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Background: Cholangiocarcinoma (CCA), a fatal bile duct cancer, has a high incidence in Western Siberia, Russian Federation. In addition, Opisthorchis felineus, a bile duct-dwelling trematode liver fluke is highly endemic. Closely related species have been shown to be cancerogenic agents in Asia. We therefore examined the association between O felineus infection and CCA in Western Siberia., Methods: We conducted a hospital-based, individually matched case-control study between January 2017 and August 2020 in Tomsk Oblast and Khanty-Mansiysk Autonomous Okrug, Yugra, Russian Federation. Histologically confirmed CCA patients (cases) were compared with matched age, sex, and place of residence hospital controls. The examination of study participants included the diagnosis of current and past O felineus infection, abdominal ultrasonographical assessment, physical examination, and interview on exposures to potential risk factors., Results: We identified 40 patients with CCA and 160 controls. Exposures to O felineus infection was strongly associated with CCA (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.4-10.8; P = .008). Also, cases reported more often that they were currently or in the past were infected by O felineus compared with controls (OR, 4.03; 95% CI, 1.7-9.5; P = .001). Furthermore, cases reported river fish consumption and fishing habits significantly more often than controls (OR, 5.5; 95% CI, 1.5-19.8; P = .009 and OR, 3.3; 95% CI, 1.4-7.7; P = .005)., Conclusions: The study results revealed a strong significantly increased risk for CCA development in O felineus-infected individuals. Elaboration of the guidelines on screening programs for early CCA diagnosis, prevention, and treatment is socially important in endemic regions., Competing Interests: Potential conflicts of interest. P. O. reports a grant from University of Geneva to plan and implement a collaborative course in epidemiology between Swiss TPH and the Siberian State Medical University outside of the submitted work. All other authors have no conflicts of interest to disclose., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Opisthorchiasis due to the liver fluke Opisthorchis felineus is highly prevalent in rural regions of Western Siberia, causing severe liver and bile duct maladies. Praziquantel administered as a three-dose regimen is the only drug used to treat O. felineus-infected individuals. A simpler single-dose treatment might serve as an alternative. The aim of this study was to compare the pharmacokinetic (PK) properties of single, ascending doses of praziquantel compared to multiple dosing in patients infected with O. felineus to contribute to updated treatment guidelines. Dried blood spots (DBSs) of 110 adults were collected at 11 time points post-drug administration at single oral doses of 20, 40, and 60 mg/kg, as well as 3× 20 mg/kg (4 h dosing interval). DBS samples were analyzed using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method, and PK parameters were obtained for R -, S -, and R-trans -4-OH-praziquantel employing noncompartmental analysis. We observed the highest drug exposure for all analytes when the triple-dose scheme was used; area under the concentration-time curve from 0 to 24 h (AUC 0-24 ) values of 8.04, 27.75, and 36.38 μg/mL·h were obtained, respectively. Maximal plasma concentrations ( C max ) values of 1.72, 4.89, and 2.69 μg/mL were calculated for R -, S -, and R-trans -4-OH-praziquantel, respectively, when patients were given a single 60-mg/kg dose, and they peaked at 1.5 and 2 h for the enantiomers and at 3 h for the metabolite. The herein-generated PK data, together with results that will be obtained from the integrated efficacy study, lay the groundwork for a possibly optimized treatment scheme for O. felineus-infected patients.

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., (Copyright © 2021. Published by Elsevier B.V.)

