title: In vivo antileishmanial efficacy of miltefosine against Leishmania (Leishmania) amazonensis.
abstract: Leishmaniasis, a disease caused by parasites of the Leishmania genus, constitutes a significant health and social problem in many countries and is increasing worldwide. The conventional treatment, meglumine antimoniate (MA), presents numerous disadvantages, including invasiveness, toxicity, and frequent therapeutic failure, justifying the attempts at finding alternatives to the first-line therapy. We have studied the comparative long-term efficacy of MA against miltefosine (MF) in Leishmania infection in experimental mice. The criteria for efficacy evaluation were footpad lesion size, anti-Leishmania antibodies level, histopathology of the site of inoculation (right footpad, RFP), splenic index (SI), and the presence of parasites in RFP, spleen, and liver, determined by polymerase chain reaction (PCR). Swiss mice, infected with Leishmania (Leishmania) amazonensis were treated, at different time points (5 and 40 days after infection) with either MA or MF. The efficacy of MF was better than that of MA for inhibiting lesions and for reducing tissue damage and presence/load of amastigotes in spleen and liver. Moreover, early administration of MF produced a clear reduction in splenomegaly and was equal in reducing antibody titles in comparison with MA. Our results demonstrated that MF is an effective and safe therapeutic alternative for leishmaniasis by L. (L.) amazonensis and is more efficacious than MA.
authors.affiliation: Instituto de Patología Experimental, Facultad de Ciencias de la Salud, Universidad Nacional de Salta. Av. Bolivia 5150 (4400), Salta Capital, República Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: García Bustos
authors.forename: Alejandra
authors.initials: A
authors.lastname: Barrio
authors.forename: Gabriela G
authors.initials: GG
authors.lastname: Prieto
authors.forename: Emma M
authors.initials: EM
authors.lastname: de Raspi
authors.forename: Rubén O
authors.initials: RO
authors.lastname: Cimino
authors.forename: Rubén M
authors.initials: RM
authors.lastname: Cardozo
authors.forename: Luis A
authors.initials: LA
authors.lastname: Parada
authors.forename: Matthew
authors.initials: M
authors.lastname: Yeo
authors.forename: Jaime
authors.initials: J
authors.lastname: Soto
authors.forename: Delfor A
authors.initials: DA
authors.lastname: Uncos
authors.forename: Cecilia
authors.initials: C
authors.lastname: Parodi
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Basombrío
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007894:Leishmania mexicana / Q000187:drug effects*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy* / Q000469:parasitology / Q000473:pathology; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000077485:Meglumine Antimoniate; D051379:Mice; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013154:Spleen / Q000473:pathology
chemical_list: D000981:Antiprotozoal Agents; D009942:Organometallic Compounds; D010767:Phosphorylcholine; C039128:miltefosine; D008536:Meglumine; D000077485:Meglumine Antimoniate