[Therapy of clonorchiasis. 2. Clinical trial of clonorchiasis with a new drug, 1, 4-bis-trichloro-methylbenzol].
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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.
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.
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.
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.
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.
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.
The authors described the clonorchiasis focus in the Vietnam province at the seaside delta of the Red River where the aforementioned invasion was accompanied with multiple invasions with intestinal nematodes. Clonorchiasis infestation rate was 28.4% ascaridiasis, 50.5%, trichocephaliasis, 21.3% ancylostomiasis, 7.0%. Clonorchiasis invasion was the result of consumed uncooked carp fish in the salad. It was revealed that the fish was reared in the ponds near the settlements and was fed untreated human and animal feces. The meal was more common among the male persons in the presence of the alcohol intake. Clinical symptoms of the mixed clonorchiasis and intestinal nematodiasis invasion was featured by pains, dyspepsia and the asthenoneurotic syndrome.
The present study applied the indirect enzyme-linked immunosorbent assay (ELISA) technique in the immunodiagnosis of clonorchiasis. Antigen used in this study was extracted from adult worms of Clonorchis sinensis obtained from cats. 132 patients with clonorchiasis, 100 healthy persons and 14 patients with other parasitic infections were studied. Mean O.D. ratio with standard deviation of clonorchiasis was 1.41 +/- 0.21 with 0.95 +/- 0.13 of healthy persons. Results revealed 90.2% to 95.5% of sensitivity and 84% to 99% specificity dependent on the two cut off values of O.D. ratio, i.e. 1.10 and 1.20. Antibody titers derived from O.D. ratio highly correlated with direct titration (Y = 0.0303 +/- 1.1766 X, r = 0.8945). Cross reactions of other parasite infections to clonorchiasis were observed in patients with angiostrongyliasis and schistosomiasis.
The first choice for treatment of Clonorchis sinensis infections is praziquantel. Experimental data suggest that artemisinin derivatives are active against C. sinensis. The efficacy of both drugs against clonorchiasis was evaluated in a pilot study in clonorchiasis patients in an endemic area in the North of Vietnam. Twenty-one patients received praziquantel 25 mg/kg o.d. for three days, the regular regimen in that area, and 21 patients were treated with artemisinin 500 mg b.i.d. for 5 days. Faecal egg counts were performed before as well as 6 days and 5 weeks after treatment. In the praziquantel group the faecal egg count decreased significantly from a mean value of 1632 eggs per gram faeces (epg) to 37 epg 5 weeks after treatment (P < 0.01) but, surprisingly, the eradication rate (95% confidence limit) at week 5 was only 29% (11-52%). In the artemisinin-treated group the reduction of the egg count was insignificant: from 1103 to 542 epg (P > 0.05). The proportion of patients (95% c.l.) with C. sinensis eggs in their stool on week 5 was 90% (70-99%) in the artemisinin group and 71% (48-89%) in the praziquantel group (P > 0.05) and the eradication rate (95% c.l.) at week 5 was only 10% (1-30%). With a sensitivity of detection of eggs in stool > 0.89, this implies a statistically significant but clinically unsatisfactory reduction for treatment with praziquantel. Sensitivity is probably less. For artemisinin there was no significant reduction. In conclusion, for human clonorchiasis in the North of Vietnam, the efficacy of praziquantel 25 mg/kg o.d. for 3 days was unsatisfactory and artemisinin for 5 days is not an effective alternative.
