Activity of tribendimidine and praziquantel combination therapy against the liver fluke Opisthorchis viverrini in vitro and in vivo.

Opisthorchiasis, caused by the liver fluke Opisthorchis viverrini, a food-borne trematode, is an important public health problem; however, only a single drug, praziquantel is available. We investigated tribendimidine-praziquantel combinations against O. viverrini in vitro and in vivo. The IC50 values of 0.16 µg/ml and 0.05 µg/ml were determined for praziquantel and tribendimidine, respectively, against adult O. viverrini in vitro. When O. viverrini was exposed to both drugs simultaneously (using a drug ratio based on the IC50 (1:3.2)) a synergistic effect was calculated (combination index (CI) at the IC50= 0.7). A similar result was observed when drug addition in vitro was spaced by the respective half-lives of the drugs (a CI of 0.78 at the IC50 for tribendimidine followed by praziquantel and a CI of 0.47 at the IC50 for praziquantel followed by tribendimidine). In vivo median-effect dose (ED50) values of 191 mg/kg and 147 mg/kg were calculated for praziquantel and tribendimidine, respectively. Low to moderate worm burden reductions (38-62%) were observed in O. viverrini infected hamsters when both drugs were administered simultaneously or on subsequent days, pointing to antagonistic effects in vivo. Further studies are necessary to understand the striking differences between the in vitro and in vivo observations using combinations of praziquantel and tribendimidine on O. viverrini.

Granulomatous, hepatolithiasis and hepatomegaly caused by Capillaria hepatica infection: first case report of Thailand.

This is the first case report in Thailand of a Capillaria hepatica infection causing a granulomatous hepatic lesion, bile duct dilatation, hepatolithiasis and hepatomegaly. The patient's chief complaint was abdominal pain with fever and chills. Imaging of the liver revealed a 3-cm mass in the postero-inferior sub-segment of the right lobe of the liver with bile duct dilatation. Right hepatectomy and cholecystectomy were performed. Gross pathology of the right hepatectomy revealed focal intrahepatic duct dilatation with prominent periductal fibrosis. The histopathological section revealed chronic inflammation and some granuloma formation surrounding the bile ducts, generalized portal infiltration, prominence of eosinophils and hepatolithiasis. Histopathotogical section revealed oblique sections of C. hepatica egg (size 35.4+/-6.38 microm in width) and brown amorphous pigment.

Expression of tenascin in bile duct cancer of hamster liver by combined treatment of dimethylnitrosamine with Opisthorchis viverrini infections.

Tenascin is an extracellular matrix glycoprotein known to be an essential factor for the modulation of reciprocal interactions between the epithelium and mesenchyme during embryogenesis and tumourigenesis. The interactions between the expression of tenascin in the liver of Syrian golden hamster and the development of bile duct cancer in an Opisthorchis viverrini-associated cholangiocarcinoma model were investigated. The tenascin was expressed in connective tissues surrounding the dilated ducts, ductal rims and the stroma of cancers, and strongly in the stroma flame of necrotic cancer nodules. The mRNA signal for tenascin was also recognized in the stroma cells. The potential roles of tenascin as prognostic tumour markers are discussed.

Ultrastructural and immunohistochemical analysis of cholangiocarcinoma in immunized Syrian golden hamsters infected with Opisthorchis viverrini and administered with dimethylnitrosamine.

Utilizing the experimental model in Syrian golden hamsters, we explored the role of immunization in carcinogenesis. The animals, which were infected with liver flukes (Opisthorchis viverrini), and administered a subcarcinogenic dose of dimethylnitrosamine, developed cancer. Pre-immunizing with a crude somatic antigen did not reduce cancer development, but accelerated carcinogenesis. Histopathological analysis of the cancer tissues was done once at week 30 and again at week 39 using H and E staining, immunostaining for the p53 tumor suppressor phosphoprotein, and electron microscopy. Thirty weeks after immunization, the immunized hamsters developed tubular adenocarcinoma at a higher rate (71.43%) than the non-immunized group (20.00%). This rate (20.00%) increased to 63.64% by week 39. The small foci cancer in the non-immunized group decreased in frequency from 80.00% (at week 30) to 36.36% (by week 39), suggesting the small foci cancer progressed to tubular adenocarcinoma during the 9-week interval. Most of the observed tubular adenocarcinoma was well differentiated. Nearly all hamsters that tested positive for cancer also tested positive for p53 immunostaining in the epithelia of the small bile ducts. The positive reaction for p53-immunostaining was localized in the rough endoplasmic reticulum, Golgi apparatus and perinuclear membranes. The electron micrographs of these positive p53-immunostained cells showed characteristics of early cancer. The detection of p53 in early cancer development makes it a candidate as a tumor marker.

Field trials in the control of Opisthorchis viverrini with an integrated programme in endemic areas of northeast Thailand.

A control programme of opisthorchiasis was carried out for three years in three villages of northeast Thailand in order to compare the effectiveness of two intervention measures. The intervention measures employed were to give praziquantel treatment to all infected people either once (village I) or twice (village II) per year with the integration of regular health education and sanitation improvement. A control village (village III) received no intervention during the study. Sampling of the population in these villages to estimate prevalence, intensity, reinfection and incidence of infection as well as knowledge of opisthorchiasis and number of latrines was performed at 6 monthly intervals throughout the duration of the study. At the initial assessment, there were no significant differences in the prevalence and intensity of infection of villages I and II. Both values were greatly reduced when assessed 6 months after the initiation of treatment, and the decrease in prevalence and intensity of infection did not differ between village I and II. The control village (village III), during the first 2 years, exhibited slight variation in the prevalence and intensity, and these decreased considerably in the third year of the study. The reinfection rate per 6 months in villages I and II was nearly equal. The incidence rate per 6 months in the two treated villages was lower than that of the control village. Marked improvement in knowledge of opisthorchiasis, behavioural changes of eating raw fish and increased numbers of latrines was evident in all of the villages during this study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute cholecystitis and Fasciola sp. infection in Thailand: report of two cases.

Two cases of fascioliasis gigantica from Northeast Thailand presenting with cholecystitis and gall stones were reported. Both cases complained of abdominal pain. On laparotomy the worms were found. In one case five worms were recovered during bile duct exploration and bile drainage; eggs were also revealed in the bile. In the other case of ectopic fascioliasis one young adult worm was found in a nodule which adhered to liver and diaphragm. The parasites were identified as Fasciola gigantica.

Ocular sparganosis: a cause of subconjunctival tumor and deafness.

We report a patient with a subconjunctival mass lesion caused by a larva of Spirometra sp. The parasite, 44 cm long and 1.0 mm wide, was removed intact and alive with complete preservation of the patient's vision. The mode of infection was probably through consumption of contaminated drinking water.