Orally Administered Bacillus Spores Expressing an Extracellular Vesicle-Derived Tetraspanin Protect Hamsters Against Challenge Infection With Carcinogenic Human Liver Fluke.

BACKGROUND: The human liver fluke Opisthorchis viverrini is a food-borne trematode that causes hepatobiliary disease in humans throughout Southeast Asia. People become infected by consuming raw or undercooked fish containing metacercariae. Development of a vaccine to prevent or minimize pathology would decrease the risk of severe morbidity, including the development of bile duct cancer. METHODS: We produced an oral vaccine based on recombinant Bacillus subtilis spores expressing the large extracellular loop (LEL) of O. viverrini tetraspanin-2 (Ov-TSP-2), a protein that is abundant on the surface of O. viverrini secreted extracellular vesicles (EVs). Recombinant spores expressing Ov-TSP-2-LEL were orally administered to hamsters prior to challenge infection with O. viverrini metacercariae. RESULTS: Vaccinated hamsters generated serum IgG as well as bile IgG and IgA responses to Ov-TSP-2-LEL, and serum IgG from vaccinated hamsters blocked the uptake of fluke EVs by a human bile duct epithelial cell line. Vaccinated hamsters had 56% reductions in both adult flukes and fecal eggs compared to the control group. CONCLUSIONS: These findings indicate that oral vaccination of hamsters with recombinant B. subtilis spores expressing Ov-TSP-2-LEL is efficacious at reducing infection intensity and could form the basis of a vaccine for control of carcinogenic liver fluke infection in humans.

Never seen before? Opisthorchiasis and Clonorchiasis.

Parasitic diseases are relatively rarely diagnosed and treated in Europe. Therefore, European clinicians are not familiar with their clinical and imaging features. In an era of increased human migration, it is fundamental for clinicians to be able to identify such diseases. We have recently described the features of cystic echinococcosis, schistosomiasis, fascioliasis and ascariasis. Here, we report on the clinical and imaging features as well as on the current therapy options of infections by the small liver flukes: Clonorchis sinensis, Opisthorchis viverrini (Southeast Asian liver fluke) and Opisthorchis felineus (cat liver fluke) and other Opisthorchis species prevalent in South Asia.

Opisthorchiasis and viral hepatitis b: clinical cases.

OBJECTIVE: Introduction: Among the cases of biohelminthosis, which are registered in Ukraine, opisthorchiasis is the most common and constitutes the second largest centre in Europe. Due to the growth of migration processes and global tourism, opisthorchiasis is becoming increasingly relevant for the countries of the European Union and the United States. Under modern conditions, the clinical course of many infectious and parasitic diseases has changed. The aim: The present paper discusses and analyzes the cases of opisthorchiasis and hepatitis B virus which are challenging in terms of diagnostics and choice of treatment tactics. CONCLUSION: Conclusion: The course of acute infections, the formation of results and the effectiveness of treatment are influenced by a number of factors, among which mixed infections are of particular interest.

[The contingency of the therapeutic effectiveness with the peculiarities of the non-pharmacological treatment of the patients presenting with chronic cholecystitis]. / Sopryazhennost' terapevticheskoi effektivnosti s osobennostyami nemedikamentoznogo lecheniya bol'nykh khronicheskim kholetsistitom.

The elaboration of new technologies for the medical rehabilitation of the patients presenting with chronic cholecystitis in combination with chronic opisthorchiasis is a topical problem facing modern clinical gastroenterology. The application of up-to-date non-pharmacological therapeutic modalities, such as ultrahigh-frequency (UHF) therapy concomitantly with group chronophysiotherapy makes it possible to significantly improve the final outcome of the treatment. The results of clinical studies give evidence of the favourable influence of the combined chronorehabilitative treatment including UHF therapy on the characteristics of the functional state of the biliary-hepatic system and of the organism as a whole. The positive dynamics of these characteristics is suggestive of the high (up to 87,5%) therapeutic effectiveness of the proposed treatment. The investigations into the relationship between this effect and the peculiarities of the combined therapeutic modalities have demonstrated their correlation (χ2=104,13; p=0,0001; V-Kramer´s coefficient =0,35) and showed that the use of combined chronorehabilitation including UHF therapy based on the application of phone resonance radiation guarantees (and is a predictor of) high therapeutic effect (percent concordance =95,6%; standard coefficient=2,13; p=0,001) of the treatment of the patients with chronic cholecystitis in combination with chronic opisthorchiasis. The statistical analysis of the results of application of the modern non-pharmacological therapeutic modalities and the chronobiological approach for the purpose of the combined treatment of patients presenting with chronic cholecystitis in combination with opisthorchiasis with the use of contingency table and logit regression, allowed not only to estimate the interdependence and interrelation between the characteristics of interest but also to reveal predictors of therapeutic effectiveness. These findings are of great practical importance since they can be used for the choice of therapeutic strategies for the management of this category of patients.

