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Background: Clonorchiasis has significant socioeconomic importance in endemic areas; however, studies investigating the disease burden in specific sub-regions are lacking. This study aims to address the gap by quantifying the current disease burden caused by clonorchiasis in Guangdong province and assessing its distribution characteristics. Methods: Comprehensive measures, including prevalence rates, disability-adjusted life years (DALYs), and direct medical costs, were used to assess the disease burden of clonorchiasis. To estimate the prevalence rate, the number of infections was divided by the examined population, based on the annual surveillance data on clonorchiasis cases during 2016–2021. The calculation of DALYs was based on the epidemiological parameters according to the definition issued by the World Health Organization. Cost data of clonorchiasis were utilized to quantify the direct medical costs. The distribution characteristics of disease burden were assessed through comparisons of groups of population defined by geographic area, time, and characteristics of people. Results: In 2021, clonorchiasis posed a significant disease burden in Guangdong Province. The prevalence rate was found to be 4.25% [95% CI (4.02%, 4.49%)], with an associated burden of DALYs of 406,802.29 [95% CI (329,275.33, 49,215,163.78)] person-years. The per-case direct medical costs of patients with clonorchiasis were estimated to be CNY 7907.2 (SD = 5154.4). Notably, while the prevalence rate and DALYs showed a steady decrease from 2016 to 2020, there was a rising trend in 2021. Spatial clustering of clonorchiasis cases and DALYs was also observed, particularly along the Pearl River and Han River. This suggests a concentration of the disease in these regions. Furthermore, significant differences in prevalence rates were found among various demographic groups, including sex, age, occupation, and education level. Additionally, patients with longer hospital stays were more likely to incur higher direct medical costs. Conclusions: The burden of clonorchiasis in Guangdong Province remains high, despite significant progress achieved through the implementation of the prevention and control programs. It is suggested that measures should be taken based on the distribution characteristics to maximize the effectiveness of prevention and control, with a primary focus on key populations and areas. [ABSTRACT FROM AUTHOR]

Background: Clonorchiasis remains a serious public health problem. However, the molecular mechanism underlying clonorchiasis remains largely unknown. Amino acid (AA) metabolism plays key roles in protein synthesis and energy sources, and improves immunity in pathological conditions. Therefore, this study aimed to explore the AA profiles of spleen in clonorchiasis and speculate the interaction between the host and parasite. Methods: Here targeted ultrahigh performance liquid chromatography multiple reaction monitoring mass spectrometry was applied to discover the AA profiles in spleen of rats infected with Clonorchis sinensis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (KEGG) was performed to characterize the dysregulated metabolic pathways. Results: Pathway analysis revealed that phenylalanine, tyrosine, and tryptophan biosynthesis and β-alanine metabolism were significantly altered in clonorchiasis. There were no significant correlations between 14 significant differential AAs and interleukin (IL)-1β. Although arginine, asparagine, histidine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine were positively correlated with IL-6, IL-10, tumor necrosis factor (TNF)-α as well as aspartate aminotransferase and alanine aminotransferase; β-alanine and 4-hydroxyproline were negatively correlated with IL-6, IL-10, and TNF-α. Conclusion: This study reveals the dysregulation of AA metabolism in clonorchiasis and provides a useful insight of metabolic mechanisms at the molecular level. [ABSTRACT FROM AUTHOR]

Abstract Background Clonorchiasis has significant socioeconomic importance in endemic areas; however, studies investigating the disease burden in specific sub-regions are lacking. This study aims to address the gap by quantifying the current disease burden caused by clonorchiasis in Guangdong province and assessing its distribution characteristics. Methods Comprehensive measures, including prevalence rates, disability-adjusted life years (DALYs), and direct medical costs, were used to assess the disease burden of clonorchiasis. To estimate the prevalence rate, the number of infections was divided by the examined population, based on the annual surveillance data on clonorchiasis cases during 2016–2021. The calculation of DALYs was based on the epidemiological parameters according to the definition issued by the World Health Organization. Cost data of clonorchiasis were utilized to quantify the direct medical costs. The distribution characteristics of disease burden were assessed through comparisons of groups of population defined by geographic area, time, and characteristics of people. Results In 2021, clonorchiasis posed a significant disease burden in Guangdong Province. The prevalence rate was found to be 4.25% [95% CI (4.02%, 4.49%)], with an associated burden of DALYs of 406,802.29 [95% CI (329,275.33, 49,215,163.78)] person-years. The per-case direct medical costs of patients with clonorchiasis were estimated to be CNY 7907.2 (SD = 5154.4). Notably, while the prevalence rate and DALYs showed a steady decrease from 2016 to 2020, there was a rising trend in 2021. Spatial clustering of clonorchiasis cases and DALYs was also observed, particularly along the Pearl River and Han River. This suggests a concentration of the disease in these regions. Furthermore, significant differences in prevalence rates were found among various demographic groups, including sex, age, occupation, and education level. Additionally, patients with longer hospital stays were more likely to incur higher direct medical costs. Conclusions The burden of clonorchiasis in Guangdong Province remains high, despite significant progress achieved through the implementation of the prevention and control programs. It is suggested that measures should be taken based on the distribution characteristics to maximize the effectiveness of prevention and control, with a primary focus on key populations and areas. Graphical Abstract

