Effect of combined treatment with praziquantel and artemether on Schistosoma japonicum and Schistosoma mansoni in experimentally infected animals

• Published in: Acta tropica 2001-09, Vol.80 (1), p.9-18
• Main Authors: Utzinger, Jürg, Chollet, Jacques, Jiqing, You, Jinyan, Mei, Tanner, Marcel, Shuhua, Xiao
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Anthelmintics - administration & dosage; Anthelmintics - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Artemether; Artemisinins; Biological and medical sciences; Combined treatment; Cricetinae; Disease Models, Animal; Drug Therapy, Combination; Female; Male; Medical sciences; Pharmacology. Drug treatments; Praziquantel; Praziquantel - administration & dosage; Praziquantel - therapeutic use; Rabbits; Schistosoma japonicum; Schistosoma japonicum - drug effects; Schistosoma mansoni; Schistosoma mansoni - drug effects; Schistosomiasis; Schistosomiasis japonica - drug therapy; Schistosomiasis japonica - parasitology; Schistosomiasis mansoni - drug therapy; Schistosomiasis mansoni - parasitology; Schistosomicides - administration & dosage; Schistosomicides - therapeutic use; Sesquiterpenes - administration & dosage; Sesquiterpenes - therapeutic use; Time Factors; Tropical medicine
• ISSN: 0001-706X; 1873-6254
• DOI: 10.1016/S0001-706X(01)00138-3

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.