[IMPACT OF OPISTHORCHIS INVASION ON THE COURSE OF A SKIN PROCESS IN PATIENTS WITH ROSACEA].

The authors give the data-and results of their investigations of 47 patents with rosacea concurrent with chronic opisthorchiasis (Group 1) and 40 patients with rosacea without opisthorhiasis (Group 2): It is found that the severer clinical manifestations of rosacea are, the lower the quality of life is in patients. The patients with rosacea concurrent with chronic opisthorchiasis were found to have severe clinical forms. Rosacea diagnostic rating scores was 1.1-fold higher than in the patients without helminthiasis, suggesting a severer course. Quality-of-life dissatisfaction in patients with rosacea concurrent with chronic opisthorchiasis was significantly higher than in those with rosacea only.

[Hepatolithiasis].

The authors present an analysis of treatment results in 14 patients with hepatolithiasis. An influence of chronic opisthorchosis invasion on the frequency was determined. Hepatolithiasis was detected in 8 (0.14%) out of 5757 patients, who underwent the operation for cholelithiasis and its complications. The disease was found out in 6 (0.31%) patients out of 1965, who had cholelithiasis and accompanying chronic opisthorchosis. It was 2,2 times more frequent due to proliferative sclerotic changes of biliary system. The trasdermal teanshepatic cholangiography was contraindicated for opisthorchiasis injuries, because of the danger of subcapsular cholangioectates damage. The endoscopic retrograde cholangiopancreatography and the endopapillosphincterotomy were complicated due to extensive structures of the large duodenal papilla and distal section of the general bile duct. The patients were treated by using the cholecystectomy, extraction of stones from ducts, reconstruction of liver passage. Choledochoduodenostomy was performed with compulsory external drainage for ducts sanation from infections and helminthes in the case of the opisthorchiasis. Interportal infusions were carried out. The surgical, conservative and endoscopic treatment was required for multiple colangiolithiasis. The lethality consisted of 7.1%.

[Opisthorchiasis: tradition and innovation].

THE PURPOSE OF THE REVIEW: Present new data on the causative agent, pathogenesis, diagnosis and treatment of opisthorchiasis. RECENT LITERATURE DATA: When samples of parasites were genotyped by novel nuclear marker Pm-int9, it was shown various properties of Opisthorchis viverrini, O. felineus and C. sinensis. It has been proven the oxidant damage to DNA of biliary epithelium cells infected with opisthorchiasis, and overexpressed of cellular protooncogene c-Ski, as well as platelet-derived growth factor alpha (Pdgfa) gene, which in some cases leads to the development of cholangiocarcinoma. Describes the innovations in the diagnosis of opisthorchiasis: primers OP1 and OP2 are used to amplify the ITS2 region rDNK eggs and metacercariae of Opisthorchis in feces. Opisthorchiasis treatment remains traditional - praziquantel, at least - with albendazole. Treatment of opisthorchiasis patients with praziquantel was shown to reduce inflammation-mediated tissue damage and carcinogenesis.

Indirect effect of a turmeric diet: enhanced bile duct proliferation in Syrian hamsters with a combination of partial obstruction by Opisthorchis viverrini infection and inflammation by N-nitrosodimethylamine administration.

