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[A Study On The Chemotherapy In Clonorchiasis: Report 1. An Experimental Study On Chemotherapy With Dithiazanine Iodide And Bithionol Sulfoxide In Clonorchiasis]

Authors carried out experimental study on chemotherapy with oral administration of Dithiazanine iodide (D.I.) and Bithionol sulfoxide(B.S.) in rabbit clonorchiasis. And the following result was obtained. 1)In change of the E.P.G (eggs per gram feces) by D.I. administration, it was rather increased in early stage of the administration than prior to administration, and thereafter decreased gradually. 2)In the change of the C.S. worm body by D.I. administration, there was not only prominent change of supporting tissue but also the change of reproductive organ was found. 3)In considering the wormicidal effect of D.I. from detecting rate of survival worms, the effect was slight in group of 100 mg(80 mg/kg) per day dosage, but the effects were very excellent and almost complete by proper times of administration in groups of 200 mg (130 mg/kg) per day or higher dosage. 4)But the side effect and intoxication sign of D.I. were appearent in groups of 200 mg or higher dosage. 5)By B.S. administration, E.P.G. was decreased gradually. 6)In changes of the C.S. worm body by B.S. administration, prominent inhibitory chnnge was seen in egg formation ability. 7)Slight wormicidal effect of B.S. was observed in groups of 140 mg (100 mg/kg) per day or higher dosage. 8)Side effect and intoxication sign of B.S. were found little in groups of 140 mg or lesser dosage.

Journal Article↗

[A Study On The Chemotherapy In Clonorchiasis. Report: 3. The Patho-Histological Study On The Liver Of Rabbit Healed From Clonorchiasis By Chemotherapy]

In the experimental rabbits which were previously infected with Clonorchis sinensis and were thereafter administered with Dithiazanine iodide, the patho-histological and some histochemical changes were observed in the healed liver(76 days after stoppage of egg excretion). And also, the patho-histological changes which appeared in the infected and healed livers respectively were compared from each other. The following results and conclusion were obtained. 1)In the infected group, grossly the liver showed a considerable increase of its weight, an increased vascular marking of its surfaces and an increase in consistency and thickness of the bile ducts. However, the healed group grossly showed no remarkable changes in the liver. 2)In the infected group, microscopically the liver showed a marked adenomatous hyperplasia of bile ducts, proliferation of bile ductules and marked periductal and periductular fibrosis with infiltration of chronic inflammatory cells in portal spaces. A histochemical study showed that the increased fibrous tissue consists largely with collagenous fibers and partly with reticulum fibers. 3)In the group with healed liver microscopically the liver showed much improvement in the histopathological changes compared to those of the infected group. In the healed lover there remained only slight histopathological changes mainly in portal spaces of the liver, such as considerably diminished periductal and periductular fibrosis. The slightly increased fibrous tissue consists largely with reticulum fibers and partly with collagen fibers.

Journal Article↗

Clinical and epidemiological features of patients with clonorchiasis.

