Xue Jian, Xu Li-Li, Qiang Hui-Qin, Zhang Yong-Nian, Xiao Shu-Hua
National Institute of Parasitic Diseases, Chinese Center for Disease Prevention and Control, Key Laboratory of Parasite and Vector Biology, MOH, WHO Collaborating Centre for Malaria, Schistosomiasis and Filariasis, Shanghai 200025, China.
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2009 Jun;27(3):215-8.
To observe the effect of tribendimidine, artesunate and praziquantel in treatment of hamsters (Mesocricetus auratus) infected with Clonorchis sinensis.
A total of 93 hamsters, each infected with 30 C. sinensis metacercariae, were treated intragastrically with above-mentioned drugs at a single dose. (1) In order to observe the effect of the drugs against juvenile C. sinensis, 20 out of 31 infected hamsters were randomly divided into 4 groups (5 hamsters per group) 14 d post-infection: artesunate 300 mg/kg, tribendimidine 100 mg/kg or 200 mg/kg, and praziquantel 200 mg/kg. Other 6 hamsters were divided equally into 2 groups 24 d post-infection and treated with tribendimidine 200 mg/kg and artesunate 300 mg/kg, respectively. The remained 5 untreated hamsters served as control. (2) Twenty-two hamsters were randomly divided into 5 groups (4-5 hamsters per group) 28 d post-infection and treated with tribendimidine 25 mg/kg or 50 mg/kg, artesunate 25 mg/kg and praziquantel 50 mg/kg, respectively. Other untreated hamsters served as control. (3) Forty hamsters 28 d after infection were randomly divided into 8 groups (4-6 hamsters per group) and treated with tribendimidine 50 mg/kg, 100 mg/kg or 200 mg/kg, artesunate 100 mg/kg or 200 mg/kg, praziquantel 100mg/kg or 200mg/kg, respectively. The remained hamsters served as control. All hamsters were sacrificed 14 d post-treatment and worms were recovered from the bile duct and liver tissue. The mean worm burden and its reduction were calculated. The differences of mean worm burden between each treated group and the corresponding control were analyzed statistically.
In hamsters infected with 14-d-old C. sinensis and treated orally with tribendimidine at a single dose of 100 or 200 mg/kg, the mean worm burdens were significantly lower than that of the control (P<0.01) with a worm reduction of 90.6% and 85.9% respectively. The mean worm burden obtained from the infected hamsters treated with praziquantel at a single dose of 200 mg/kg was also significantly lower than that of the control (P<0.05) with a worm reduction of 71.9%. However, the difference of mean worm burden between artesunate and control groups was not statistically significant. The juvenile parasites developed into adult worms 24 d after infection. By administering tribendimidine 200 mg/kg to the adult C. sinensis-infected hamsters, the mean worm burden was significantly lower than that of the control (P<0.01) with a worm reduction of 89.8%. Whilst the administration of artesunate at a higher dose of 300 mg/kg, all hamsters were cured. Further tests indicated that tribendimidine in a lower dose of 25 mg/kg to the hamsters 28 d after infection resulted in a significantly lower mean worm burden compared to the control (P<0.05) with a worm reduction of 71.8%. With an increased dose of tribendimidine 100 mg/kg, all hamsters were cured. The worm reduction was only 20.0% and 56.4% when 25 mg/kg and 100 mg/kg of artesunate were administered. With 200 mg/kg artesunate, the worm reduction reached as high as 98.5% and the mean worm burden was significantly lower than that of the control (P<0.01). Furthermore, administration of praziquantel at a dose of 100 mg/kg or 200 mg/kg at 28 d post-infection resulted in a significantly lower mean worm burden than that of the control (P<0.05) with a worm reduction of 78.9% and 83.5% respectively.
In hamster model, tribendimidine and praziquantel exhibit promising effect against both juvenile and adult C. sinensis, while artesunate is only efficacious against adult worms.
观察三苯双脒、青蒿琥酯和吡喹酮对感染华支睾吸虫的金黄仓鼠的治疗效果。
选取93只感染30条华支睾吸虫囊蚴的金黄仓鼠,单剂量灌胃给予上述药物。(1)为观察药物对华支睾吸虫幼虫的作用,感染后14天,将31只感染仓鼠中的20只随机分为4组(每组5只):青蒿琥酯300mg/kg、三苯双脒100mg/kg或200mg/kg、吡喹酮200mg/kg。另外6只仓鼠在感染后24天平均分为2组,分别给予三苯双脒200mg/kg和青蒿琥酯300mg/kg。其余5只未治疗的仓鼠作为对照。(2)感染后28天,将22只仓鼠随机分为5组(每组4 - 5只),分别给予三苯双脒25mg/kg或50mg/kg、青蒿琥酯25mg/kg和吡喹酮50mg/kg。其余未治疗的仓鼠作为对照。(3)感染后28天,将40只仓鼠随机分为8组(每组4 - 6只),分别给予三苯双脒50mg/kg、100mg/kg或200mg/kg、青蒿琥酯100mg/kg或200mg/kg、吡喹酮100mg/kg或200mg/kg。其余仓鼠作为对照。所有仓鼠在治疗后14天处死,从胆管和肝组织中回收虫体。计算平均虫荷及其减少率。对各治疗组与相应对照组的平均虫荷差异进行统计学分析。
感染14日龄华支睾吸虫的仓鼠,单剂量口服100mg/kg或200mg/kg三苯双脒后,平均虫荷显著低于对照组(P<0.01),虫体减少率分别为90.6%和85.9%。单剂量200mg/kg吡喹酮治疗的感染仓鼠的平均虫荷也显著低于对照组(P<0.05),虫体减少率为71.9%。然而,青蒿琥酯组与对照组的平均虫荷差异无统计学意义。感染后24天幼虫发育为成虫。给予感染华支睾吸虫成虫的仓鼠200mg/kg三苯双脒,平均虫荷显著低于对照组(P<0.01),虫体减少率为89.8%。而给予300mg/kg较高剂量青蒿琥酯时,所有仓鼠均被治愈。进一步试验表明,感染后28天给予仓鼠25mg/kg较低剂量三苯双脒,其平均虫荷显著低于对照组(P<0.05),虫体减少率为71.8%。三苯双脒剂量增加到100mg/kg时,所有仓鼠均被治愈。给予25mg/kg和100mg/kg青蒿琥酯时,虫体减少率分别仅为20.0%和56.4%。给予200mg/kg青蒿琥酯时,虫体减少率高达98.5%,平均虫荷显著低于对照组(P<0.01)。此外,感染后28天给予100mg/kg或200mg/kg吡喹酮,平均虫荷显著低于对照组(P<0.05),虫体减少率分别为78.9%和83.5%。
在仓鼠模型中,三苯双脒和吡喹酮对华支睾吸虫幼虫和成虫均有良好疗效,而青蒿琥酯仅对成虫有效。