The present study revealed the indirect effect of a turmeric (TUR) diet on the histopathological changes and proliferating cell nuclear antigen staining in Syrian hamsters with partial obstruction by liver fluke (Opisthorchis viverrini) infection and inflammation by N-nitrosodimethylamine (NDMA) administration. The result of the analysis of histopathological changes shows that a TUR diet has an anti-inflammatory property in the case of a single condition of NDMA administration or O. viverrini infection, as has been reported previously. Unfortunately, an adverse indirect effect of TUR was observed in the combination of infection with O. viverrini and administration of NDMA, with a 30-50% increase in new bile duct formation, correlated with an increase in proliferating cell nuclear antigen. Our present result suggests that the properties of curcumin are anti-inflammation and antioxidant including enhancing biliary contraction and bile flow. Thus, a combination of factors (treated with O. viverrini, NDMA, and TUR diet) result in an increasing bile duct proliferation which may cause from biliary homeostasis.

[Principles of therapy of hepatobiliary and pancreatic pathology in elderly people with chronic opisthorchiasis].

THE PURPOSE OF RESEARCH: studying of features of clinical current, diagnostics, treatment chronic opisthorchiasis at persons of elderly and senile age. 117 patients are surveyed. In bile in 100% of cases, a sladg-syndrome in 66.6%, infringement of motor function of a bilious bubble in 92.3%, macrobiocenosis in 98.3%, an allergic syndrome--microscopic changes are found out in 93%. The diagnostic importance of triad Paltseva at observable patients is confirmed. It is shown, that chronic [Russian characters: see text] is system disease at which leading value the pathology hepatobiliar and pancreatic system has.

[Biorhythms to improve efficiency of the treatment of patients with chronic opisthorchosis].

To make the treatment of bile-excreting dysfunctions more effective still remains an actual problem of clinical medicine. Use of chronobiological approach in the treatment is possible to resolve that problem. For any system including bile-excreting one, its own biorhythms are typical. Lesion of these systems causes changes of the biorhythms. Use of parameters of biorhythms of bile-excreting system activity expects an individual or group chronobiological approach in the treatment of patients with chronic opisthorchosis. The combined treatment of opisthorchosis with the use of such approach makes possible to improve efficiency of the treatment and to maintain received effect up to 6 months. It indicates increase the terms of remission and prevents development of early recidivation.

[Nondrug treatment for opisthorchiasis].

In vitro experimental studies of the antiopisthorchiasis properties of currently available non-drug treatment are ofgreat practical value. The studies demonstrated that the herbal drug ecorsol and the background resonance radiation of the Opisthorchis spectrum exerted an anti-helminthic effect that was evaluated by the marital death and amounted to 83.6 to 96.4%. The experimental studies provided evidence that the background radiation, by using the electromagnetic spectrum of Opisthorchis, had a sufficient helminthocidal effect on mature Opisthorchis felineus in the in vitro experiment, which allows these means to be recommended for the non-drug treatment of chronic opisthorchiasis.

[Systemic responsiveness and the efficiency of antihomotoxic therapy for chronic opisthorchiasis. 3. Responsiveness].

The authors consider systematic responsiveness in chronic opisthorchiasis and a relationship between acute inflammation and responsiveness. A number of regularities that take place in the patho- and sanogenesis of chronic disease in general and that are important in the evaluation of the severity and prognosis of the disease and the efficiency of therapy are demonstrated on a model of severe opisthorchiasis. The reversion syndrome indicative of recovered responsiveness during therapy is described in detail. Differences in the interpretation of the helminthoovoscopic findings are shown in the context of the priority of clinical data.

[Molecular genetic approaches in parasitology (in case of opisthorchiasis)].

Light, electron microscopy, polymerase chain reaction (PCR), and immunohistochemistry were used to reveal the proliferative, alterative processes of hepatic parenchymal cells, P 53, K-ras, B-raf, c-Kit, p 16, APC, immunoreactive proteins Ki-67, cytokeratins 9, 14, 20, EMA, c-erb B-2, CD-117, mutated p 53 and bcl-2 genes. P53, K-ras, B-raf, c-Kit, and p 16 gene mutations were detected in the liver of animals with experimental superinvasive opisthorchiasis (SO) and cholangiocellular carcinoma (CCC). Mutations of these genes were found in the plasma samples taken from SO patients. The CCC tissue from SO patients displayed expression of the following genes: p 53 (100.0%), p 53+B-raf (50.0%), K-ras+c-Kit (33.3%), K-ras+B-rafat more than 5 cm from the tumor in 2 cases. Following 2 years, target therapy (canglait, megamin, immunomodulators) leveled mutations in 91.25% of the patients with SO.