AIM: To study the clinical and epidemiological features of patients with clonorchiasis so as to provide scientific evidences for the diagnosis and prevention of clonorchiasis. METHODS: Stools from 282 subjects suspected of having clonorchiasis were examined for helminth eggs with modified Kato's thick smear and sedimentation methods, and their sera were tested for HAV-DNA, HBV-DNA, HCV-RNA, HDV-RNA and HEV-RNA with polymerase chain reaction (PCR). Clinical symptoms of patients with clonorchiasis only were analyzed, and their blood samples were tested for circulating antigen (CAg) with Dot-ELISA, eosinophilic granulocyte count, and alanine aminotransferase (ALT). Meanwhile, they were asked to provide data of occupation, eating habit, hygienic habit and knowledge of clonorchiasis. In addition, the ecosystem of the environment in epidemic areas was surveyed. RESULTS: Among the 282 patients, 61 (21.43%) were infected with clonorchis sinensis only, 97 (34.64%) were co-infected with clonorchis sinensis and other pathogens, 92 (32.86%) were infected with hepatitis virus only and 31 (11.07%) neither with clonorchis sinensis nor hepatitis virus. Among the 61 patients with clonorchiasis only, there were 14 (22.95%) subjects with discomfort over hepatic region or epigasfrium, 12 (19.67%) with general malaise or discomfort and inertia in total body, 6 (9.84%) with anorexia, indigestion and nausea, 4 (6.56%) with fever, dizziness and headache (6.56%), and 25 (40.98%) without any symptoms; sixty one (100%) with CAg (+), 98.33% (59/60) with eosinophilic granulocytes increased and 65.00% (39/60) with ALT increased. B-mode ultrasonography revealed 61 cases with dilated and thickened walls of intrahepatic bile duct, and blurred patchy echo acoustic image in liver. Twenty-six cases had stones in the bile duct, 39 cases had slightly enlarged liver with diffuse coarse spots in liver parenchyma. Twenty cases had enlarged gallbladder with thickened coarse wall and image of floating plagues, 9 cases had slightly enlarged spleen. By analysis of epidemiological data, we found that the ecologic environment was favorable for the epidemiology of clonorchiasis. Most patients with clonorchiasis were lack of knowledge about the disease. Their living environment, hygienic habits, eating habits and their occupations were the related factors that caused the prevalence of the disease. CONCLUSION: The clinical symptoms of clonorchiasis are non-specific, and the main evidences for diagnosis of clonorchiasis should be provided by etiologic examination, B-mode ultrasonography and clinical history. The infection of clonorchis sinensis is related to occupations, bad eating habits and lack of knowledge about prevention of the disease.

Adolescent↗

Clonorchiasis and cholangiocarcinoma: etiologic relationship and imaging diagnosis.

Despite a gradual decrease in prevalence, clonorchiasis is still prevalent in East Asia. A large and compelling body of evidence links clonorchiasis and cholangiocarcinoma, although the mechanisms involved are not completely understood. Clonorchiasis induces biliary epithelial hyperplasia and metaplasia, and this could facilitate at least one stage of the carcinogenesis, which is promoting effect. In areas of endemic infection, more clonorchiasis cases are now diagnosed incidentally during radiological examinations such as cholangiography, ultrasonography, and computed tomography. Radiological findings are regarded as pathognomonic for clonorchiasis since they reflect the unique pathological changes of this disorder. These radiological examinations currently play important roles in the diagnosis, staging, and decision-making process involved in the treatment of cholangiocarcinoma. The morphological features and radiological findings of clonorchiasis-associated cholangiocarcinoma are essentially combinations of the findings for the two diseases. The morphological features of clonorchiasis- associated cholangiocarcinoma, observed in radiological examinations, do not differ from those of the usual cholangiocarcinoma. In patients diagnosed with or suspected to have clonorchiasis, radiological findings should be carefully scrutinized for occult cholangiocarcinoma.

Adult↗

A Clonorchis sinensis-specific antigen that detects active human clonorchiasis.

A Clonorchis sinensis-specific antigen in excretory-secretory product of C. sinensis (CsE) was assessed in human clonorchiasis by immunoblot. Thirty and 7 kDa antigens of CsE2, one of four different batches of CsEs reacted strongly with infection sera from clonorchiasis patients; however, the antigens reacted weakly with 6-month post-treatment sera from praziquantel-cured cases, but were still highly detected by the sera from praziquantel-failed patients, indicating that the 30 and 7 kDa antigens can detect antibodies during an active infection. The 30 kDa antigen showed some cross reactions with sera from patients with Paragonimus westermani and Metagonimus yokogawai, while the 7 kDa antigen did not, suggesting that the 7 kDa antigen has high specificity. The 30 kDa antigen reacted with some past clonorchiasis sera, whereas the 7 kDa antigen did not, supporting that antibodies to the 7 kDa antigen are not present in sera from past clonorchiasis patients. In an endemic area, 92% (23/25) of active clonorchiasis patients and 91% (10/11) of mixed infection patients with C. sinensis and M. yokogawai had IgG antibodies to the 7 kDa antigen, while 40% (6/15) of past clonorchiasis individuals and 43% (3/7) of metagonimiasis patients cross-reacted to the antigen. These data suggest that the 7 kDa antigen in an excretory-secretory antigen may serve as a marker of an active clonorchiasis with reliable specificities in past clonorchiasis, paragonimiasis and metagonimiasis.

