Pharmacokinetics of Ascending Doses of Praziquantel in Adults Infected with Opisthorchis felineus in Western Siberia, Russian Federation.

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 (AUC0-24) values of 8.04, 27.75, and 36.38 µg/mL·h were obtained, respectively. Maximal plasma concentrations (Cmax) 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.

Opisthorchis felineus infection, risks, and morbidity in rural Western Siberia, Russian Federation.

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.

A cross-national perspective of migration and cancer: incidence of five major cancer types among resettlers from the former Soviet Union in Germany and ethnic Germans in Russia.

BACKGROUND: Few studies compared cancer incidence among migrants both to their host countries and to their population of origin. We aimed to compare cancer incidence of ethnic Germans who migrated from the former Soviet Union to Germany (resettlers) to those living in Russia as well as to the German and the Russian general populations. METHODS: The cancer registry of North Rhine-Westphalia identified incident cases of stomach, colorectal, lung, breast and prostate cancer in resettlers and the general population of the administrative district of Münster (Germany) between 2004 and 2013. The Tomsk cancer registry collected the same data in ethnic Germans and the general population of the Tomsk region (Russia). We used standardised incidence rate ratios (SIRs) to compare rates of resettlers and ethnic Germans with the respective general populations. RESULTS: The total number of person-years under risk was 83,289 for ethnic Germans, 8,006,775 for the population of Tomsk, 219,604 for resettlers, and 20,516,782 for the population of Münster. Incidence of the five investigated cancer types among ethnic Germans did not differ from incidence of the general population of Tomsk. Compared to the general population of Tomsk, incidence among resettlers was higher for colorectal cancer in both sexes (females: SIR 1.45 [95% CI 1.14-1.83], males: SIR 1.56 [95% CI 1.23-1.97]), breast cancer in females (SIR 1.65 [95% CI 1.40-1.95]), and prostate cancer (SIR 1.64 [95% CI 1.34-2.01]). Incidence rates of these cancer types among resettlers were more similar to rates of the general population of Münster. Incidence of stomach and lung cancer did not differ between resettlers and the general population of Tomsk. CONCLUSIONS: After an average stay of 15 years, we observed that incidence of colorectal, breast and prostate cancer among resettlers converged to levels of the general population of Münster. Resettler's incidence of stomach and lung cancer, however, was comparable to incidence in their population of origin. Causes must be investigated in subsequent analytical studies.