Objective: Foodborne zoonotic trematodes (FZT), which infect the liver, lungs and intestines of humans, are an emerging public health concern in tropical countries including Vietnam. In northern Vietnam, Clonorchis sinensis is recognised as the most important species of the FZT. Up to now, small‐scale studies conducted in the country have indicated that health education could improve participants' knowledge and practices related to clonorchiasis, however strong evidence is still lacking. We conducted an intervention trial between 2020 and 2021 in four communes in Yen Bai and Thanh Hoa province, aiming to evaluate the impact of an extended educational package on knowledge, attitude and practices related to clonorchiasis, as well as on knowledge on the large liver fluke and minute intestinal flukes. Methods: To this end, baseline and post‐intervention questionnaires were conducted. Generalised estimating equations models were run to analyse the impact of the intervention on knowledge, attitudes and practices over time in the intervention versus control group. Finally, 172 people in the intervention group and 162 in the control group were included for analysis. Results: Results demonstrated that the intervention significantly improved clonorchiasis knowledge, attitudes and practices, with higher odds for a correct knowledge response (odds ratio (OR) = 2.80, 95% confidence interval (CI) = 1.84–4.27, p‐value < 0.001), increased average mean attitude score (mean = 0.363, 95%CI = 0.182–0.544, p‐value < 0.001), and a reduced odds of consuming raw fish (OR = 0.15, 95%CI = 0.06–0.40, p = 0.002) in the intervention group compared to the control group post‐intervention versus baseline. Additionally, participants in the intervention group exhibited enhanced basic knowledge of the large liver fluke and minute intestinal flukes post‐intervention. Conclusions: These findings demonstrate the potential of health education programs in preventing clonorchiasis in endemic areas, emphasising the importance of continued health education as a critical component of integrated control programs for clonorchiasis. [ABSTRACT FROM AUTHOR]

Abstract Background Clonorchiasis and opisthorchiasis, caused by the liver flukes Clonorchis sinensis and Opisthorchis viverrini respectively, represent significant neglected tropical diseases (NTDs) in Asia. The co-existence of these pathogens in overlapping regions complicates effective disease control strategies. This study aimed to clarify the distribution and interaction of these diseases within Southeast Asia. Methods We systematically collated occurrence records of human clonorchiasis (n = 1809) and opisthorchiasis (n = 731) across the Southeast Asia countries. Utilizing species distribution models incorporating environmental and climatic data, coupled machine learning algorithms with boosted regression trees, we predicted and distinguished endemic areas for each fluke species. Machine learning techniques, including geospatial analysis, were employed to delineate the boundaries between these flukes. Results Our analysis revealed that the endemic range of C. sinensis and O. viverrini in Southeast Asia primarily spans across part of China, Vietnam, Thailand, Laos, and Cambodia. During the period from 2000 to 2018, we identified C. sinensis infections in 84 distinct locations, predominantly in southern China (Guangxi Zhuang Autonomous Region) and northern Vietnam. In a stark contrast, O. viverrini was more widely distributed, with infections documented in 721 locations across Thailand, Laos, Cambodia, and Vietnam. Critical environmental determinants were quantitatively analyzed, revealing annual mean temperatures ranging between 14 and 20 °C in clonorchiasis-endemic areas and 24–30 °C in opisthorchiasis regions (P

Abstract Background The latest national survey on the distribution of human parasites in China demonstrated that Guangdong was among the endemic provinces with the highest Clonorchis sinensis infection rates. High-resolution, age- and gender-specific risk maps of the temporal and spatial distributions are essential for the targeted control work. Methods Disease data on the prevalence of C. sinensis infection from 1990 onwards, either age- and gender-specific or aggregated across age and gender, were collected through systematic review and four large-scale surveys in Guangdong Province. Environmental and socioeconomic variables were obtained from open-access databases and employed as potential predictors. A Bayesian geostatistical model was developed to estimate the C. sinensis infection risk at high spatial resolution. Results The final dataset included 606 surveys at 463 unique locations for C. sinensis infection. Our findings suggested that following an initial increase and stabilization, the overall population-adjusted prevalence had declined to 2.2% (95% Bayesian credible interval: 1.7–3.0%) in the period of 2015 onwards. From 2015 onwards, moderate and high infection risks were found in the northern regions (e.g. Heyuan and Shaoguan cities) and the southern Pearl River Delta (e.g. Foshan, Zhongshan, Zhuhai and Jiangmen cities), respectively. Age- and gender-specific risk maps revealed that males had a higher infection risk than females, and the infection risk was higher in adults compared to children. Conclusions Our high-resolution risk maps of C. sinensis infection in Guangdong Province identified the spatial, temporal, age and gender heterogeneities, which can provide useful information assisting tailored control strategies. Graphical Abstract

