Blood groups and HLA antigens in paracoccidioidomycosis

The frequencies of blood groups, Rh and HLA antigens were studied in a series of patients with paracoccidioidomycosis as well as in control subjects. Statistical analysis of the results showed that only 2 antigens (HLA-A9 and HLA-B13) had a significantly increased frequency among patients with paracoccidioidomycosis compared with healthy controls. Among patients with paracoccidioidomycosis antigen HLA-A9 was significantly more prevalent in progressive pulmonary forms of the disease than in patients with extra pulmonary involvement. These observations suggest that HLA-A9 may influence susceptibility to the mycosis as well as its course.     

Neoplasia and paracoccidioidomycosis

Published studies on the association between cancer and paracoccidioidomycosis consist either isolated cases or clinical data based on hospital cohorts of paracoccidioidomycosis. The frequency of neoplasia in series of ≥80 patients with paracoccidioidomycosis ranges from 0.16 to 14.1%, mean of 3.96%. There are only two retrospective controlled studies, one of them showing greater incidence of carcinoma in biopsy and necropsy samples of paracoccidioidomycosis (12 cases in 147 patients with the mycosis: 8.2%) than in the necropsies of the control group (320 cases in 7,302 necropsies: 4.9%). In the other, 22,409 autopsies were reviewed and 4,372 cases of cancer were found; of the 85 patients with paracoccidioidomycosis, 12 were diagnosed with cancer. No differences were observed in the frequency of malignancies between the group of patients with paracoccidioidomycosis (14.1%) and the control group (19.5%). Considering all the reported cases, carcinoma was more frequent than hematological malignancies, and was more often found at the same site or in a neighboring site affected by the mycosis, usually occurring after the diagnosis of the mycosis. Commonly, the basic cause of death was related to secondary infections or neoplasia. Lymphoma was associated with poorly organized rich in fungi granuloma. The clinical course and mortality were related to the cancer evolution or secondary infections and was worse in lymphoid series, metastatic carcinoma or in patients under cytotoxic chemotherapy. Additionally, as in several cases the clinical and histopathological data may mimick neoplasia, the correct diagnosis of both diseases is essential to guarantee an early and safe intervention.     

Chronic pulmonary paracoccidioidomycosis in the state of Rio Grande do Sul,Brazil

Since 1942, when paracoccidioidomycosis was first identified in the state of Rio Grande do Sul, paracoccidioidal pulmonary lesions became a great concern to physicians. The present study focuses on 53 patients diagnosed over a seven-year period who presented paracoccidioidal lesions circumscribed to the lungs. These patients presented clinical and radiological features that simulated several pulmonary infectious and non-infectious conditions. Four unusual cases are briefly discussed. A sequence of laboratorial tests should be established for the diagnosis of pulmonary paracoccidioidomycosis. This revised version was published online in June 2006 with corrections to the Cover Date.     

Revisiting Langerhans cells in paracoccidioidomycosis: expression of CD207/langerin in human cutaneous and mucosal lesions

Langerhans cells are identified by the expression of langerin. We detected this molecule in cutaneous and mucosal lesions in paracoccidioidomycosis, an important infection in Latin America. Langerin+ cells were scarcely distributed, with short dendrites in epidermis and epithelium and were frequent in the dermis and corium, in the inflammatory infiltrate and granulomas. Mucosal lesions presented a higher expression of langerin in lesions with loose granulomas. For the first time we presented the expression of langerin in paracoccidioidomycosis. Positive cells in dermis and corium could represent migrating Langerhans cells or a new subset of langerin+ cells with a role in paracoccidioidomycosis.     

Evaluation of DNA polymorphisms amplified by arbitrary primers (RAPD) as genetically associated elements to differentiate virulent and non-virulent Paracoccidioides brasiliensis isolates

Randomly amplified polymorphic DNA (RAPD) analysis of 35 Paracoccidioides brasiliensis isolates was carried out to evaluate the correlation of RAPD profiles with the virulence degree or the type of the clinical manifestations of human paracoccidioidomycosis. The dendrogram presented two main groups sharing 64% genetic similarity. Group A included two isolates from patients with chronic paracoccidioidomycosis; group B comprised the following isolates showing 65% similarity: two non-virulent, six attenuated, five virulent, eight from patients with chronic paracoccidioidomycosis and two from patients with acute paracoccidioidomycosis. The virulent Pb18 isolate and six attenuated or non-virulent samples derived from it were genetically indistinguishable (100% of similarity). Thus, in our study, RAPD patterns could not discriminate among 35 P. brasiliensis isolates according to their differences either in the degree of virulence or in the type of the clinical manifestation of this fungal infection.     

