The global epidemiology of clonorchiasis and its relation with cholangiocarcinoma.
ABSTRACT: This paper reviews the epidemiological status and characteristics of clonorchiasis at global level and the etiological relationship between Clonorchis sinensis infection and cholangiocarcinoma (CCA). A conservative estimation was made that 15 million people were infected in the world in 2004, of which over 85% distributed in China. The epidemiology of clonorchiasis is characterized by rising trend in its prevalence, variability among sexes and age, as well as endemicity in different regions. More data indicate that C. sinensis infection is carcinogenic to human, and it is predicted that nearly 5 000 CCA cases attributed to C. sinensis infection may occur annually in the world decades later, with its overall odds ratio of 4.47. Clonorchiasis is becoming one major public health problem in east Asia, and it is worthwhile to carry out further epidemiological studies.
Project description:Clonorchiasis is caused by infection with food-borne liver fluke, namely Clonorchis sinensis, which is also considered to be a neglected tropical disease. It is estimated that over 10 million people are infected with C. sinensis in China and, subsequently, several thousand new cholangiocarcinoma cases occur annually. On May 18, 2014, China Central Television broadcasted an episode on the habit of raw-fish eating and its potential to cause clonorchiasis in a programme called Health on the tip of the tongue. Here, I briefly introduce the content of the episode and discuss its significance for clonorchiasis control in China.
Project description:Clonorchiasis, known as the Chinese liver fluke disease, is caused by Clonorchis sinensis infection with food-borne liver fluke, which is transmitted via snails to freshwater fish and then to human beings or other piscivorous mammals. Clonorchis sinensis infection is mainly related to liver and biliary disorders, especially cholangiocarcinoma, and has an increased human-health impact due to the greater consumption of raw freshwater fish. In this article, we propose a deterministic model to describe the spread of clonorchiasis among human-snail-fish populations and use the model to simulate the data on the numbers of inspected and infected individuals of Foshan City, located in Guangdong Province in the southeast of P.R China, from 1980-2010. Mathematical and numerical analyses of the model are carried out to understand the transmission dynamics of clonorchiasis and explore effective control measures for the local outbreaks of the disease. We find that (i) the transmission of clonorchiasis from cercariae to fish plays a more important role than that from eggs to snails and from fish to humans; (ii) As the cycle of infection-treatment-reinfection continues, it is unlikely that treatment with drugs alone can control and eventually eradicate clonorchiasis. These strongly suggest that a more comprehensive approach needs to include environmental modification in order to break the cercariae-fish transmission cycle, to enhance awareness about the disease, and to improve prevention measures.
Project description:Recent publication of the global epidemiology of clonorchiasis and its relationship with cholangiocarcinoma in the journal of Infectious Diseases of Poverty has stressed the importance of Clonorchis sinensis infection. To further demonstrate its threat on public health, especially in China, comparisons between clonorchiasis and hepatitis B are made in terms of epidemiology, clinical symptoms and carcinogenicity, disability, as well as changing trends. Furthermore, major problems and prioritized researches are argued, from basic biology to intervention. Imbalance between the majority of infected population and the minority of researches in China urges for more work from Chinese scientists and international cooperation.
Project description:BACKGROUND:Clonorchiasis, one of the most important food-borne trematodiases, affects more than 12 million people in the People's Republic of China (P.R. China). Spatially explicit risk estimates of Clonorchis sinensis infection are needed in order to target control interventions. METHODOLOGY:Georeferenced survey data pertaining to infection prevalence of C. sinensis in P.R. China from 2000 onwards were obtained via a systematic review in PubMed, ISI Web of Science, Chinese National Knowledge Internet, and Wanfang Data from January 1, 2000 until January 10, 2016, with no restriction of language or study design. Additional disease data were provided by the National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention in Shanghai. Environmental and socioeconomic proxies were extracted from remote-sensing and other data sources. Bayesian variable selection was carried out to identify the most important predictors of C. sinensis risk. Geostatistical models were applied to quantify the association between infection risk and the predictors of the disease, and to predict the risk of infection across P.R. China at high spatial resolution (over a grid with grid cell size of 5×5 km). PRINCIPAL FINDINGS:We obtained clonorchiasis survey data at 633 unique locations in P.R. China. We observed that the risk of C. sinensis infection increased over time, particularly from 2005 onwards. We estimate that around 14.8 million (95% Bayesian credible interval 13.8-15.8 million) people in P.R. China were infected with C. sinensis in 2010. Highly endemic areas (? 20%) were concentrated in southern and northeastern parts of the country. The provinces with the highest risk of infection and the largest number of infected people were Guangdong, Guangxi, and Heilongjiang. CONCLUSIONS/SIGNIFICANCE:Our results provide spatially relevant information for guiding clonorchiasis control interventions in P.R. China. The trend toward higher risk of C. sinensis infection in the recent past urges the Chinese government to pay more attention to the public health importance of clonorchiasis and to target interventions to high-risk areas.
