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An. bras. dermatol ; 96(3): 346-348, May-June 2021. graf
Article in English | LILACS | ID: biblio-1285064


Abstract Paracoccidioidomycosis is an endemic systemic mycosis caused by Paracoccidioides brasiliensis complex and P. lutzii. It is a rare disease in non-HIV-induced immunosuppressed individuals. In organ transplant recipients, it is more frequently associated with immunosuppression after kidney transplantation. In a liver transplant patient, only one case has been published in the literature to date. The present report comprises the case of a 47-year-old female patient with disseminated skin lesions associated with signs and symptoms of systemic involvement of paracoccidioidomycosis that manifested one year after liver transplantation and under an immunosuppression regimen with tacrolimus and mycophenolate mofetil.

Humans , Female , Paracoccidioides , Paracoccidioidomycosis/diagnosis , Paracoccidioidomycosis/diagnostic imaging , Kidney Transplantation , Liver Transplantation/adverse effects , Transplant Recipients , Middle Aged
Arq. bras. neurocir ; 40(2): 195-199, 15/06/2021.
Article in English | LILACS | ID: biblio-1362266


Neuroparacoccidiodimycosis (NPDM) is an uncommon granulomatous disease, which more frequently affects immunocompromised male patients over 30 years of age in the course of chronic lung disease. Paracoccidioides brasiliensis (PB) is an endemic fungus in Brazil, and grows as thick-walled yeast (with round to oval bodies) measuring 10 µm to 60 µm in diameter. Neuroparacoccidiodimycosi may develop many years after transmission and/or primary lung involvement. The authors describe a case of NPDM affecting a male patient, 52 years of age, farmer, heavy smoker, with clinical complaint of headache, asthenia, seizures, and prostration in the previous nine months. Upon physical examination, the patient presented regular general condition, without other relevant physical alterations. Computed tomography (CT) showed multiple bilateral pulmonary nodules associated to enlargement of the mediastinal lymph node. Magnetic resonance imaging (MRI) and CTscans of the central nervous system showed six heterogeneous nodular lesions compromising the frontal and parietal lobes, the largest one measuring 3.8 3.2 3.2 cm. The hypothesis of a neoplastic process compromising the lung and brain was considered. A biopsy of the mediastinal lymph node showed epithelioid granulomas, which exhibited round, thin-walled fungal structures in Grocott silver stain. The stereotactic biopsy of the frontal lesion was constituted by necrotic tissue admixed with some round to oval, thin-walled fungi measuring 10 µm to 60 µm, compatible with PB (identified on Grocott silver stain/confirmed in culture). The diagnosis of NPDM was then established. The employed therapeutic regimen was intravenous amphotericin B, itraconazole, and sulfamethoxazole-trimetropin. After ninety days of clinical follow-up, no episodes of seizures/neurological deficits were identified, and a marked decrease in the number and size of the lung and brain lesions were found.

Humans , Male , Middle Aged , Paracoccidioidomycosis/therapy , Immunocompromised Host , Central Nervous System Fungal Infections/surgery , Antifungal Agents/therapeutic use , Paracoccidioides , Paracoccidioidomycosis/diagnostic imaging , Central Nervous System Fungal Infections/diagnostic imaging
Braz. j. infect. dis ; 25(5): 101607, 2021. tab
Article in English | LILACS | ID: biblio-1350318


ABSTRACT Purpose: In-house Paracoccidioides spp. antigens are commonly used in the serological diagnosis of paracoccidioidomycosis (PCM). The sensitivity and specificity of a commercial Paracoccidioides spp. antigen was assessed for PCM serological testing. Method: Counterimmunoelectrophoresis and double immunodiffusion were used to evaluate the Paracoccidioides ID Antigen reagent in sera from PCM cases and patients with other diseases. Results: All active PCM sera (n=24) were reactive using counterimmunoelectrophoresis (sensitivity = 100%), including 11 cases of infection by P. brasiliensis sensu stricto and one by P. americana. Fifteen (88%) out of 17 sera from patients on treatment or cured were reactive, including one case of P. lutzii infection. One to three bands of antigen-antibody precipitate were observed on the agarose gel, with a predominance of two to three bands in the test with untreated PCM sera or at the beginning of antifungal therapy. All sera from patients with histoplasmosis (n=7), aspergillosis (n=5), and other diseases (n=27) tested negative (specificity = 100%). The overall sensitivity and specificity using the commercial antigen and double diffusion test were 75% and 100%, respectively. Conclusion: The commercial antigen performed satisfactorily and may contribute to the dissemination of the use of serological tests for the PCM diagnosis.

Humans , Paracoccidioides , Paracoccidioidomycosis/diagnosis , Counterimmunoelectrophoresis , Immunodiffusion , Antigens, Fungal
Braz. j. infect. dis ; 25(4): 101605, 2021. tab, graf
Article in English | LILACS | ID: biblio-1339437


