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

Author(s)

Ferreira, Bianca A. ; Coser, Elizabeth M. ; Saborito, Cristiele ; Yamashiro-Kanashiro, Edite H. ; Coelho, Adriano C. ; Lindose, Jose Angelo L.

• Document type: Journal article
• Source: Experimental Parasitology; v. 246, p. 7-pg., 2023-01-17.

Abstract

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 mu M 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 mu M 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. (AU)

• FAPESP's process: 19/02717-6 - Investigation of the prevalence of LRV1 virus in clinical isolates of Leishmania (Viannia) spp. from patients with cutaneous leishmaniasis of a reference hospital
• Grantee: Cristiele Saborito da Silva
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 16/21171-6 - Paromomycin for the treatment of Tegumentary Leishmaniasis: investigation in vitro, in vivo and in the identification of molecular markers associated with susceptibility and resistance
• Grantee: Adriano Cappellazzo Coelho
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/01948-1 - Evaluation of susceptibility in vitro of clinical and dog isolates of Leishmania spp. to alternative drugs
• Grantee: Bianca Alves Ferreira
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 19/22175-3 - Identification and functional validation of genes associated with susceptibility and resistance to paromomycin in Leishmania spp
• Grantee: Elizabeth Magiolo Coser
• Support Opportunities: Scholarships in Brazil - Doctorate