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: praziquan tel against adult worms and artemether against schistosomula. A combined tr eatment has been suggested as a strategy for transmission control. Recent l aboratory experiments with rabbits with a mixed infection of Schistosoma ja ponicum parasites of different ages confirmed the effectiveness of a combin ation therapy. In the present work. we assessed the effect of a combined tr eatment 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 com bined treatment with 75 mg/kg praziquantel and 150 mg/kg artemether was adm inistered to hamsters infected with juvenile and adult S. mansoni. The two drugs, administered simultaneously or spaced by 6 h, 1, 3 or 7 days, result ed in significantly higher worm reduction rates than a single treatment wit h praziquantel. A combination therapy with increased doses of 100 mg/kg pra ziquantel and 300 mg/kg artemether showed very high worm reduction rates of 90% and above, however, some hamsters died in five different combined trea tment 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 f orms a foundation for designing respective clinical trials in humans. (C) 2 001 Elsevier Science B.V. All rights reserved.