ABSTRACT Background: Paracoccidioidomycosis is a systemic mycosis considered endemic and limited to Latin America with the majority of registered cases originating from Brazil. The purpose of this paper was to report a case of a female patient with paracoccidioidomycosis mimicking inflammatory bowel disease and to systematically review available cases of the intestinal presentation of this infectious disease. Case report: Female patient, 32-years old, previously asymptomatic, presenting with acute pain in the lower right abdomen, associated with signs of peritoneal irritation and abdominal distension. Urgent surgery was performed, which identified a severe suppurative perforated ileitis. The anatomopathological study revealed fungal structures shaped as a ship's pilot wheel in Grocott-Gomori's staining, suggestive of Paracoccidioides spp. Methods: Studies were retrieved based on Medical Subject Headings and Health Sciences Descriptors, which were combined using Boolean operators. Searches were run on the electronic databases Scopus, Web of Science, MEDLINE (PubMed), BIREME (Biblioteca Regional de Medicina), LILACS (Latin American and Caribbean Health Sciences Literature), SciELO (Scientific Electronic Library Online), Embase, and Languages were restricted to English, Spanish and Portuguese. There was no date of publication restrictions. The reference lists of the studies retrieved were searched manually. Simple descriptive analysis was used to summarize the results. Results: Our search strategy retrieved 581 references. In the final analysis, 34 references were included, with a total of 46 case reports. The most common clinical finding was abdominal pain and weight loss present in 31 (67.3%) patients. Most patients were treated with itraconazole (41.3%) and amphotericin B (36.9%). All-cause mortality was 12.8%. Conclusions: Paracoccidioidomycosis should be suspected in endemics areas, specially as a differential diagnosis for inflammatory bowel disease. Endoscopic tests and biopsy are useful for diagnosis and treatment with antifungal drugs seem to be the first treatment option to achieve a significant success rate.

Humans , Female , Adult , Paracoccidioides , Paracoccidioidomycosis/diagnosis , Paracoccidioidomycosis/drug therapy , Amphotericin B , Itraconazole , Antifungal Agents/therapeutic use
Mem. Inst. Oswaldo Cruz ; 116: e210203, 2021. tab, graf
Article in English | LILACS | ID: biblio-1346579


BACKGROUND Paracoccidioidomycosis (PCM) is a systemic mycosis endemic to Latin America. Etiological agents are Paracoccidioides species that diverge phylogenetically throughout South America. OBJECTIVES This study aimed to document the epidemiology of PCM in Venezuela. METHODS We have performed a retrospective cross-sectional descriptive study in 31,081 clinical records of patients from two reference centres during 65 years (1954-2019). FINDINGS PCM diagnosis was confirmed in 745 patients. Chronic PCM was the most prevalent form (90.06% cases); 80.67% were male and the most affected age range was 41-60. Farming and construction were the most prevalent occupation and Miranda State had a higher prevalence. Lung and skin were the most affected organs, followed by oral manifestations. Direct examination, culture and serology showed a high sensibility, and no statistical difference was observed among the diagnostic tools. Out of 17 Paracoccidioides isolates genotyped from Venezuela, one was typed as Paracoccidioides americana and 16 as Paracoccidioides venezuelensis. MAIN CONCLUSIONS Clinical manifestations observed, information about the epidemiology and molecular profile is essential not only for diagnosis but also for understanding therapeutic responses to mycotic drugs and prognosis. Therefore, it is necessary to sequence all positive isolated strains in order to confirm the dominance of P. venezuelensis in Venezuela.

Humans , Male , Paracoccidioides/genetics , Paracoccidioidomycosis/genetics , Paracoccidioidomycosis/epidemiology , Venezuela/epidemiology , Cross-Sectional Studies , Retrospective Studies
Mem. Inst. Oswaldo Cruz ; 116: e200592, 2021. tab, graf
Article in English | LILACS | ID: biblio-1154883


BACKGROUND Paracoccidioidomycosis (PCM) is a systemic mycosis with high prevalence in Latin America that is caused by thermodimorphic fungal species of the Paracoccidioides genus. OBJECTIVES In this study, we used quantitative polymerase chain reaction (qPCR) to investigate the expression of genes related to the virulence of Paracoccidioides brasiliensis (Pb18) and P. lutzii (Pb01) strains in their mycelial (M) and yeast (Y) forms after contact with alveolar macrophages (AMJ2-C11 cell line) and fibroblasts (MRC-5 cell line). METHODS The selected genes were those coding for 43 kDa glycoprotein (gp43), enolase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 14-3-3 protein (30 kDa), phospholipase, and aspartyl protease. FINDINGS In the Pb18 M form, the aspartyl protease gene showed the highest expression among all genes tested, both before and after infection of host cells. In the Pb18 Y form after macrophage infection, the 14-3-3 gene showed the highest expression among all genes tested, followed by the phospholipase and gp43 genes, and their expression was 50-fold, 10-fold, and 6-fold higher, respectively, than that in the M form. After fibroblast infection with the Pb18 Y form, the 14-3-3 gene showed the highest expression, followed by the phospholipase and aspartyl protease genes, and their expression was 25-fold, 10-fold, and 10-fold higher, respectively, than that in the M form. Enolase and aspartyl protease genes were expressed upon infection of both cell lines. After macrophage infection with the Pb01 Y form, the 14-3-3 gene showed the highest expression, followed by the phospholipase and aspartyl protease genes, and their expression was 18-fold, 12.5-fold, and 6-fold higher, respectively, than that in the M form. MAIN CONCLUSIONS In conclusion, the data show that the expression of the genes analysed may be upregulated upon fungus-host interaction. Therefore, these genes may be involved in the pathogenesis of paracoccidioidomycosis.

Humans , Paracoccidioides/genetics , Paracoccidioidomycosis/genetics , Virulence Factors/genetics , Fibroblasts , Macrophages , Paracoccidioides/pathogenicity , Gene Expression , Latin America
Arq. bras. neurocir ; 39(4): 306-310, 15/12/2020.
Article in English | LILACS | ID: biblio-1362343


Paracoccidioidomycosis is a systemicmycosis caused by the Paracoccidioides brasiliensis fungus, which is endemic in Latin America. Brazil is the country with the highest number of cases. The affection of the central nervous system (CNS), a potentially fatal condition, occurs in 12% of the cases. The following forms of presentation are identified:meningeal, which is unusual;meningoencephalitic; and pseudotumoral, the latter two being more frequent. Imaging tests are essential for the diagnosis, but the histological identification of the fungus is required for confirmation of the pathology. The clinical picture depends on the neuraxial location.We present a case of amale rural worker, with expansive lesions in the CNS compatible with paracoccidioidomycosis.

