title: Effect of combined treatment with praziquantel and artemether on Schistosoma japonicum and Schistosoma mansoni in experimentally infected animals.
abstract: Praziquantel and artemether are safe and efficacious antischistosomal drugs that act against different developmental stages of the parasite: praziquantel against adult worms and artemether against schistosomula. A combined treatment has been suggested as a strategy for transmission control. Recent laboratory experiments with rabbits with a mixed infection of Schistosoma japonicum parasites of different ages confirmed the effectiveness of a combination therapy. In the present work, we assessed the effect of a combined treatment on adult worms of S. japonicum and found significantly higher worm reduction rates than with a single dose of praziquantel. In a next step, we extended the study of the combined treatment to Schistosoma mansoni. A combined treatment with 75 mg/kg praziquantel and 150 mg/kg artemether was administered to hamsters infected with juvenile and adult S. mansoni. The two drugs, administered simultaneously or spaced by 6 h, 1, 3 or 7 days, resulted in significantly higher worm reduction rates than a single treatment with praziquantel. A combination therapy with increased doses of 100 mg/kg praziquantel and 300 mg/kg artemether showed very high worm reduction rates of 90% and above, however, some hamsters died in five different combined treatment experiments, suggesting that these drug concentrations were too high. We conclude that a combined treatment with praziquantel and artemether at the lower doses is safe and more effective than praziquantel alone, which forms a foundation for designing respective clinical trials in humans.
authors.affiliation: Swiss Tropical Institute, P.O. Box, CH-4002, Basel, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Utzinger
authors.forename: J
authors.initials: J
authors.lastname: Chollet
authors.forename: J
authors.initials: J
authors.lastname: You
authors.forename: J
authors.initials: J
authors.lastname: Mei
authors.forename: M
authors.initials: M
authors.lastname: Tanner
authors.forename: S
authors.initials: S
authors.lastname: Xiao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000627:therapeutic use*; D000077549:Artemether; D037621:Artemisinins; D006224:Cricetinae; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D008297:Male; D011223:Praziquantel / Q000008:administration & dosage / Q000627:therapeutic use*; D011817:Rabbits; D012549:Schistosoma japonicum / Q000187:drug effects*; D012550:Schistosoma mansoni / Q000187:drug effects*; D012554:Schistosomiasis japonica / Q000188:drug therapy* / Q000469:parasitology; D012555:Schistosomiasis mansoni / Q000188:drug therapy* / Q000469:parasitology; D012556:Schistosomicides / Q000008:administration & dosage / Q000627:therapeutic use*; D012717:Sesquiterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D000871:Anthelmintics; D037621:Artemisinins; D012556:Schistosomicides; D012717:Sesquiterpenes; D011223:Praziquantel; D000077549:Artemether