Reduced tissue parasitic load and infectivity to sand flies in dogs naturally infected by Leishmania (Leishmania) chagasi following treatment with a liposome formulation of meglumine antimoniate

Departamento de Parasitologia, ICB; Faculdade de Farmácia; Departamento de Patologia Geral, ICB; Departamento de Fisiologia e Biofísica, ICB; Departamento de Química, ICEX; Av. Antônio Carlos 6627, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil

^* To whom correspondence should be addressed. Email: michalik{at}icb.ufmg.br.

	Abstract

The toxicity and antileishmanial effectiveness of a novel liposome formulation of meglumine antimoniate have been investigated in mongrel dogs with visceral leishmaniasis (VL) obtained from an endemic region for VL in Brazil. Groups of 12 animals received by i.v. route four doses (with 4 days-intervals) of either liposomal meglumine antimoniate (GI, 6.5 mg Sb/kg/dose), empty liposomes (GII) or isotonic saline (GIII). Evaluation of markers of hematopoietic, hepatic and renal functions before and just after treatment showed no significant change. On the other hand, transitory adverse reactions, including prostration, defecation, tachypnea and sialorrhea, were observed during the first 15 min after injections in GI and GII. Parasitological evaluation of sternal bone marrow four days after the last dose showed a significant reduction of parasite burden in GI, compared to the other groups. Immunocytochemical evaluations of the skin, bone marrow, cervical lymph nodes, liver and spleen of dogs for parasites, 150 days after treatment, indicated significant parasite suppressions (higher than 95.7%) in the lymph nodes, liver and spleen of GI, when compared to control groups. Feeding of Lutzomyia (L.) longipalpis phlebotomines on dogs from GI, 150 days after treatment, resulted in a significant reduction of sand fly infection efficiency, when compared to feeding on animals from GII and GIII. This is the first report of both long-term parasite suppression and reduction of infectivity to sand flies in naturally-infected dogs, following treatment with a liposome-encapsulated drug. Importantly, this was achieved using 20-fold lower cumulative dose of Sb, when compared to conventional antimonial treatment.