Effect of combined treatment with praziquantel and artemether on Schistosoma japonicum and Schistosoma mansoni in experimentally infected animals.
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.
Utzinger
J
J
Swiss Tropical Institute, P.O. Box, CH-4002, Basel, Switzerland.
Chollet
J
J
You
J
J
Mei
J
J
Tanner
M
M
Xiao
S
S
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
D000871:Anthelmintics; D037621:Artemisinins; D012556:Schistosomicides; D012717:Sesquiterpenes; D011223:Praziquantel; D000077549:Artemether