Animals↗

Clonorchiasis: a key foodborne zoonosis in China.

The oriental liverfluke, Clonorchis sinensis, is of major socioeconomic importance in parts of Asia, including China, Japan, Korea, Taiwan, and Vietnam. The parasite is transmitted via snails to freshwater fish, and then to human beings and other piscivorous mammals, and causes substantial clinical or subclinical disease, known as clonorchiasis. There is considerable evidence for an aetiological relation between clonorchiasis and cholangiocarcinoma in human beings. It is estimated that about 35 million people are infected globally, of whom approximately 15 million are in China. Although very little information from China has been published in the English language, recent analyses of epidemiological data sets suggest that clonorchiasis is having an increased human-health impact due to the greater consumption of raw freshwater fish. To gain an improved insight into clonorchiasis in China, this review provides a background on the parasite and its life cycle, summarises key aspects regarding the pathogenesis, diagnosis, and treatment of clonorchiasis, describes the geographic distribution and prevalence of clonorchiasis, and makes some recommendations for future research and the control of this important disease.

Animals↗

CT findings of clonorchiasis.

Clonorchiasis is a snail-transmitted trematodiasis caused by Chinese liver fluke, Clonorchis sinensis. Forty-two patients with the disease were examined with CT. Seventeen patients had clonorchiasis alone, and 25 patients had clonorchiasis with hepatobiliary malignancies (20 cholangiocarcinomas, four hepatocellular carcinomas, one carcinoma of the ampulla of Vater). In three of the 17 patients with clonorchiasis alone, the CT scans were normal. In 14 patients (82%), CT showed diffuse, minimal, or mild dilatation of the intrahepatic bile ducts. None of the patients had marked dilatation. The extrahepatic biliary tree was normal in all 17 patients. All 25 patients with clonorchiasis and hepatobiliary malignancies had diffuse dilatation of the intrahepatic bile ducts on CT, including 18 patients with minimal or mild dilatation and seven patients with marked dilatation. All seven patients with marked dilatation had extrahepatic biliary malignancies. Clonorchis sinensis per se or thickening of the bile duct wall could not be recognized on CT scans. Additional abnormalities evident on CT included pyogenic liver abscesses in two patients and gallstones in five patients. The diagnosis of clonorchiasis can be suspected when CT shows diffuse, uniform, and minimal or mild dilatation of the intrahepatic bile ducts, particularly in the periphery of the liver, without evidence of extrahepatic biliary dilatation.

Adenoma, Bile Duct↗

Clonorchiasis in Korea.

Since the first report on the incidence of egg positiveness of Clonorchis sinensis by Matsumoto in 1915, clonorchiasis has been recognized as one of the most important endemic diseases in Korea. Most of the works on clonorchiasis after then had been studied by Japanese workers until 1945. After the Korean War in 1950-1953, health problems of Koreans were extremely aggravated. This gave us attentions for the prevention of contagious diseases as well as parasitic infections in public health point of view. It was greatly recognized that not only ascariasis, hookworm infections, and trichuriasis, but also clonorchiasis and paragonimiasis constitute the important helminthic diseases in Korea. In the late 1950s, several Korean workers conducted studies of C. sinensis on its biology, epidemiology, pathology, clinical symptoms as well as treatment. Thereafter overall epidemiological surveys were carried out actively throughout the country since 1960s. From these surveys, it became clear that endemic areas of clonorchiasis are scattered all over the country along the Nakdong, Kum, Mankyong, Yeongsan and Han rivers. The most extensive and intensive endemic regions were found mainly along the Nakdong river. Since then, clonorchiasis has been one of the most extensively studied subjects during the past 30 years. The present review mainly deals with current results obtained by Korean investigators on the prevalence of clonorchiasis, as well as its biology, epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, prevention and control.

Animals↗

The clinical and cholangiographic picture of hepatic clonorchiasis.