Animal Models and Antifungal Agents in Paracoccidioidomycosis: An Overview

Paracoccidioides brasiliensis is the etiologic agent of paracoccidioidomycosis, the most prevalent systemic mycosis in Latin America. The morbidity and mortality associated with paracoccidioidomycosis necessitate our understanding of fungal pathogenesis and discovering of new agents to treat this infection. Animal models have contributed much to the knowledge of fungal infections and their corresponding therapeutic treatments. This is true for animal models of the primary fungal pathogens such as P. brasiliensis. This review describes the development, details and utility of animal models of paracoccidioidomycosis for studying and developing the current antifungal agents used for therapy of this fungal disease and novel agents with antifungal properties against P. brasiliensis.     

Paracoccidioidomycosis in a Woman with Idiopathic Hirsutism

Paracoccidioidomycosis, especially the chronic pulmonary form of the disease, is not commonly described in females. Data from in vitro and vivo studies support the hypothesis that estrogens might influence the pathogenesis of paracoccidioidomycosis in humans by inhibition of transition of conidia or mycelia to yeast form of Paracoccidioides brasiliensis. The authors describe a chronic progressive pulmonary form of paracoccidioidomycosis in a woman with idiopathic hirsutism. In addition to estrogens, the present report suggests that other hormonal factors might play an important role in the pathogenesis of paracoccidioidomycosis, including the increased production of 5alpha-dehydrotestosterone frequently described in individuals with idiopathic hirsutism.     

Oral exfoliative cytology in the diagnosis of paracoccidioidomycosis

OBJECTIVE: To assess the efficacy of conventional oral exfoliative cytology as a diagnostic tool in paracoccidioidomycosis. STUDY DESIGN: Cytologic smears and incisional biopsies were obtained from 10 patients with a clinical suspicion and oral manifestations of paracoccidioidomycosis. Cytologic smears and sections of the incisional biopsy underwent methenamine silver staining for fungi according to the Gomori-Grocott method. The dry glass slides were examined at 400 or 1,000 x magnification, and the presence and shape of yeasts of Paracoccidioides brasiliensis were investigated. RESULTS: Yeasts of the fungus P brasiliensis were clearly identified in cytologic smears and sections from incisional biopsies in all cases analyzed (100.0%). CONCLUSION: Cytology of oral samples proved an effective diagnostic method for the detection of paracoccidioidomycosis in humans.     

Paracoccidioidomicosis en pediatría: descripción de 4 casos

BackgroundParacoccidioidomycosis is the most frequent systemic mycosis in Latin America, caused by the dimorphic fungus Paracoccidioides. Paracoccidioidomycosis in children is uncommon. Our aim is to describe clinical features of patients who had a confirmed diagnosis of paracoccidioidomycosis in our hospital in the last 10 years.Case reportsWe describe 4 cases of paracoccidioidomycosis in previously healthy children from the north of our country. Diagnoses were made by biopsy or culture.ConclusionsThe diagnosis of paracoccidioidomycosis should be considered in a patient coming from regions where Paracoccidioides is endemic, and presenting with a lymphoproliferative syndrome, anemia, eosinophilia and hypergammaglobulinemia.     

Enzyme-linked immunosorbent assay (ELISA) in the paracoccidioidomycosis

An enzyme-linked immunosorbent assay (ELISA) for detection and quantification of antibodies antiParacoccidioides brasiliensis is described. Polystyrene plates have been used as solid phase to absorb P. brasiliensis metabolic yeast phase antigen. Twenty sera of proven paracoccidioidomycosis, 11 of histoplasmosis due Histoplasma capsulatum, 20 of aspergillosis and 20 human normal sera were tested. Ninety-five percent of the paracoccidioidomycosis sera had O.D. superior to 0.150 (from 0.163 to 2.650) at 1/400 serum dilution. ELISA assay was compared with counterimmunoelectrophoresis and erythro-immunoassay tests; a correlation was observed only with erythro-immunoassay. ELISA test should give new perspectives for the serodiagnosis of paracoccidioidomycosis.     

Lymphoabdominal paracoccidioidomycosis simulating primary neoplasia of the biliary tract

The lymphoabdominal involvement in the sub-acute form of paracoccidioidomycosis shows a wide variety of clinical manifestations, ranging from fever and lymph node enlargement to infiltration of all abdominal organs, which can lead to a situation of abdominal surgical emergency. This case report presents paracoccidioidomycosis mimicking carcinoma of the biliary tract, The purpose of this paper is to call the general physician’s attention for this important differential diagnosis of abdominal masses. Although paracoccidioidomycosis is rarely encountered in the United States and Europe, it should be considered in patients who are suspected of having a fungal infection and have had previous exposure in an endemic area for this disease.*Fábio Luis Silva do Prado and Renata Prado contributed equally to this work.     

