboratorios de diferentes áreas geográficas. Participaron 25 centros de salud provenientes de 12 provincias y de la Ciudad Autónoma de Buenos Aires. Fueron analizados en el laboratorio de origen 965 sueros de pacientes con sospecha clínica de histoplasmosis (HP, paracoccidioidomicosis (PCM, coccidioidomicosis (CM y aspergilosis. Todos los sueros positivos y el 35% de los negativos fueron reevaluados en el laboratorio de referencia por inmunodifusión doble en agar. La concordancia entre los resultados obtenidos en los centros de origen y el de referencia fue de 98,8%. Se detectaron anticuerpos específicos en 120 sueros correspondientes a 98 pacientes. El 71,4% (70 casos de los diagnósticos correspondió a micosis endémicas (HP, PCM y CM y el resto a aspergilosis. PCM fue diagnosticada en 47,9% (47 casos, aspergilosis en 28,6% (28 casos, HP en13,3% (13 casos y CM en 10,2% (10 casos. La participación en este estudio fue voluntaria y no todos los centros del país estaban representados, sin embargo, las frecuencias de enfermedades fúngicas fueron las esperadas y coincidentes con estudios previos realizados a nivel nacional.In order to contribute to the knowledge of the relative frequency of chronic fungal diseases and assess the performance of diagnostic laboratories in Argentina, a multicenter study was performed with the participation of 25 medical centers located in 12 different provinces and Buenos Aires City. Between 04-01-2000 and 03-30-2001, 965 serum specimens from patients clinically suspected of having histoplasmosis (HP, paracoccidioidomycosis (PCM, coccidioidomycosis (CM or aspergilosis were analyzed. Agar immunodiffusion tests (IDD were done locally. All positive and 35% of negative

Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

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Martins, Estefania M.N.; Andrade, Antero S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN-CNEN/MG), Belo Horizonte, MG (Brazil)], e-mail: estefaniabio@yahoo.com.br, e-mail: antero@cdtn.br; Resende, Maria Aparecida de [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Microbiologia], e-mail: maresend@mono.icb.ufmg.br; Reis, Bernardo S.; Goes, Alfredo M. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia], e-mail: goes@mono.icb.ufmg.br, e-mail: brsgarbi@mono.icb.ufmg.br

2009-07-01

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - {gamma}, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-{gamma} production was maintained indicating that a Th1 pattern was

Detection of Anti-Paracoccidioides brasiliensis antibodies in suspected tuberculosis patients = Detecção de anticorpos anti-Paracoccidioides brasiliensis em pacientes suspeitos de tuberculose

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Maria Luiza Dias Fraga Peron

2010-07-01

Full Text Available Paracoccidioidomycosis (PCM is an important systemic mycosis in LatinAmerica that occurs as active disease in 1-2% of Paracoccidioides brasiliensis infected people. Like PCM, tuberculosis (TB affects mainly the lungs and the clinical and radiological aspects do notalways allow differentiation between them. The aim of this study was to carry out serological investigation for detecting anti-P. brasiliensis antibodies, by three serological methods, in patientswith symptoms suggestive of pulmonary TB. From August 2005 to September 2006, 76 patients with pulmonary symptoms suspected for TB were attended at the Regional Specialties Center Laboratory in the city of Paranavaí, Paraná, Brazil and submitted to microbiological TB research, ELISA, immunodiffusion and immunoblotting for PCM. Of all the individuals, 21 (27.63% were reactive to P. brasiliensis by ELISA and 11 (14.47% showed a laboratory diagnosis of pulmonary TB. Of all the individuals serologically reactive to P. brasiliensis, by ELISA, none had positive results by immunodiffusion and one reacted with antigen 43 kDa when Immunobloting was carried out. Our results lead us to reflect a necessity to obtain a more specific serologic test for diagnosis of PCM disease in patients with respiratory symptoms considering the high number of individuals reactive to P. brasiliensis especially in endemic areas.Paracoccidioidomicose (PCM é importante micose sistêmica na América Latina, que ocorre como doença ativa em 1-2% dos indivíduos infectados com Paracoccidioides brasiliensis. Assim como a PCM, a tuberculose (TB afeta principalmente os pulmões, porém os aspectos clínicos e radiológicos nem sempre permitem a diferenciação entreessas doenças. O objetivo deste estudo foi realizar um inquérito sorológico para a detecção de anticorpos anti-P. brasiliensis, utilizando três métodos sorológicos, em pacientes com sintomassugestivos de tuberculose pulmonar. De agosto de 2005 a setembro de

Immunization with Paracoccidioides brasiliensis radioattenuated yeast cells induces Th1 immune response in Balb/C mice

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Martins, Estefania M.N.; Andrade, Antero S.R.; Resende, Maria Aparecida de; Reis, Bernardo S.; Goes, Alfredo M.