Humans , Male , Middle Aged , Paracoccidioidomycosis/surgery , Paracoccidioidomycosis/drug therapy , Paracoccidioidomycosis/epidemiology , Central Nervous System Fungal Infections/therapy , Paracoccidioides/pathogenicity , Paracoccidioidomycosis/diagnostic imaging , Central Nervous System Fungal Infections/mortality , Central Nervous System Fungal Infections/diagnostic imaging
J. venom. anim. toxins incl. trop. dis ; 26: e20200023, 2020. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1135136


Endemic systemic mycoses remain a health challenge, since these opportunistic diseases are increasingly infecting immunosuppressed patients. The simultaneous use of antifungal compounds and other drugs to treat infectious or non-infectious diseases has led to several interactions and undesirable effects. Thus, new antifungal compounds should be investigated. The present study aimed to evaluate the activity of liriodenine extracted from Annona macroprophyllata on agents of systemic mycoses, with emphasis on the genus Paracoccidioides. Methods: The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined by the microdilution method. The cellular alterations caused by liriodenine on a standard P. brasiliensis (Pb18) strain were evaluated by transmission and scanning electron microscopy. Results: Liriodenine was effective only in 3 of the 8 strains of the genus Paracoccidioides and in the Histoplasma capsulatum strain, in a very low concentration (MIC of 1.95 µg.mL-1); on yeasts of Candida spp. (MIC of 125 to 250 µg.mL-1), including C. krusei (250 µg.mL-1), which has intrinsic resistance to fluconazole; and in Cryptococcus neoformans and Cryptococcus gattii (MIC of 62.5 µg.mL-1). However, liriodenine was not effective against Aspergillus fumigatus at the studied concentrations. Liriodenine exhibited fungicidal activity against all standard strains and clinical isolates that showed to be susceptible by in vitro tests. Electron microscopy revealed cytoplasmic alterations and damage to the cell wall of P. brasiliensis (Pb18). Conclusion: Our results indicate that liriodenine is a promising fungicidal compound that should undergo further investigation with some chemical modifications.(AU)

Paracoccidioides , Microscopy, Electron , Microbial Sensitivity Tests , Cryptococcus neoformans , Cryptococcus gattii , Mycoses , Antifungal Agents/isolation & purification
Mem. Inst. Oswaldo Cruz ; 115: e200208, 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1135227


Paracoccidioides spp. isolation from environmental samples is rare and hardly reproducible. Molecular techniques have facilitated the fungal detection. However, it can be still difficult. Some strategies to enhance the capacity of DNA detection have been adopted, including the analysis of soil samples belonging to the habitat of animals from which Paracoccidioides spp. have already been isolated, notably armadillo burrows. To date, the detection of Paracoccidioides spp. has not yet been reported from outbreak hotspots. Clusters and outbreaks of acute paracoccidioidomycosis (PCM), usually a more severe clinical form, have currently occurred in urban areas being associated to climate changes, deforestation, and great constructions. These occurrences potentially signalise the fungus' environmental niche, a riddle not yet solved. The authors performed an environmental investigation in a deeply disturbed area, after a highway construction in Rio de Janeiro, Brazil, where a recent outbreak of acute PCM occurred. Specific DNA sequences of Paracoccidioides brasiliensis were detected in shallow soil samples around the highway, reinforcing the association between the road construction and this PCM outbreak.

Animals , Paracoccidioides/isolation & purification , Paracoccidioidomycosis/microbiology , Armadillos , DNA, Fungal/genetics , Paracoccidioides/growth & development , Paracoccidioides/genetics , Soil Microbiology , Brazil , Base Sequence , Sequence Analysis, DNA , Ecosystem
Mem. Inst. Oswaldo Cruz ; 115: e200238, 2020. tab, graf
Article in English | LILACS, SES-SP | ID: biblio-1135258


BACKGROUND Paracoccidioides spp. causes paracoccidioidomycosis (PCM), an important and frequent systemic mycosis that occurs in Latin America. The infectious process begins with contact between the fungus and lung cells, and the molecular pattern of this interaction is currently poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the gene expression in many biological processes, including in the infections. OBJECTIVE This study aimed to analyse the expression of miRNAs in lung cells as response to infection by Paracoccidioides spp. METHODS A quantitative real-time polymerase chain reaction (RT-qPCR) based screening was employed to verify differentially expressed miRNAs in human lung cells infected with three different species; Paracoccidioides lutzii, Paracoccidioides americana, and Paracoccidioides brasiliensis. Furthermore, the in silico predictions of target genes and pathways for miRNAs were obtained. FINDINGS The results showed that miRNAs identified in the lung cells were different according to the species studied. However, based on the predicted targets, the potential signaling pathways regulated by miRNAs are common and related to adhesion, actin cytoskeleton rearrangement, apoptosis, and immune response mediated by T cells and TGF-β. MAIN CONCLUSIONS In summary, this study showed the miRNAs pattern of epithelial cells in response to infection by Paracoccidioides species and the potential role of these molecules in the regulation of key pathogenesis mechanisms of PCM.