Background: Clonorchiasis and opisthorchiasis, caused by the liver flukes Clonorchis sinensis and Opisthorchis viverrini respectively, represent significant neglected tropical diseases (NTDs) in Asia. The co-existence of these pathogens in overlapping regions complicates effective disease control strategies. This study aimed to clarify the distribution and interaction of these diseases within Southeast Asia. Methods: We systematically collated occurrence records of human clonorchiasis (n = 1809) and opisthorchiasis (n = 731) across the Southeast Asia countries. Utilizing species distribution models incorporating environmental and climatic data, coupled machine learning algorithms with boosted regression trees, we predicted and distinguished endemic areas for each fluke species. Machine learning techniques, including geospatial analysis, were employed to delineate the boundaries between these flukes. Results: Our analysis revealed that the endemic range of C. sinensis and O. viverrini in Southeast Asia primarily spans across part of China, Vietnam, Thailand, Laos, and Cambodia. During the period from 2000 to 2018, we identified C. sinensis infections in 84 distinct locations, predominantly in southern China (Guangxi Zhuang Autonomous Region) and northern Vietnam. In a stark contrast, O. viverrini was more widely distributed, with infections documented in 721 locations across Thailand, Laos, Cambodia, and Vietnam. Critical environmental determinants were quantitatively analyzed, revealing annual mean temperatures ranging between 14 and 20 °C in clonorchiasis-endemic areas and 24–30 °C in opisthorchiasis regions (P < 0.05). The machine learning model effectively mapped a distinct demarcation zone, demonstrating a clear separation between the endemic areas of these two liver flukes with AUC from 0.9 to1. The study in Vietnam delineates the coexistence and geographical boundaries of C. sinensis and O. viverrini, revealing distinct endemic zones and a transitional area where both liver fluke species overlap. Conclusions: Our findings highlight the critical role of specific climatic and environmental factors in influencing the geographical distribution of C. sinensis and O. viverrini. This spatial delineation offers valuable insights for integrated surveillance and control strategies, particularly in regions with sympatric transmission. The results underscore the need for tailored interventions, considering regional epidemiological variations. Future collaborations integrating eco-epidemiology, molecular epidemiology, and parasitology are essential to further elucidate the complex interplay of liver fluke distributions in Asia. [ABSTRACT FROM AUTHOR]

Background: Multi-factorial reasons are an induction to cause cancer. Different infections and infestations with viruses, bacteria, and parasites have been detected for many years to be related to human carcinogenesis. Purpose: The study aimed to review all ideas of tumor carcinogenesis and its associations with parasitic infections and infestations. Methods: We reviewed several articles (published and imprinted) by selecting, extracting, and synthesizing data about the relationship between cancers and parasites. Results: Several helminths infections as schistosomiasis, are highly carcinogenic agents for bladder cancer, whereas trypanosomiasis has a bi-model role in cancer development. Leishmaniasis may be a cause of hepatocarcinoma, skin cancer, and lymphomas. In addition, malaria appears to be causative in the carcinogenesis of some cancers; as Burkitt lymphoma. Also, data from previous studies suggested that Strongyloides stercoralis may be a relevant co-factor in lymphomas. Conclusion: There are different mechanisms of parasitic infection to be enhancing in carcinogenesis of cancer in human. [ABSTRACT FROM AUTHOR]

Background: The latest national survey on the distribution of human parasites in China demonstrated that Guangdong was among the endemic provinces with the highest Clonorchis sinensis infection rates. High-resolution, age- and gender-specific risk maps of the temporal and spatial distributions are essential for the targeted control work. Methods: Disease data on the prevalence of C.sinensis infection from 1990 onwards, either age- and gender-specific or aggregated across age and gender, were collected through systematic review and four large-scale surveys in Guangdong Province. Environmental and socioeconomic variables were obtained from open-access databases and employed as potential predictors. A Bayesian geostatistical model was developed to estimate the C.sinensis infection risk at high spatial resolution. Results: The final dataset included 606 surveys at 463 unique locations for C.sinensis infection. Our findings suggested that following an initial increase and stabilization, the overall population-adjusted prevalence had declined to 2.2% (95% Bayesian credible interval: 1.7–3.0%) in the period of 2015 onwards. From 2015 onwards, moderate and high infection risks were found in the northern regions (e.g. Heyuan and Shaoguan cities) and the southern Pearl River Delta (e.g. Foshan, Zhongshan, Zhuhai and Jiangmen cities), respectively. Age- and gender-specific risk maps revealed that males had a higher infection risk than females, and the infection risk was higher in adults compared to children. Conclusions: Our high-resolution risk maps of C. sinensis infection in Guangdong Province identified the spatial, temporal, age and gender heterogeneities, which can provide useful information assisting tailored control strategies. [ABSTRACT FROM AUTHOR]