Among 380 bone marrow transplant (BMT) recipients, five cases (1.3%) of clonorchiasis were observed from 1991 to 1996. Clonorchis sinensis infection was evident in the results of stool examinations performed for screening purposes 7 days before bone marrow transplantation. Salmonella species were isolated concomitantly from the stools of two of the five patients. None of the patients had symptoms due to clonorchiasis. Ultrasonography did not show dilated hepatobiliary ducts, stones, or periportal fibrosis. Fatty liver changes were detected in one patient. All five patients received praziquantel (25 mg/kg po t.i.d. for 1 day) before bone marrow transplantation. Only two patients who underwent allogeneic transplantation had mild venoocclusive disease of the liver with transient hyperbilirubinemia and mildly elevated liver enzyme levels, whereas hyperbilirubinemia or elevated serum alanine aminotransferase levels, related to conditioning toxicity, occurred in two other patients. After treatment with praziquantel, stool examination for all five patients were negative for C. sinensis ova. In addition, Salmonella species were not detected after ciprofloxacin prophylaxis. All five patients survived for > 300 days. Given the availability of effective therapy and in the absence of excessive complications, clonorchiasis is not a contraindication to bone marrow transplantation.
In 74 patients with clonorchiasis, the efficacy and safety of praziquantel was evaluated in a two-phase study: a double-blind, randomized controlled trial of praziquantel versus placebo (42 patients) and an open study (32 patients). All but one of the patients were Laotians. The intensity of clonorchiasis was light in 85% (63 of 74) and moderate in 15% (11 of 74) of the patients. Cure based on our established criteria was noted in 67 of 67 patients (100%) treated with praziquantel at a dose of 75 mg/kg per day. In contrast, four patients (20%) in the placebo group, each with light infection, ceased passing eggs and were, according to our established protocol, considered spontaneous cures (P less than 0.0001). Adverse effects of praziquantel were transient and included nausea and vomiting (15%), vertigo (12%), hepatomegaly (4.5%), headache (1.5%), rash (1.5%), and hypotension (1.5%). Of 20 patients who received placebo, 1 (5%) developed transient skin rash, fever, and chills. Clinically minor and transient, but statistically significant, changes in hemoglobin, total protein in serum, and levels of uric acid, cholesterol, and bilirubin in serum were noted. Results of this study showed that praziquantel is safe, well tolerated, and effective and should be considered as the drug of choice for treatment of clonorchiasis. In moderate infections, a second course of praziquantel therapy may be necessary to eliminate infection.
Clonorchiasis is a parasitic disease of the bile ducts that occurs in endemic areas after ingestion of the raw flesh of freshwater fish. We analyzed the sonographic findings in 59 patients with clonorchiasis, suspected prospectively from sonographic findings and proved subsequently by demonstration of eggs in their stools. Diffuse dilatation of the small intrahepatic bile ducts with no or minimal dilatation of the large intra- and extrahepatic ducts was observed in all cases. The extrahepatic ducts were patent throughout in all except one case. This characteristic finding reflects diffuse intrahepatic bile duct obstruction and resultant proximal dilatation caused by an adult worm or aggregates of worms, as worms reside diffusely in the medium and small intrahepatic bile ducts. Cholangitis and multifocal periductal fibrosis with proximal dilatation may play an additional role. Increased echogenicity of the intrahepatic bile duct wall was present in 39 cases (66%), reflecting cholangitis and periductal fibrosis. In 17 cases (29%), floating or dependent, discrete, nonshadowing, intraluminal, echogenic foci caused by adult worms in the bile were demonstrated in the gallbladder. These echogenic foci were distinguished from stones because they were fusiform, weak in echogenicity, and floated with a change in position. Clonorchiasis should be considered when sonography discloses the characteristic pattern of bile duct dilatation with increased wall echogenicity and nonshadowing, discrete, echogenic foci in the gallbladder lumen.