Humans , Paracoccidioides/pathogenicity , Paracoccidioidomycosis , MicroRNAs/metabolism , Real-Time Polymerase Chain Reaction , Latin America , Lung/cytology
Rev. Inst. Adolfo Lutz ; 78: 1-9, dez. 2019. graf
Article in Portuguese | LILACS, ColecionaSUS, SES-SP, CONASS, SESSP-ACVSES, SESSP-IALPROD, SES-SP, SESSP-IALACERVO | ID: biblio-1147471


Oitenta porcento dos casos de paracoccidioidomicose (PMC) ocorrem no Brasil. As regiões brasileiras com maior número de casos são: sul, sudeste e centro-oeste, sendo emergente no norte e nordeste. A imunodifusão dupla em gel de agarose assume grande importância no diagnóstico, por permitir o monitoramento da doença e por oferecer subsídios para levantamentos soroepidemiológicos. O objetivo deste trabalho foi de avaliar e caracterizar os pacientes atendidos no Laboratório de Imunodiagnóstico das Micoses do Instituto Adolfo Lutz de São Paulo, em 2016. Trata-se de um estudo retrospectivo realizado utilizando-se dados secundários e avaliando-se as seguintes informações: idade, sexo, procedência do pedido médico, resultado e histórico sorológico dos pacientes. Dos 1.408 pacientes, 12,8% apresentaram reatividade sorológica para Paracoccidioides brasiliensis. Destes, 42,5% não possuiam histórico sorológico, sendo considerados como casos novos da doença. A classificação dos pacientes reagentes por gênero demonstrou que 83,4% eram do sexo masculino, com razão de masculinidade de 5:1. A faixa etária variou de um (1) a 92 anos, e aproximadamente 40% dos pacientes eram da faixa etária de 41 a 60 anos. Este estudo demonstra e reforça a importância da implementação dos estudos soroepidemiológicos como ferramenta auxiliar para nortear as ações de vigilância e políticas em saúde na PCM. (AU)

Eighty percent of paracoccidioidomycosis (PMC) cases occur in Brazil. The highest numbers occur in south, southeast and center-west region, being emergent in the north and northeast areas. The double immunodiffusion in agarose gel is valuable for its diagnosis, as it allows the monitoring of the disease and offers subsidies for the seroepidemiological surveys. This study evaluated and characterized the patients attended in 2016 at the Mycoses Immunodiagnosis Laboratory of Adolfo Lutz Institute of São Paulo. This retrospective study, based on the secondary data, evaluated the information: age, sex, medical request origin, result and serological history of the patients. Of 1,408 patients, 12.8% presented positive serological reactivity for Paracoccidioides brasiliensis. Of them, 42.5% had no serological history and they were considered as new cases. The classification of reactive patients by gender showed that 83.4% were males, being the masculinity ratio of 5:1. The age range was one (1) to 92 years old, and ±40% of the patients were of age ranging from 41-60 years old. This study reinforces the importance of the implementation of the seroepidemiological studies as to guide the surveillance actions and the public health politics in PCM. (AU)

Paracoccidioides , Paracoccidioidomycosis , Patients , Immunologic Tests
Infectio ; 23(2): 167-174, Apr.-June 2019. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-989948


Resumen Objetivo: Evaluar la validez diagnóstica de las pruebas inmunológicas en la infección por Paracoccidioides, a partir de un metaanálisis de la literatura publicada entre 1972-2017. Métodos: Se realizó un metanálisis según las fases de identificación, tamización, elección e inclusión descritas en la guía PRISMA. Se evaluó la calidad metodológica con la guía QUADAS y se garantizó la reproducibilidad en la selección de estudios y extracción de la información. Se estimó la sensibilidad, especificidad, razones de verosimilitud, OR diagnóstica y área bajo la curva ROC usando Meta-DiSc. Resultados: Se identificaron 21 estudios que evaluaron 32 pruebas diagnósticas con una población de 1.404 individuos sanos, 2.415 con otras infecciones y 2.337 con Paracoccidioides. La mayoría de pacientes son de Brasil y Colombia. Las pruebas analizadas incluyen inmunodifusión, western blot, ELISA, aglutinación en látex. Las pruebas presentaron una sensibilidad y especificidad superior al 90%, razón de verosimilitud positiva y negativa de 24,7 y 0,08 respectivamente. La OR diagnóstica fue 495,9 y el área bajo la curva de 0,99. En la meta-regresión por tipo de antígeno se encontró que las mezclas de antígenos y el gp43 presentaron resultados satisfactorios en todos los parámetros; por su parte, los que utilizaron el antígeno p27 no presentaron resultados aceptables en ninguno de los parámetros. Conclusión: La elevada validez diagnóstica hallada en las pruebas serológicas que utilizan mezclas de antígenos o gp43 purificada evidencia la pertinencia de su uso en clínica y en programas de tamización.

Abstract Objective: To evaluate the diagnostic validity of the immunological tests in Paracoccidioides infection, from a meta-analysis of the literature published between 1970-2017. Methods: Meta-analysis according to the identification, screening, eligibility and inclusion phases of PRISMA. The methodological quality was evaluated with the QUADAS guide and the reproducibility in the selection of studies and extraction of the information was guaranteed. Sensitivity, specificity, likelihood ratios, diagnostic OR and area under the ROC curve were estimated using Meta-DiSc. Results: We identified 21 studies that evaluated 32 diagnostic tests with a population of 1404 healthy individuals, 2415 with other infections and 2337 with Paracoccidioides. The majority of patients are from Brazil and Colombia. The tests analyzed include immunodiffusion, western blot, ELISA, latex agglutination. The tests presented a sensitivity and specificity higher than 90%, positive and negative likelihood ratio of 24,7 and 0,08 respectively. The diagnostic OR was 495,9 and the area under the curve was 0,99. In the meta-regression by type of antigen it was found that mixtures of antigens and gp43 showed satisfactory results in all parameters; those who used the p27 antigen did not present acceptable results in any of the parameters. Conclusion: The diagnostic validity of the serological tests using mixtures of antigens or purifed gp43 is clinically similar, for the other antigens the validity was scarce.