Background: Clonorchiasis is an important foodborne parasitic disease. The omics-based-techniques could illuminate parasite biology and further make innovations in the research for parasitic diseases. However, knowledge about the serum metabolic profiles and related metabolic pathways in clonorchiasis is very limited. Methods: A untargeted ultra-high performance liquid tandem chromatography quadrupole time of flight mass spectrometry (UHPLC-QTOF-MS) was used to profile the serum metabolites of rats at both 4 and 8 weeks post infection (wpi) with Clonorchis sinensis (C. sinensis). Additionally, multivariate statistical analysis methods were employed to identify differential metabolites. Next, serum amino acids and phosphatidylcholines (PCs) levels were determined by targeted metabolomics analysis. Result: A total of 10530 and 6560 ions were identified in ESI+ and ESI-modes. The levels of phosphatidylcholines, glycerophosphocholine and choline were significantly changed, with the shift in lipid metabolism. Significant changes were also observed in amino acids (isoleucine, valine, leucine, threonine, glutamate and glutamine). Targeted analysis showed that BCAAs (isoleucine, valine, leucine) levels significantly increased at 4 wpi and decreased at 8 wpi; threonine was increased at 8 wpi, whereas glutamate and glutamine showed a decreasing trend at 8 wpi. Additionally, the level of 17 PCs were significantly changed in infected rats. Marked metabolic pathways were involved in clonorchiasis, including glycerophospholipid metabolism, alanine, aspartate and glutamate metabolism, histidine metabolism and pyrimidine metabolism. Conclusion: These results show that C. sinensis infection can cause significant changes in the rat serum metabolism, especially in amino acids and lipids. The metabolic signature together with perturbations in metabolic pathways could provide more in depth understanding of clonorchiasis and further make potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Clonorchis sinensis is a carcinogenic liver fluke that causes clonorchiasis—a neglected tropical disease (NTD) affecting ~35 million people worldwide. No vaccine is available, and chemotherapy relies on one anthelmintic, praziquantel. This parasite has a complex life history and is known to infect a range of species of intermediate (freshwater snails and fish) and definitive (piscivorous) hosts. Despite this biological complexity and the impact of this biocarcinogenic pathogen, there has been no previous study of molecular variation in this parasite on a genome‐wide scale. Here, we conducted the first extensive nuclear genomic exploration of C. sinensis individuals (n = 152) representing five distinct populations from mainland China, and one from Far East Russia, and revealed marked genetic variation within this species between "northern" and "southern" geographical regions. The discovery of this variation indicates the existence of biologically distinct variants within C. sinensis, which may have distinct epidemiology, pathogenicity and/or chemotherapic responsiveness. The detection of high heterozygosity within C. sinensis specimens suggests that this parasite has developed mechanisms to readily adapt to changing environments and/or host species during its life history/evolution. From an applied perspective, the identification of invariable genes could assist in finding new intervention targets in this parasite, given the major clinical relevance of clonorchiasis. From a technical perspective, the genomic‐informatic workflow established herein will be readily applicable to a wide range of other parasites that cause NTDs. [ABSTRACT FROM AUTHOR]

Objective Quantitative assessment of risk factors of clonorchiasis can provide prevention for clonorchiasis. Methods Articles were retrieved in Chinese and English electronic databases from January 1, 2000 to December 31, 2020, including Wanfang Data, CNKI, PubMed, Web of Science, Embase. All studies were screened based on inclusion and exclusion criteria, and the quality of all enrolled literatures was evaluated. The software RevMan version 5.3 was used for Meta-analysis. The heterogeneity, sensitivity and publication bias of all included studies were analyzed. Results A total of 95 articles were retrieved, and 6 were included in this Meta-analysis which were case-control studies. There were 5 articles in Chinese and 1 in English. There was no single literature with a large impact on the results, and the results of this study were relatively stable. There were 1 170 cases of clonorchiasis in total and 1 291 cases in control. Most of the cases were from hospital patients and community residents, and the floating population was small. Meta-analysis showed that there were three independent risk factors: raw or semi-raw fish, raw or semi-raw shrimp, mix raw and cooked cutting boards, with a combined OR (95%CI) of 2.32 (1.86, 2.88), 3.99(2.42, 6.58), 2.18(1.51, 3.14), respectively, with low heterogeneity consistent with the results of the total sample study: I2 values for risk factors were 30%, 12%, 27%, respectively. The results of bias tests showed no publication bias (P=0.731, 0.725, 0.334, P>0.05). Conclusions The key risk factors of clonorchiasis are raw or semi-raw fish, raw or semiraw shrimp, mix raw and cooked cutting boards. Guidance and health education should be strengthened. It is necessary to strengthen the surveillance of clonorchiasis in the floating population, such as traveler, businessman and student. [ABSTRACT FROM AUTHOR]

