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KMID : 0438219750120020425
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Korea University Medical Journal
1975 Volume.12 No. 2 p.425 ~ p.457
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Studies on the Chemotherapy of Trematode Infections in Korea
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Rim Han-Jong
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Abstract
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Trematode infections, especially clonorchiasis, paragonimiasis, heterophyidiasis and fasciolopsiasis are the most important public health problems in certain countries in the Far East and South Eastern countries. Three common species of trematodes of medical importance have been reported in Korea, namely, Clonorchis sinensis, Paragonimus westermani and Metagonimus yokogawai. These trematode infections have long been recognized as an important public health problem in Korea. There is no report of human infection of Fasciola hepatica and Eurytrema pancreaticum which are common in Korean cattle. The occurrence of Fasciolopsis buski in Korea has.not yet been reported. Some other small intestinal flukes, such as Echinostoma spp., Echinochasmus sp. and Reterophyes spp, are also found in animals, however there are of no medical importance in Korea.
Since last 10 years, there is no practically any big changes on the chemotherapy for the trematode infections except schistosomiasis. Bithionol is the drug of choice in the chemotherapy for paragonimiasis and tetrachlorethylene is the drug of choice for heterophyidiasis and fasciolopsiasis. However, there is none of the drug of choice for the treatment of clonorchiasis and opisthorchiasis up to now.
In the present study several new drugs were attempted to the clinical trials for the treatment of clonorchiasip, paragonimiasis and metagonimiasis.
The results are as follows:
1. Study on the chemotherapy for clonorchiasis
Many earlier investigators have studied the treatment of clonorchiasis with various drugs, how-ever none has proved to be effective as well as non-toxic to the host. Clonorchiasis is the most important disease in Korea, and this disease has been known to be of public health concern in many areas of southern part of Korea, but there is not any specific treatment for clonorchiasis. It would be desirable to find a therapeutic agent in the treatment of this disease.
(1). Activity of drugs on Clonorchis sinensis infection of rabbits.
In order to find a highly efficient compound against Clonorchis infection, the anthelmintic acti-
vity of hetol (1,4 bis-t rich toromethyl-benzo1), dehydroemetine and bilevon (niclofolan) were tested against C. sinensis experimentally infected rabbits. All drugs showed a progressive increase in efficacy as the dose rate. They were highly efficient against Clonorchis infection if sufficiently high, potentially toxic doses were given. The efficacy was evaluated by the number of detected worms with vital condition at autopsy after the treatment with above drugs. The high efficacy was observed at the following dose rates of each drugs, i.e. hetol at the daily doses from 50 to 100 mg/kg for 5 to 10 consecutive days, dehydroemetine at the daily dose of 10 mg/kg for at least 10 consecutive days, and a single dose of 8 mg/kg of bilevon.
(2). Clinical observation on the chemotherapeutic effect of hetol.
The therapeutic effect of hetol in various dosages and duration of medication was observed in 32 cases were treated with hetol at the dosage of 50 mg, 100 mg and 150 mg per kg body weight daily or every other day for 5 to 12 medication days. The dosage of 50 mg per kg daily for 5 medication days can obtain complete cure in the light infection cases (1-999 EPG), but the dosage for the treatment of the moderate infection (1, 000-9, 999 EPG) and heavy infection cases (10,000 and over EPG) require at least 50 mg per kg body weight daily for 12 medication days or 100 mg per kg daily for 7 medication days. However a dosage of 50 mg per kg daily for 5 to over 12 medication days depending on the severity of infection appears to be safe and appropriate for the treatment of clonorchiasis sinensis.
(3) Clinical observation on the chemotherapeutic effect of dehydroemetine
Forty-five clonorchiasis patients were treated with dehydroemetine late-release tablets. These patients were divided into 5 groups and each group was given different dosages of dehydroemetine. In the results, high effectiveness showed at the dose of 2.5 mg/kg every other day for 25 to 30 days. In most of cases the EPG of faeces turned negative from the 30th day to the 40th day of treatment, but a very small number of eggs was detected again by concentration method at their follow up for over 6 months. During and after treatment, most patients showed marked improvement, usually with disappearance of upper abdominal pain and recovery of appetite. Some side effects such as diarrhea, anorexia, weakness and headache were reported in the most treated cases. However dehydroemetine should not be given to patients with cardiac insufficiency.