BACKGROUND: Hepatic clonorchiasis is endemic in areas of the Far East, including Taiwan, where people commonly eat raw or partially cooked freshwater fish. GOALS: To analyze and explore the cholangiographic findings of hepatic clonorchiasis with respect to the clinical data. STUDY: From February 1990 to May 1999, 64 patients were diagnosed with hepatic clonorchiasis in the Kaoshiung Veterans General Hospital. Eighteen of the 64 patients were indicated for endoscopic retrograde cholangiopancreatography (ERCP). The final diagnosis was confirmed by identification of ova in bile or worms in the biliary tract. RESULTS: Fifteen (83%) of 18 patients had history of raw fish consumption and seven patients (39%) came from an endemic area. Clinically, cholangitis (8 of 18) was the most frequent indication for ERCP. All of the patients were diagnosed by the presence of ova in bile. Only seven (39%) patients had peripheral eosinophilia, and seven (39%) had ova in stool. The most characteristic cholangiographic finding of hepatic clonorchiasis in ERCP is filamentous or elliptic filling defects of the biliary tract (16 of 18). CONCLUSION: When presented with biliary symptoms, a history of raw fish consumption in an endemic area should arouse suspicion of hepatic clonorchiasis. Filamentous filling defects in ERCP with bile analysis may confirm the diagnosis.

Adult↗

Cystatin capture enzyme-linked immunosorbent assay for serodiagnosis of human clonorchiasis and profile of captured antigenic protein of Clonorchis sinensis.

Enzyme-linked immunosorbent assay (ELISA) with crude extracts of adult Clonorchis sinensis has been reported to have a high degree of sensitivity with a moderate degree of specificity for the serodiagnosis of clonorchiasis. The cystatin capture ELISA was investigated for its usefulness for the serodiagnosis of human clonorchiasis. Cystatin bound specifically to cysteine proteinases in crude extracts of adult C. sinensis worms, and its binding capacity was not hindered competitively by the other proteinase inhibitors tested. The cystatin capture ELISA for clonorchiasis showed a higher degree of specificity than the conventional ELISA, which produced some cross-reactivities to sera from patients with cysticercosis, sparganosis, and opisthorchiasis. Immunoglobulin G antibodies to C. sinensis cysteine proteinases were produced in experimental rabbits at week 3, and their levels increased rapidly and remained at a plateau after 8 weeks of infection. Of the proteins from the C. sinensis crude extract captured with cystatin, seven proteins were reactive with the serum from patients with clonorchiasis. The cystatin capture ELISA is indicated to be a sensitive and highly specific immunodiagnostic assay for serodiagnosis of human clonorchiasis.

Animals↗

[Evaluation of two kinds of enzyme linked immunosorbent assay method for clonorchiasis].

In this present study, adult worm antigen of Clonorchis sinensis and the indirect and double sandwich enzyme linked immunosorbent assay (ELISA) were used to detect the serum antibody of clonorchiasis patients from the endemic area of Miao-Li county. The results of indirect ELISA revealed a good correlation between the egg stool count and IgG strength of patients sera. Focusing on the different immunoglobulin classes in serum, the patient group has significantly higher level than that of control group, and the IgG level was distinguishly higher than the other Igs. The result also showed that the sensitivity and specificity on the detection of IgG for clonorchiasis patient were 83.23% and 100%, respectively. After praziquantel treatment, the antibody titer of patients decreased in accord with the time period, and the decrease rate of antibody titer in patients with moderate infection was more closely related to the time after treatment than those in the other degree infection groups. When double sandwich ELISA method was used to detect serum antibody to C. sinensis in patients with the different parasitic infection, it was shown that antibody levels in patients with clonorchiasis were significantly higher than those in the un-identical parasitic infection patients. Both of the sensitivity and specificity by using this method were 100%. Based on the results of the indirect and double sandwich ELISA methods, it is recommended that uses of the double sandwich ELISA incorporated with the indirect ELISA may give a sufficient results on the epidemiological study of human clonorchiasis. It may also be recommended that double sandwich ELISA method can be used for a mass survey and indirect ELISA method for further detection in the patients with clonorchiasis.

Animals↗

An Epidemiologic Study On Clonorchiasis And Metagonimiasis In Riverside Areas In Korea.

