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

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 (Ld50 = 0.03±0.04) than Amphotericin B (Ld50 = 0.02±0.01). Body weight in infected mice increased significantly (P = 0.0007) from day 7 to day 37 following infection (P = 0.026). However, body weight remained comparable in all mice groups during treatment (P = 0.16). The diminazene–chloroquine combination significantly reduced splenic parasite numbers as compared to individual drug therapies (P = 0.0001) although Amphotericin B was still more efficacious than any other treatment (P = 0.0001). 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.

Antileishmanial activity of a new chloroquine analog in an animal model of Leishmania panamensis infection

“…( Hanif et al., 2016 ). Chloroquine and its derivatives have been previously shown to be active against several Leishmania species, including L. amazonensis ( Rocha et al., 2013 ), L. donovani ( Mwololo et al., 2015 ) and L. braziliensis ( Soares et al., 2017 ). Authors have shown that some of these compounds appear to be more active against amastigotes and can accumulate in relatively high concentrations within acidic vacuoles in the infected host cells ( Rocha et al., 2013 ).…”

Therapeutic effect of Prosopis strombulifera (LAM) BENTH aqueous extract on a murine model of cutaneous leishmaniasis

“…Mwololo et al., 2015 indicated that there is a correlation of high antibody levels during active disease and a reduction in antibody levels following successful cure. 24 Furthermore, it has been demonstrated that IgG1 antibodies are increased in mice infected by Leishmania . 25 For that, a reduction of IgG1 observed in the PsAE treated group compared to the control PBS group, indicates PsAE induces a switch in the immune response with bias to Th1 profile.…”

Safety and Efficacy of Prosopis juliflora Leaf Extract as a Potential Treatment against Visceral Leishmaniasis in Balb/c Mice

“…Plant extracts of serial concentrations ranging from 100 to 0.78125 μg/ml were prepared and the extracts, negative control (normal saline), and positive control (with sodium stibogluconate) were added to the wells on a 96 well plate ( 11 ). The tests were performed as previously described earlier ( 12 ). Late Stationary-phase promastigotes harvested ( 8 ) were counted and suspended in a concentration of 2.0 × 10 6 parasites/ml in culture medium.…”