Comparative study of the effects of artemether and artesunate on juvenile and adult Schistosoma mansoni in experimentally infected mice.
Artemether and artesunate, derivatives of the antimalarial artemisinin, also exhibit antischistosomal properties. There is a need to assess comparatively the activity of both compounds against different developmental stages of schistosome parasites. Since artemisinin derivatives will be increasingly used to treat malaria, it is important to study the effects of 7-day monotherapy regimens on schistosome infections. We carried out experiments with mice, infected with juvenile or adult Schistosoma mansoni, and treated with artemether or artesunate at various doses and regimens including those currently used for monotherapy of malaria. Three doses of artemether, at concentrations of 150 or 300 mg/kg, administered to mice with juvenile S. mansoni resulted in worm reductions of 88-97%, which were significantly higher than the 67-77% obtained with artesunate (P < 0.05). Total concentrations of 600 or 800 mg/kg artemether, administered over 2 or 4 consecutive days to mice with adult S. mansoni, reduced the worm burden significantly by 46-51% (P < 0.05). The reduction of the worm burden observed with artesunate was considerably lower, 24-33%, and not significant when compared with untreated control mice. Seven-day monotherapy regimens of artemether or artesunate given at different concentrations to mice with adult S. mansoni showed total worm reductions of 53-61% or 34-49%, respectively. We conclude that artemether and artesunate are efficacious antischistosomal agents, with artemether displaying consistently higher activities. Our findings may contribute to the current strategic discussions on the effect and use of artemisinin derivatives against schistosomes when they are used in malaria chemotherapy in areas of co-endemicity of both parasites.
Utzinger
Jürg
J
Swiss Tropical Institute, P.O. Box, CH-4002 Basel, Switzerland.
Chollet
Jacques
J
Tu
Zuwu
Z
Xiao
Shuhua
S
Tanner
Marcel
M
D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage*; D000077549:Artemether; D037621:Artemisinins; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D012550:Schistosoma mansoni / Q000302:isolation & purification; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000469:parasitology; D012717:Sesquiterpenes / Q000008:administration & dosage*
D000871:Anthelmintics; D037621:Artemisinins; D012717:Sesquiterpenes; C031327:artemisinin; D000077549:Artemether