Humans , Male , Female , Paracoccidioides , Tropical Medicine , Mass Screening , Meta-Analysis , Resource Guide , Diagnosis , Infections
HU rev ; 45(1): 93-97, 2019.
Article in Portuguese | LILACS | ID: biblio-1048670


Introdução: a paracoccidioidomicose (PCM) é uma micose sistêmica causada pelo fungo Paracoccidioides brasiliensis. O Brasil é considerado país endêmico da doença, que afeta principalmente trabalhadores rurais adultos, do sexo masculino, em contato constante com a vegetação e solo. Objetivo: relatar o caso clínico de uma paciente gestante de 23 anos, apresentando linfadenomegalia em região cervical, supraclavicular e axilar de origem desconhecida, moradora de área urbana em Juiz de Fora - MG e seguimento de diagnóstico e tratamento durante período de internação em unidade hospitalar. Relato de caso: as informações foram obtidas por meio de revisão do prontuário a partir da assinatura do Termo de Consentimento Livre e Esclarecido, entrevista com a paciente, registro fotográfico dos métodos diagnósticos aos quais a paciente foi submetida e revisão da literatura; realizada biópsia do linfonodo acometido, obtendo o laudo histopatológico de Paracoccidioidomicose. Terapêutica medicamentosa específica foi administrada em regime hospitalar e o quadro sintomático da paciente prosseguiu com involução. Apaciente segue em acompanhamento em pré-natal na unidade, não observando, até o momento, repercussões materno-fetais ao uso da Anfotericina B, prosseguindo assim, com involução do quadro. Conclusão: verificou-se que a Paracoccidioidomicose na gravidez deve ser abordada clinicamente de forma atenta e enérgica tendo em vista minimizar ou tornar nulas as repercussões materno-fetais graves

Introduction: paracoccidioidomycosis (PCM) is a systemic mycosis caused by the fungus Paracoccidioides brasiliensis. Brazil is considered endemic to this disease, affecting mainly adult rural male workers in constant contact with vegetation and soil. Objective: to report the clinical case of a 23-year-old pregnant woman, showing lymphadenomegaly in the cervical, supraclavicular and axillary spots, living in an urban area. Case report: the information was obtained by reviewing the medical files after the Free Informed Consent was signed, interviewing the patient along with pictures of the diagnostic methods the patient was submitted and literature review; a biopsy of the affected lymph node obtained the histopathological report of Paracoccidioidomycosis. Specific drug therapy was started on an in-patient basis, and the patient's clinical picture proceeded with involution. The follow up has been made on out-patient prenatal care, and has not observed, until now, maternal-fetal repercussions on the use of Amphotericin B, followed by clinical signs involution. Conclusion: It has been observed that paracoccidioidomycosis in pregnancy should be approached more aggressively in order to minimize or render serious maternal-fetal repercussions void.

Humans , Female , Adult , Paracoccidioides , Paracoccidioidomycosis , Therapeutics , Pregnancy , Amphotericin B , Pregnant Women , Diagnosis , Lymphadenopathy
Sci. med. (Porto Alegre, Online) ; 29(2): ID32705, 2019.
Article in Portuguese | LILACS | ID: biblio-1022316


OBJETIVOS: Avaliar a eficácia da terapia fotodinâmica com Brilliant Blue G no tratamento de um modelo experimental de artrite por Paracoccidioides brasiliensis (P. brasiliensis). MÉTODOS: Após a indução de artrite experimental com isolado de P. brasiliensis da linhagem Pb18 nos joelhos de ratos Wistar, os animais foram divididos em grupos e submetidos a terapia fotodinâmica com fotossensibilizador Brilliant Blue G intra-articular e a laserterapia apenas, sem o Brilliant Blue G. Todos os grupos receberam seus respectivos tratamentos do sétimo ao 11º dia. Para análise do edema foi mensurado o diâmetro latero-lateral do joelho de cada animal diariamente e após o período de tratamento os animais foram sacrificados para dissecação do joelho experimental e coleta de sangue para análise por ELISA, a fim de quantificar os níveis de anticorpos anti-P. brasiliensis. RESULTADOS: A aplicação da terapia fotodinâmica foi capaz de impedir a formação de edema quando comparado ao controle (p>0,005), bem como a produção de anticorpos anti-Gp-43 de P. brasiliensis (p=0,001). No exame anatomopatológico foi possível observar maior grau de sinovite e maior presença de granulomas com o fungo em seu interior no grupo que não recebeu tratamento quando comparado aos grupos que receberam a terapia fotodinâmica. CONCLUSÕES: A terapia fotodinâmica foi eficaz para atenuar a artrite experimental induzida por P. brasiliensis no modelo articular proposto.

AIMS: To evaluate the effectiveness of photodynamic therapy with Brilliant Blue G in the treatment of an experimental model of arthritis by Paracoccidioides brasiliensis (P. brasiliensis). METHODS: After the induction of experimental arthritis with isolated from P. brasiliensis of lineage Pb18 in the knees of Wistar rats, the animals were divided into groups and submitted to photodynamic therapy with intra-articular Brilliant Blue G photosensitizer and laser therapy only, without Brilliant Blue G. All groups received their respective treatments from the seventh to the 11th day. For edema analysis, the knee lateral-lateral diameter of each animal was measured daily and after the treatment period the animals were sacrificed for experimental knee dissection and blood collection for analysis by ELISA, in order to quantify levels of anti-P. brasiliensis antibodies. RESULTS: The results showed that the application of photodynamic therapy was able to prevent the formation of edema when compared to the control (p>0.005), as well as the production of anti-Gp-43 antibodies from P. brasiliensis (p=0.001). In the anatomopathological examination it was possible to observe a higher degree of synovitis and a greater presence of granulomas with the fungus inside the group that did not receive treatment when compared to the groups that received the photodynamic therapy. CONCLUSIONS: Photodynamic therapy was effective in attenuating the experimental arthritis induced by P. brasiliensis in the proposed joint model.

