Spontaneous regression of pulmonary paracoccidioidomycosis

The Fusarium and Myrothecium mycotoxins roridin A, diacetoxyscirpenol, verrucarin A, T-2 toxin and zearalenone (10(-2) and 10(-3) mg/ml) inhibit the unspecific dehydrogenase activity of baker's yeast (Saccharomyces cerevisiae) in vivo. The action of these toxins is in the same order as that of aflatoxin B1. It is suggested that at least the trichothecenes decrease the dehydrogenase activity by an interaction with thiol groups of the active center of the enzymes.     

The gamut of progressive pulmonary paracoccidioidomycosis

Paracoccidioidomycosis is an important Latin American endemy. The lung is the portal of entrance of the infection and the lesions are confined to this organ in, at least, 30 per cent of the progressive cases. Twelve case histories of patients with the progressive pulmonary form are presented in order to illustrate the repetitious clinical manifestations but the large variety of radiological presentations. The mycologic diagnosis is also emphasized.Pesquisador I-B do CNPqBolsista do CNPq     

Sputum cytology in the diagnosis of pulmonary paracoccidioidomycosis

The presence of Paracoccidioides brasiliensis was determined in sputum samples from 50 patients with paracoccidioidomycosis using four different techniques: (a) cell-block preparations stained with silver methenamine, (b) direct microbiologie examination, (c) smears stained with Shorr, and (d) smears stained with silver methenamine. Overall, cell-block preparations and smears stained with silver methenamine proved to be the most sensitive techniques, followed by smears stained with Shorr and direct microbiologic examination in decreasing order of sensitivity. Sputum cytology tended to be less positive in patients with interstitial pulmonary lesions as determined by chest X-ray than in patients with alveolar lesions. In addition to its high sensitivity, cell-block preparation technique allows storage of blocks and slides for further studies.     

Bronchoalveolar lavage findings in pulmonary paracoccidioidomycosis

Bronchoalveolar fluid cytology from six progressive pulmonary paracoccidioidomycotic patients showed an alveolitis of neutrophilic pattern which was independent of the of the duration of the chronic fungal disease. The percentage of neutrophils in paracoccidioidomycotic alveolitis was higher than in other neutrophilic alveolitis conditions.     

Fine needle aspiration in the diagnosis of pulmonary paracoccidioidomycosis

Six cases of pulmonary paracoccidioidomycosis diagnosed only by transthoracic fine needle aspiration are presented. The clinical and radiological presentation is varied. The most frequent use of this technique will permit the diagnosis of early lesions of mycosis. This revised version was published online in June 2006 with corrections to the Cover Date.     

Acute pulmonary paracoccidioidomycosis in an immunosuppressed patient

A case of an acute pulmonary paracoccidioidomycosis following the use of immunosuppressive therapy in a solid cancer patient is reported.Pesquisador IB do CNPq.     

The primary pulmonary lymph node complex in paracoccidioidomycosis

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

Flow-cytometric analysis of cytokine production in human paracoccidioidomycosis

Human infection with Paracoccidioides brasiliensis may result in three major outcomes: paracoccidioidomycosis-infection (PI), which is observed in healthy carriers living in endemic areas and the adult form (AF) and juvenile form (JF) of the disease. In this study we proposed to examine the intracellular expression of IFN-gamma, TNF-alpha, IL-2, IL-10, IL-12, CXCL8, CXCL9 and CXCL10 by peripheral blood mononuclear cells (PBMC) of patients with the JF and AF of the disease, as well as of PI individuals stimulated with PMA plus ionomycin, LPS or anti-CD3 plus anti-CD28, by flow cytometry. The results showed that PI individuals present a higher percentage of cells producing IFN-gamma, TNF-alpha, IL-2, CXCL9 and CXCL10 when compared to AF and JF patients. IFN-gamma was predominantly detected in CD3(+)CD8(+) T cells, whereas IL-2 and TNF-alpha were mainly expressed in CD3(+)CD4(+) cells. Monocytes of PI individuals also presented higher expression of CD80 and lower expression of CD86 when compared to JF and AF patients, and higher expression of HLA-DR, only when compared to JF patients. These results indicate that the differential production of cytokines and chemokines, as well as the expression of co-stimulatory molecules involved in antigen presentation, may influence the outcome of PCM infection.     

Pseudotumoral presentation of chronic pulmonary paracoccidioidomycosis: Report of a case

A case of unilateral paracoccidioidal pulmonary lesion simulating a neoplasm is reported.This case was presented on the XVII World Congress on Diseases of the Chest, Amsterdam, The Netherland, June 1993.     

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.     

Comparative genomic analysis of human fungal pathogens causing paracoccidioidomycosis

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 species of Onygenales to transfer from soil to animal hosts.     

Model of in vitro granulomatous hypersensitivity in human paracoccidioidomycosis

With the purpose of studying the immunological components of granulomatous hypersensitivity in patients infecteded with Paracoccidioides brasiliensis, we used the model of in vitro granuloma formation developed for schistosomiasis studies, that correlates with in vivo granulomatous reactivity occurring around eggs trapped in organs of infected donors. In this case, granuloma formation can be determined examining cellular reactivity manifested as multiple cell layers surrounding antigen-conjugated polyacrilamide beads. Our results showed that peripheral blood mononuclear cells (PBMC) obtained from acute treated and chronic paracoccidioidomycosis patients proliferate and generate in vitro granulomas in response to P. brasiliensis antigens (PbAg). In contrast, no proliferation or granuloma formation were observed when PBMC from acute non-treated patients were used. These studies demonstrate the feasibility of investigating granulomatous hypersensitivity in P. brasiliensis-infected patients by using an in vitro granuloma model. This revised version was published online in June 2006 with corrections to the Cover Date.     

