Opisthorchis Felineus Infection Research Articles

Plastoquinone-Derivative SkQ1 Improved the Biliary Intraepithelial Neoplasia during Liver Fluke Infection.

Carcinogenic food-borne liver fluke infections are a serious epidemiological threat worldwide. The major complications of Opisthorchis felineus infection are chronic inflammation and biliary intraepithelial neoplasia. Although evidence has accumulated that increased reactive oxygen species production is observed in liver fluke infection, a direct relationship between the oxidative stress and biliary intraepithelial neoplasia has not been shown. Quinones and SkQ1, a derivative of plastoquinone, have been demonstrated to be cytoprotective in numerous liver injuries due to their potent antioxidant properties. This study is aimed to assess the level of biliary intraepithelial neoplasia in O. felineus-infected hamsters after treatment with mitochondria-targeted SkQ1. SkQ1 significantly reduced the biliary intraepithelial neoplasia, which was accompanied by a decrease in lipid and DNA oxidation byproducts, mRNA expression and level of proteins associated with inflammation (TNF-α, CD68) and fibrogenesis (CK7, αSMA), and was also associated with an activation of the Keap1-Nrf2 pathway. Thus, a direct relationship was found between oxidative stress and the severity of biliary intraepithelial neoplasia in O. felineus-infected hamsters. The hepatoprotective effect of plastoquinone-derivative SkQ1 was established; therefore, this compound is a promising agent in complex therapy in the treatment of opisthorchiasis.

Hepatic vascular changes associated with Opisthorchis felineus infection in Syrian hamsters and humans

The liver fluke Opisthorchis felineus is a foodborne zoonotic pathogen endemic to Russia, Kazakhstan, and several European countries. The adult flukes affect the hepatobiliary system of piscivorous mammals and humans, thereby causing numerous complications, including liver fibrosis. Detailing the mechanisms of progression of the fibrotic complications is a hot topic in the field of research on opisthorchiasis pathogenesis. Pathologic angiogenesis appears to be associated with the fibrogenic progression due to active participation in the recruitment of inflammatory cells and many factors involved in the modulation of the extracellular matrix. The aim of the study was to evaluate neoangiogenesis and amyloid deposits in liver tissues of model animals and patients with confirmed chronic opisthorchiasis. In addition, we assessed a possible correlation of neoangiogenesis with liver fibrosis. We found a significant increase in the number of newly formed vessels and amyloid deposits in the liver of people with chronic opisthorchiasis compared to that of uninfected ones. Thus, for the first time we have demonstrated neoangiogenesis and amyloid deposits during O. felineus infection in a Mesocricetus auratus model. Regression analysis showed that CD34+ newly formed vessels correlate with fibrosis severity in the course of the infection. Our results indicate the potential contribution of angiogenesis to the progression of liver fibrosis, associated with O. felineus infection.

The influence of Opisthorchis felineus infection on the nutritional quality of fish meat and an assessment of fish processing methods

The influence of Opisthorchis felineus infection on the nutritional quality of fish meat and an assessment of fish processing methods

Jagged-1/Notch Pathway and Key Transient Markers Involved in Biliary Fibrosis during Opisthorchis felineus Infection.

Chronic opisthorchiasis associated with Opisthorchis felineus infection is accompanied by severe fibrotic complications. It is of high practical significance to elucidate the mechanisms of hepatic fibrosis in chronic infection dynamics. The goal of the study is to investigate the temporal profile of key markers and the Jagged1/Notch signaling pathway in the implementation of fibrosis in a chronic O. felineus infection. For the first time, using histological methods and real-time PCR analysis, we demonstrated the activation of the Jagged1/Notch pathway in liver fibrogenesis, including the activation of the Hes1 and Hey1 target genes during experimental opisthorchiasis in Mesocricetus auratus. Cluster analysis followed by regression analysis of key markers during the infection showed that Jagged1 and Mmp9have the greatest contribution to the development of cholangiofibrosis and periductal fibrosis. Moreover, we detected a significant increase in the number of Jagged1-positive cells in the liver of chronic opisthorchiasis patients compared to that of the control group without infection. The results of the study are extremely informative both in terms of investigation both diverse fibrosis mechanisms as well as potential targets in complex antihelmintic therapy.