Photochemotherapy , Paracoccidioides , Arthritis, Experimental , Rheumatology , Medicine
An. bras. dermatol ; 93(6): 902-904, Nov.-Dec. 2018. graf
Article in English | LILACS | ID: biblio-1038284


Abstract: Molecular studies have shown more than one species of the genus Paracoccidioides to be the causal agent of paracoccidioidomycosis. Efforts have been made to correlate the identified species with epidemiological and clinical data of patients, aiming to determine the real meaning and impact of new species. Bearing this objective in mind, the authors report a clinical case of paracoccidioidomycosis, from São Paulo state, Brazil, that manifested as uncommon sarcoid-like cutaneous lesions and was caused by Paracoccidioides brasiliensis sensu stricto (S1a). The patient was treated with itraconazole 200mg/day for 12 months, with complete clinical remission.

Humans , Male , Middle Aged , Paracoccidioides/classification , Paracoccidioidomycosis/diagnosis , Paracoccidioidomycosis/microbiology , Sarcoidosis/diagnosis , Paracoccidioides/isolation & purification , Paracoccidioidomycosis/drug therapy , Itraconazole/therapeutic use , Diagnosis, Differential , Antifungal Agents/therapeutic use
Acta méd. colomb ; 43(2): 111-114, abr.-jun. 2018. graf
Article in Spanish | LILACS, COLNAL | ID: biblio-949548


Resumen La paracoccidioidomicosis es una enfermedad crónica, sistémica y progresiva, sólo descrita en América Latina. Su presentación clínica crónica multifocal es la más prevalente, afectando mayormente a hombres adultos y comprometiendo principalmente a pulmones, sin embargo, puede diseminarse a cualquier órgano generando múltiples complicaciones en el paciente. Presentamos el caso de un paciente masculino, inmunocompetente, caficultor, quien debuta con compromiso de la glándula suprarrenal y en quien posteriormente se documenta compromiso pulmonar. El diagnóstico se confirmó mediante biopsia de lesiones en glándula suprarrenal, inmunodifusión en gel de agar y reacción en cadena de la polimerasa, la cual mostró compromiso por Paracoccidioides brasiliensis. (Acta Med Colomb 2018; 43: 111-114).

Abstract Paracoccidioidomycosis is a chronic, systemic and progressive disease which is described only in Latin America. Its chronic and multifocal clinical presentation is the most prevalent, affecting mainly adult men and compromising mainly lungs; however, it can spread to any organ generating multiple complications in the patient. The case of an immunocompetent male patient, coffee grower, who debuted with compromise of the adrenal gland and in who subsequently pulmonary involvement was documented, is presented. The diagnosis was confirmed by biopsy of lesions in the adrenal gland, agar gel immunodiffusion and polymerase chain reaction, which showed compromise by Paracoccidioides brasilensis. (Acta Med Colomb 2018; 43: 111-114).

Humans , Male , Middle Aged , Paracoccidioides , Azoles , Fungemia , Adrenal Insufficiency , Lung Diseases, Fungal
Medicina (B.Aires) ; 78(3): 180-184, jun. 2018. ilus
Article in Spanish | LILACS | ID: biblio-954974


La paracoccidioidomicosis (PCM) es una de las micosis sistémicas que son endémicas exclusivamente en América Latina. Está causada por hongos termodimorfos del género Paracoccidoides: P. brasiliensis (S1), P. americana (PS2), P. restrepiensis (PS3), P. venezuelensis (PS4) y P. lutzii. Paracoccidioides habita y produce conidios infecciosos en suelos de zonas subtropicales húmedas. En Argentina está presente al norte del paralelo 34.5° S. Poco se sabe sobre su nicho ecológico específico, lo que dificulta el diseño de medidas de control de la PCM. La infección ocurre en hospederos susceptibles cuando inhalan conidios aerosolizados. Los trabajadores rurales varones son el grupo más expuesto a contraer PCM. La primoinfección puede ser asintomática o causar un cuadro respiratorio leve; este, a su vez, puede autolimitarse o progresar a enfermedad, ya sea pulmonar o diseminada. Existen dos formas de presentación: (i) aguda/subaguda, en niños, adolescentes y personas con sistemas inmunes comprometidos; y (ii) crónica progresiva, en adultos. La cicatrización de las lesiones resulta en secuelas fibróticas que pueden causar disfagia, disfonía, insuficiencia suprarrenal y obstrucción intestinal. Aunque existen herramientas para su diagnóstico, la PCM es rara vez sospechada precozmente porque sus manifestaciones clínicas iniciales son inespecíficas. Sumados, el diagnóstico tardío y la baja adherencia a los efectivos pero largos tratamientos antimicóticos permiten el avance de la enfermedad y el desarrollo de fibrosis tisular extensa, lo que compromete gravemente la función respiratoria y suprarrenal, altera permanentemente la calidad de vida del paciente y puede causar su muerte.

