Efficacy of miltefosine treatment in Leishmania amazonensis-infected BALB/c mice

Abstract

Leishmaniasis is one of the most serious worldwide diseases caused by protozoan parasites of the Leishmania genus, affecting millions of people around the world. All currently available treatments present severe toxic side effects, require long-term compliance, cause serious side effects and are uncomfortable for patients. Leishmania amazonensis, a species endemic to Brazil, causes severe localised or diffuse skin lesions in humans. Owing to the unsatisfactory nature of the currently available chemotherapies, new approaches have been assessed for improved therapeutic intervention strategies against leishmaniasis. Miltefosine is an alkylphospholipid analogue that exhibits potent activity against the different clinical manifestations of leishmaniasis. Thus, the aim of this study was to investigate the long-term efficacy of miltefosine in BALB/c mice infected with L. amazonensis owing to the lack of a profound study demonstrating its dose-dependent and long-term effects. It was observed that animals treated with 20-50 mg/kg/day of miltefosine exhibited a significant dose-dependent reduction in lesion size; furthermore, in mice receiving higher doses, lesions disappeared after the end of treatment. To confirm a possible parasitological cure, mice up to 250 days after the end of treatment were analysed. No lesions or presence of parasite DNA were found in mice treated with 30, 40 and 50 mg/kg/day of miltefosine. In summary, these results show that miltefosine may be used to treat cutaneous leishmaniasis caused by L. amazonensis, alone or as combination therapy.

In Vitro and In Vivo Miltefosine Susceptibility of a Leishmania amazonensis Isolate from a Patient with Diffuse Cutaneous Leishmaniasis

“…The World Health Organization recommends 2.5 mg/kg/day MF for 28 days for the treatment of CL or VL in humans. This scheme is not effective for obtaining complete cure in L. amazonensis infected BALB/c mice [36]. Previous studies in our laboratory indicated that MF was effective in the treatment of L. amazonensis infections in BALB/c mice if used at 13 mg/kg/day for 15 days by the oral route (data not shown).…”

Ursolic Acid Potentializes Conventional Therapy in Experimental Leishmaniasis

“…Forty BALB/c mice (four weeks old; weight ~ 25 g) were inoculated at the base of the tail with 2 × 10 7 promastigote forms of L. amazonensis in stationary phase of growth (final volume 25 µL) as described in previous published works [ 9 , 46 , 47 , 48 , 49 ]. Five healthy control group was injected only with physiological solution.…”

“…All the treatments were given with a single daily dose of 20 µL, under intralesional route. The highest doses of 50.0 mg/kg from Glu was selected based on previously published works [ 47 , 50 , 51 ]. Treatment outcome was determined by skin parasitism that was analyzed one week after the end of treatment.…”

To investigate the therapeutic potential of immunochemotherapy with cisplatin + 78 kDa + MPL‐A against Leishmania donovani in BALB/c mice

“…In the absence of any suitable vaccine against visceral leishmaniasis (VL), chemotherapy is the only option for control of the disease. Although the treatment for leishmaniasis was introduced in the early 20th century, parenteral administration of pentavalent antimony compounds (meglumine antimoniate and sodium stibogluconate) remains the first‐choice treatment for all forms of leishmaniasis . In the case of antimonial resistance, the second‐choice treatment includes amphotericin B (deoxycholate or liposomal formulation) .…”

“…Although the treatment for leishmaniasis was introduced in the early 20th century, parenteral administration of pentavalent antimony compounds (meglumine antimoniate and sodium stibogluconate) remains the first‐choice treatment for all forms of leishmaniasis . In the case of antimonial resistance, the second‐choice treatment includes amphotericin B (deoxycholate or liposomal formulation) . However, each of these therapies has important limitations, such as long‐term parenteral administration, toxic side effects, high cost in endemic countries and an increase in number of resistance cases .…”