These observations prompt a modification of the current paradigms of the pathogenesis of malaria and clear the way to investigate the pathophysiology of P. vivax infections.

Abstract. This paper describes the clinical-seroepidemiologic characteristics of patients with paracoccidioidomycosis (PCM) who visited the University Hospital at the State University of Campinas (Campinas, São Paulo, Brazil). The study group consisted of 584 individuals (492 males and 92 females) with ages ranging from 5 to 87 years. The highest incidence of the disease occurred between the ages of 41 and 50 years for men and between 11 and 40 years for women. Rural activities were the principal occupation of 46% of the patients. The diagnosis was confirmed by histopathologic examination and demonstration of fungus in scrapings, secretions, or in the sputum. Serologic test results for PCM were positive in 80% of the 584 patients studied. The significant number of patients, including 33 children less than 14 years old, indicates the presence of the fungus in the area and that this region is an important endemic area for PCM.Paracoccidioidomycosis (PCM) is a systemic mycosis caused by the thermally dimorphic fungus Paracoccidioides brasiliensis. Almost all South and Central American countries have large regions where PCM is endemic, particularly in Brazil, Colombia, Venezuela, and Argentina. The disease has a limited geographic distribution from 23ЊN (southern Mexico) to 34.5ЊS (Argentina and Uruguay).1 The endemic areas have mild temperatures (17-24ЊC), moderate rainfall (900-1,810 mm/year), abundant forests, numerous small rivers, and indigenous trees, and a short winter and rainy summer. 2 This disease typically manifests between the third and sixth decades of life. Two main clinical forms of the disease are recognized by the International Committee for PCM, 3 namely, an acute or subacute form and a unifocal or multifocal chronic form. The acute form affects young patients of both sexes and involves mainly the reticuloendothelial system, whereas the chronic form, is most prevalent in adult males and has a predominant pulmonary and/or mucocutaneous involvement. 4,5 The higher frequency of the disease in men was initially attributed to their more intense exposure to the fungus' habitat (soil) through agricultural work. This disease is less frequent in females once they reach puberty because of the protective role of estrogen. This female hormone inhibits the transition of conidia-mycelial propagules to the yeast form, a critical step in the pathogenesis of the disease. 6,7 Since the reporting of PCM is not compulsory, it is difficult to establish the real prevalence of the disease. However, current data indicate a high incidence in Brazil, particularly in the State of São Paulo and the surrounding southern region, where there are various specialized health centers or hospitals.Patients suspected of having a systemic mycosis are usually sent to general hospitals where they undergo a precise diagnosis and are advised about how to treat the condition. The University Hospital at the State University of Campinas (UH-UNICAMP), which is located in Campinas, a city of approximately 1 million inhabitants in São Paulo Sta...

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Patients with paracoccidioidomycosis (PCM) exhibit a suppression of the cellular immune response characterized by negative delayed-type hypersensitivity (DTH) to Paracoccidioides brasiliensis antigens, the apoptosis of lymphocytes, and high levels of expression of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA-4), interleukin-10 (IL-10), and transforming growth factor ␤ (TGF-␤). The aim of this study was to investigate whether and how regulatory T cells (Treg cells) are involved in this immunosuppression by analyzing the number, phenotype, and activity of these cells in patients with active disease (AD group) and patients who had received treatment (TD group). Our results showed that the AD patients had more Treg cells than the TD patients or controls (C group) and also had elevated levels of expression of regulatory markers (glucocorticoidinduced tumor necrosis factor [TNF] receptor-related protein [GITR], CTLA-4, CD95L, LAP-1, and CD38). An analysis of regulatory activity showed that Treg cells from the AD group had greater activity than did cells from the other groups and that cell-cell contact is mandatory for this activity in the C group but was only partially involved in the regulatory activity of cells from AD patients. The addition of anti-IL-10 and anti-TGF-␤ neutralizing antibodies to the cultures showed that the production of cytokines may be another mechanism used by Treg cells. In conclusion, the elevated numbers of these cells with an increased regulatory phenotype and strong suppressive activity suggest a potential role for them in the immunosuppression characteristic of paracoccidioidomycosis. In addition, our results indicate that while Treg cells act by cell-cell contact, cytokine production also plays an important role.

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