Authors

A C Coelho¹;  ¹ Universidade Estadual de Campinas

Discussion

The treatment of cutaneous leishmaniasis in Brazil is based on the use of the parenteral drugs antimony, amphotericin B and pentamidine, which exhibit several undesirable effects. Reports of clinical failure have been described in the last years, particularly in the case of antimony. Recently, the efficacy of miltefosine for the treatment of visceral leishmaniasis has been described and the drug has been mainly used in treatment of visceral and cutaneous leishmaniasis in Asia and in Colombia respectively. In this study, we evaluated in vitro and in vivo miltefosine susceptibility of clinical isolates of the main species responsible for cutaneous leishmaniasis in Brazil: Leishmania amazonensis and L. braziliensis. In vitro assays demonstrated differential susceptibility among clinical isolates of both species. Due to this difference, we investigated whether polymorphisms in genes previously associated with miltefosine resistance were related to the differential susceptibility phenotype of the isolates. In addition, studies were conducted to evaluate the correlation between the in vitro susceptibility and efficacy of miltefosine in vivo. Miltefosine was effective in vivo, in BALB/c mice infected with both species of the parasite, although relapses have been observed. It was also observed that animals infected with a resistant strain of L. amazonensis selected in vitro were completely refractory to treatment due to a mutation in the miltefosine transporter gene of this resistant strain. This study has provided data on the evaluation of the potential use of miltefosine for the treatment of cutaneous leishmaniasis in Brazil and has contributed to a better understanding of the mechanism of action of this drug.  
Financial Support: FAPESP and CNPq