Evaluation of drugs against Onchocerca microfiliariae in an inbred mouse model.
The model of Onchocerca lienalis microfilariae (mf) injected into CBA mice has been examined for its application to chemotherapy studies in onchocerciasis. Parasite recoveries following treatment relative to the levels obtained from controls were not significantly affected by suramin, whereas they were reduced by up to 56% with amoscanate, 71% with levamisole, 82% with mebendazole, 82% with diethylcarbamazine (DEC) and 100% with ivermectin. More detailed evaluation of the latter two compounds demonstrated that far greater intrinsic microfilaricidal activity was possessed by ivermectin compared with DEC. Single doses of ivermectin down to 0.2 mg/kg destroyed 83% of the mf within 12 hours and 100% within 5 days. The same dose administered at various times prior to mf injection reduced parasite recoveries by 92% after four days and by 35-40% for up to one month. In contrast, DEC was only effective at doses of 5 X 50 mg/kg or higher, reducing mf levels by an equivalent amount following subcutaneous or intraperitoneal routes of administration. However, it was of limited efficacy when given to mice during the first week after mf injection compared with the third week, when parasite levels in untreated rodents start to decline under a host immune response. DEC treatment during the third week after mf injection resulted in a smaller depression in parasite recoveries from T-cell deprived mice compared with intact animals, but in similar levels of reduction in CBA/H (normal) and CBA/N (B-cell deficient) mice. Depletion of C3 complement levels in mice with cobra venom factor had a negligible effect on drug efficacy.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D004049:Diethylcarbamazine / Q000627:therapeutic use; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004546:Elapid Venoms / Q000494:pharmacology; D005260:Female; D005369:Filaricides / Q000627:therapeutic use*; D007559:Ivermectin; D007783:Lactones / Q000627:therapeutic use; D008212:Lymphocyte Depletion; D051379:Mice; D008808:Mice, Inbred CBA; D008842:Microfilariae / Q000302:isolation & purification; D009855:Onchocerciasis / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D012867:Skin / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology
D000871:Anthelmintics; D004546:Elapid Venoms; D005369:Filaricides; D007783:Lactones; C016310:cobra venom factor; D007559:Ivermectin; D004049:Diethylcarbamazine