Effect of artemether, artesunate, OZ78, praziquantel, and tribendimidine alone or in combination chemotherapy on the tegument of Clonorchis sinensis.
We investigated the morphological effects of half-strength treatments with praziquantel, artemether, artesunate, OZ78 and tribendimidine as well as combinations of praziquantel with artemether, artesunate, OZ78 and tribendimidine and an artesunate-tribendimidine combination in rats harboring adult Clonorchis sinensis. Rats were infected with C. sinensis, dosed orally with single agents or combination treatments and flukes recovered at 3 or 5 days post-treatment. The number of flukes was counted, the viability recorded and surface changes monitored by scanning electron microscopy. Drug effects induced by the individual drugs at sub-curative doses 3 days post-treatment were minor with the exception of flukes recovered from rats treated with artemether and tribendimidine. Treatment with the praziquantel combinations of artesunate, OZ78 and tribendimidine did not produce a greater disruption of the tegument than the individual drugs 3 days post-treatment. On the other hand, at this time point many worms treated with artemether-praziquantel had died and eruptions, roughening or blebbing were observed on all worms examined. Five days post-treatment flukes exposed to any of the praziquantel combinations in rats had died. Rats treated with an artesunate-tribendimidine combination resulted in a rapid death of flukes, 3 days post-treatment all worms had been expelled. In conclusion, we have confirmed the promising clonorchicidal properties of different drug combinations in rats. Differences in the extent and time-scale of tegumental disruption have been observed. The effect of drug combinations against C. sinensis requires further scientific inquiry, e.g. in transmission electron microscopy studies and in the C. sinensis-rabbit model.
Keiser
Jennifer
J
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland. jennifer.keiser@unibas.ch
Vargas
Mireille
M
D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D000077549:Artemether; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D003003:Clonorchiasis / Q000188:drug therapy* / Q000469:parasitology; D003004:Clonorchis sinensis / Q000187:drug effects* / Q000648:ultrastructure; D004359:Drug Therapy, Combination; D005260:Female; D008855:Microscopy, Electron, Scanning; D010655:Phenylenediamines / Q000627:therapeutic use*; D011223:Praziquantel / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012867:Skin / Q000187:drug effects / Q000648:ultrastructure; D016896:Treatment Outcome
D000871:Anthelmintics; D037621:Artemisinins; C518172:OZ78 compound; D010655:Phenylenediamines; C056017:tribendimidine; D000077332:Artesunate; D011223:Praziquantel; D000077549:Artemether; D000218:Adamantane