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JAC Advance Access published online on March 31, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl125
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received December 5, 2005
Revised March 13, 2006
Accepted March 14, 2006

Original article

Artesunate and artemether are effective fasciolicides in the rat model and in vitro

Jennifer Keiser 1 *, Xiao Shu-Hua 2, Marcel Tanner 1, and Jürg Utzinger 1

1 Swiss Tropical Institute, PO Box, CH-4002 Basel, Switzerland
2 National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai 200025, People's Republic of China

* To whom correspondence should be addressed.
Jennifer Keiser, E-mail: jennifer.keiser{at}unibas.ch


  Abstract

Objectives: 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 µg/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 to10 µg/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 µg/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.

Keywords: Fasciola hepatica; food-borne trematodiasis; artemisinin; dihydroartemisinin; in vitro studies; in vivo studies; scanning electron microscopy.
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