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蒿甲醚作为吡喹酮治疗小鼠埃及曼氏血吸虫病的辅助疗法。

Artemether as adjuvant therapy to praziquantel in murine Egyptian schistosomiasis mansoni.

作者信息

Mahmoud M R, Botros S S

机构信息

Pharmacology Department, Theodor Bilharz Research Institute, Giza 12411, Egypt.

出版信息

J Parasitol. 2005 Feb;91(1):175-8. doi: 10.1645/GE-322R.

Abstract

We investigated the activity of artemether (ART) against different developmental stages of schistosomes alone and in addition to praziquantel (PZQ). ART was administered orally (400 mg/kg) 4 and 6 wk postinfection (PI), 4 and 5 wk PI, or 4 or 6 wk PI alone and in addition to oral PZQ (500 x 2 mg/kg) 6 wk PI. Mice were killed in parallel to infected untreated controls 8 wk PI. Parasitological parameters and histological changes in the liver were studied. ART given 4 and 6 wk PI reduced worm burdens by 59 and 55% and tissue egg load by 96 and 90%, respectively. Moreover, eggs in different developmental stages were not found. The reduction in worm and egg burden (63 and 58%, and 96 and 99%, respectively) in mice treated with ART 4 and 5 wk or 4 and 6 wk PI was comparable with that in ART-treated mice at 4 or 6 wk PI. Compared with PZQ alone, combined treatment of PZQ and ART (4 and 5 wk or 4 and 6 wk PI) did not enhance worm eradication, but there was a complete absence of parasite eggs. Livers revealed no granulomata when ART was given 4 and 5 wk or 4 and 6 wk PI, with minimal central necrosis in those treated 4 and 6 wk PI. In conclusion, combined treatment of ART (4 and 6 wk PI) and PZQ resulted in >90% worm eradication and amelioration of Schistosoma mansoni eggs from the tissues, with minor histological changes in the liver.

摘要

我们研究了蒿甲醚(ART)单独以及联合吡喹酮(PZQ)对血吸虫不同发育阶段的活性。蒿甲醚在感染后(PI)4周和6周、4周和5周口服(400mg/kg),或仅在感染后4周或6周口服,此外在感染后6周口服PZQ(500×2mg/kg)。在感染后8周,将小鼠与未治疗的感染对照平行处死。研究了寄生虫学参数和肝脏的组织学变化。在感染后4周和6周给予蒿甲醚分别使虫负荷减少59%和55%,组织虫卵负荷减少96%和90%。此外,未发现处于不同发育阶段的虫卵。在感染后4周和5周或4周和6周用蒿甲醚治疗的小鼠中,虫和卵负荷的减少(分别为63%和58%,以及96%和99%)与在感染后4周或6周用蒿甲醚治疗的小鼠相当。与单独使用吡喹酮相比,联合使用吡喹酮和蒿甲醚(感染后4周和5周或4周和6周)并未增强驱虫效果,但完全没有寄生虫卵。当在感染后4周和5周或4周和6周给予蒿甲醚时,肝脏未显示肉芽肿,在感染后4周和6周治疗的小鼠中仅有轻微的中央坏死。总之,联合使用蒿甲醚(感染后4周和6周)和吡喹酮可使曼氏血吸虫的虫体清除率>90%,并减轻组织中的虫卵,肝脏的组织学变化较小。

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