Abstract Background Clonorchiasis is a widespread yet neglected foodborne disease with over 85% of all cases found in China. Guangxi province, located in southeastern China, ranks among the highest endemic provinces. We explore the epidemiological status and determinants of Clonorchis sinensis (C. sinensis) infection in humans and freshwater fish in Guangxi, China. Methods Data on C. sinensis infection in humans from January 2008 to December 2017were extracted from the China Information System for Disease Control and Prevention. An active surveillance of C. sinensis infection in fish was conducted in 2016–2017. County level data including potential environmental, social-economical and behavioral determinants was also collected. Univariate and multivariate logistic regression models were used to explore the determinants of C. sinensis infection in humans and fish. Simple and multiple zero-inflated Poisson regression models were fit to assess the associated factors of clonorchiasis in humans at the county level. Results Totally, 4526 C. sinensis cases were reported between 2008 and 2017, with an annual prevalencerate of 0.96/100,000 persons. Of 101 counties in Guangxi, 97 reported at least 1 case. Among 2,098 fish samples, 203 (9.7%) from 70 counties contained C. sinensis. The rate was higher in small fish including Pseudorasbora parva (45.3%), Misgurnus anguillicaudatus (41.2%), Hemicculter leuciclus (34.5%), unclassified small fishes (30.9%), Cyprinidae (20.0%), Cirrhinus molitorella (16.4%), Carassius auratus (13.6%) and Cyprinus carpio (13.3%), while it was lower in fish species that are usually used in preparing raw fish dishes including Ctenopharyngodon idellus (3.6%), Spinibarbus denticulatus (3.7%), Monopterus albus (6.4%), Cyprinus carpio (4.4%), Oreochromis mossambicus (3.3%) and Spualiobarbus Curriculus (6.6%). The C. sinensis infection in fish was only associated with fish species. The estimated human clonorchiasis prevalence at the county level was positively associated with raw fish consumption habits and certain rivers. Conclusions Clonorchiasis is highly prevalent in both humans and freshwater fish in Guangxi. Environmental, social-economic and behavioral determinants contribute to the high prevalence as well as the significant differential distribution by county. Regular surveillance should be implemented for clonorchiasis to demonstrate the change in epidemiology and burden, which will benefit the design of interventions.

Clonorchiasis, also known as the liver fluke disease, is caused by eating raw freshwater fish or shrimps that contain Clonorchis sinensis cyst larvae, which mainly involves the hepatobiliary system. Chronic abdominal pain and distention, loss of appetite, and hepatomegaly are the most common clinical manifestation. Persistent infection with Clonorchis sinensis would result in chronic inflammation, epithelial hyperplasia, and periductal fibrosis and even progress to cholangiocarcinoma. Nevertheless, the majority of the infected people are asymptomatic or mildly symptomatic, contributing to its high misdiagnosis rate. Alpha-fetoprotein (AFP) is a well-known biomarker for hepatocellular carcinoma (HCC). A high level of AFP can also be caused by several benign diseases, causing confusion and influencing treatment decisions. So far, clonorchiasis with a markedly elevated level of AFP has been rarely reported. We present a case of clonorchiasis with a high level of AFP in a 52-year-old man. We hope to raise clinical awareness of this food-borne disease. Clonorchiasis should be considered in patients with extremely high levels of AFP, excluding HCC and germ cell tumors, especially if the patient has a history of ingesting raw freshwater fish or shrimps.

This study provides an overview of the current status of clonorchiasis and cholangiocarcinoma (CCA), and their relationship in Korea during 2012-2020. Data were obtained from the Health Insurance Review & Assessment Service of Korea. Cluster, trend, and correlation analyses were performed. Gyeongsangnam-do and Seoul had the highest average number of cases (1,026 and 4,208) and adjusted rate (306 and 424) for clonorchiasis and CCA, respectively. The most likely clusters (MLC) for clonorchiasis and CCA were Busan/Gyeongsangnam-do/Ulsan/Daegu/Gyeongsangbuk-do (Relative Risk; RR=4.55, Likelihood Ratio; LLR=9,131.115) joint cluster and Seoul (RR=2.29, LLR=7,602.472), respectively. The MLC for clonorchiasis was in the southeastern part of Korea, while that for CCA was in the southern part. Clonorchiasis showed a decreasing trend in the southeastern districts, while increased in the southwestern districts. Cities in the central region had a decreasing trend, while the western districts had an increasing trend. In most adults (30-59), infection rate of clonorchiasis showed a significant decrease until 2018, while thereafter increased, although not significant. CCA showed a sharply decreasing tendency. The incidence of clonorchiasis and CCA were positively correlated. In general, the correlation was weak (r=0.39, P<0.001), but it was strongly positive around the 4 river basins (r=0.74, P<0.001). This study might provide an analytic basis for developing an effective system against clonorchiasis and CCA. [ABSTRACT FROM AUTHOR]