Project description:A cDNA expression library of Clonorchis sinensis adult worm was constructed, and screened out immunologically. One clone, pBCs31, was selected in view of its predominant reactivity with an experimentally infected rabbit serum. Recombinant C. sinensis antigen with 28 kDa as a beta-galactosidase fusion protein produced in Escherichia coli was identified by immunoblot analysis. The cloned gene was composed of 16 copies of a 30 base pair repeat and an additional 320 bases. The deduced amino acid sequence of the tandem repeat was AQPPKSGDGG. On RNA slot blot analysis. C. sinensis adult worm RNA showed a positive reaction with the cloned gene. Enzyme-linked immunosorbent assay using a purified recombinant antigen of pBCs31 showed high specificity for diagnosis of clonorchiasis.
Project description:Clonorchis sinensis is a group-I bio-carcinogen for cholangiocarcinoma (CCA). Although the epidemiological evidence links clonorchiasis and CCA, the underlying molecular mechanism involved in this process is poorly understood. In the present study, we investigated expression of oncogenes and tumor suppressors, including PSMD10, CDK4, p53 and RB in C. sinensis induced hamster CCA model.Different histochemical/immunohistochemical techniques were performed to detect CCA in 4 groups of hamsters: uninfected control (Ctrl.), infected with C. sinensis (Cs), ingested N-nitrosodimethylamine (NDMA), and both Cs infected and NDMA introduced (Cs+NDMA). The liver tissues from all groups were analyzed for gene/protein expressions by quantitative PCR (qPCR) and western blotting.CCA was observed in all hamsters of Cs+NDMA group with well, moderate, and poorly differentiated types measured in 21.8% ± 1.5%, 13.3% ± 1.3%, and 10.8% ± 1.3% of total tissue section areas respectively. All CCA differentiations progressed in a time dependent manner, starting from the 8th week of infection. CCA stroma was characterized with increased collagen type I, mucin, and proliferative cell nuclear antigen (PCNA). The qPCR analysis showed PSMD10, CDK4 and p16INK4 were over-expressed, whereas p53 was under-expressed in the Cs+NDMA group. We observed no change in RB1 at mRNA level but found significant down-regulation of RB protein. The apoptosis related genes, BAX and caspase 9 were found downregulated in the CCA tissue. Gene/protein expressions were matched well with the pathological changes of different groups except the NDMA group. Though the hamsters in the NDMA group showed no marked pathological lesions, we observed over-expression of Akt/PKB and p53 genes proposing molecular interplay in this group which might be related to the CCA initiation in this animal model.The present findings suggest that oncogenes, PSMD10 and CDK4, and tumor suppressors, p53 and RB, are involved in the carcinogenesis process of C. sinensis induced CCA in hamsters.
Project description:We produced a recombinant cysteine proteinase of Clonorchis sinensis and tested its value as an antigen for serologic diagnosis of C. sinensis infections. The predicted amino acid sequence of the cysteine proteinase of C. sinensis was 58, 48, and 40% identical to those of cathepsin L cysteine proteinases from Paragonimus westermani, Schistosoma japonicum, and Fasciola hepatica, respectively. Western blotting analysis showed that sera from patients infected with C. sinensis strongly reacted with the recombinant protein and that sera from patients infected with S. japonicum weakly reacted with the recombinant protein. Antibody against the recombinant protein stained proteins migrating at about 37 and 28 kDa in C. sinensis adult worm crude extracts. Immunostaining revealed that the cysteine proteinase of C. sinensis was located in the intestinal epithelial cells of the adult parasite and in intrauterine eggs. The specificity and sensitivity of the recombinant antigen or C. sinensis adult worm crude extracts were assessed by an enzyme-linked immunosorbent assay (ELISA) using serum samples from humans infected with different parasites, including 50 patients with clonorchiasis, and negative controls. The sensitivities of the ELISA with the recombinant antigen and C. sinensis adult worm crude extracts were 96 and 88%, respectively. The specificities of the ELISA with the recombinant antigen and C. sinensis adult worm crude extracts were 96.2 and 100%, respectively. The results suggested that the recombinant cysteine proteinase-based ELISA could provide a highly sensitive and specific assay for diagnosis of clonorchiasis.