Behavioral effects and inflammatory markers in the brain and periphery after repeated social defeat stress burdened by Opisthorchis felineus infection in mice

The combination of 4-week repeated social defeat stress (RSDS) and Opisthorchis felineus infection was modeled in C57BL/6 mice. Various parameters were compared between three experimental groups of male mice (SS: mice subjected to RSDS, OF: mice infected with O. felineus, and OF + SS: mice subjected to both adverse factors) and behavior-tested and intact (INT) controls. The combination caused liver hypertrophy and increased the blood level of proinflammatory cytokine interleukin 6 and proteolytic activity of cathepsin B in the hippocampus. Meanwhile, hypertrophy of the spleen and of adrenal glands was noticeable. Anxious behavior in the elevated plus-maze test was predominantly due to the infection, with synergistic effects of an interaction of the two adverse factors on multiple parameters in OF + SS mice. Depression-like behavior in the forced swimming test was caused only by RSDS and was equally pronounced in SS mice and OF + SS mice. Helminths attenuated the activities of cathepsin B in the liver and hypothalamus (which were high in SS mice) and increased cathepsin L activity in the liver. The highest blood level of corticosterone was seen in SS mice but was decreased to control levels by the trematode infection. OF mice had the lowest level of corticosterone, comparable to that in INT mice. Thus, the first data were obtained on the ability of O. felineus helminths—even at the immature stage—to modulate the effects of RSDS, thereby affecting functional connections of the host, namely “helminths → liver↔brain axis.”

The impact of Opisthorchis felineus infection and praziquantel treatment on the intestinal microbiota in children

The presence of some species of helminths is associated with changes in host microbiota composition and diversity, which varies widely depending on the infecting helminth species and other factors. We conducted a prospective case-control study to evaluate the gut microbiota in children with Opisthorchis felineus infection (n=50) before and after anthelmintic treatment and in uninfected children (n=49) in the endemic region. A total of 99 children and adolescents aged between 7 and 18 years were enrolled to the study. Helminth infection was assessed before and at 3 months after treatment with praziquantel. A complex examination for each participant was performed in the study, including an assessment of the clinical symptoms and an intestinal microbiota survey by 16S rRNA gene sequencing of stool samples. There was no change in alpha diversity between O. felineus-infected and control groups. We found significant changes in the abundances of bacterial taxa at different taxonomic levels between the infected and uninfected individuals. Enterobacteriaceae family was more abundant in infected participants compared to uninfected children. On the genus level, O. felineus-infected participants’ microbiota showed higher levels of Lachnospira, Escherichia-Shigella, Bacteroides, Eubacterium eligens group, Ruminiclostridium 6, Barnesiella, Oscillibacter, Faecalitalea and Anaerosporobacter and reduction of Blautia, Lachnospiraceae FCS020 and Eubacterium hallii group in comparison with the uninfected individuals. Following praziquantel therapy, there were significant differences in abundances of some microorganisms, including an increase of Faecalibacterium and decrease of Megasphaera, Roseburia. Enterobacteriaceae and Escherichia abundances were decreased up to the control group values. Our results highlight the importance of the host-parasite-microbiota interactions for the community health in the endemic regions.

The pathogenic potential of the combined action of chronic Opisthorchis felineus infection and repeated social defeat stress in C57BL/6 mice

Parasitic food-borne diseases and chronic social stress are frequent attributes of day-to-day human life. Therefore, our aim was to model the combined action of chronic Opisthorchis felineus infection and repeated social defeat stress in C57BL/6 mice. Histological examination of the liver revealed inflammation sites, pronounced periductal fibrosis, and cholangiofibrosis together with proliferation of bile ducts and hepatocyte dystrophy in the infected mice, especially in the stress-exposed ones. Simultaneously with liver pathology, we detected significant structural changes in the cerebral cortex. Immunohistochemical analysis of the hippocampus indicated the highest increase in numerical density of Iba 1-, IL-6-, iNOS-, and Arg1-positive cells in mice simultaneously subjected to the two adverse factors. The number of GFAP-positive cells rose during repeated social defeat stress, most strongly in the mice subjected to both infection and stress. Real-time PCR analysis showed that the expression of genes Aif1 and Il6 differed among the analysed brain regions (hippocampus, hypothalamus, and frontal cortex) and depended on the adverse factors applied. In addition, among the brain regions, there was no consistent increase or decrease in these parameters when the two adverse treatments were combined: (i) in the hippocampus, there was upregulation of Aif1 and no change in Il6 expression; (ii) in the hypothalamus, expression levels of Aif1 and Il6 were not different from controls; and (iii) in the frontal cortex, Aif1 expression did not change while Il6 expression increased. It can be concluded that a combination of two long-lasting adverse factors, O. felineus infection and repeated social defeat stress, worsens not only the hepatic but also brain state, as evidenced behaviorally by disturbances of the startle response in mice.