Background: The liver fluke, Opisthorchis felineus, is widely distributed throughout Europe and large parts of the Russian Federation. In Western Siberia, information about opisthorchiasis is lacking although infection may lead to severe liver and bile duct diseases. We aimed to assess the current prevalence of O. felineus infection along with associated risk factors and morbidity in rural Western Siberia., Methods: We conducted a community-based, cross-sectional study in the rural Shegarskiy district, Tomsk Oblast, Russian Federation. All household members (≥ 7 years) present on the survey day were enrolled (n = 600). Two stool samples per person were examined for helminth eggs, using PARASEP (DiaSys Ltd, UK). The number of eggs per gram (EPG) of feces was recorded. Each study participant was interviewed to determine risk factors, using a pre-tested questionnaire. An abdominal ultrasonography examination of liver and bile ducts was performed with a mobile, high resolution ultrasound device. In total, 488 persons completed assessments (two stool samples, completed questionnaires); of those, 436 individuals had an ultrasonography (US) examination., Results: We observed a prevalence of O. felineus infection of 60.2%. Significant risk factors for infection were the consumption of river fish (odds ratio from adjusted analysis [aOR] 2.4, 95% CI 1.52-3.95, p<0.001), particularly stock fish (OR from multivariable analysis [mOR] 3.2, 95% CI 2.63-3.80, p<0.001), smoked fish (mOR 1.5, 95% CI 1.24-1.72, p<0.001), frozen fish (mOR 1.6, 95% CI 1.29-2.02, p<0.001), and raw fish (mOR 1.4, 95% CI 1.05-1.84, p = 0.02); and fishing activities (mOR 1.2, 95% CI 1.03-1.43, p = 0.019). Women had a higher risk of infection than men. Infection was associated positively with age and negatively with socio-economic status. The respondents' general awareness of opisthorchiasis was quite high (93.2%), but their knowledge about infection transmission and prevention was insufficient. Children aged 7-18 years old had a lower level of awareness compared to adults. The abdominal ultrasonography results demonstrated a strong association between O. felineus infection and gallbladder stones (mOR 2.8, 95% CI 1.33-6.04, p = 0.007) and periductal fibrosis of intrahepatic bile ducts (mOR 1.9, 95% CI 1.08-3.46, p = 0.026)., Conclusion: O. felineus infection is highly prevalent in rural regions of Western Siberia, and associated with severe hepatobiliary pathology. Identified risk factors will be used to develop a comprehensive targeted O. felineus infection control program., Competing Interests: The authors have declared that no competing interests exist.

Cholangiocarcinoma (CCA) is a cancer with high mortality owing to its aggressiveness and resistance to therapy. The liver flukes of the Opisthorchiidae family have been recognized as risk factors of CCA. Opisthorchis felineus infection occurs in Western Siberia, the biggest endemic area in the Russian Federation, and is associated with chronic inflammation of the bile ducts, which may be linked to severe hepatobiliary morbidity. We report two cases of confirmed CCA who had a chronic O. felineus infection. Both cases presented unspecific symptoms at the onset of the disease, a stage when severe pathological changes already had occurred. Both patients were living in endemic areas but did not receive any antihelminthic treatment. This report underlines the need for assessment of O. felineus infection as a causative factor of CCA. The results will provide further arguments for control of O. felineus in the Russian Federation.

In this study we reviewed Russian scientific literature (scientific publications, book chapters, monographs) published between 1 January 1979 and 31 August 2015 from two sources: Main database of the Russian Scientific Electronic Library (eLIBRARY, http://elibrary.ru/), and the Scientific Medical Library of Siberian State Medical University (http://medlib.tomsk.ru/). Specifically, the review details the infection prevalence of Opisthorchis felineus (O. felineus) in Western Siberia, Russian Federation. From the primary key words screening, 1591 records were identified from which 32 Russian-language publications were relevant. The lowest O. felineus infection rate of 0.4% was reported in Tatarstan Republic, and the highest reached 83.9% in the Khanty-Mansiysk Autonomous Okrug. The infection prevalence was lower in children than in adults and increased with age. O. felineus infection was detected more often in indigenous population than in migrants. Infection intensity in western regions (Permskaya, Bryanskaya Oblast) was low and varied from 15 to 336 eggs per gram stool (epg), while in endemic regions it reached more than 2000 epg. In some settlements the mean intensity infection was 5234 epg. The high rates of intensity were registered in regions with a high prevalence of infection. Based on obtained data, a map of O. felineus infection prevalence in Western Siberia was developed. After mapping the results, the highest prevalence was detected in Tyumenskaya Oblast with over 60%, while the Tomskaya Oblast had the lowest prevalence at fewer than 19.0%. Khanty-Mansiysk Autonomus Okrug, Altaiskii Krai, Novosibirskaya Oblast and Omskaya Oblast had an average level of O. felineus infection of 20-39%. According to the results of the review, Western Siberia must be considered as highly endemic region for opisthorchiasis in the Russian Federation. The development of a control program specific for the Russian community is warranted., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Most studies on the relationship between helminth infections and atopic disorders have been conducted in (sub)tropical developing countries where exposure to multiple parasites and lifestyle can confound the relationship. We aimed to study the relationship between infection with the fish-borne helminth Opishorchis felineus and specific IgE, skin prick testing, and atopic symptoms in Western Siberia, with lifestyle and hygiene standards of a developed country., Methods: Schoolchildren aged 7-11 years were sampled from one urban and two rural regions. Skin prick tests (SPT) and specific IgE (sIgE) against food and aeroallergens were measured, and data on allergic symptoms and on demographic and socioeconomic factors were collected by questionnaire. Diagnosis of opisthorchiasis was based on PCR performed on stool samples., Results: Of the 732 children included, 34.9% had opisthorchiasis. The sensitization to any allergen when estimated by positive SPT was 12.8%, while much higher, 24.0%, when measured by sIgE. Atopic symptoms in the past year (flexural eczema and/or rhinoconjunctivitis) were reported in 12.4% of the children. SPT was positively related to flexural eczema and rhinoconjunctivitis, but not to wheezing. Opisthorchiasis showed association with lower SPT response, as well as borderline association with low IgE reactivity to any allergen. However, the effect of opisthorchiasis on SPT response was not mediated by IgE, suggesting that opisthorchiasis influences SPT response through another mechanism. Opisthorchiasis also showed borderline association with lower atopic symptoms., Conclusions: There is a negative association between a chronic helminth infection and skin prick test reactivity even in a developed country., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: To determine the mechanism of food sensitization in children with chronic Opisthorchis felineus invasion., Patients and Methods: During the epidemiological study the groups of patients (7-10 years) with chronic opisthorchiasis (n = 237) and children without chronic opisthorchiasis (n = 496) were formed. The investigation included interviewing of parents/guardians, measurement of total IgE, specific IgE to food allergens and component-resolved diagnostic, real-time PCR in stool samples., Results: The chronic opisthorchiasis invasion in children is associated with reduced risk of food sensitization, compared with non-infected group (9.7 vs 16.94%, OR = 0.53; 95% CI 0.31-0.88; p = 0.01). Opisthorchiasis of high intensity negatively correlated with increased level of specific IgE to food allergens in serum (OR = 0.46; 95% CI 0.24-0.91; p = 0.023). The association between level of total IgE and intensity of opisthorchiasis combinated with food sensitization was found. The sensitization to allergens class I (cyp c1, cor a11, gal d2, pru p3) is more prevalent in patients with opisthorchiasis, in uninfected children the sensitization to bet v1-homologues (mal d1, pru p1, cor a1, ara h8) is most common., Conclusions: The epidemiological data on the effect of the Opisthorchis felineus invasion on mechanisms of food sensitization in children were obtained.

