Effect of artemether on Schistosoma mansoni: dose-efficacy relationship, and changes in worm morphology and histopathology.
OBJECTIVE
To investigate the effects of artemether on Schistosoma mansoni harboured in mice, with particular consideration on single dose-efficacy relationship, hepatic shift and artemether-induced alterations in worm morphology and histopathology.


METHODS
Groups of mice, infected with 21 d old S. mansoni, were treated with artemether at single oral doses of 12.5 mg/kg to 600 mg/kg. Worm burden reduction was assessed 28 d post-treatment. The hepatic shift was investigated in mice infected with 46 d old S. mansoni and treated with artemether at a single oral dose of 400 mg/kg within a period of 14 d post-treatment. Morphological and histopathological observations were made in adult worms in mice, subject to single oral dose of artemether at 400 mg/kg.


RESULTS
The minimum effective dose of oral artemether against juvenile worms in mice was 200 mg/kg, resulting in a worm burden reduction of 81%. The hepatic shift commenced 8 h post-treatment, and all worms shifted to the liver 3-7 d post-treatment. Fourteen days post-treatment, 31% of the worms returned to the mesenteric veins. Treatment with artemether resulted in decreased worm body size, expansion of the pharynx and dilation of the gut with marked reduction in pigment. Focal tegumental damage was observed among female worms with adherence of host leukocytes and degeneration of ovary and vitelline glands, as well as atrophy of testis in male worms. Artemether-damaged worms were surrounded and infiltrated by eosinophils.


CONCLUSIONS
The minimum effective dosage of artemether against 21 d old S. mansoni in mice is 200 mg/kg. Artemether also exhibits effect against adult schistosomes, including shrinkage and degeneration, and can lead to worm death. The predominant inflammatory cell surrounded and infiltrated into the artemether-damaged worm is eosinophil.
Xiao
Shu-hua
SH
National Institute of Parasitic Diseases, Chinese Centre for Disease Control and Prevention, Shanghai 200025, China. shxiao1@yahoo.com
Guo
Jian
J
Chollet
Jacques
J
Wu
Jia-tong
JT
Tanner
Marcel
M
Utzinger
Jurg
J
D000818:Animals; D000077549:Artemether; D037621:Artemisinins / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000469:parasitology / Q000473:pathology; D051379:Mice; D012550:Schistosoma mansoni / Q000166:cytology / Q000187:drug effects*; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000473:pathology; D012556:Schistosomicides / Q000494:pharmacology* / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use
D037621:Artemisinins; D012556:Schistosomicides; D012717:Sesquiterpenes; D000077549:Artemether