(4) Clinical observation on the chemotherapeutic effect of bilevon(niclofolan)
A new drug which is bilevon (niclofolan, menichlofolan) has been used in the treatment of clonorchiasis. In order to obtain a minimum effective dose, various dosages and duration of medication of bilevon were applied for the treatment of clinical cases with different degree of infection. Bile-
von was given at the dosages of 0. 2, 0.4, 0. 8, 1. 0, and 2.0 mg/kg body weight in once or twice equally divided doses daily for one to 15 medicaion days in 35 cases consisting all degree of infection. In each 5 cases received bilevon at the doses of 0.2 mg/kg and 0.4 mg/kg body weight for 15 consecutive days, the mean egg reduction rates at 6 months after treatment were shown 69.1 per cent and 94.4 per cent respectively. On the other hand, in each 5 cases received a relatively higher doses at 0.8 mg/kg body weight for 5 consecutive days, 1.0 mg/kg for 3 consecutive days and 2.0 mg/kg for 2 consecutive days, the mean egg reduction rates were shown 95.4%, 98.9% and 99.5% respectively at 3 or 6 months after treatment. In the most cases the EPG failed rapidly in the number of Clonorchis ova within 20 days after the beginning of treatment. On follow-up examination on,3 to 6 months after treatment, most patients showed marked clinical impovement. And also in the cases previously affected liver, much improvement of their liver function test showed after treatment with bilevon. Bilevon was well tolerated, but some side effects were noted such as
with weakness, muscle pain On sacral region and lower extremities. The possibility that human clonorchiasis could be successfully treated with a few doses of bilevon can be promised from this study. Therefore, bilevon is a very promising drug for mass treatment against Clonorchis sinensis infection.
I. Study on the chemotherapy for paragonimiasis
Paragonimiasis has been known as a medically important endemic disease linked with eating habit of fresh water crustaceans, particularly in Far East Asian countries for a long time. Bithionol is the drug of choice in paragonimiasis and has been used extensively in the past 15 years. However, the multiple doses and it´s side reactions are hampered. in mass treatment with bithionol in the field. In the present study bilevon has been used in the treatment of paragonimiasis for the first time. The experimental chemotherapy with bilevon for the infected dogs and cats with P, westermani were carried out. It was proved that a single or two doses of 2.0 mg/kg of bilevon were evidently effective for the infected dogs or cats with the lung fluke.
In the clinical trial 25 paragonimiasis cases who have shown the eggs in their bloody sputa were treated with bilevon at a single dose of 2.0 mg/kg body weight. The number of eggs and the amounts of sputa were gradually decreased until 3 weeks after medication. The eggs in sputa of all cases were disappeared within one month after medication, and no relapses were found from the results of the follow-up investigations during the period from 6 to 12 months after medication. Fifteen out of 25 cases were examined periodically chest X-ray. Among them 5 cases who have shown abnormal X-ray shadows disappeared between the period from 2 to 4 months after medication. Bilevon was well tolerated and side effects were noted as transient weakness and muscle pain on sacral region in some cases but did not require treatment. There was no significant alteration in ECG, blood counts, blood biochemistry and urine analysis of all 15 cases before and after med-
ication. The possibility that human paragonimiasis could be successfully treated with a single dose of bilevon can be presumed from this study. Therefore, bilevon is a very promising drug for mass treatment against paragonimiasis as well as clonorchiasis.
1. Study on the chemotherapy for metagonimiasis
The heterophyids are extremely small flukes inhabiting the intestine of man and fish eating mammals and birds. The infection of Metagonimus yokogawai has been known to be present nationwidely and endemic in some parts of Korea. In order to select a highly effective compound against Metagonimus infection, the therapeutic effects were observed in 101 cases were treated with several anthelmintics, i, e, tetrachlorethylene, bephenium hydroxynaphthoate (alcopar) , pyrantel pamoate (combantrin), oxantel and pyrantel pamoate mixture and niclosamide (yomesan) . Among the above drugs Metagonimus was removed by tetrachlorethylene and niclosamide at a single dose. From the results niclosamide was well tolerated, and no side effects were observed. Overall egg reduction rate was 96.2 per cent and radical cure was obtained by using a dosage of 100-125 mg/kg body weight in children.
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