A study was carried out to figure the cases and to observe the endemic status of clonorchiasis and metagonimiasis in endemic areas in Korea. Total 13,373 inhabitants living in 40 villages along 7 main rivers and 9 small streams were subjected to stool examination. They were selected randomly among the riverside population. Their specimens were examined both by cellphane thick smear method and Stoll's egg countung technique. This study was performed during the period from May 1979 to April 1980. The results obtained are as follows: 1. The egg positive rate of any kind of helminths was 58.7% out of 13,373 examned cases, and the egg positive rates by each helminth were; Clonorchis sinensis 21.5%, Metagonimus yokogaqai 4.8%, large type Metagonimus eggs 0.4%, Ascaris lumbricoides 22.9%, Trichuris trichiura 35.2%, hookworm 0.2%, Taenia sp. 0.5%, Hymenolepis nana 0.07%, Paragonimus westermani 2 cases, Fasciola sp. 4 cases, Echinostoma sp. 1 case and Hymenolepis diminuta 1 case respectively. 2. Many endemic foci of clonorchiasis were revealed along the 7 major rivers. The egg positive rates of each river basin differed from each other significantly; Nagdonggang 40.2%, Yeongsangang 30.8%, Seomjingang 17.3%, Hangang 15.7%, Tamjingang 15.9%, Geumgang 12.0% and Mangyeonggang 8.0%. The cases of clonorchiasis were estimated in range 830,000 to 890,000 in riverside areas of the 7 rivers. By grading the infection intensity, 64.7% was in Grade I(EPG 0-900), 28.6% in Grade II (EPG 1000-9,900), 5.5% in Grade III (EPG 10,000-29,900) and 1.3% in Grade IV (EPG over 30,000). The proportion of the cases in Grade III and IV was 6.8% among positive cases. Therefore 60,000 cases at least were regarded to suffer from it clinically. Males of 30-60 years of age showed higher positive rate and heavier burden of infection. This makes clonorchiasis more important socially because the patients lose their social productivity. 3. A few endemic foci of metagonimiasis were detected newly by egg detection; Samcheong 28.5% egg positive rate, Uljin 21.3%, Yeuongdeog 46.3%, Milyang 6.7%, Yeongil 9.2% and Geoje 18.2%. The mean EPG values were in range of 320-7, 120 by the focus. The egg positive rate and proportion of EPG Grade varied greatly by the area, and mean proportion of the positive cases were 69.7% in Grade I, 24.1% in Grade II, 5.0% in Grade III and 1.2% in Grade IV. Males of 30-60 years were infected in higher rate also. The large sized eggs of Metagonimus were found also in upper basin of Hangang and Geumgang mainly. They were regarded as eggs of M. takahashii which is mediated by the cyprinid fishes. Its significance should be studied further. Clonorchiasis and metagonimiasis should be realized as important public health problems in Korea by their wide distribution, high prevalence rate and heavy infection intensity. Comprehensive measures against them are needed urgently.

Journal Article↗

MRI of clonorchiasis and cholangiocarcinoma.

Intrahepatic cholangiocarcinomas are usually categorized as peripheral cholangiocarcinoma or hilar cholangiocarcinoma on the basis of the site of origin. Clonorchiasis is a trematodiasis caused by chronic infestation of liver flukes, which are largely confined to the Orient, from Japan to Vietnam. The close relationship between clonorchiasis and cholangiocarcinoma has long been emphasized. This paper discusses the efficacy and possible roles of MRI for imaging clonorchiasis and cholangiocarcinoma of the liver. Although sonography, CT, and direct cholangiography have been used traditionally to diagnose these diseases, the role of MRI has been increasing rapidly with dramatic progress of the MRI techniques. We review MRI findings of clonorchiasis and cholangiocarcinoma and discuss the potential usefulness of MRI.

Bile Duct Diseases↗

Carcinoma of the gallbladder associated with clonorchiasis: clinicopathologic and CT evaluation.

