In vitro miltefosine and amphotericin B susceptibility of strains and clinical isolates of Leishmania species endemic in Brazil that cause tegumentary leishmaniasis

• Published in: Experimental parasitology Vol. 246; p. 108462
• Main Authors: Ferreira, Bianca A., Coser, Elizabeth M., Saborito, Cristiele, Yamashiro-Kanashiro, Edite H., Lindoso, José Angelo L., Coelho, Adriano C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2023
• Subjects: Amphotericin B; Amphotericin B - pharmacology; Amphotericin B - therapeutic use; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - therapeutic use; Brazil - epidemiology; Drug susceptibility; Humans; Leishmania; Leishmaniasis - drug therapy; Leishmaniasis, Cutaneous - drug therapy; Leishmaniasis, Cutaneous - epidemiology; Leishmaniasis, Cutaneous - parasitology; Miltefosine; Phosphorylcholine - pharmacology; Phosphorylcholine - therapeutic use; Tegumentary leishmaniasis; Brazil; PBS; LRV1; AI; ITS; Drug susceptibility; Tegumentary leishmaniasis; BMDM; DCL; Miltefosine; Amphotericin B; LCL; Leishmania; FBS; AmB; MCL; TL; MF; PCR
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2023.108462

Tegumentary leishmaniasis encompasses a spectrum of clinical manifestations caused by the parasitic protozoa of the genus Leishmania. In Brazil, there are at least seven Leishmania species that are endemic and responsible for this set of clinical manifestations of the disease. Current treatment is limited to a restricted number of drugs that in general have several drawbacks including parenteral use, toxicity, and severe side effects. Amphotericin B is considered a second-line drug for tegumentary leishmaniasis in Brazil, while miltefosine was recently approved for clinical use in the treatment of this disease. In this study, we investigated the in vitro susceptibility of Leishmania strains representative of the species endemic to Brazil, as well as a panel of thirteen clinical isolates of tegumentary leishmaniasis, to both amphotericin B and miltefosine. A moderate variation in the susceptibility to both drugs was found, where the EC50 values varied from 11.43 to 52.67 μM for miltefosine and from 12.89 to 62.36 nM for amphotericin B in promastigotes, while for the intracellular amastigotes, values ranged from 1.08 to 9.60 μM and from 1.69 to 22.71 nM for miltefosine and amphotericin B respectively. Furthermore, the clinical isolates and strains of the subgenus Viannia were evaluated for the presence of Leishmania RNA virus 1 (LRV1), as this is an important factor associated with disease severity and treatment outcome. These findings provide a preclinical dataset of the activity of these drugs against the causative species of tegumentary leishmaniasis in Brazil. [Display omitted] •A moderate variation in in vitro susceptibility to miltefosine and amphotericin B of Leishmania strains and clinical isolates responsible for tegumentary leishmaniasis was observed in both stages of parasite.•For both drugs, intracellular amastigotes were more susceptible than promastigotes.•LRV1 was not detected in clinical isolates of the subgenus Viannia evaluated in this study.