EVALUATION OF SURAMIN, IVERMECTIN AND CGP-20376 IN A NEW MACROFILARICIDAL DRUG SCREEN, ONCHOCERCA-OCHENGI IN AFRICAN CATTLE

To aid the development of a macrofilaricidal agent for Onchocerca volv ulus, the African bovine parasite, O. ochengi, was evaluated as a drug screen by testing three known filaricidal drugs. Groups of five Zebu cattle, naturally infected with more than 15 palpable O. ochengi nodul es in the ventral skin, were treated with either suramin (10 mg/kg/day i.v. for 6 days), ivermectin (200 mu g/kg, s.c.), CGP 20376 (20 mg/kg orally) or left untreated as controls and examined at intervals up to 137 days post-treatment (d.p.t.). After ivermectin treatment, microfi larial densities in the skin decreased within one week to virtually ze ro and remained at a very low level. A similar rapid and profound redu ction was seen after CGP 20376 treatment, but by 137 d.p.t. microfilar ial skin densities were approaching pre-treatment levels. With suramin , skin microfilarial densities fell to very low levels after 12 weeks but rose slightly by 137 d.p.t. Effects on the macrofilariae were asse ssed by sequential nodulectomies at -3 and 28, 84 and 137 d.p.t.. By 1 37 d.p.t. embryogenesis was almost completely interrupted in the CGP 2 0376 and ivermectin treated animals, although not in the suramin treat ed group, but in all three groups the majority of remaining intrauteri ne microfilariae were pathologically altered. Degenerating intrauterin e microfilariae accumulated in the ivermectin and in the CGP 20376, bu t not in the suramin treated worms. The motility of male and female wo rms was not reduced by any treatment except for female worms at 84 d.p .t. with CGP 20376. Viability of the worms as indicated by the MTT-for mazan reduction assay was not reduced in any of the treatment groups. This trial has shown the feasibility and potential value of this new m odel. Effects on micro- and macrofilariae were similar to those report ed at the same dosages and times post-treatment for O. volvulus in man in the case of ivermectin and suramin whilst CGP 20376 is not yet tes ted in man.