Review 10.1586/14787210.6.2.251 © 2008 Future Drugs Ltd ISSN 1478-7210 251 www.future-drugs.com Treatment options for paracoccidioidomycosis and new strategies investigated Expert Rev. Anti Infect. Ther. 6(2), 251–262 (2008) Luiz R Travassos † , Carlos P Taborda and Arnaldo L Colombo † Author for correspondence Universidade Federal de São Paulo, São Paulo, SP 04023–062, Brazil Tel.: +55 115 084 2991 Fax: +55 115 571 5877 travassos@unifesp.br Paracoccidioidomycosis is the most prevalent systemic endemic mycosis in South America with most reported cases in Brazil. It is a major cause of disability and death among young adult rural workers during their most productive years of life. Sequels are frequent and the evolution of the disease and mortality burden are strongly influenced by the socio–economic status of the patients. Although long periods of antifungal therapy (sulfamethoxazole/trimethoprim, itraconazole and amphotericin B) are used in clinical practice, relapses remain a significant unresolved problem. Early diagnosis is hampered by structural factors, ranging from the high costs of reagents, the lack of trained personnel and limited access to the healthcare system by rural workers. A peptide vaccine aimed at immunotherapy of paracoccidioidomycosis, as an adjuvant to chemotherapy, is being studied. The protective effects obtained in mice intratracheally infected with Paracoccidioides brasiliensis, and the promiscuous binding of the peptide P10 to HLA-DR molecules, suggest that it could be used as a vaccine to reduce the duration of chemotherapy and the risk of relapse. KEYWORDS: ajoene • gene therapy • IFN-γ • immunosuppressed animal • immunotherapy • itraconazole • Paracoccidioides brasiliensis • paracoccidioidomycosis • peptide vaccine • sulfamethoxazole–trimethoprim Epidemiology Paracoccidioidomycosis (PCM), previously known as South American blastomycosis, is an endemic fungal infection caused by the ther- mally dimorphic fungus Paracoccidioides brasil- iensis. The disease was first described in 1908 by Adolpho Lutz in São Paulo, and is the most prevalent systemic fungal infection in Central and South America. The majority of cases are reported in Brazil, followed by Colombia, Ven- ezuela and Argentina. Currently, no single autochthonous case has been reported in Chile, Nicaragua or The Antilles. Imported cases of PCM have been observed in the USA, some European countries and Asia, all of them repre- sented by individuals who had previously vis- ited endemic areas in Latin America. There- fore, PCM may also be regarded as a disease of travelers or those who have lived for extended periods in endemic areas [1,2]. Characterization of the fungus’ habitat has been hindered by the long latency periods of the disease as well as the lack of outbreaks. The reservoir of P. brasiliensis in nature is probably represented by soil and decaying vegetation, where the fungus dwells in the mycelial phase. In addition to humans, it is now well docu- mented that armadillos may also be infected by P. brasiliensis [3,4]. Furthermore, positive para- coccidioidin reactions and/or specific antibody responses to P. brasiliensis have been reported in cattle, horses, sheep, monkeys and dogs [5,6]. The true role of the infected animals in the ecoepidemiology of PCM is still not com- pletely understood. Apparently, these animals may be infected without representing a link in the fungal transmission. Infection may start with conidia entering the respiratory tract and lungs through inhalation [1,2]. The primary pulmonary infection is usually unapparent or oligosymptomatic, and individ- uals may remain infected throughout life with- out ever developing symptoms. A few infected patients may develop a clinical picture of the disease weeks to months after inhalation of the fungal propagules (acute or subacute form). Most symptomatic patients develop the disease years after the acquisition of the infection owing to reactivation of quiescent foci (chronic