2009-01-01

Paracoccidioides brasiliensis is the agent of paracoccidioidomycosis, the most prevalent mycosis in Latin America. To date, there is no effective vaccine. In our laboratory yeast cells of P. brasiliensis were attenuated by gamma irradiation. We defined an absorbed dose in which the pathogen loses the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins and the oxidative metabolism. The immunization with these cells was able to confer protection in BALB/c mice. The aim of the present work was evaluate the immune response pathway activated in mice immunized with P. brasiliensis radioattenuated yeast cells. The protector effect was evaluated in BALB/c mice groups immunized once or twice, respectively. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. These groups were called G1A, G1B and G1C in the group immunized once and G2A, G2B and G2C in the group immunized twice. Recovery of CFUs and cytokines determination (IFN - γ, IL - 10 and IL IV 4) were performed three months post challenge. Quantitative RT-PCR was the method of choice used to quantify the expression of cytokines. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. A significant reduction in CFUs recovery was verified 90 days post challenge in mice submitted to one immunization: 73.0%, 96.0% and 76.3% for sub-groups G1A, G1B and G1C, respectively. In the group submitted to two immunizations, a remarkable increase in the protection was obtained. No CFUs was recovered from sub-groups G2B and G2C and very few CFUs (reduction of 98.6%) were recovered from the lungs of sub group G2A. In mice submitted to one immunization, Th1 and Th2 cytokines were simultaneously produced. In the group submitted to two immunizations, levels of IL-10 and IL-4 were very low, while IFN-γ production was maintained indicating that a Th1 pattern was dominant. For

Expressão das citoceratinas em dermatoses infecto- parasitárias associadas à hiperplasia epidérmica Expression of the cytokeratins in infectious and parasitic skin diseases associated with epidermal hyperplasia

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Maria Christina Marques Nogueira-Castañon

2004-12-01

hyperplasia. METHODS: Histological sections obtained from formalin-fixed and paraffin-embedded tissue from cromomycosis, paracoccidioidomycosis, leishmaniasis and condylomata acuminata lesions were marked with the DEK10, LL025, LL002 and AE1 antibodies by the immunoperoxidase technique (avidina-botina. RESULTS: Different degrees of epidermal hyperplasia were observed predominantly or exclusively in the following four diseases: absence of immunoreactivity to DE-K10 in areas of intense epidermal hyperplasia and delayed K10 immunohistochemical staining in areas of moderate to discreet/absent hyperplasia; superbasal expression pattern for K16, regardless of the degree of hyperplasia as well as superbasal epitops discharging for LL002 (C14 and AE1 (C10, 14, 16, 19. CONCLUSIONS: The modifications indicate that regardless of the nature of the etiologic agent and degree of hyperplasia, changes in keratinocyte differentiation and proliferation may occur.

Opacidades em vidro fosco nas doenças pulmonares difusas: correlação da tomografia computadorizada de alta resolução com a anatomopatologia Ground-glass opacity in diffuse lung diseases: high-resolution computed tomography-pathology correlation

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Maria Lúcia de Oliveira Santos

2003-12-01

, association with other radiological, clinical and pathological findings must be considered for an accurate diagnostic interpretation. In this paper were reviewed 62 computed tomography examinations of patients with diffuse pulmonary diseases of 14 different etiologies in which ground-glass opacity was the only or the most remarkable finding, and correlated this findings with pathology abnormalities seen on specimens obtained from biopsies or necropsies. In pneumocystosis, ground-glass opacities correlated histologically with alveolar occupation by a foaming material containing parasites, in bronchioloalveolar cell carcinoma with thickening of the alveolar septa and occupation of the lumen by mucus and tumoral cells, in paracoccidioidomycosis with thickening of the alveolar septa, areas of fibrosis and alveolar bronchopneumonic exsudate, in sarcoidosis with fibrosis or clustering of granulomas and in idiopathic pulmonary fibrosis with alveolar septa thickening due to fibrosis. Alveolar occupation by blood was found in cases of leptospirosis, idiopathic hemosiderosis, metastatic kidney tumor and invasive aspergillosis whereas oily vacuoli were seen in lipoid pneumonia, proteinaceus and lipoproteinaceus material in silicoproteinosis and pulmonary alveolar proteinosis, and edematous fluid in cardiac failure.

Brazilian blood donation eligibility criteria for dermatologic patients Critérios brasileiros de elegibilidade à doação de sangue para pacientes dermatológicos

