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| 1 | In vitro activity and in vivo efficacy of a combination therapy of diminazene and chloroquine against murine visceral leishmaniasis显示文摘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(Ld_(50)=0.03±0.04) than Amphotericin B(Ld_(50)=0.02±0.01).Body weight in infected mice increased significantly(P=0.0007) from day7 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. | Samuel W.Mwololo Joshua M.Mutiso John C.Macharia Alain J.Bourdichon Michael M.Gicheru | 2015 | The Journal of Biomedical Research2015，29，3： | 3 |
| 2 | Development ofLeishmania vaccines:predicting the future from past and present experience显示文摘Leishmaniasis is a disease that ranges in severity from skin lesions to serious disfigurement and fatal systemic infection. Resistance to infection is associated with a T-helper-1 immune response that activates macrophages to kill the intracellular parasite in a nitric oxide-dependent manner. Conversely, disease progression is generally associated with a T-helper-2 response that activates humoral immunity. Current control is based on chemotherapeutic treatments which are expensive, toxic and associated with high relapse and resistance rates. Vaccination remains the best hope for control of all forms of the disease, and the development of a safe, effective and affordable antileishmanial vaccine is a critical global public-health priority. Extensive evidence from studies in animal models indicates that solid protection can be achieved by immunization with defined subunit vaccines or live-attenuated strains of Leishmania. However, to date, no vaccine is available despite substantial efforts by many labo-ratories. Major impediments in Leishmania vaccine development include: lack of adequate funding from national and international agencies, problems related to the translation of data from animal models to human disease, and the transition from the laboratory to the field. Furthermore, a thorough understanding of protective immune responses and generation and maintenance of the immunological memory, an important but least-studied aspect of antiparasitic vaccine development, during Leishmania infection is needed. This review focuses on the progress of the search for an effective vaccine against human and canine leishmaniasis. | Joshua Muli Mutiso John Chege Macharia Maria Ndunge Kiio James Maina Ichagichu Hitler Rikoi Michael Muita Gicheru | 2013 | The Journal of Biomedical Research2013，27，2： | 2 |
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