Biliary Microbiota and Bile Acid Composition in Cholelithiasis.

Background A functional interplay between BAs and microbial composition in gut is a well-documented phenomenon. In bile, this phenomenon is far less studied, and with this report, we describe the interactions between the BAs and microbiota in this complex biological matrix. Methodology. Thirty-seven gallstone disease patients of which twenty-one with Opisthorchis felineus infection were enrolled in the study. The bile samples were obtained during laparoscopic cholecystectomy for gallstone disease operative treatment. Common bile acid composition was measured by LC-MS/MS. Gallbladder microbiota were previously analyzed with 16S rRNA gene sequencing on Illumina MiSeq platform. The associations between bile acid composition and microbiota were analyzed. Results Bile acid signature and Opisthorchis felineus infection status exert influence on beta-diversity of bile microbial community. Direct correlations were found between taurocholic acid, taurochenodeoxycholic acid concentrations, and alpha-diversity of bile microbiota. Taurocholic acid and taurochenodeoxycholic acid both show positive associations with the presence of Chitinophagaceae family, Microbacterium and Lutibacterium genera, and Prevotella intermedia. Also, direct associations were identified for taurocholic acid concentration and the presence of Actinomycetales and Bacteroidales orders, Lautropia genus, Jeotgalicoccus psychrophilus, and Haemophilus parainfluenzae as well as for taurochenodeoxycholic acid and Acetobacteraceae family and Sphingomonas genus. There were no differences in bile acid concentrations between O. felineus-infected and noninfected patients. Conclusions/Significance. Associations between diversity, taxonomic profile of bile microbiota, and bile acid levels were evidenced in patients with cholelithiasis. Increase of taurochenodeoxycholic acid and taurocholic acid concentration correlates with bile microbiota alpha-diversity and appearance of opportunistic pathogens.

Association between cholangiocarcinoma and liver flukes: review of epidemiological studies

According to official medical statistics, liver fluke infections caused by Opisthorchis felineus , Opisthorchis viverrini and Clonorchis sinensis , are reported annually in the Southeast Asia, European countries and the Russian Federation. These infections are the main cause of digestive system diseases in the population of endemic regions. The aim of the review is to analyze the findings of epidemiological studies and to assess the relationship between liver and bile duct cancer and Opisthorchiidae liver fluke infections. Materials and methods. The authors reviewed original studies published in 1974–2019 via the MEDLINE databases and the eLIBRARY scientific digital library. Results . The studies have shown that cholangiocarcinoma is a significant medical and social problem in the trematode-endemic areas of Southeast Asia due to the absence of specific symptoms, long asymptomatic course, resistance to therapy and high mortality of patients. Long-term infection caused by trematodes Opisthorchis viverrini and Clonorchis sinensis is associated with a significant risk of developing cholangiocellular cancer. An epidemiological multicenter study is required to establish the relationship between the Opisthorchis felineus infection and cholangiocarcinoma in the population of endemic regions in the Russian Federation.

Plasma metabolomics of the time resolved response to Opisthorchis felineus infection in an animal model (golden hamster, Mesocricetus auratus).

