Artesunate and artemether are effective fasciolicides in the rat model and in vitro.
OBJECTIVE
To study the fasciocidal properties of artesunate and artemether in the rat model and in vitro.


METHODS
Adult Fasciola hepatica were exposed in vitro to 1, 10 and 100 microg/mL of artesunate, artemether and dihydroartemisinin for 72 h. Female Wistar rats were administered a single oral dose of artesunate and artemether (100-400 mg/kg) commencing 3 or 10-14 weeks post-infection and worm burden reductions were assessed against infected but untreated control rats. F. hepatica were also observed by scanning electron microscopy (SEM) after recovery from bile ducts of rats given a single oral dose of 200 mg/kg artesunate 24 and 72 h post-treatment.


RESULTS
F. hepatica exposed for 72 h to 10 microg/mL of artesunate, artemether and dihydroartemisinin in vitro showed poor mobility, swelling of the worm body, roughness, damage of the tegument and blebbing. Exposure to drug concentrations of 100 microg/mL resulted in the death of all F. hepatica by 72 h. One hundred per cent worm burden reductions were achieved in rats infected with adult F. hepatica after treatment with artesunate and artemether at 400 and 200 mg/kg, respectively. Administration of artesunate and artemether at a dose of 200 mg/kg to rats harbouring juvenile F. hepatica resulted in worm burden reductions of 46% and 82%, respectively. F. hepatica recovered from rats' bile ducts 24 h after administration of 200 mg/kg artesunate showed normal activity and SEM observations revealed that there was no visible damage. Seventy-two hours post-treatment F. hepatica displayed very poor mobility and there was focal swelling of the tegument and spines.


CONCLUSIONS
Artesunate and artemether exhibit promising fasciocidal activities, with the latter showing better tolerability by the hosts.
Swiss Tropical Institute PO Box, CH-4002 Basel, Switzerland. jennifer.keiser@unibas.ch
Jennifer
J
Keiser
Xiao
X
Shu-Hua
Marcel
M
Tanner
Jürg
J
Utzinger
D000818:Animals; D000980:Antiplatyhelmintic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage / Q000494:pharmacology*; D000077332:Artesunate; D001652:Bile Ducts / Q000469:parasitology / Q000648:ultrastructure; D004195:Disease Models, Animal; D005210:Fasciola hepatica / Q000166:cytology / Q000187:drug effects*; D005211:Fascioliasis / Q000188:drug therapy*; D005260:Female; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017208:Rats, Wistar; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000494:pharmacology*
D000980:Antiplatyhelmintic Agents; D037621:Artemisinins; D012717:Sesquiterpenes; D000077332:Artesunate; C039060:artenimol; D000077549:Artemether