Paracoccidioidomycosis Marcio Nucci, MD, Arnaldo L. Colombo, MD, and Flavio Queiroz-Telles, MD Corresponding author Marcio Nucci, MD University Hospital, Federal University of Rio de Janeiro, Rua Professor Rodolpho Paulo Rocco, 255 Sala 4A 12, Rio de Janeiro, 21941-913 Brazil. E-mail: mnucci@hucff.ufrj.br Current Fungal Infection Reports 2009, 3: 15–20 Current Medicine Group LLC ISSN 1936-3761 Copyright © 2009 by Current Medicine Group LLC Paracoccidioidomycosis is the most frequent endemic mycosis in South America. The infection is more preva- lent in rural workers, and recent epidemiologic data suggest that changes in agricultural practices (such as a decrease in coffee plantations and an increase in sugar cane plantations) may result in a reduction in the incidence of infection. After being inhaled, Paracoccidi- oides brasiliensis usually causes a benign and transient pulmonary infection that may progress to an acute form or, more frequently, reactivate later as a chronic disease. The diagnosis is usually made by direct exami- nation and culture of clinical specimens; serologic tests may be of help, especially antigen detection. The drug of choice for the chronic form is oral itraconazole, whereas patients with more severe forms may be treated with intravenous amphotericin B or sulfamethoxazole- trimethoprim. The newer azole voriconazole is also effective, and it may be a good alternative because it can be given by oral or intravenous route. Introduction Paracoccidioidomycosis (PCM) is a systemic endemic mycotic disease caused by Paracoccidioides brasiliensis, a thermo-dimorphic fungus with geographic distribution limited to Latin America. The majority of cases have been reported in Brazil, followed by Colombia, Venezuela, and Argentina, and it is considered to be the most important systemic endemic mycosis in South America [1••,2]. So far, no cases have been reported in Chile, Nicaragua, or the Antilles. Imported cases were observed in countries outside Latin America, all represented by infected indi- viduals who had previously lived in an endemic area [3–6]. Therefore, PCM may be also regarded as a disease of travelers who have lived in endemic areas. Reporting the fungal disease to the health authorities is not required in Latin American countries. Consequently, there are few data on the incidence of PCM in endemic areas. Data generated by intradermal sensitivity surveys with paracoccidioidin suggest that the prevalence rate of P. brasil- iensis infection in endemic areas may be as high as 50% to 75% in the adult population [7]. It has been estimated that almost 10 million people may be infected. In terms of mor- tality, based on data obtained from the Brazilian Ministry of Health’s Mortality Information System [8,9], a total of 3181 PCM deaths were reported in Brazil between 1980 and 1995, corresponding to a mortality rate of 1.45 deaths per 1 million inhabitants. PCM is predominantly found among male workers in rural areas who are 30 to 50 years of age. As in other systemic fungal infections, any organ in the body can be affected. After being inhaled, P. brasiliensis usually causes a benign and transient pulmonary infection that may progress to the acute form of the disease or, more frequently, reactivate later as a chronic disease [10••]. In the 100 years since the original description of PCM, there have been several substantial advances in under- standing the biology of the fungal pathogen, mechanisms of infection of P. brasiliensis, and host response. More sensitive and speci ic diagnostic tools were developed, but unfortunately they were not incorporated into the routine of most public medical centers because of the cost issues and lack of people trained in medical mycology [11]. Epidemiology and Pathogenesis According to recent molecular data, P. brasiliensis is taxonomically related to the family Onygenacea (order Ony- genales, Ascomycota), which is the same common group of most of the agents of endemic systemic mycoses (Blastomy- ces dermatitidis, Coccidioides immitis and C. posadasii, and Histoplasma capsulatum). These agents are biologically related to a fungal group that phylogenetically evolved in association with mammalian hosts [12•]. Recently, molecular tools have been extensively used to revise the taxonomy of human fungal pathogens. The use of different molecular methods showed that P. brasiliensis is not a single species but is a species complex that includes at least three cryptic species: PS1, present in Brazil, Argen- tina, Paraguay, Peru and Venezuela; PS2, present in Brazil