Sensitivity of SbV-resistant <i>L. panamensis</i> parasites to edelfosine.

<p>(A) Two groups of eight golden hamsters each were infected in the nose with wild type and SbV-resistant <i>L. panamensis</i> (<i>Lp</i>) promastigotes, and after the sixth week post-infection, they were treated with a daily intramuscular injection of Glucantime (SbV) for 4 weeks. Disease evolution rate was measured along the whole process through determining nose thickness as compared to figures obtained before infection. (B) Golden hamsters inoculated with SbV-resistant (SbV-R) <i>L. panamensis</i> (<i>Lp</i>) did not respond to treatment with Glucantime (inflamed nose) (upper left panel), and nose smears showed amastigotes within macrophages (arrow) following Giemsa staining (lower left panel). However, hamsters infected with wild type (wt) <i>L. panamensis</i> (<i>Lp</i>) fully responded to Glucantime treatment, showing uninflamed nose and negative staining for amastigotes in nose smears (upper and lower right panels). (C) IC₅₀ values of edelfosine, miltefosine, perifosine, and erucylphosphocholine (ErPC) for <i>in vitro</i> growth inhibition of wild type (wt) and SbV-resistant (SbV-R) <i>L. panamensis</i> (<i>Lp</i>) promastigotes were determined by XTT assays. (D–F) Golden hamsters were infected with 1×10⁶ SbV-resistant <i>L. panamensis</i> promastigotes in the nose, and after nose inflammation was evident, hamsters were randomized into drug-treated (26 mg edelfosine/kg of body weight, daily oral administration for 28 days) and control (water vehicle) groups of 7 hamsters each. (D) Lesion development was monitored by measuring nose thickness at regular intervals and comparison to values obtained before treatment (evolution index). (E) Parasite load was determined by limiting dilution assays after completion of the 4-week <i>in vivo</i> assay. (F) Edelfosine treatment led to a dramatic decrease and amelioration in parasite-induced nose thickness and damage, as shown by photographs from drug-free control and edelfosine-treated hamsters. Data are means ± SD or representative experiments (<i>n</i> = 7). Asterisks indicate that differences between control and edelfosine-treated groups, or between wild type and SbV-resistant parasites treated with SbV, are statistically significant. (*) <i>P</i><0.05. (**) P<0.01.