Survival of adult female worms of Onchocerca change in gerbils and hamsters: implications for the development of an in vivo macrofilaricide screening model

Abstract

Abstract Onchocerciasis, the second leading infectious cause of blindness, afflicts approximately 21 million people globally. Its control is limited to the use of the microfilaricidal drugs, ivermectin and moxidectin. Both drugs are unable to kill the adult worms which can survive for up to 15 years in patients, justifying the urgent need for potent and novel macrofilaricides that kill adult worms. The development of such drugs has been mired by the lack of an appropriate small laboratory animal model to evaluate potential drug candidates in vivo. This study assessed the survival of O. change female worms and their embryos over time in two laboratory rodents: gerbils and hamsters and tested using ‘proof-of-concept’ studies, whether known macrofilaricidal drugs can kill these worms. Animals were surgically implanted with mechanical or enzyme-liberated O. change female worms, and sacrificed at various time points to test for survival. Recovered worms were assessed for viability by biochemical analysis (MTT/formazan assay) or fecundity (embryogram). Flubendazole (FBZ) administered at 20 mg/kg body weight was used to validate both rodent models. By day 26 post-implantation, 58.6 ± 7.5% female worms were recovered from hamsters, and 20 ± 3.5% from gerbils. Those recovered from gerbils were mostly disintegrated or fragmented, with significantly higher fragmentation observed with enzymatically-liberated worms. FBZ had no significant effect on the number worms recovered, but enhanced embryo degradation in gerbils and reduced worm viability in hamsters. This exploratory study has revealed the gerbil and hamster as permissible rodents to adult female worms of O. change. The hamsters appeared to maintain the worms longer, compared to gerbils.