Paracoccidioidomycosis (PCM) is among the systemic mycoses which are endemic only in Latin America. In Argentina, the vast majority of the cases are reported at north of latitude 34.5° S. The disease is produced by thermodimorphic fungi of the genus Paracoccidoides: P. brasiliensis (S1), P. americana (PS2), P. restrepiensis (PS3), P. venezuelensis (PS4) y P. lutzii. The natural habitat of members of this genus is the soil, where they produce infectious conidia. Little is known, however, about their specific ecologic niche(s), and this knowledge gap hampers the design of measures to control the infection. Rural male workers are the group most at risk of developing PCM. Infection occurs by inhalation of aerosolized conidia and may either be asymptomatic or cause mild respiratory symptoms. In turn, this primary infection may be self-limited or progress to severe pulmonary or disseminated disease. The disease has two clinical presentations: (i) acute or subacute (juvenile), frequent in children, adolescents and people with immunodeficiencies; and (ii) chronic progressive, in adults. Active lesions often resolve into fibrotic scars which can cause dysphagia, dysphonia, adrenal insufficiency, and intestinal obstruction. Although efficient tools are available for diagnosis and treatment, the nonspecific nature of PCM clinical manifestations frequently delay the diagnosis. In addition, the poor adherence to long antifungal treatments allows the advance of the disease and the development of extensive fibrosis compromising severely and permanently respiratory and adrenal functions, thus altering the patient´s quality of life and even causing his/her death.

Humans , Paracoccidioides/classification , Paracoccidioidomycosis/diagnosis , Paracoccidioidomycosis/parasitology , Paracoccidioidomycosis/therapy , Neglected Diseases
Rev. Soc. Bras. Med. Trop ; 51(1): 111-114, Jan.-Feb. 2018. graf
Article in English | LILACS | ID: biblio-897041


Abstract The authors report the first case of fatal septic shock, a rare clinical presentation of paracoccidioidomycosis (PCM) caused by Paracoccidioides brasiliensis S1. We also provide an immunological evaluation of the patient. Severe clinical signs such as organ dysfunction and digital gangrene occurred in this case. The patient presented a remarkable cell activation profile and diminished percentage of peripheral blood T regulatory cells. A decrease in anti-inflammatory IL-1RA plasma level showed the potential for endothelium damage, probably contributing to a vasculitis process. Together with P. lutzii, P. brasiliensis appears to be involved in severe cases of PCM.

Humans , Male , Young Adult , Paracoccidioides/genetics , Paracoccidioidomycosis/complications , Paracoccidioidomycosis/diagnosis , Phylogeny , Shock, Septic/microbiology , Severity of Illness Index , Fatal Outcome , Immunocompetence
São Paulo; s.n; s.n; 2018. 125 p. ilus, graf, tab.
Thesis in Portuguese | LILACS | ID: biblio-881081


Os receptores do tipo Toll compreendem a família de receptores de reconhecimento de padrões melhor caracterizados, que podem ativar diferentes respostas imunes, dependendo de quais receptores e conjuntos de adaptadores são utilizados. Os TLRs, como TLR2, TLR4 e TLR9, e sua sinalização foram implicados no reconhecimento de P. brasiliensis e na regulação da resposta imune, no entanto, o papel do TLR3 ainda não está claro. Assim, a compreensão da função endossomal do TLR3 na PCM experimental é crucial. Utilizamos modelos in vitro e in vivo de infecção por P. brasiliensis, camundongos C57Bl/6 e TLR3-/-, para avaliar a contribuição da TLR3 no desenvolvimento da infecção. Mostramos que ausência de TLR3 leva o aumento de óxido nítrico e a capacidade fagocítica por macrófagos nas primeiras 4 horas de interação com leveduras P. brasiliensis. Mostramos ainda que os camundongos TLR3-/- desempenham papel protetor após 30 dias de infecção intratraqueal com P. brasiliensis, mostrando diminuição do aumento de CFU, perfil de resposta Th1 e Th17, bem como aumento de células citotóxicas T CD8+ produtoras de IFN-γ e IL-17. As células citotóxicas T CD8+ mostraram ser essenciais para o controle da infecção nos camundongos TLR3-/-, uma vez que a depleção dessas células levou a progressão da doença. Em estágios iniciais, 3 e 5 dias de infecção, observamos aumento do recrutamento de neutrófilos para o pulmão. Estudos recentes indicam que o TLR3 é um receptor importante para a resposta imune na micose e sua ausência favorece a infecção por fungos. Em contraste, nossos resultados mostram que, no caso do PCM, o TLR3 é prejudicial ao hospedeiro, sugerindo que a ativação do TLR3 pode ser um possível mecanismo de escape de P. brasiliensis

Toll-like receptors comprise the best-characterized pattern-recognition receptor family that can activate different immune responses, depending on which receptor and adaptor set are utilized. TLRs, such as TLR2, TLR4 and TLR9, and their signaling have been implicated in the recognition of P. brasiliensis and regulation of the immune response, however, the role of TLR3 remains unclear. Thus, understanding the endosomal function of TLR3 in experimental PCM is crucial. We used in vitro and in vivo models of infection by P. brasiliensis, C57Bl/6 and TLR3-/- mice, to assess the contribution of TLR3 on development of infection. We show that absence of TLR3 leads to increased nitric oxide and phagocytic capacity by macrophages in the first 4 hours of interaction with yeasts P. brasiliensis. We also showed that TLR3-/- mice play a protective role after 30 days of intratracheal infection with P. brasiliensis, showing a decrease in the CFU increase, Th1 and Th17 response profile, as well as an increase in cytotoxic CD8+ cells producing IFN-γ and IL-17. The cytotoxic T CD8+ cells were shown to be essential for the control of infection in TLR3-/- mice, since the depletion of these cells led to the progression of the disease. In the initial stages, 3 and 5 days of infection, we observed increased recruitment of neutrophils to the lung. Recent studies indicate that TLR3 is an important receptor for the immune response in mycosis and its absence favors fungal infection. In contrast, our results show that in the case of PCM, TLR3 is detrimental to the host, suggesting that TLR3 activation may be a possible escape mechanism of P. brasiliensis

Animals , Female , Mice , Paracoccidioidomycosis/prevention & control , Toll-Like Receptor 3/analysis , Paracoccidioides/pathogenicity , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Enzyme Assays/methods , Flow Cytometry/methods
São Paulo; s.n; 2018. 199 p. graf, tab, ilus, mapas.


