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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.

Competing Interests: Competing interests: None declared.

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.

Food allergy to peanuts and nuts is an actual problem of practical health care, associated with significant prevalence of this disease, severe clinical symptoms and difficulty of diet organization. Purpose of the study--to study the prevalence of food allergy to peanut and hazelnut in Russian children, the investigation of clinical characteristics of this disease, and the mechanisms of sensitization to allergen components. The cross-sectional study was performed in the framework of the EuroPrevall (No FP6-2006-TTC-TU-5 Proposal 045879). The first stage was performed in random samples of primary schoolchildren aged 7-10 years (n = 13 010) from the Tomsk Region, Russia using a standardized questionnaire. The case-control sample was recruited for the second stage (n = 1288). Thus who reported adverse reactions to food in the screening stage were considered as cases (n = 652), children without reported reactions were controls (n = 636). The case-control stage included the completion of a clinical questionnaire, skin-prick test (ALK-Abelly, Spain), serum specific IgE measurement and component-resolved diagnostic: IgE measurement of allergen components of peanut (Ara h1, Ara h26, Ara h34, Ara h8), hazelnut (Cor a1, Cor a8, Cor a11) and birch allergen Bet v1 (ImmunoCAP, Phadia, Sweden). The prevalence of food allergy to peanut and hazelnut in children aged 7-10 years in the Tomsk region is 0.08 and 0.09%, respectively. The manifestation of the food allergy to nuts occurs in the preschool years, main reactions associated with allergy to nuts were oral allergy syndrome (75-80%), gastrointestinal disorders (60-80%) and itching skin rash (20-50%). Sensitization to birch is significantly correlated with the level of specific IgE to hazelnut (r = 0.53, p < 0.05) and peanut (r = 0.56, p < 0.05). Sensitization to heat-labile proteins peanut Ara h8 (12.3%) and hazelnut Cor a1 (8.8%) (homologues of Bet v1) dominates in the sample of children with food sensitization, that determines the cross-reactivity mechanism in the formation of food sensitization in the studied sample. The prevalence of allergies to peanut and hazelnut in Russia is much lower than in Europe and North America. Sensitization to these foods develops by the mechanism of cross-reactivity with birch pollen allergen. This type of sensitization determines mild clinical symptoms of allergy to hazelnut and peanut.

Genome-wide association studies are currently considered as one of the most powerful tools to establishing the genetic basis of complex diseases. A number of such studies were carried out for allergic diseases; however, in Russian population this analysis has not been performed so far. For the first time, we performed genome-wide association study of allergic diseases in Russian inhabitants of Western Siberia. Two new loci associated with childhood bronchial asthma were identified (20q13.12, rs2425656, P = 1.99 x 10(-7); 1q32.1, rs3817222, rs12734001, P = 2.18 x 10(-7) and 2.79 x 10(-7), respectively) as well as one locus, associated with allergic rhinitis (2q36.1, rs1597167, P = 3.69 x 10(-7)). Genes located in the loci, YWHAB and PPP1R12B for asthma and KCNE4 for allergic rhinitis, are new genes for these diseases. It was found that BAT1 (6p21.33), MAGI2 (7q21.11) and ACPL2 (3q23) genes are, likely, common (syntropic) genes of allergic disease and a topic sensitisation. It was shown that RIT2 (18q12.3) and (5q31.1) genes can be involved in the control of lung function. The results of the study enlarge the body of data on genetic factors of allergy and expand the list of genes underlying these diseases.