Heliminthic paramyosin is a multifunctional protein that not only acts as a structural protein in muscle layers but as an immune-modulatory molecule interacting with the host immune system. Previously, we found that paramyosin from Clonorchis sinensis (CsPmy) is bound to human complement C9 protein (C9). To analyze the C9 binding region on CsPmy, overlapping recombinant fragments of CsPmy were produced and their binding activity to human C9 was investigated. The fragmental expression of CsPmy and C9 binding assays revealed that the C9 binding region was located at the C-terminus of CsPmy. Further analysis of the C-terminus of CsPmy to narrow the C9 binding region on CsPmy indicated that the region flanking 731Leu-780Leu was a potent C9 binding region. The CsPmy fragments corresponding to the region effectively inhibited human C9 polymerization. These results provide a precise molecular basis for CsPmy as a potent immunomodulator to evade host immune defenses by inhibiting complement attack. [ABSTRACT FROM AUTHOR]

Clonorchiasis is a zoonotic disease mainly caused by eating raw fish and shrimp, and there is no vaccine to prevent it. More than 30 million people are infected worldwide, of which China alone accounts for about half, and is one of the countries most seriously affected by Clonorchiasis. In this work, we formulate a novel Ordinary Differential Equation (ODE) model to discuss the biological attributes of fish within authentic ecosystems and the complex lifecycle of Clonorchis sinensis. This model includes larval fish, adult fish, infected fish, humans, and cercariae. We derive the basic reproduction number and perform a rigorous stability analysis of the proposed model. Numerically, we use data from 2016 to 2021 in Guangxi, China, to discuss outbreaks of Clonorchiasis and obtain the basic reproduction number R 0 =1.4764. The fitted curve appropriately reflects the overall trend and replicates a low peak in the case number of Clonorchiasis. By reducing the release rate of cercariae in 2018, the fitted values of Clonorchiasis cases dropped rapidly and almost disappeared. If we decrease the transmission rate from infected fish to humans, Clonorchiasis can be controlled. Our studies also suggest that strengthening publicity education and cleaning water quality can effectively control the transmission of Clonorchiasis in Guangxi, China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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Background: Clonorchiasis is a widespread yet neglected foodborne disease with over 85% of all cases found in China. Guangxi province, located in southeastern China, ranks among the highest endemic provinces. We explore the epidemiological status and determinants of Clonorchis sinensis (C. sinensis) infection in humans and freshwater fish in Guangxi, China. Methods: Data on C. sinensis infection in humans from January 2008 to December 2017were extracted from the China Information System for Disease Control and Prevention. An active surveillance of C. sinensis infection in fish was conducted in 2016–2017. County level data including potential environmental, social-economical and behavioral determinants was also collected. Univariate and multivariate logistic regression models were used to explore the determinants of C. sinensis infection in humans and fish. Simple and multiple zero-inflated Poisson regression models were fit to assess the associated factors of clonorchiasis in humans at the county level. Results: Totally, 4526 C. sinensis cases were reported between 2008 and 2017, with an annual prevalencerate of 0.96/100,000 persons. Of 101 counties in Guangxi, 97 reported at least 1 case. Among 2,098 fish samples, 203 (9.7%) from 70 counties contained C. sinensis. The rate was higher in small fish including Pseudorasbora parva (45.3%), Misgurnus anguillicaudatus (41.2%), Hemicculter leuciclus (34.5%), unclassified small fishes (30.9%), Cyprinidae (20.0%), Cirrhinus molitorella (16.4%), Carassius auratus (13.6%) and Cyprinus carpio (13.3%), while it was lower in fish species that are usually used in preparing raw fish dishes including Ctenopharyngodon idellus (3.6%), Spinibarbus denticulatus (3.7%), Monopterus albus (6.4%), Cyprinus carpio (4.4%), Oreochromis mossambicus (3.3%) and Spualiobarbus Curriculus (6.6%). The C. sinensis infection in fish was only associated with fish species. The estimated human clonorchiasis prevalence at the county level was positively associated with raw fish consumption habits and certain rivers. Conclusions: Clonorchiasis is highly prevalent in both humans and freshwater fish in Guangxi. Environmental, social-economic and behavioral determinants contribute to the high prevalence as well as the significant differential distribution by county. Regular surveillance should be implemented for clonorchiasis to demonstrate the change in epidemiology and burden, which will benefit the design of interventions. [ABSTRACT FROM AUTHOR]