BACKGROUND: The computed tomographic (CT) features of three cases with pathologically proven adenocarcinoma of the gallbladder associated with clonorchiasis. METHODS: CT scans of three cases with pathologically proven adenocarcinoma of the gallbladder associated with clonorchiasis were retrospectively reviewed. Scans were analyzed for the following parameters: (a) gross morphologic pattern (intralumenal mass lesion, mass replacing the gallbladder, focal or diffuse wall thickening); (b) contrast enhancement of the tumors; (c) associated gallstones or Chlonorchis sinensis worms; (d) direct invasion into the liver; (e) metastasis to adjacent viscera (pancreas, duodenum); (f) the extrahepatic bile duct (dilatation, metastasis, stone, C. sinensis worms); (g) the intrahepatic bile duct (dilatation); and (h) lymphadenopathy and metastasis. RESULTS: The gross morphologic pattern of three cases with carcinoma of the gallbladder was an intralumenal mass lesion (the least common type), whereas the patterns of infiltration and a mass replacing the gallbladder were not identified. Mild contrast enhancement of the tumors relative to the liver was demonstrated in all patients. Gallstones and C. sinensis worms were not visualized in the gallbladder and the extrahepatic bile duct. An unusual metastasis to the distal common bile duct and the pancreas was found in this series. CONCLUSION: Three cases with adenocarcinoma of the gallbladder associated with clonorchiasis showed intralumenal mass lesions within the gallbladder lumen. The cause-and-effect relation between clonorchiasis and gallbladder carcinoma is discussed.

Adenocarcinoma↗

Clonorchiasis: an update.

Clonorchis sinensis, the Chinese or oriental liver fluke, is an important human parasite and is widely distributed in southern Korea, China (including Taiwan), Japan, northern Vietnam and the far eastern part of Russia. Clonorchiasis occurs in all parts of the world where there are Asian immigrants from endemic areas. The human and animal reservoir hosts (dogs, pigs, cats and rats) acquire the infection from the ingestion of raw fish containing infectious metacercariae. The first intermediate snail hosts are mainly species of Parafossarulus and Bithynia. Numerous species of freshwater fish serve as the second intermediate hosts of C. sinensis. Extensive studies of clonorchiasis during several decades in Japan, Korea, China and other countries have shown much progress in proving its morphological features including ultrastructure, biology, pathogenesis, epidemiology, clinical manifestations and chemotherapy. The present review deals with mainly current results obtained on the epidemiological, pathological and clinical aspects, as well as control measures in endemic areas. As for the complications of clonorchiasis, formation of calculi in the intrahepatic biliary passages is one of the most characteristic pathological features. It is sometimes accompanied by suppurative cholangitis, cholecystitis, cholangiohepatitis and ultimately can cause cholangiocarcinoma. Experimental results on the relationship to the occurrence of cholangiocarcinoma are presented. Clinical diagnosis by radiological findings including cholangiography, sonography and computerized tomography as well as magnetic resonance imaging for biliary or pancreatic ducts are outlined. Current studies on immunology and molecular biology of C. sinensis were introduced. Praziquantel is the drug of choice for clonorchiasis. The most effective regimen is 25 mg kg(-1) three times daily (total dose, 75 mg kg(-1)) administered orally at 5- to 6-h intervals over a single day. Prevention and control measures are also discussed.

Animals↗

[A survey on the epidemiological factors of clonorchiasis in the Pohang industrial belt along the Hyungsan river, Kyongsangbuk-do].

The employees at the Pohang industrial area, where Clonorchis sinensis has been known to be endemic along the Hyungsan River, were examined parasitologically for clonorchiasis and a part of the infected cases were surveyed with a questionnaire to outline the recent infection status of C. sinensis and epidemiological parameters in the area. Total of 3,180 cases were tested by intradermal inoculation of C. sinensis antigen (Green Cross Co., Korea), and 834 (26.2%) were found positive. Out of the positive cases, 598 were subjected to fecal examination for helminth ova. The examination revealed 129 (21.6%) ova positive cases of C. sinensis, and Trichuris trichiura 1.7%, Ascaris lumbricoides 0.3%, and Metagonimus yokogawai 0.2%. The questionnaire analysis showed some significant differences between the infected and non-infected (control) groups. The infected cases were less educated than the control, and they lived at the closer area to the river, and most of them lived there over 20 years. Also they preferred eating raw fresh water fish. Most of the detected cases were treated with praziquantel and found negative for the eggs in 85.3% of them 1 year after the treatment. The present data reveal markedly decreased endemicity of clonorchiasis compared with previous prevalence rates but still clonorchiasis is endemic in the Hyungsan river basin. A comprehensive measure including case detection, treatment and education for parasite control should be applied to control clonorchiasis in such endemic areas.

Adult↗