BackgroundOpisthorchiasis is a hepatobiliary disease caused by flukes of the trematode family Opisthorchiidae. Opisthorchiasis can lead to severe hepatobiliary morbidity and is classified as a carcinogenic agent. Here we investigate the time-resolved metabolic response to Opisthorchis felineus infection in an animal model.MethodologyThirty golden hamsters were divided in three groups: severe infection (50 metacercariae/hamster), mild infection (15 metacercariae/hamster) and uninfected (vehicle-PBS) groups. Each group consisted of equal number of male and female animals. Plasma samples were collected one day before the infection and then every two weeks up to week 22 after infection. The samples were subjected to 1H Nuclear Magnetic Resonance (NMR) spectroscopy and multivariate statistical modelling.Principal findingsThe time-resolved study of the metabolic response to Opisthorchis infection in plasma in the main lines agrees with our previous report on urine data. The response reaches its peak around the 4th week of infection and stabilizes after the 10th week. Yet, unlike the urinary data there is no strong effect of the gender in the data and the intensity of infection is presented in the first two principal components of the PCA model. The main trends of the metabolic response to the infection in blood plasma are the transient depletion of essential amino acids and an increase in lipoprotein and cholesterol concentrations.ConclusionsThe time resolved metabolic signature of Opisthorchis infection in the hamster’s plasma shows a coherent shift in amino acids and lipid metabolism. Our work provides insight into the metabolic basis of the host response on the helminth infection.

Prevalence and pathology of fish trematode Opisthorchis felineus in domestic cats in Mymensingh, Bangladesh

Background: Opisthorchis felineus infection is important both for health of cats and health of people. Objective of the research was to determine the prevalence of Opisthorchis felineus and the pathological lesions caused by Opisthorchis felineus infection in domestic and stray cats in Mymensingh district, Bangladesh. Methods: A total of 36 cats were examined. The study was carried out in the Department of Parasitology and the Department of Pathology, Bangladesh Agricultural University, Mymensingh, Bangladesh. Results: Out of 36 examined cats, only 30 (83%) were infected with Opisthorchis felineus. A lower prevalence was observed in young cats <1 year old (66.66%) followed by adult cats >1 year (91.66%). Older cats were 5.5 times more susceptible to Opisthorchis felineus infection than that of young cats. Females (85.0%) were 1.30 times more susceptible to Opisthorchis felineus infection than that of males (81.25%). The prevalence of Opisthorchis felineus was very high all the year round. The rate of infection was 92.00%, 83.33% and 72.72% during summer, rainy and winter seasons respectively. At necropsy, the affected liver was apparently normal in size and shape. But in one case, paler and cream-colourcd area were found on the surface of liver. This liver was infected with 376 Opisthorchis felineus. Microscopically, fatty changes and mild hepatitis were detected. Conclusion: The present study indicates that Opisthorchis felineus infection in domestic and stray cats is a problem irrespective of age, sex and season of the year.

Characteristics of liver fibrosis associated with chronic Opisthorchis felineus infection in Syrian hamsters and humans

The food-borne liver trematode Opisthorchis felineus causes severe liver damage, including fibrosis. This study shows a comparison of the characteristics between cholangiofibrosis and periductal fibrosis in infected people and in the golden hamster as an experimental model. Comparative evaluation was carried out regarding collagen composition, the number of basic-producing cells, and extracellular-matrix degradation. The results revealed that characteristics of chronic opisthorchiasis due to O. felineus infection in humans and in Syrian hamsters are similar and include well-pronounced development of fibrotic complications in the liver parenchyma. Besides, a difference in fibrogenesis development was demonstrated between chronic O. felineus infection and noninfectious cholecystitis. In this study, we for the first time compared fibrogenesis between humans and model animals against the background of chronic O. felineus infection.

Fundamental Approaches to Optimize the Diagnostics and Treatment of the Opisthorchis felineus Infection in Endemic Regions: Study Methodology

Fundamental Approaches to Optimize the Diagnostics and Treatment of the Opisthorchis felineus Infection in Endemic Regions: Study Methodology

Life by the river: neglected worm infection in Western Siberia and pitfalls of a one-size-fits-all control approach

The One Health movement aims to provide integrated responses to problems that emerge at the intersections of human, animal, and ecological health. However, it risks derailment due to over-reliance on top-down global responses and generalisations that often fail to fit real-world settings. In this article, we examine the case of parasitic Opisthorchis felineus infection in Western Siberia and argue that understanding the local social dynamics of disease exposure and transmission, and how people live their lives in interactions with other species is crucial for making One Health work in practice. This qualitative study was conducted in preparation for developing an opisthorchiasis control programme and involved 20 in-depth interviews, participant observation, and multiple unstructured interviews in the village of Melnikovo. We explored the social dynamics of O. felineus transmission and designed a participatory model of these dynamics. This model attests to the specificity of transmission dynamics in Western Siberia and demonstrates the importance of understanding this public health issue as embedded in social networks and animated by a variety of locally-specific linkages between ways of life, food and health cultures, health-care systems, economies, and landscapes. Our work highlights that such participatory approaches have to be an integral part of One Health interventions if these interventions are to be effective and legitimate.

