Evaluation of suramin, ivermectin and CGP 20376 in an new macrofilaricidal drug screen, Onchocerca ochengi in African cattle

To aid the development of a macrofilaricidal agent for Onchocerca volvulus, 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 nodules in the ventral skin, were treated with either suramin (10 mg/kg/day i.v. for 6 days), ivermectin (200 μg/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, microfilarial densities in the skin decreased within one week to virtually zero and remained at a very low level. A similar rapid and profound reduction was seen after CGP 20376 treatment, but by 137 d.p.t. microfilarial 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 assessed by sequential nodulectomies at −3 and 28, 84 and 137 d.p.t.. By 137 d.p.t. embryogenesis was almost completely interrupted in the CGP 20376 and ivermectin treated animals, although not in the suramin treated group, but in all three groups the majority of remaining intrauterine microfilariae were pathologically altered. Degenerating intrauterine microfilariae accumulated in the ivermectin and in the CGP 20376, but not in the suramin treated worms. The motility of male and female worms 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-formazan reduction assay was not reduced in any of the treatment groups. This trial has shown the feasibility and potential value of this new model. Effects on micro- and macrofilariae were similar to those reported at the same dosages and times post-treatment for O. volulus in man in the case of ivermectin and suramin whilst CGP 20376 is not yet tested in man