Proteomic analysis of serum samples of paracoccidioidomycosis patients with severe pulmonary sequel

BackgroundPulmonary sequelae (PS) in patients with chronic paracoccidioidomycosis (PCM) typically include pulmonary fibrosis and emphysema. Knowledge of the molecular pathways involved in PS of PCM is required for treatment and biomarker identification.Methodology/Principal findingsThis non-concurrent cohort study included 29 patients with pulmonary PCM that were followed before and after treatment. From this group, 17 patients evolved to mild/ moderate PS and 12 evolved severe PS. Sera from patients were evaluated before treatment and at clinical cure, serological cure, and apparent cure. A nanoACQUITY UPLC-Xevo QT MS system and PLGS software were used to identify serum differentially expressed proteins, data are available via ProteomeXchange with identifier PXD026906. Serum differentially expressed proteins were then categorized using Cytoscape software and the Reactome pathway database. Seventy-two differentially expressed serum proteins were identified in patients with severe PS compared with patients with mild/moderate PS. Most proteins altered in severe PS were involved in wound healing, inflammatory response, and oxygen transport pathways. Before treatment and at clinical cure, signaling proteins participating in wound healing, complement cascade, cholesterol transport and retinoid metabolism pathways were downregulated in patients with severe PS, whereas signaling proteins in gluconeogenesis and gas exchange pathways were upregulated. At serological cure, the pattern of protein expression reversed. At apparent cure pathways related with tissue repair (fibrosis) became downregulated, and pathway related oxygen transport became upregulated. Additionally, we identified 15 proteins as candidate biomarkers for severe PS.Conclusions/SignificanceDevelopment of severe PS is related to increased expression of proteins involved in glycolytic pathway and oxygen exchange), indicative of the greater cellular activity and replication associated with early dysregulation of wound healing and aberrant tissue repair. Our findings provide new targets to study mechanisms of PS in PCM, as well as potential biomarkers.     

Palpebral paracoccidioidomycosis

This paper describes two cases of eyelid paracoccidioidomycosis (South American blastomycosis) in which it was the first signal of the disease. In both cases the first clinical diagnosis made was not a fungal infection, but a neoplastic disease that was not confirmed by the pathology study. In the first patient we suspected a primary infection on the eyelid, because there was no other systemic signs of the disease, and in the second patient we noted a very advanced pulmonary lesions caused by the Paracoccidioides brasiliensis. We believe that, in endemic areas, the histopathological study should be made before every excisional procedures to avoid unnecessary palpebral mutilation. This revised version was published online in June 2006 with corrections to the Cover Date.     

Histopathologic and immunologic effects of the itraconazole treatment in a murine model of chronic pulmonary paracoccidioidomycosis

A comparative study, based on histopathologic findings (inflammation, cellularity, and fibrosis) and immunologic parameters (pro-inflammatory and anti-inflammatory cytokines), was carried out in order to evaluate the effects of itraconazole (ITC) treatment and its starting time in a BALB/c murine model of chronic pulmonary paracoccidioidomycosis (PCM), induced by intranasal inoculation of Paracoccidioides brasiliensis (Pb) conidia. Two different groups of mice were exposed to ITC therapy beginning at the 4th or 8th week after Pb infection, respectively. ITC was administered daily, via gavage, for a period of sixty days. At weeks 0, 4, 8, 12 and 16 the animals were sacrificed and their lungs removed for histology staining with hematoxylin and eosin (H&E), Masson’s trichromic and Gomori–Grocott; pulmonary levels of IL-1β, TNF-α, IFN-γ, IL-13 and TGF-β were also measured by ELISA. The development or absence of the principal pulmonary PCM sequela, lung fibrosis, was directly related to the therapy’s starting time. This and other histopathologic findings were related to the behavior of cytokine levels.     

Serology of paracoccidioidomycosis

The purposes of the present work were: i) to study the positivity indices and compare titers obtained with the indirect immunofluorescence (II), tube precipitation (TP), complement fixation (CF) and double immunodiffusion on agar gel (ID) tests in the sera of 196 patients with paracoccidioidomycosis before treatment, and ii) to compare the initial titers of II with those obtained 1 year or more after treatment. II was the most sensitive serologic reaction (85.2%), and the positivity indices for CF, ID and TP were 67.7%, 66.0% and 50.0%, respectively. The sera tended to show parallel mean titers in II, CF and TP tests. One year after treatment there was a fall in titers of II in 66.2% of patients. The data, taken as a whole, demonstrate the usefulness of the indirect immunofluorescent test and the importance of using 2 or more serologic tests for the diagnosis and monitoring of patients with paracoccidioidomycosis.     

Serology of paracoccidioidomycosis

This review provides the background for understanding the role of a battery of diagnostic methods in paracoccidioidomycosis (PCM). This systemic mycosis is a disease endemic in many regions of Latin America, with sporadic cases also occurring throughout the world (mycosis of importation). Although excellent laboratory methods for diagnosis are available, there are deficiencies that must be met by continued research. Understanding the uses and limitations of a battery of laboratory methods is essential to diagnose PCM. Clinicians and laboratory directors must be familiar with the uses and limitations of a battery of serologic and mycological tests to accurately diagnose of PCM. Antibody and antigen detections are valuable adjuncts to histopathology and culture. More recently, the gp43 and gp70 antigen detection assay have improved the methodology of diagnosis of this mycosis, which improves reproducibility and facilitates monitoring antigen clearance during antifungal treatment. Furthermore, detection of antigen in cerebrospinal fluid and in bronchoalveolar lavage fluid increases the sensitivity for diagnosis of PCM in central nervous system and in pulmonary infections, respectively.