Keiser Jennifer, Vargas Mireille
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, Basel, Switzerland.
Parasitol Int. 2010 Sep;59(3):472-6. doi: 10.1016/j.parint.2010.04.003. Epub 2010 Apr 20.
We investigated the morphological effects of half-strength treatments with praziquantel, artemether, artesunate, OZ78 and tribendimidine as well as combinations of praziquantel with artemether, artesunate, OZ78 and tribendimidine and an artesunate-tribendimidine combination in rats harboring adult Clonorchis sinensis. Rats were infected with C. sinensis, dosed orally with single agents or combination treatments and flukes recovered at 3 or 5 days post-treatment. The number of flukes was counted, the viability recorded and surface changes monitored by scanning electron microscopy. Drug effects induced by the individual drugs at sub-curative doses 3 days post-treatment were minor with the exception of flukes recovered from rats treated with artemether and tribendimidine. Treatment with the praziquantel combinations of artesunate, OZ78 and tribendimidine did not produce a greater disruption of the tegument than the individual drugs 3 days post-treatment. On the other hand, at this time point many worms treated with artemether-praziquantel had died and eruptions, roughening or blebbing were observed on all worms examined. Five days post-treatment flukes exposed to any of the praziquantel combinations in rats had died. Rats treated with an artesunate-tribendimidine combination resulted in a rapid death of flukes, 3 days post-treatment all worms had been expelled. In conclusion, we have confirmed the promising clonorchicidal properties of different drug combinations in rats. Differences in the extent and time-scale of tegumental disruption have been observed. The effect of drug combinations against C. sinensis requires further scientific inquiry, e.g. in transmission electron microscopy studies and in the C. sinensis-rabbit model.
我们研究了吡喹酮、蒿甲醚、青蒿琥酯、OZ78和三苯双脒半量治疗以及吡喹酮与蒿甲醚、青蒿琥酯、OZ78和三苯双脒的联合用药，还有青蒿琥酯 - 三苯双脒联合用药对感染华支睾吸虫成虫的大鼠的形态学影响。大鼠感染华支睾吸虫后，口服单药或联合治疗药物，在治疗后3天或5天回收虫体。计算虫体数量，记录活力，并通过扫描电子显微镜监测表面变化。除了从用蒿甲醚和三苯双脒治疗的大鼠中回收的虫体外，治疗后3天各单药在亚治疗剂量下引起的药物效应较小。治疗后3天，吡喹酮与青蒿琥酯、OZ78和三苯双脒的联合用药对虫体皮层的破坏程度并不比单药更大。另一方面，在这个时间点，许多用蒿甲醚 - 吡喹酮治疗的虫体已经死亡，并且在所有检查的虫体上都观察到了表皮破溃、粗糙或起泡现象。治疗后5天，大鼠中暴露于任何吡喹酮联合用药的虫体均已死亡。用青蒿琥酯 - 三苯双脒联合治疗的大鼠导致虫体迅速死亡，治疗后3天所有虫体均被排出。总之，我们已经证实了不同药物组合在大鼠体内具有良好的杀华支睾吸虫特性。观察到了皮层破坏程度和时间尺度的差异。药物组合对华支睾吸虫的作用需要进一步的科学研究，例如在透射电子显微镜研究和华支睾吸虫 - 兔模型中。
