Comparative Drug Response of Sensitive and Resistant Strains of Malarial Parasites Using In Vitro Bioassays and Animal Models

摘要

Anti-relapse activity of WR 238605 in a shorter 3 dose regimen has been established which would be operationally more acceptable. WR 238605 has also exhibited significant blood schizontocidal, gametocytocidal and causal prophylactic activities, which can be exploited. A new combination regimen comprising WR 238605 plus halofantrine/desbutyl halofantrine has been evaluated. This combination shows additive response and would be useful for management of chloroquine resistant P. vivax infections. Antihistaminic agents have been found to exert causal prophylactic and suppressive blood schizontocidal activities in rodent model. Cyproheptadine also exerts mefloquine resistance reversal action against P. knowlesi and combination may be useful for treatment of mefloquine resistant cases. Azithromycin has also shown causal prophylactic and blood schizontocidal activity in rodent and simian models. In vitro bioassay for evaluation of antimalarials using synzhronized P. knowlesi was developed. Ex vivo bioassay for estimation of drug concentration in serum has been established using P. knowlesi in vitro. Recombinant IL-12 has shown promising prophylactic activity against P. cynomolgi sporozoite challenge.