Accordingly to numerous surveys food allergy affects up to 2-6% of population in different countries and varies due to numerous factors including the prevalence of helminths infestation. The food allergy prevalence data in Russia are based on official medical statistics. The study was performed as part of "The Prevalence, Cost and Basis of Food Allergy Across Europe" (EU funded project No FP6-2006-TTC-TU-5 Proposal 045879 EuroPrevall). The aim is to create the concept offood allergy in children in opisthorchiasis endemic area based on epidemiological study of the prevalence, risk factors and clinical features. The main objective of the study will be the working out of the food safety regulations. This article describes the study design and its methodology.

Opisthorchiasis is one of the significant naturofocal diseases in Russia. The diagnosis of opisthorchiasis may mask some diseases, such as opisthorchiasis, metorchiasis, and clonorchiasis - biohelminthoses that are induced by various representatives of the family Opisthorchiidae-Opisthorchis felineus/O.viverrini, Metorchis bilis, and Clonorchis sinensis, respectively. Coproovoscopy and serologic methods fail to accurately define the species-specific affiliation; in this connection the identification of opisthorchids, by using DNA diagnostic techniques, becomes urgent. The present paper gives the results of development of DNA diagnosticum, which differentiates parasitic diseases induced by O. felineus and M. bills. The ribosomal RNA gene cluster fragment incorporating internal transcribed spacer 2 (ITS2) was used as a diagnostic marker. A system for diagnosing opisthorchiasis was developed as a multiplex polymerase chain analysis and tested on 37 patients infected with various species of opisthorchids.

The study was aimed to estimate the relationship between the prevalence of allergic disease and helminth invasion by the trematode Opisthorchis felineus in rural and urban populations of Tomsk Oblast (West Siberia, Russia). Two hundred and one people from Kargasok village of Tomsk Oblast and 196 from the city of Tomsk were screened for the presence of atopy and O. felineus invasion. Opisthorchosis was found in 66 participants (32.8%) from Kargasok and in 22 people (11.2%) from Tomsk. Atopic diseases were more common in the urban population than in the rural: 52.8 and 31.4%, respectively. Positive skin-prick tests were significantly higher in the urban population than in rural people: 83.2 vs 24.4%, respectively. It was found that in the city, the presence of antibodies to O. felineus negatively correlates with the atopic sensitization by skin-prick tests. However, in the village, opisthorchosis was positively associated with atopic diseases. The data obtained confirm the negative association of rural lifestyle and atopic diseases prevalence and indicate that O. felineus invasion might be a modifying factor of this relationship in Tomsk Oblast.