In vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasis

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dc.contributor.authorMwololo, Samuel W.
dc.contributor.authorMutiso, Joshua M.
dc.contributor.authorMacharia, John C.
dc.contributor.authorBourdichon, Alain J.
dc.contributor.authorGicheru, M. M.
dc.date.accessioned2016-02-09T08:39:03Z
dc.date.available2016-02-09T08:39:03Z
dc.date.issued2015
dc.descriptionDOI: 10.7555/JBR.29.20140072en_US
dc.description.abstractThe 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.en_US
dc.identifier.citationThe Journal of Biomedical Research, 2015, 29(3):214-223en_US
dc.identifier.urihttp://ir-library.ku.ac.ke/handle/123456789/14124
dc.language.isoenen_US
dc.publisherPubMed Centralen_US
dc.subjectEfficacyen_US
dc.subjectDiminazene-chloroquineen_US
dc.subjectCombination therapyen_US
dc.subjectLeishmania donovanien_US
dc.subjectVisceral leishmaniasisen_US
dc.subjectBALB/c miceen_US
dc.titleIn vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasisen_US
dc.typeArticleen_US
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