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.

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.

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.

Opisthorchis felineus infection prevalence in Western Siberia: A review of Russian literature.

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.