Background: To understand Clonorchis sinensis reinfection and the determinants of reinfection in endemic areas is important in establishment of control measures.Methods: A prospective cohort study was implemented in Hengxian County, Guangxi, China. Individuals with C. sinensis infection were completely treated, and those cured were enrolled as study subjects and followed up for 3, 6, and 12 months. The reinfection frequency and incidence were calculated, and a multivariable Cox proportional hazard model was constructed to capture reinfection determinants.Results: Among 635 enrolled subjects, 436 (68.7%) completed follow-up. Of these, 177 (40.6%) were reinfected; 133 (75.1%) were reinfected once, 41 (23.2%) twice, and 3 (1.7%) three times. The incidence of reinfection was 64.0 per 100 person-years. Men (adjusted hazard ratio [aHR], 1.67; 95% confidence interval [CI], 1.14-2.44), those with underlying diseases (aHR, 1.41; 95% CI, 1.02-1.95), and those with moderate- or heavy-intensity infections (aHR, 1.45; 95% CI, 1.14-1.85) had increasing reinfection probabilities.Conclusions: C. sinensis reinfection is high in endemic areas. Men and high-intensity infection are important determinants of reinfection. Repeated chemotherapy is necessary to control reinfection and its associated morbidities, especially in high-risk individuals. In addition, behavioral education is advised to decrease overall reinfection in endemic areas. [ABSTRACT FROM AUTHOR]

Clonorchiasis is recognized as an important zoonotic parasitic disease worldwide. However, the roles of host long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the response to Clonorchis sinensis (C. sinensis) infection remain unknown. Here we compared the expression of lncRNAs and mRNAs in the liver tissue of mice infected with C. sinensis , in order to further understand the molecular mechanisms of clonorchiasis. A total of 388 lncRNAs and 1,172 mRNAs were found to be differentially expressed with absolute value of fold change (FC) ≥ 2.0 and p < 0.05 by microarray. Compared with controls, Gm6135 and 4930581F22Rik were the most over- and under-expressed lncRNAs; flavin-containing monooxygenase 3 (Fmo3) and deleted in malignant brain tumors 1 (Dmbt1) were the most over- and under-expressed mRNAs. Moreover, functional annotation showed that the significantly different mRNAs were related with "FOXO signaling pathway", "Wnt signaling pathway", and "AMPK signaling pathway". Remarkably, lncRNA Gm8801 were significantly correlated with mRNA glycerol-3-phosphate acyltransferase mitochondrial (Gpam), insulin receptor substrate 2 (Irs2), and tumor necrosis factor receptor superfamily member 19 (Tnfrsf19) in ceRNA networks. These results showed that the expression profiles of lncRNAs and mRNAs in the liver changed after C. sinensis infection. Our results provided valuable insights into the lncRNAs and mRNAs involved in clonorchiasis pathogenesis, which may be useful for future control strategies. [ABSTRACT FROM AUTHOR]

Clonorchiasis is recognized as an important zoonotic parasitic disease worldwide. However, the roles of host long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in the response to Clonorchis sinensis (C. sinensis) infection remain unknown. Here we compared the expression of lncRNAs and mRNAs in the liver tissue of mice infected with C. sinensis, in order to further understand the molecular mechanisms of clonorchiasis. A total of 388 lncRNAs and 1,172 mRNAs were found to be differentially expressed with absolute value of fold change (FC) ≥ 2.0 and p < 0.05 by microarray. Compared with controls, Gm6135 and 4930581F22Rik were the most over- and under-expressed lncRNAs; flavin-containing monooxygenase 3 (Fmo3) and deleted in malignant brain tumors 1 (Dmbt1) were the most over- and under-expressed mRNAs. Moreover, functional annotation showed that the significantly different mRNAs were related with “FOXO signaling pathway”, “Wnt signaling pathway”, and “AMPK signaling pathway”. Remarkably, lncRNA Gm8801 were significantly correlated with mRNA glycerol-3-phosphate acyltransferase mitochondrial (Gpam), insulin receptor substrate 2 (Irs2), and tumor necrosis factor receptor superfamily member 19 (Tnfrsf19) in ceRNA networks. These results showed that the expression profiles of lncRNAs and mRNAs in the liver changed after C. sinensis infection. Our results provided valuable insights into the lncRNAs and mRNAs involved in clonorchiasis pathogenesis, which may be useful for future control strategies.

