In vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasis
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Date
2015
Authors
Mwololo, Samuel W.
Mutiso, Joshua M.
Macharia, John C.
Bourdichon, Alain J.
Gicheru, M. M.
Journal Title
Journal ISSN
Volume Title
Publisher
PubMed Central
Abstract
The present study evaluated the in vitro activity and in vivo efficacy of diminazene combined with chloroquine as
a potential drug against Leishmania donovani. Amphotericin B was used as a positive control drug. In vitro activity
involved incubation of various drug concentrations with promastigotes or vero cells in culture before determination
of parasite growth inhibition or cell death while in vivo evaluations involved infection of various mice groups with
virulent L. donovani parasites and treatment with test drug compounds following disease establishment. Weight
changes in experimental mice were also evaluated before infection and throughout the experiment. The results indicated
that the diminazene-chloroquine combination was at least nine times more efficacious than individual drugs in
killing promastigotes in culture. The diminazene-chloroquine combination was safer (Ld5050.03¡0.04) than
Amphotericin B (Ld5050.02¡0.01). Body weight in infected mice increased significantly (P50.0007) from day
7 to day 37 following infection (P50.026). However, body weight remained comparable in all mice groups during
treatment (P50.16). The diminazene-chloroquine combination significantly reduced splenic parasite numbers as
compared to individual drug therapies (P50.0001) although Amphotericin B was still more efficacious than any
other treatment (P50.0001). Amongst the test compounds, the diminazene-chloroquine combination showed the
lowest level of IgG antibody responses with results indicating significant negative correlation between antileishmanial
antibody responses and protection against disease. These findings demonstrate the positive advantage and the
potential use of a combined therapy of diminazene-chloroquine over the constituent drugs. Further evaluation is
recommended to determine the most efficacious combination ratio of the two compounds.
Description
DOI: 10.7555/JBR.29.20140072
Keywords
Efficacy, Diminazene-chloroquine, Combination therapy, Leishmania donovani, Visceral leishmaniasis, BALB/c mice
Citation
The Journal of Biomedical Research, 2015, 29(3):214-223