Leukocyte immunophenotypes in bronchoalveolar lavage fluid and peripheral blood of paracoccidioidomycosis, sarcoidosis and silicosis.

Leukocyte subsets in bronchoalveolar lavage (BAL) fluid and peripheral blood of patients with paraccoccidioidomycosis, sarcoidosis and silicosis were characterized using monoclonal antibodies and an immunoperoxidase technique. In paraccocidioidomycosis, the number of T-helper/inducer CD4-positive lymphocytes was lower in peripheral blood than in BAL fluid. Additional analysis showed that the expression of HLA-DR was very similar in alveolar macrophages, lung and blood T-cells. In sarcoidosis and silicosis there were higher proportions of T-helper/inducer cells in peripheral blood than in BAL fluid. The alterations in the T-helper/inducer/T-suppressor/cytoxic CD4/CD8 ratio in sarcoidosis and silicosis were more appreciable in peripheral blood than in BAL fluid, contrasting with the results in paracoccidioidomycosis. The expression of HLA-DR by alveolar macrophages in sarcoidosis was the highest of all the disease studied. No statistically significant differences were observed between chronic multifocal and chronic unifocal paracoccidioidomycosis disease, stage II and stage III sarcoidosis, and chronic and accelerated silicosis. The three granulomatous diseases analyzed had a few alveolar macrophages expressing the CD4 molecule on their surface. These findings and the technique of analyzing both peripheral blood and BAL leukocyte subsets may help to understand the pathogenesis of interstitial lung diseases.     

Immunohistochemical Cross-Reactivity Between <Emphasis Type="Italic">Paracoccidioides</Emphasis> sp. from Dolphins and <Emphasis Type="Italic">Histoplasma capsulatum</Emphasis>

Paracoccidioidomycosis ceti is a cutaneous disease of cetaceans caused by uncultivated Paracoccidioides brasiliensis or Paracoccidioides spp. Serological cross-reactions between paracoccidioidomycosis ceti and paracoccidioidomycosis, paracoccidioidomycosis and histoplasmosis, and paracoccidioidomycosis and coccidioidomycosis have been reported before. The present study aimed to detect immunohistochemical cross-reaction between antibodies to Paracoccidioides sp. and Histoplasma capsulatum, and vice versa. Thirty murine sera, obtained from experimental infections of 6 isolates of H. capsulatum, were reacted with paraffin-embedded yeast-form cells of Paracoccidioides sp. derived from a case of paracoccidioidomycosis ceti in Japan. The murine sera were also reacted with human isolates of H. capsulatum yeast cells, with P. brasiliensis yeast cells, and with fungal cells of Coccidioides posadasii. Three dolphins’ sera from cases of paracoccidioidomycosis ceti, two human sera from patients with paracoccidioidomycosis, and a serum from a healthy person with a history of coccidioidomycosis were used in order to determine that the tested fungal cells reacted properly. Sera derived from mice infected with an isolate of H. capsulatum reacted positively against yeast cells of Paracoccidioides sp., yeast cells of P. brasiliensis, and fungal cells of C. posadasii, while those derived from other strains were negative. The present study recorded for the first time the cross-reaction between the yeast cells of H. capsulatum and antibodies against Paracoccidioides spp., the yeast cells of Paracoccidioides sp. and antibodies against H. capsulatum, the yeast cells of Paracoccidioides sp. and antibodies against Coccidioides sp., and fungal cells of C. posadasii and antibodies against Paracoccidioides spp.     

Toll-like receptors and fungal infections: the role of TLR2, TLR4 and MyD88 in paracoccidioidomycosis

The aim of this minireview is to present a concise view of the most important pattern recognition receptors used by the innate immune system to sense and control pathogen growth into host tissues. A brief review of the role of Toll-like receptors (TLRs) in fungal infections followed by some recent results on the function of TLR4, TLR2 and the MyD88 adaptor molecule in the pathogenesis of paracoccidioidomycosis are presented.     

Paracoccidioidal infection in the wife of a patient with paracoccidioidomycosis.

Three agar immunoprecipitin techniques (double immunodiffusion, immunoelectrophoresis and immunoelectroosmophoresis-immunodiffusion) made with paracoccidioidin and serum of a paracoccidioidomycosis patient's wife, permitted us to observe a specific band in 6 successive samples of blood taken from the wife over a period of 21 months. The case represents an example of a subclinical paracoccidioidomycosis infection that is usually diagnosed in its disseminated, progressive form. Three possible sources of infection are discussed. But an interhuman contagion appears to be the most feasible.     

