Characterization of Leishmania (v.) braziliensis clinical isolates susceptibility to miltefosine in vitro and in vivo

Abstract

Leishmaniasis is a disease caused by parasites of Leishmania genus. In Brazil, the cutaneous form of the disease is mainly caused by Leishmania (V.) braziliensis, with an annual incidence of approximately 26,000 cases in 2012. The drugs available for the treatment of leishmaniasis have limitations as high toxicity and the need of parenteral administration, which can result in interruption of treatment and consequent selection of resistant parasites. Miltefosine is an oral drug, already available for the treatment of leishmaniasis in some countries, but is not used in Brazil yet. It is known that susceptibility to miltefosine varies among species and among isolates of the same Leishmania species and yet there are not available data showing the susceptibility of L. (V.) braziliensis Brazilian isolates to miltefosine. Thus, this project aims to evaluate the susceptibility of clinical isolates of patients from two different geographical regions of Brazil to miltefosine and elucidate the molecular basis of the differences in susceptibility to miltefosine in these isolates. Thus, inhibitory concentrations of miltefosine in vitro, using intracellular amastigotes of 9 clinical isolates, will be determined. Based on these data, the two isolates with higher and lower susceptibility to the drug isolates will be selected for in vivo studies. The two selected isolates, will also be characterized by the transport of phospholipids in the plasma membrane and the nucleotide sequences of the genes encoding the miltefosine transporter, in order to verify if polymorphisms in these genes can be associated with susceptibility variation found in these isolates. (AU)