Onchocerca volvulus and O. lienalis: the microfilaricidal activity of moxidectin compared with that of ivermectin in vitro and in vivo.
The activity of the veterinary drug moxidectin against Onchocerca volvulus and On. lienalis microfilariae (mf), both in vitro and in experimentally infected CBA/Ca mice, was compared with that of ivermectin. The in-vitro results demonstrated that both compounds (at a concentration of 10(-7) M) significantly reduced the mf motility index (MI) throughout the 7-day culture period and that this reduction was similar for the two compounds. Mice were treated with moxidectin and ivermectin by subcutaneous injection (sc) or orally (po); the two routes were equally efficacious. When mice infected with On. lienalis were treated with one of the drugs at 3.2, 1.6, 0.8, 0.4 or 0.2 micrograms/kg.day on days 3-7 post-infection, with necropsy on day 18, moxidectin cleared more mf than ivermectin at all of the doses examined. In mice treated with a single dose (on day 3 post-infection), 150 or 15 micrograms/kg moxidectin completely cleared the mf whereas 1.5 micrograms/kg produced a 90%-96% reduction in mf recoveries. Following ivermectin treatment at the same doses, mf were virtually cleared at 150 micrograms/kg, with a 98% reduction at 15 micrograms/kg but no significant effect at 1.5 micrograms/kg. When mice with On. volvulus infections were treated with a single dose of moxidectin at 15 or 1.5 micrograms/kg, there were reductions in mf recoveries of 96% and 23%, respectively, compared with only a 48% reduction with 15 micrograms ivermectin/kg and a 2% increase with 1.5 micrograms ivermectin/kg. In order to examine the persistence and activity of each drug, mice were treated with a single dose of 150 micrograms/kg up to 28 days before infection. Moxidectin was found to be more efficacious (with subsequent 99.9% reduction in mf when given 28 days pre-infection and a 100% reduction when give 16 or 4 days before or 3 days after infection) than ivermectin (giving reductions of 57.1%, 66.7%, 100% and 100%, respectively). The further evaluation of moxidectin and its potential usefulness for the treatment of human onchocerciasis are discussed.
International Institute of Parasitology, St Albans, U.K.
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Tagboto
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Townson
D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents; D004305:Dose-Response Relationship, Drug; D007559:Ivermectin / Q000627:therapeutic use*; D018942:Macrolides / Q000627:therapeutic use; D051379:Mice; D008808:Mice, Inbred CBA; D008842:Microfilariae / Q000187:drug effects; D017181:Onchocerca volvulus; D009855:Onchocerciasis / Q000188:drug therapy* / Q000469:parasitology; D013997:Time Factors
D000871:Anthelmintics; D000900:Anti-Bacterial Agents; D018942:Macrolides; D007559:Ivermectin; C027837:moxidectin