Specific double diffusion microtechnique for the diagnosis of aspergillosis and paracoccidioidomycosis using monospecific antisera.

Using experimental reference sera against species-specific antigens of Aspergillus fumigatus and Paracoccidioides brasiliensis in a microdouble diffusion technique, a simple and specific test for the immunodiagnosis of aspergillosis and paracoccidioidomycosis has been developed. Only sera that produced lines of identity with either one of the bands formed by the anti-C2 or the anti-E2 reference sera were considered positive for aspergillosis or paracoccidioidomycosis, respectively. The sensitivity of the diagnostic test was similar to those of the classical double diffusion and the immunoelectrophoresis test. No false positives were found in sera obtained from patients affected by other mycoses, nor from healthy controls. The amount of reagents for the specific test was ten fold less than that required by the classical double diffusion test.     

Production and standardization of Paracoccidioides brasiliensis, Histoplasma capsulatum and Aspergillus fumigatus antigens to be used in immunodiagnosis. Comparison between immunodiffusion and immunoelectrophoresis

Soluble antigens (Ag) from Paracoccidioides brasiliensis, Histoplasma capsulatum and Aspergillus fumigatus were prepared and standardized by double immunodiffusion (DID) and immunoelectroosmophoresis (IEOP). No difference in sensitivity was observed between the two techniques; 100% of standard patient sera were positive with P. brasiliensis and A. fumigatus Ag and 83.3% were positive with H. capsulatum Ag. The specificity of the tests was verified testing 96 sera from patients with paracoccidioidomycosis, histoplasmosis, systemic candidiasis, sporotrichosis, tuberculosis, lung cancer, visceral or cutaneous leishmaniasis and 18 sera from healthy individuals. All the three antigens were 100% specific with the DID (using the identification pattern indicated by the confluence of test serum with standard serum precipitin lines as a positive criterium). However in the IEOP, the specificity varied with each Ag. Positive reactions with P. brasiliensis Ag were observed in 16.7% of histoplasmosis sera and in 10% of cutaneous leishmaniasis sera. On the other hand 31.8% of paracoccidioidomycosis and 10% of cutaneous leishmaniasis sera reacted with H. capsulatum Ag. The high sensitivity and specificity of the DID test, its easy reproducibility and low cost, led us to consider it highly appropriate as a routine procedure for the screening of patients with respiratory infections.     

Chronic Paracoccidioidomycosis of the Intestine as Single Organ Involvement Points to an Alternative Pathogenesis of the Mycosis

Current knowledge on the natural history of paracoccidioidomycosis states that the chronic form of the disease results from reactivation of quiescent foci established years or decades before during the primary lung infection. Once reactivated, the fungi can disseminate to virtually any organ or system. We present herein two chronic paracoccidioidomycosis patients with a single organ involvement that points to an alternative pathogenesis of the mycosis. These patients suggest that the chronic form may also arise from reactivation of foci not confined to the lungs, due to the early dissemination of yeast cells during the primary infection.     

The primary pulmonary lymph node complex in paracoccidioidomycosis

A case of primary pulmonary lymph node complex in paracoccidioidomycosis is reported.     

Production of pro- and anti-inflammatory cytokines by monocytes from patients with paracoccidioidomycosis

Monocytes and macrophages can produce a large repertoire of cytokines and participate in the pathogenesis of granulomatous diseases. We investigated the production of pro- and anti-inflammatory cytokines by monocytes from patients with active paracoccidioidomycosis. Peripheral blood monocytes from 37 patients and 29 healthy controls were cultivated with or without 10 microg/ml of lipopolysaccharide (LPS) for 18 h at 37 degrees C, and the cytokine levels were determined in the culture supernatants by enzyme immunoassay. The results showed that the endogenous levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8, IL-10 and transforming growth factor beta detected in the supernatant of patient monocytes cultivated without stimulus were significantly higher than those produced by healthy controls. These data demonstrated that monocytes from patients with active paracoccidioidomycosis produce high levels of cytokines with both inflammatory and anti-inflammatory activities. However, patient monocytes produced significantly lower TNF-alpha and IL-6 levels in response to LPS when compared to normal subjects, suggesting an impairment in their capacity to produce these cytokines after LPS stimulation. Concentrations of IL-1beta, IL-8 and IL-10 in cultures stimulated with LPS were higher in patients than in controls. These results suggest that an imbalance in the production of pro- and anti-inflammatory cytokines might be associated with the pathogenesis of paracoccidioidomycosis.