title: Effects of artemether, artesunate and dihydroartemisinin administered orally at multiple doses or combination in treatment of mice infected with Schistosoma japonicum.
abstract: Artemether and artesunate, derivatives of the antimalarial artemisinin, as well as their main metabolite, dihydroartemisinin, all exhibit antischistosomal activities. The purpose of the current study was to compare the effects of artemether, artesunate and dihydroartemisinin administered orally at multiple doses or combination in treatment of mice infected with Schistosoma japonicum. We carried out experiments with mice, infected with 40 cercariae of S. japonicum, and treated with artemether, artesunate and dihydroartemisinin (all at a single dose of 300 mg/kg, and the dose of the mixed three drugs is also 300 mg/kg) at multiple doses or combination therapy on days 6-8 or 34-36 post-infection. Administration with artemether, artesunate or dihydroartemisinin for 3 successive days reduced total worm burdens by 79.5-86% (30.86 ± 4.98 of mean total worm burden in control), female worm burdens by 79.4-86.7% (11.29 ± 2.63 of mean female worm burden in control) (all P values <0.01 vs. control), depending on different treatment protocols given on days 6-8 post-infection. However, no differences were seen between each treatment group (all P > 0.05). While the same treatment was given on days 34-36 post-infection, total worm burden reductions of 73.8-75.8% were achieved (29.44 ± 3.36 of mean total worm burden in control), which were significant when compared with the untreated control group (all P values <0.01). In all different treatment groups, female worm reductions (ranging from 88.7% to 93.1%, while the mean female worm burden in control is 10.33 ± 1.80) were consistently higher than the total worm reductions, resulting always in significantly lower female worm burdens when compared to the corresponding control (all P values < 0.01). However, there were no significant differences found between each treatment group (all P values >0.05). It is concluded that artemether, artesunate and dihydroartemisinin can be used to control schistosomiasis japonica, as a strategy to prevent S. japonicum infection. Administration with artemether, artesunate and dihydroartemisinin at multiple doses or in combined treatment damages both juvenile and adult S. japonicum, without statistically significant differences among the three drugs at the same dose.
authors.affiliation: Jiangsu Institute of Parasitic Diseases, Key Laboratory on Technology for Parasitic Disease Prevention and Control, Ministry of Health, 117 Yangxiang, Meiyuan, Wuxi, 214064 Jiangsu Province, China.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: You-Zi
authors.initials: YZ
authors.lastname: Li
authors.forename: Guo-Li
authors.initials: GL
authors.lastname: Qu
authors.forename: Yun-Tian
authors.initials: YT
authors.lastname: Xing
authors.forename: Yong-Hui
authors.initials: YH
authors.lastname: Tao
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wei
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Dai
authors.forename: You-Sheng
authors.initials: YS
authors.lastname: Liang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage*; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage*; D000077332:Artesunate; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D012376:Rodent Diseases / Q000188:drug therapy; D012549:Schistosoma japonicum / Q000187:drug effects*; D012554:Schistosomiasis japonica / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000981:Antiprotozoal Agents; D037621:Artemisinins; D000077332:Artesunate; C039060:artenimol; D000077549:Artemether