Paracoccidioidomycosis

Paracoccidioidomycosis (PCM) is an endemic disease geographically restricted to Latin America, from Mexico to Argentina; Brazil is the country with the highest endemicity. Chile and the Caribbean islands are not affected. No outbreaks have been reported, but recently two clusters have been described. Currently, phylogenetic studies divide the Paracoccidioides genus into five species, namely P. brasiliensis, P. americana, P. restrepiensis, P. venezuelensis, and P. lutzii. These species have a widespread distribution except for the central and northern regions of Brazil which are preferred locations of P. lutzii. They are thermally dimorphic, existing as a mold at temperatures under 28 °C and as a yeast in cultures at 35-37 °C, and in tissues. The yeast reproduces by multiple budding, leading to a shape that resembles a pilot's wheel. The natural habitat of the Paracoccidioides spp. complex has not been defined, although it is suspected to be the soil, preferentially at sites where the environment has a high rainfall index and the soils show optimal permeability, a combination that is associated with high relative humidity and abundance of vegetation and watercourses. Paracoccidioides spp. is capable of entering into prolonged periods of latency, as is demonstrated by those patients diagnosed outside the recognized endemic areas several years after having left the endemic Latin American zones. The mycosis predominates in adult males (13:1), but no such gender difference is observed in children or adolescents. Two types of clinical presentations are recognized, the acute-subacute (juvenile) and the chronic (adult) forms of the disease. A residual, non-mycotic active form characterized by fibrosis is also recognized. The initial stages of the host-fungal interactions are not known, as the habitats of the Paracoccidioides complex remain undefined; experimental animal models have shown that inhaled conidia settle in the lungs and convert into yeast cells, thereby initiating tissue colonization and dissemination through blood/lymphatic vessels. The classical PCM diagnosis combines clinical evaluation and laboratory techniques, including direct examination, histopathology, culture-based techniques, and immunological and molecular assays. With the advances in characterizing the Paracoccidioides genus, a higher complexity has been added to the standardization of laboratory techniques for diagnosing PCM to the species level. Many efforts are being made and are underway to search for new markers, new epitopes, and new techniques. As for treatment, three different classes of antifungals are currently used to treat this mycosis. They include sulfonamides, the polyene amphotericin B and its lipid formulations, and certain azoles. Azoles, including itraconazole and voriconazole, have emerged as therapeutic options for the control of PCM, with the former being the current agent of choice. Mortality is usually low but the disease persists as an important cause of morbidity and sequels, especially when the diagnosis is delayed.