Activity of artemether and OZ78 against triclabendazole-resistant Fasciola hepatica.
Triclabendazole is the drug of choice against Fasciola hepatica infections in humans and animals. However, parasite resistance against triclabendazole is spreading in the veterinary field, and there are no drugs of comparable activity currently available for the treatment and control of fascioliasis. We investigated the efficacy of single oral doses of artemether and OZ78 against adult triclabendazole-resistant F. hepatica harboured in rats, and compared the results with triclabendazole administered at two different doses. Single oral doses of 100 mg/kg OZ78 and 200 mg/kg artemether resulted in worm burden reductions of 100%. Whereas a single 10 mg/kg dose of triclabendazole achieved a worm burden reduction of only 4.0%, a five-fold higher dose yielded a significant worm burden reduction of 60.9%. However, the lower dose of triclabendazole administered to rats harbouring a triclabendazole-sensitive F. hepatica isolate resulted in a worm burden reduction of 95.3%. Our findings confirm that artemether and OZ78 possess good fasciocidal properties, even against a triclabendazole-resistant F. hepatica isolate, and hence these drugs might become useful in areas where triclabendazole resistance is common.
Keiser
Jennifer
J
Department of Medical Parasitology and Infection Biology, Swiss Tropical Institute, P.O. Box, CH-4002 Basel, Switzerland. jennifer.keiser@unibas.ch
Utzinger
Jürg
J
Vennerstrom
Jonathan L
JL
Dong
Yuxiang
Y
Brennan
Gerry
G
Fairweather
Ian
I
D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000284:Administration, Oral; D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000627:therapeutic use*; D000077549:Artemether; D037621:Artemisinins / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use; D001652:Bile Ducts / Q000469:parasitology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004351:Drug Resistance; D005210:Fasciola hepatica / Q000187:drug effects*; D005211:Fascioliasis / Q000188:drug therapy*; D005260:Female; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D000077682:Triclabendazole
D000980:Antiplatyhelmintic Agents; D037621:Artemisinins; D001562:Benzimidazoles; C518172:OZ78 compound; D000077682:Triclabendazole; D000077549:Artemether; D000218:Adamantane