Many earlier investigators have studied the treatment of clonorchiasis with antimony preparations, gentian violet, emetine hydrochloride, chloroquine diphosphate, bithionol and dithiazanine iodide etc. However, clinical improvement and negative or reduced egg counts were temporarily noted but the permanent results were questionable.
. Since 1965, in Japan and Korea, the extensive investigations of 1, 4-bis-trichloromethylbenzol (Hetol) in human clonorchiasis have been strongly suggested that the drug is highly promising as the therapeutic agent. Hexachloroparaxylol, which is supposed to be the same compound as Hetol, is used for the treatment of clonorchiasis in China and opisthorchiasis in USSR. However, Hoechst AG, the maker of Hetol, stopped its production because in chronic toxicity tests using even 60 mg/kg bwt for 30 consecutive days on dogs, it caused remarkable hypochromic anemia by the end of study.
Prolonged oral dehydroemetine treatment and only two doses of niclofolan (Bayer 9015, Bilevong) treatment are shown both therapeutic effect on Clonorchis infection in animals as well as in human being by killing the flukes in bile ducts. However the side reactions are observed in the most of treated cases.
Recently Rim et al. treated successfully human clonorchiasis with a new drug, praziquantel (Embay 8440; BiltricideO), which is known as an excellent activity against all species of cestodes and schistosomes in man and animals. According to them, 3 doses of 25 mg/kg bwt of praziquantel in a single day or 2 days treatment could obtain complete cure without any serious side effects.
Praziquantel has shown marked biological activity against C. sinensis in vitro and in experimental animals. It was found that worms were contracted and intensive vacuolization occurred at distinct sites of the tegument in vitro experiments. In the fine structural changes of C. sinensis obtained from experimentally infected rats after treatment, the degeneration of mitochondria and vesicles in the nerve bulb of the sensory papillae around two suckers and excretory pore was observed at 6 hours after treatment. After 12 hours degenerated changes on the tegument of C. sinensis were occurred by a considerable vacuolization of the tegumental syncytium near the sensory papillae. The vacuolization had increased markedly in the course of time and formed bleb-like structures. The bleb-like structures
were increased in number all over the surface of the worm. The balloon-shaped structure formed at ante. for part of worm from 12 hours after treatment is supposed to be caused by t)e accumulated excretory material due to the loss of excretory function. Therefore the bleb-like structure on the surface of worms led to its death by the bursting of the tegument in this region.
From the above results, in the activity of praziquantel against C. sinensis, contraction and subsegien. paralysis due to the degeneration of vesicle in the nerve bulb of the sensory papillae around the suckers must be regarded as a primary effect of praziquantel. We know that most of Clonorchis worms are primarily affected in such a way that they are immobilized and dislodged through common bile duct into the intestine. This result was demonstrated by collecting tae non-damaged Clonorchis worms from the diarrheic stools in a few hours after the appl`(at*)n of a single dose of 40mg/kg of praziquantel.
In the animal experiments, praziquantel showed a high degree of activity against young larvae as well as adult worms of C. sinensis. It was equally effective against all developmetnal stages of C. sinensis. Therefore praziquantel has a high chemoprophylactic activity against C. sinensis infection.
Praziquantel was well tolerated and side effects consisted particularly of mild and transient headache, dizziness and abdonimal discomfort etc. However, there was no any differences in regard to frequency and intensity of untoward side effects among the different dosage groups.
Concerning of the Clonorchis infection in Korean population, clonorchiasis represents a major clinical and socio-economic problems in the southern Korea. It is therefore important that effort should be made to control of clonorchiasis in endemic area. The results obtained in the field studies suggest that a single dose of 40 mg/kg bwt for light infection, 2 x 30 mg/ kg bwt for moderate infection and 3 x 25 mg/kg bwt for heavy infection group will be recommended for mass campaigns to the clonorchiasis patients with praziquantel. This may have important financial implications, especially in population control programmes.
Considering the ease of administration and the good acceptance as well as very good efficacy, praziquantel will have a great role to play in the control of clonorchiasis in the near future.
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