Parasitic causes of pancreatic and biliary tract disease: a growing concern in a highly mobile population.

A leading cause of biliary tract disease and pancreatitis worldwide is parasitic disease. In the United States, increased global travel and the AIDS epidemic has led to a rise in the frequency of parasitic disease. Biliary disease and pancreatic disease secondary to parasitic infestation is relatively new in this country, with the first case being described in 1977. These diseases are no longer the exclusive realm of infectious disease specialists and require general practitioners and gastroenterologists to be well versed in the spectrum of parasitic pancreatic and biliary disease.

[Treatment and rehabilitation of patients with chronic opisthorchiasis with skin manifestations]. / Lechenie i reabilitatsiia bol'nykh khronicheskim opistorkhozom s kozhnymi proiavleniiami.

Our studies demonstrated that chronic opisthorchosis with a skin syndrome is accompanied by a severer clinical course. The course of rehabilitation measures with the use of resort recreation (mud-bad cure) combined with traditional treatment stages makes it possible to considerably enhance the efficiency of treatment of both opisthorchosis and its skin manifestations, and should be applied more often in practice.

[Acute opisthorchiasic cholecystocholangitis]. / Ostryi opistorkhoznyi kholetsistokholangit.

Morphologic alterations in the major duodenal papilla were studied in 36 corpses of people with opisthorchiasis. Experience with the treatment of 1135 patients with acute opisthorchiasic cholecystocholangitis (AOChCh) has been analysed. Conservative treatment was used in 852 patients, operations were performed on 283 patients, 31 of them died. The trigger for the appearance of AOChCh is thought to be occlusion of the common bile duct and the presence of infection in bile ducts. The treatment should be started by conservative methods. Surgery is indicated if they proved to be ineffective.

[Prevention and treatment of opisthorchiasis of the liver]. / Profilaktika i lechenie oslozhnenii opistorkhoza pecheni.

Rare cases of lethal outcomes after surgical operations on the liver were analyzed which were caused by invasion of helminth Opisthorchis felineus. It was shown that prolonged and massive invasion, in the absence of specific treatment, can result in failure of the compensatory potencies of the liver. It occurs mainly due to activation of the pathogenic flora in the bile tree against the background of the intraductal hypertension characteristic of opisthorchiasis. Destructive purulent cholangitis, cholangitic abscesses in the liver and suppuration of opisthorchiasis cysts can develop. The direct cause of death was progressing hepatic insufficiency. The postoperative lethality among patients with opisthorchiasis cysts of the liver was 5.7%, with liver abscesses--12.5%. The external drainage of the biliary tree in patients with this pathology and intraportal infusions reduce lethality and the number of specific postoperative complications.

Opisthorchis felineus and Metorchis bilis are the main agents of liver fluke infection of humans in Russia.

Liver fluke infections are gradually transforming from a local problem of individual geographic regions to a widespread problem. The observed expansion is likely to be connected with the ever-increasing intensity of traffic flow and migration of the infected carriers between cities, regions, and countries. Opisthorchis felineus, the trematode belonging to the family Opisthorchiidae, is a well known causative agent of the infection called opisthorchiasis. Metorchis bilis, also a member of the family Opisthorchiidae, causes metorchiasis, a disease very close to opisthorchiasis in symptomatology. Genetic markers can be used to develop methods for differential diagnostics of these diseases. However, the questions connected with epidemiology of these trematode infections, their clinical characteristics, prognosis and therapy remain open. This review briefs the general biological characteristics of O. felineus and M. bilis persisting in various countries of Eurasia, their geographical range, epidemiology and molecular diagnostics of these liver flukes.