This study was conducted to evaluate the current endemicity and the transition mode of the Clonorchis infection in Sanchong-gun Kyongsangnam-do. The areas of investigation, villages and schools surveyed, method and techniques used in this study were the same as in 1984. The egg positive rate of clonorchiasis in the general population of Sanchong-gun was 37.6% out of 837 examined persons. In the schoolchildren, the rate was 9.7% out of 145 persons examined. In the intensity of the infection among the cases, the mean EPG (Egg per gram of feces) in the inhabitants and schoolchildren were 3,310 (male 4,221, female 1,978) and 711 (male 620, female 833), respectively. Of the inhabitants with clonorchiasis, the cases of light infection (EPG < 1,000) and moderate infection (1,000 < EPG < 10,000) were 93.9%. The proportion with experience of eating raw freshwater-fish was 90.5% among the infecteds. Out of 138 inhabitants examined in both 1984 and 1992, the number of the positives by both examinations was 31 (22.5%), positive to negative conversion was 35 (25.4%), negative to positive conversion was 22 (15.9%). The present results reveal that there are no changes of the egg positive rate of clonorchiasis among inhabitants in Sanchong and the eating habit of raw freshwater-fish persists there. In this community, the eating habit is the most important problem to be solved for control of this endemic disease.
In Korea, Clonorchis sinensis infection is still highly prevalent because case detection in the field is difficult and the detected cases used to be incompletely cured due to treatment failure. The present study tried to control clonorchiasis in an endemic village by repeated treatments with praziquantel every 6 months and to evaluate sonography as a diagnostic measure. By stool examinations, the egg positive rate in the endemic village was 22.7%, but it decreased to 19.6% at 6 months, 15.1% at 12 months. 12.2% at 18 months, 6.3% at 24 months, 11.4% at 30 months, and 6.3% at 42 months after the beginning of repeated praziquantel administration. The sonography showed 61 (49.6%) positive cases of 123 screened residents: among egg-positives the sonography positive rate was 52.2% and among egg-negatives it was still 49%. The rate among cured cases was 64.3% after 6 months, 50.0% after 12 months, 50.0% after 18 months, and 66.7% after 24 months. In a non-endemic village, 64 residents were found egg-negative by fecal examination, but 20 (31.3%) of them were positive by sonography. The present findings indicate that control of clonorchiasis in an endemic village by repeated praziquantel treatment for 42 months is still insufficient and sonography is of little value for diagnosis of clonorchiasis.
Examinations of 1599 residents of a polyinvasion focus at a seaside province Ha Nam Nin, Vietnam, have revealed clonorchiasis in approximately 13.9% of the examinees; in subjects aged over 30 this value was 29.3%. Factors conducive to a lower incidence of clonorchiasis were detected, among them a moderate intensity of the invasion: the mean arithmetic was 1419 +/- 306 eggs/g, the mean geometric 673 egg/g, as shown by the Kato-Kats' technique. Analysis of five therapeutic schemes used in clonorchiasis, making use of chloxilin, medamin or praziquantel, has demonstrated a low efficacy of all of them. Praziquantel therapy in a daily dose of 25 mg/kg for 2 days was found the most effective (52%), being conducive to a reduction of the invasion intensity by at least 90%. Such therapy was associated with a high incidence of side effects (91.2%), this ruling out a higher dosage.
Since Ohi in 1915 found clonorchiasis patients in Taiwan, many surveys have shown that Miao-li in the north, Sun-moon Lake in the middle and Mei-nung in the south of Taiwan are three important endemic areas of clonorchiasis. In recent studies, the disease showed a tendency to extend its endemicity. Rats, cats, dogs and pigs are the natural reservoir hosts, and 17 species of fresh water fish are also infected with metacercaria. One definitive snail host, Parafossarulus manchouricus, and two other suggested snails, Semisulcospira libertina and Thiara granifera, may serve as the first intermediate host. The human incidence is about 20-50% in endemic areas and 10-20% in newly infected localities. Higher infection rates and more intensities of the worm burden are observed in the adult males. A higher incidence is also observed in the Hakkanense ethnic group. The infection according to the occupation has changed from merchants and government employees to farmers. Praziquantel, 60 mg/kg body weight divided into three doses by oral route in one day, has been given to 356 patients and revealed a 96% cure rate and a 99% egg reduction rate. This regimen is highly recommended for the treatment of clonorchiasis.