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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: Experimental Parasitology; v. 246, p. 7-pg., 2023-01-17.

Resumo

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)

• Processo FAPESP: 19/02717-6 - Investigação da prevalência do vírus LRV1 em isolados clínicos de Leishmania (Viannia) spp. provenientes de pacientes com leishmaniose tegumentar de um hospital referência
• Beneficiário: Cristiele Saborito da Silva
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica
• Processo FAPESP: 16/21171-6 - Paromomicina no tratamento da Leishmaniose Tegumentar: investigação in vitro, in vivo e na identificação de marcadores moleculares associados à suscetibilidade e resistência
• Beneficiário: Adriano Cappellazzo Coelho
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 20/01948-1 - Avaliação da suscetibilidade in vitro a fármacos alternativos em isolados clínicos e de cães de Leishmania spp
• Beneficiário: Bianca Alves Ferreira
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 19/22175-3 - Identificação e validação funcional de genes associados à suscetibilidade e resistência à paromomicina em Leishmania spp
• Beneficiário: Elizabeth Magiolo Coser
• Modalidade de apoio: Bolsas no Brasil - Doutorado