Mechanisms of trematodiases pathogenicity: the presence of the secretory proteins from the liver fluke Opisthorchis felineus in the gallbladder tissues of the patients with chronic opisthorchiasis

Opisthorchiasis caused by the liver fluke Opisthorchis felineus infection remains a serious public health problem in the former USSR and Eastern European countries. O. felineus infests the bile ducts, the liver and gallbladder of many fish-eating mammalian species, including humans. Opisthorchiasis leads to a number of related diseases of the liver and pancreas: liver fibrosis, cholangitis, cholecystitis, liver cysts and pancreatitis. Excretory-secretory products of the parasite are considered to be key factors in host-parasite relationships and mediate pathogenic pleiotropic effects on the host organism. The aim of this study was to determine the helminthic proteins (thioredoxin peroxidase and glutathione-S-transferase) in the gallbladder tissues of the experimental animals and patients with opisthorchiasis disease. We demonstrated by immunohistochemistry assay using antibodies against recombinant O. felineus proteins that thioredoxin peroxidase and glutathione-S-transferase could be detected in the biliary duct epithelium of the experimental animals and in human gallbladder tissues. Moreover, these proteins could also be detected in human gallbladder infiltrated cells and underlying connective tissues. The results are important for understanding the molecular mechanisms of opisthorchiasis pathogenesis, as well as for improvement of the immunodiagnostics of the opisthorchiasis and opisthorchiasis-related diseases.

Opisthorchis felineus infection and cholangiocarcinoma in the Russian Federation: A review of medical statistics

Opisthorchis felineus (O. felineus) occurs in Western Siberia and many other parts of the Russian Federation (RF). The true extent of its distribution is not known. Chronic infection may lead to severe hepatobiliary morbidity. According to surgical and experimental reports, long-term infestation might significantly increase the risk for cholangiocarcinoma (CCA). To date, no association between O. felineus infection and CCA has been demonstrated. The objective of this study was to review existing health data on the incidence of O. felineus infection and on the incidence of CCA in the RF. We reviewed the official medical statistics on reported O. felineus infection and CCA in 83 political/geographical units of the RF, covering the period January 2011–December 2013. Annual incidence data were obtained from Rospotrebnadzor and from official medical statistics. We calculated the average annual incidence of infection and cancer. The average annual incidence of O. felineus was 24.7±9.0 cases per 100,000 population. The highest incidence was observed in Khanty-Mansiysk district (599.7 cases per 100,000 population per year). In 27 geographical units, no O. felineus cases were reported. The incidence of liver and intrahepatic bile duct cancers was 4.8±0.2 cases per 100,000 population; the highest rate was reported in Sakha Republic and Tomsk Oblast (14.5 and 9.3 cases per 100,000 population), and the lowest in Yamalo-Nenets Autonomous Okrug (0.9 cases per 100,000 population). O. felineus incidence was not associated with the mean annual incidence of liver and intrahepatic bile duct cancers (r=0.20, p=0.07). This study documents the importance of opisthorchiasis in certain endemic areas and presents the best available data on associations between O. felineus infection and liver/intrahepatic bile duct cancers in RF. The findings support the need to implement a public health control programme against liver fluke infections and to increase the availability of anthelmintic treatment. Further studies are warranted to assess the contribution of opisthorchiasis to the CCA in RF.

Analysis of Opisthorchis felineus infection and liver and intrahepatic bile ducts cancer incidence rate in Russian Federation