Project description:BACKGROUND:Clonorchiasis, caused by Clonorchis sinensis (C. sinensis) infection, is a serious food-borne zoonotic disease that is often asymptomatic or shows only mild symptoms, which leads to delayed treatment and chronic clonorchiasis and results in various complications, such as cholelithiasis, cholangitis, cholecystitis and cholangiocarcinoma. However, acute shock caused by C. sinensis infection has not been reported. Here, for the first time, we describe a fatal case of acute shock caused by C. sinensis infection. CASE PRESENTATION:A patient with a history of eating raw or undercooked freshwater fish was hospitalized with acute shock caused by severe abdominal pain. Physical examination suggested acute abdomen with severe abdominal pain and rigidity. Computed tomography (CT) detection indicated acute cholecystitis and cholelithiasis. After cholecystectomy, several liver flukes were found in the drainage tube. Furthermore, morphological analysis and polymerase chain reaction (PCR) identified the pathogen as C. sinensis. The liver gradually restored normal function after anthelmintic therapy with praziquantel. CONCLUSIONS:In this fatal case, C. sinensis infection was the cause of acute shock, which is rarely found in the clinic environment. This report aims to increase awareness of the hazards and complications related to clonorchiasis. The PCR diagnosis method used in this report might be helpful in reducing the misdiagnosis of clonorchiasis and unnecessary cholecystectomy.
Project description:Clonorchiasis remains an important zoonotic parasitic disease worldwide. The molecular mechanisms of host-parasite interaction are not fully understood. Non-coding microRNAs (miRNAs) are considered to be key regulators in parasitic diseases. The regulation of miRNAs and host micro-environment may be involved in clonorchiasis, and require further investigation. MiRNA microarray technology and bioinformatic analysis were used to investigate the regulatory mechanisms of host miRNA and to compare miRNA expression profiles in the liver tissues of Clonorchis sinensis-infected rats and controls.A total of eight miRNAs were downregulated and two were upregulated, which showed differentially altered expression profiles in the liver tissue of C. sinensis-infected rats. Further analysis of the differentially expressed miRNAs revealed that many important signal pathways were triggered after infection with C. sinensis, which were related to clonorchiasis pathogenesis, such as cell apoptosis and inflammation, as well as genes involved in signal transduction mechanisms, such as pathways in cancer and the Wnt and Mitogen-activated protein kinases (MAPK) signaling pathways.This dysregulation in miRNA expression may contribute to the etiology and pathophysiology of clonorchiasis. These results also provide new insights into the regulatory mechanisms of miRNAs in clonorchiasis, which may present potential targets for future C. sinensis control strategies. Overall design: We collected liver from control and 3 weeks post-infection with clonorchis sinensis of rat, respectively.
Project description:Clonorchis sinensis, the causative agent of clonorchiasis, is classified as one of the most neglected tropical diseases and affects more than 15 million people globally. This hepatobiliary disease is highly associated with cholangiocarcinoma. As key molecules in the infectivity and subsistence of trematodes, glycolytic enzymes have been targets for drug and vaccine development. Clonorchis sinensis pyruvate kinase (CsPK), a crucial glycolytic enzyme, was characterized in this research.Differences were observed in the sequences and spatial structures of CsPK and PKs from humans, rats, mice and rabbits. CsPK possessed a characteristic active site signature (IKLIAKIENHEGV) and some unique sites but lacked the N-terminal domain. The predicted subunit molecular mass (Mr) of CsPK was 53.1 kDa. Recombinant CsPK (rCsPK) was a homopentamer with a Mr. of approximately 290 kDa by both native PAGE and gel filtration chromatography. Significant differences in the protein and mRNA levels of CsPK were observed among four life stages of C. sinensis (egg, adult worm, excysted metacercaria and metacercaria), suggesting that these developmental stages may be associated with diverse energy demands. CsPK was widely distributed in adult worms. Moreover, an intense Th1-biased immune response was persistently elicited in rats immunized with rCsPK. Also, rat anti-rCsPK sera suppressed C. sinensis adult subsistence both in vivo and in vitro.The sequences and spatial structures, molecular mass, and expression profile of CsPK have been characterized. rCsPK was indicated to be a homopentamer. Rat anti-rCsPK sera suppressed C. sinensis adult subsistence both in vivo and in vitro. CsPK is worthy of further study as a promising target for drug and vaccine development.