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Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model.

ABSTRACT: It has been suggested that repeated infection of Opisthorchis viverrini followed by repeated treatment with praziquantel (PZQ) increases risk of development of cholangiocarcinoma (CCA). Evidence for the prediction has accumulated based on findings of indirect approaches involving molecular changes and epidemiological trends. By contrast, here we directly monitored the impact of repeated liver fluke infection and treatment with PZQ on cholangiocarcinogenesis in a rodent model of human opisthorchiasis, using magnetic resonance imaging (MRI) and histopathology. Twenty five Syrian golden hamsters were assigned to five treatment groups: 1) infection with O. viverrini (OV group), 2) treatment with the carcinogen N-nitrosodimethylamine (NDMA) at 12.5ppm (DMN), 3) O. viverrini infection in tandem with NDMA (OD), 4) O. viverrini infection, NDMA, and treatment with PZQ (ODP), and 5) uninfected, untreated control. The repeated infections were established by intragastric inoculation of 50 metacercariae of O. viverrini to the OV, OD and ODP hamsters at weeks 0, 5 and 10. PZQ at 300mg/kg body weight was given to each hamster of the ODP group on weeks 4, 9 and 13 (four weeks after each infection). Imaging by MRI was undertaken on weeks 5, 10 and 14 (i.e. one week after each PZQ treatment). MRI revealed that the ODP hamsters did not develop CCA, whereas necropsy at week 40 revealed CCA in hamsters of the OD and DMN groups. Findings for histopathology and for proliferating cell nuclear antigen index conformed to the MRI findings. In overview, and notwithstanding that the immune response of individual hosts may play roles in cholangiocarcinogenesis, three cycles of the infection with O. viverrini followed treatment of the infection with PZQ did not increase the risk of bile duct cancer in this hamster model of liver fluke infection-induced CCA.

SUBMITTER: Hanpanich P

PROVIDER: S-EPMC5086443 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model.

Hanpanich Petcharakorn P Laha Thewarach T Sripa Banchob B Mairiang Eimorn E Sereerak Piya P Upontain Songkaid S Tangkawattana Prasarn P Brindley Paul J PJ Tangkawattana Sirikachorn S

Parasitology international 20160430 4

It has been suggested that repeated infection of Opisthorchis viverrini followed by repeated treatment with praziquantel (PZQ) increases risk of development of cholangiocarcinoma (CCA). Evidence for the prediction has accumulated based on findings of indirect approaches involving molecular changes and epidemiological trends. By contrast, here we directly monitored the impact of repeated liver fluke infection and treatment with PZQ on cholangiocarcinogenesis in a rodent model of human opisthorchi ...[more]

PMID: 27143606

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Project description:BackgroundOpisthorchis viverrini infection is highly prevalent in northeast Thailand. This liver fluke is classified as a carcinogen due to its causal links with cholangiocarcinoma (CCA) development. Although treatment with praziquantel (PZQ) effectively cures O. viverrini infection, the prevalence remains high due to the traditional consumption of raw fish. Therefore, re-infection is common in the endemic community, leading to severe hepato-biliary morbidities including the fatal CCA. In this study, we evaluate the association between the frequency of previous PZQ treatment and current O. viverrini infections among Thai adults living in the endemic area of northeast Thailand.MethodsThis study includes all participants who were screened for O. viverrini infection in the Cholangiocarcinoma Screening and Care Program (CASCAP), northeast Thailand. History of PZQ treatment was recorded using a health questionnaire. O. viverrini infections were diagnosed using urine antigen detection. Associations between PZQ and O. viverrini were determined by adjusted odds ratio (aOR) and 95% confidence interval (CI) using multiple logistic regression.ResultsAmong participants, 27.7% had previously been treated once with PZQ, 8.2% twice, 2.8% three times, and 3.5% more than three times. Current O. viverrini prevalence was 17% (n = 524). Compared with participants who never used PZQ, the aOR for infection among those who used the drug once was 1.09 (95% CI: 0.88-1.37), twice was 1.19 (95% CI: 0.85-1.68), three times was 1.28 (95% CI: 0.74-2.21), and more than three times was 1.86 (95% CI: 1.18-2.93; P = 0.007).ConclusionsThe population with a frequent history of PZQ use and still continued raw fish consumption showed high levels of repeated reinfection with O. viverrini. They were infected, treated and re-infected repeatedly. These findings suggest that certain participants continue raw fish consumption even after previous infection. This is a particular problem in highly endemic areas for O. viverrini and increases the risk of CCA.

Project description:BackgroundSchistosomiasis and opisthorchiasis are of public health importance in Southeast Asia. Praziquantel (PZQ) is the drug of choice for morbidity control but few dose comparisons have been made.MethodologyNinety-three schoolchildren were enrolled in an area of Lao PDR where Schistosoma mekongi and Opisthorchis viverrini coexist for a PZQ dose-comparison trial. Prevalence and intensity of infections were determined by a rigorous diagnostic effort (3 stool specimens, each examined with triplicate Kato-Katz) before and 28-30 days after treatment. Ninety children with full baseline data were randomized to receive PZQ: the 40 mg/kg standard single dose (n?=?45) or a 75 mg/kg total dose (50 mg/kg+25 mg/kg, 4 hours apart; n?=?45). Adverse events were assessed at 3 and 24 hours posttreatment.Principal findingsBaseline infection prevalence of S. mekongi and O. viverrini were 87.8% and 98.9%, respectively. S. mekongi cure rates were 75.0% (95% confidence interval (CI): 56.6-88.5%) and 80.8% (95% CI: 60.6-93.4%) for 40 mg/kg and 75 mg/kg PZQ, respectively (P?=?0.60). O. viverrini cure rates were significantly different at 71.4% (95% CI: 53.4-84.4%) and 96.6% (95% CI: not defined), respectively (P?=?0.009). Egg reduction rates (ERRs) against O. viverrini were very high for both doses (>99%), but slightly lower for S. mekongi at 40 mg/kg (96.4% vs. 98.1%) and not influenced by increasing diagnostic effort. O. viverrini cure rates would have been overestimated and no statistical difference between doses found if efficacy was based on a minimum sampling effort (single Kato-Katz before and after treatment). Adverse events were common (96%), mainly mild with no significant differences between the two treatment groups.Conclusions/significanceCure rate from the 75 mg/kg PZQ dose was more efficacious than 40 mg/kg against O. viverrini but not against S. mekongi infections, while ERRs were similar for both doses.Trial registrationControlled-Trials.com ISRCTN57714676.

Dataset Information

Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model.

Publications

Decreased risk of cholangiocarcinogenesis following repeated cycles of Opisthorchis viverrini infection-praziquantel treatment: Magnetic Resonance Imaging (MRI) and histopathological study in a hamster model.

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