The purpose of this paper is to perform the pilot review of the official medical statistics on reported Opisthorchis felineus (O. felineus) infection and liver and intrahepatic bile duct cancer in Russian Federation, covering the period 2011–2013. Materials and methods. Statistical data collected from 81 regions of Russia, reflecting the incidence of opisthorchiasis over a period from the 1st of January 2011 to the 31st of December 2013 was analyzed. The analysis of official health statistics of malignant hepatic lesions and intrahepatic bile duct was conducted in 82 regions of Russia over the same period. The data was obtained from the annual reports of the Russian center of information technologies and epidemiological studies in the field of oncology. Results. The average annual incidence of O. felineus was 24,7 ± 9,0 cases per 100,000 population. The highest incidence was observed in Khanty-Mansiysk Autonomous Okrug, Yamalo-Nenets Autonomous Okrug, Tyumen Oblast, Tomsk Oblast, Omsk Oblast and Novosibirsk Oblast. We did not observe any significant change in O. felineus infection rates within last 20 years. However, we found that infection incidence had increased in some geographical units of Western Siberia. The incidence of liver and intrahepatic bile duct cancers was 4,8 ± 0,2 cases per 100,000 population; the highest rate was reported in Far East regions, Siberia and Volgograd Oblast. This study documents the importance of opisthorchiasis in certain endemic areas and presents the best available data on associations between O. felineus infection and liver/intrahepatic bile duct cancers in endemic areas of Russian Federation.

Effect of Opisthorchis felineus infection and dimethylnitrosamine administration on the induction of cholangiocarcinoma in Syrian hamsters

The food-borne liver trematode Opisthorchis felineus is an emerging source of biliary tract diseases on the territory of the former Soviet Union and Eastern Europe. This parasite along with trematodes Opisthorchis viverrini and Clonorchis sinensis belong to the triad of epidemiologically important liver flukes of the Opisthorchiidae family.It is known that O. viverrini and С. sinensis are the main risk factors of cholangiocarcinoma (CCA) in the endemic regions. The carcinogenic potential of О. felineus has not been well researched because of the absence of systematic pathomorphological, clinical, and epidemiological studies on O. felineus opisthorchiasis.In the present study, we show the results of detailed histopathological analysis and comprehensive evaluation of inflammation, bile duct dysplasia, periductal fibrosis, bile duct hyperplasia, bile duct proliferation, egg granuloma, cysts, cholangiofibrosis, and CCA from 10 to 30weeks following infection of Syrian hamsters with O. felineus accompanied by oral administration of dimethylnitrosamine (DMN). The results revealed that O. felineus contributes to bile duct cancer development in the hamster model. During the combined action of O. felineus and DMN, morphological features of the liver underwent dramatic changes at the cellular and organ levels. Already in the early stages of the experiment, we observed extensive periductal fibrosis, active inflammation, proliferation of the bile duct, bile duct dysplasia and egg granulomas. Later, against the background of all these changes, cholangiofibrosis and CCA were found.Our work is the first step in the study of carcinogenic potential of O. felineus. Obtained data indicate the risk of CCA of patients having chronic О. felineus opisthorchiasis, and underscore the need for the development of programs for control of this helminthiasis.

<i>Opisthorchis felineus</i> Infection and Harmful Metals Bio-Concentration: A Pilot Study in Hamster Model

Nowadays, the question about the negative impacts of liver fluke on the host organism and mechanisms of this damage is open. The bio-concentration of some heavy and toxic metals in tissue of adult forms of Opisthorchis felineus and its accumulation in liver tissue and cardiac muscle in the Syrian Golden Hamster (Mesocricetus auratus) model was analyzed. It is outlined, that Opisthorchis felineus infection leads to accumulating aluminum in a liver tissue of the host. It was also found, that adult fluke bio-concentrates iron and aluminum in their tissue. The shortage of such essential elements as Mn, Zn and Сu in infected organism is discussed.

Endemic Opisthorchis Felineus Infection Limits Changes of Individual with Mutant Cyp1a1 and Gstm1 Genes to be Effectively Involved in Oil Field Working in the North of Siberia

More than 90% of the population of the north of Siberia (Russian Federation) inhabiting near oil field sites is infected with the en- demic helminth of Opisthorchis felineus. We demonstrated that the oil industry workers with the length of service at oil fields more than ten years do not have homozygous mutant alleles of CYP1A1 and GSTM1 genes of xenobiotic biotransformation system. Moreover, opisthorchiasis infection induces among the workers with homozygous mutant alleles of the genes significant increase in the frequency of cytogenetical abnormal cells as well as the deterioration of their health. It has been found that the Opisthorchis felineus infected workers with mutant alleles of the genes generally fail to work effectively and are retired. The habit of smoking among the workers also significantly increased the frequency of micronucleated cells.