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Carlos Gustavo Wambier

2012-08-01

Full Text Available A focused and commented review on the impact of dermatologic diseases and interventions in the solidary act of donating blood is presented to dermatologists to better advise their patients. This is a review of current Brazilian technical regulations on hemotherapeutic procedures as determined by Ministerial Directive #1353/2011 by the Ministry of Health and current internal regulations of the Hemotherapy Center of Ribeirão Preto, a regional reference center in hemotherapeutic procedures. Criteria for permanent inaptitude: autoimmune diseases (>1 organ involved, personal history of cancer other than basal cell carcinoma, severe atopic dermatitis or psoriasis, pemphigus foliaceus, porphyrias, filariasis, leprosy, extra pulmonary tuberculosis or paracoccidioidomycosis, and previous use of etretinate. Drugs that impose temporary ineligibility: other systemic retinoids, systemic corticosteroids, 5-alpha-reductase inhibitors, vaccines, methotrexate, beta-blockers, minoxidil, anti-epileptic, and anti-psychotic drugs. Other conditions that impose temporary ineligibility: occupational accident with biologic material, piercing, tattoo, sexually transmitted diseases, herpes, and bacterial infections, among others. Discussion: Thalidomide is currently missing in the teratogenic drugs list. Although finasteride was previously considered a drug that imposed permanent inaptitude, according to its short halflife current restriction of 1 month is still too long. Dermatologists should be able to advise their patients about proper timing to donate blood, and discuss the impact of drug withdrawal on treatment outcomes and to respect the designated washout periods.Uma revisão centrada no impacto de doenças e intervenções dermatológicas no ato solidário de doar sangue é apresentada aos dermatologistas para melhor aconselhamento dos seus pacientes. Esta é uma revisão das atuais normas técnicas brasileiras sobre procedimentos hemoterápicos conforme

Evaluation of the protection induced by the immunization with radioiodinated yeast cells of Paracoccidioides brasiliensis in animal model

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Martins, Estefania Mara do Nascimento

2007-01-01

Paracoccidioides brasiliensis is fungus agent of paracoccidioidomycosis (PCM), a chronic systemic disease prevalent in Latin American. To date, there is no effective vaccine. The potential of gamma radiation for pathogens attenuation and vaccine development was explored in this work. In our laboratory were developed yeast cells of P. brasiliensis attenuated by gamma radiation, which lose the reproductive ability, while retaining the morphology, the synthesis and secretion of proteins, the oxidative metabolism and the expression of the antigens present in the native yeast. The aim of the present work was to evaluate the protection elicited by the immunization with this cells in animal model. The virulence attenuated was evaluated in BALB/c and Nude-Nude mice. The protector effect was evaluated in BALB/c mice groups immunized once or twice. Each group was divided in three sub groups that were challenge 30, 45 or 60 days after the immunization. The mice were sacrificed 30 and 90 days after challenge. The removed organs were used for colony forming units (CFU's) recover, histopathological analysis and cytokine determination. The sera were collected weekly to evaluate the IgG antibody titers and the IgG1 and IgG2a pattern in the course of infection. To evaluate the type of elicited immune response the cytokines IFN - γ, TNF - α, IL - 10 and IL - 5 were determined by real time PCR. The radio attenuated yeast loses its virulence since fails in producing infection in BALB/c and Nude-Nude mice. No CFU's were recovered neither histological changes observed in the mice infected with the radio attenuated cells. The mice infected with the not irradiated P. brasiliensis showed a high level of antibody production while the infection with the radio attenuated yeast did not significantly change the antibody level. The mice infected with the radio attenuated yeast presented an increase in the IFN - γ and TNF - α production and an inhibition of the IL-10 synthesis, indicating a

Kinetic analysis of gene expression during mycelium to yeast transition and yeast to mycelium germination in Paracoccidioides brasiliensis Análisis de la cinética de expresión de genes durante la transición de micelio a levadura y la germinación levadura a micelio en Paracoccidioides brasiliensis

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Ana María García

2011-06-01

Full Text Available Introduction.Paracoccidioidomycosis is an endemic systemic mycosis caused by Paracoccidioides brasiliensis, a thermally dimorphic fungus that in tissues and cultures at 37ºC grows as a yeast while at lower temperatures (less than 24 ºC it becomes a mold; however the genes that rule these processes and their expression are poorly understood.
Objective.This research focused on the kinetic expression of certain genes in P. brasiliensis throughout the dimorphic process, one that involves the transition from the mycelium-to-yeast(M-Y forms and the germination from the yeast-to-mycelium(Y- M form.
Materials and methods. A real-time quantitative polymerase chain reaction(RT-qPCR was optimized to measure the expression of ten genes connected with diverse cellular functions including cell synthesis and wall structure, oxidative stress response, heat shock response, metabolism, proteins' processing, solute transport across the cell membrane and signal transduction pathways at different time points during the M-Y transition, as well as in the Y-M germination processes.
Results.Genes involved in cell synthesis and wall structure, metabolism and signal transduction were differentially expressed and highly up-regulated during the Y-M germination process; on the other hand, genes involved in heat shock response, cell synthesis and wall structure were highly up-regulated during the M-Y transition process. The remaining genes were differentially regulated during both processes.
Conclusion.In this work the up-regulation of certain genes involved in the morphological changes occurring in P. brasiliensis yeast and mycelia forms were confirmed, indicating that these biological processes play an important role during the host-pathogen interactions, as well as in the fungus adaptation to environmental conditions
Introducción. La paracoccidioidomicosis es una micosis sistémica causada por el hogo termo-dimórfico Paracoccidioides