[Therapeutic effect of tribendimidine, artesunate and praziquantel administered to hamsters infected with Clonorchis sinensis].
OBJECTIVE
To observe the effect of tribendimidine, artesunate and praziquantel in treatment of hamsters (Mesocricetus auratus) infected with Clonorchis sinensis.


METHODS
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.


RESULTS
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.


CONCLUSIONS
In hamster model, tribendimidine and praziquantel exhibit promising effect against both juvenile and adult C. sinensis, while artesunate is only efficacious against adult worms.
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.
Jian
J
Xue
Li-Li
LL
Xu
Hui-Qin
HQ
Qiang
Yong-Nian
YN
Zhang
Shu-Hua
SH
Xiao
D000818:Animals; D000871:Anthelmintics / Q000627:therapeutic use*; D037621:Artemisinins / Q000627:therapeutic use*; D000077332:Artesunate; D003003:Clonorchiasis / Q000188:drug therapy*; D003004:Clonorchis sinensis / Q000187:drug effects*; D006224:Cricetinae; D008647:Mesocricetus; D010655:Phenylenediamines / Q000627:therapeutic use*; D011223:Praziquantel / Q000627:therapeutic use*; D016896:Treatment Outcome
D000871:Anthelmintics; D037621:Artemisinins; D010655:Phenylenediamines; C056017:tribendimidine; D000077332:Artesunate; D011223:Praziquantel