A paracoccidioidomicose (PCM) é causada por fungos do gênero Paracoccidioides: Paracoccidioides brasiliensis e P. lutzii. A micose apresenta alta endemicidade na América do Sul e aproximadamente 80% dos casos descritos são registrados no Brasil. P. lutzii, tem sido apontado como agente causal da PCM, especialmente nas regiões Centro-Oeste e Norte, entretanto, alguns grupos têm relatado, a ausência de reatividade sorológica dos pacientes frente ao antígeno de referência de P. brasiliensis, conhecida por apresentar em sua composição a molécula de 43 kDa. Este estudo tem como principal objetivo estabelecer um protocolo para a produção de antígenos de P. lutzii que possam ser utilizados como referência em ensaios sorológicos para esta espécie. As preparações antigênicas foram obtidas a partir de três isolados (01, 66 e 8334), cultivados à 37ºC, empregando-se dois meios de cultura distintos, ágar Fava-Netto modificado e ágar Sabouraud-dextrose, segundo os protocolos descritos por Freitas (2005) e Assis et al. (1989), sendo que um terceiro protocolo foi proposto durante o desenvolvimento deste projeto. Os antígenos foram obtidos após cinco (5), 10 e 20 dias de cultivo e foram avaliados in natura, 10 e 20 vezes concentrados por liofilização. Considerando-se os diferentes pontos avaliados, este projeto gerou a produção de 90 preparações antigênicas. O screening das preparações antigênicas com potencial aplicabilidade no imunodiagnóstico da PCM causada por P. lutzii, permitiu a seleção de seis antígenos: quatro produzidos a partir do protocolo descrito por Freitas (2005), sendo três obtidos em ágar Fava-Netto modificado e um em ágar Sabouraud-dextrose e dois obtidos segundo o protocolo proposto durante o desenvolvimento deste projeto, ambos obtidos em Fava-Netto modificado. Verificou-se que todas as seis preparações antigênicas, apresentaram reatividade cruzada frente a soros de pacientes com PCM confirmada e residentes em região não endêmica para P. lutzii, bem como para soros de pacientes com PCM confirmada ou com suspeita clínica da micose, residentes em regiões endêmicas para P. lutzii. Observou-se que o uso do immunoblotting melhorou a sensibilidade do diagnóstico da PCM, porém, reafirmou a ocorrência de reatividade cruzada entre as espécies de Paracoccidioides sp, já que diversas amostras de soro reconheceram tanto os marcadores sorológicos da infecção por P. brasiliensis (gp43 e gp70), assim como diversas frações de P. lutzii, com destaque a fração de 60 kDa. A comparação do perfil eletroforético, por SDS-PAGE, confirmou o compartilhamento de componentes antigênicos entre ambas as espécies de Paracoccidioides, justificando assim, a ocorrência de reatividade cruzada. Diante destes resultados, conclui-se que não é possível discriminar, sorologicamente PCM causada por P. brasiliensis daquela causada por P. lutzii. (AU)

Paracoccidioidomycosis (PCM) is caused by fungi of the genus Paracoccidioides: Paracoccidioides brasiliensis and P. lutzii. Mycosis has high endemicity in South America and approximately 80% of the described cases are registered in Brazil. P. lutzii, has been reported as a causative agent of PCM, especially in the Midwest and North regions. However, some groups have reported the absence of serological reactivity of the patients against the reference antigen of P. brasiliensis, known to present in its composition to the 43 kDa molecule. This study has as main objective to establish a protocol for the production of P. lutzii antigens that can be used as reference in serological tests for this species. The antigenic preparations were obtained from three isolates (01, 66 and 8334) grown at 37ºC using two different culture media, modified Fava-Netto agar and Sabouraud-dextrose agar, according to the protocols described by Freitas (2005 ) and Assis et al. (1989), and a third protocol was proposed during the development of this project. Antigens were obtained after five (5), 10 and 20 days of culture and were evaluated in natura, 10 and 20 times concentrated by lyophilization. Considering the different evaluated points, this project generated the production of 90 antigenic preparations. The screening of the antigenic preparations with potential applicability in the PCM immunodiagnosis caused by P. lutzii allowed the selection of six antigens: four produced from the protocol described by Freitas (2005), three being obtained on modified FavaNetto agar and one on Sabouraud-dextrose agar and two obtained according to the proposed protocol during the development of this project, both obtained in modified Fava-Netto. All six antigenic preparations were cross reactive to sera from patients with confirmed PCM and resident in a region not endemic to P. lutzii, as well as to sera from patients with confirmed PCM or with clinical suspicion of mycosis residing in endemic regions for P. lutzii. It was observed that the use of immunoblotting improved the sensitivity of the PCM diagnosis, but reaffirmed the occurrence of cross reactivity among the species of Paracoccidioides sp, since several serum samples recognized both the serological markers of infection by P. brasiliensis (gp43 and gp70), as well as several fractions of P. lutzii, with emphasis on the fraction of 60 kDa. The comparison of the electrophoretic profile, by SDS-PAGE, confirmed the sharing of antigenic components between both species of Paracoccidioides, thus justifying the occurrence of cross-reactivity. In view of these results, we conclude that it is not possible to discriminate serologically PCM caused by P. brasiliensis from that caused by P. lutzii.(AU)

Immunologic Tests , Antigens , Paracoccidioides , Paracoccidioidomycosis , Serologic Tests