Background: Extensive parasitic diseases epidemiology in Zhejiang province has not been carried out since the second national survey in 2004. Therefore, dynamics in prevalence and infection pattern of the major intestinal parasites should be explored.Methods: The distribution of three parasites including soil-transmitted helminths (STH), intestinal protozoa and C. sinensis in Zhejiang from 2014 to 2015 were explored. Kato-Katz technique was used for STH and C. sinensis detection, whereas transparent adhesive paper anal swab was used for pinworm detection, and iodine smear was used for protozoa detection. A questionnaire survey on alimentary habits and sanitary behaviors was conducted in half of the studied counties.Results: This study recruited 23,552 participants: 19,935 from rural and 3617 from urban area. Overall prevalence of intestinal helminth infections was 1.80%. In this study, seven helminth species were identified including A. duodenale, N. americanus, Trichuris trichiura, Ascaris lumbricoides, C. sinensis, Fasciolopsis buski and pinworm. The average prevalence of STH infection was 1.71%: 1.94% in rural and 0.44% in urban area. Hookworm was the most prevalent infection at 1.58%: 1.79% in rural and 0.44% in urban area. Prevalence varied considerably in the studied counties. Prevalence was highest in Yongkang county at 10.25%. Only 2.79% of children from rural area were infected with pinworm. A proportion of 0.40% of rural participants were infected with protozoa, whereas Endolimax nana was the most prevalent at 0.23%. C. sinensis showed infection only in one man. Awareness on C. sinensis was 24.47% in rural and 45.96% in urban area, respectively.Conclusions: Prevalence of STH and protozoa infections declined considerably whereas C. sinensis infections remained few in Zhejiang province compared with the prevalence reported in previous large scale surveys (19.56% for national STH infection in 2004, 18.66% and 4.57% for provincial STH and protozoa infection, respectively in 1999). The findings of this study showed that hookworm, mainly N. americanus remained a parasitic threat to population health, mainly in the central and western Zhejiang. Therefore, more health education regarding fertilization and farming habits is necessary in rural areas. The awareness concerning hookworm infection should be reinforced. [ABSTRACT FROM AUTHOR]

Chronic human liver fluke infections caused by Opisthorchis viverrini and Clonorchis sinensis can last for decades and cause liver and biliary diseases, including life-threatening pathology prior to cholangiocarcinoma (CCA). CCA generally has a poor prognosis. Serological diagnosis can support parasitological examination in diagnosing disease and screening for the risk of CCA. Here, we present an improved and innovative lateral flow immunochromatographic test (ICT) kit that uses whole-blood samples (WBS) rather than serum to diagnose human opisthorchiasis, which also successfully diagnosed human clonorchiasis. This ICT includes a soluble worm extract of O. viverrini adults and colloidal-gold-labeled conjugates of the IgG antibody to evaluate the diagnostic values with simulated WBS (n = 347). Simulated WBS were obtained by the spiking infection sera with red blood cells. The diagnostic sensitivity, specificity, positive and negative predictive values, and accuracy for detecting opisthorchiasis were 95.5%, 87.0%, 80.5%, 97.2%, and 90.1%, respectively. For clonorchiasis, these findings were 85.7%, 87.0%, 53.6%, 97.2%, and 86.8%, respectively. Combined for both diseases, they were 93.2%, 87.0%, 84.0%, 94.6%, and 89.6%, respectively. The ICT kit can possibly replace the ICT platforms for antibody detection in serum samples in field surveys in remote areas where sophisticated equipment is not available.

Clonorchis sinensis , Opisthorchis viverrini , and Opisthorchis felineus are important liver flukes that cause a considerable public health burden in eastern Asia, southeastern Asia, and eastern Europe, respectively. The life cycles are complex, involving humans, animal reservoirs, and two kinds of intermediate hosts. An interplay of biological, cultural, ecological, economic, and social factors drives transmission. Chronic infections are associated with liver and biliary complications, most importantly cholangiocarcinoma. With regard to diagnosis, stool microscopy is widely used in epidemiologic surveys and for individual diagnosis. Immunologic techniques are employed for screening purposes, and molecular techniques facilitate species differentiation in reference laboratories. The mainstay of control is preventive chemotherapy with praziquantel, usually combined with behavioral change through information, education and communication, and environmental control. Tribendimidine, a drug registered in the People's Republic of China for soil-transmitted helminth infections, shows potential against both C. sinensis and O. viverrini and, hence, warrants further clinical development. Novel control approaches include fish vaccine and biological control. Considerable advances have been made using multi-omics which may trigger the development of new interventions. Pressing research needs include mapping the current distribution, disentangling the transmission, accurately estimating the disease burden, and developing new diagnostic and treatment tools, which would aid to optimize control and elimination measures., Competing Interests: The authors declare no conflict of interest.

To investigate the effects of co-infection with Clonorchis sinensis (C. sinensis) on T cell exhaustion levels in patients with chronic hepatitis B, we enrolled clinical cases in this study, including the patients with concomitant C. sinensis and HBV infection. In this study, we detected inhibitory receptors and cytokine expression in circulating CD4+ and CD8+ T cells by flow cytometry. PD-1 and TIM-3 expression levels were significantly higher on CD4+ T and CD8+ T cells from co-infected patients than on those from the HBV patients. In addition, CD4+ T cells and CD8+ T cells function were significantly inhibited by C. sinensis and HBV co-infection compared with HBV single infection, secreting lower levels of Interferon gamma (IFN-γ), Interleukin-2 (IL-2), and TNF-α. Our current results suggested that C. sinensis co-infection could exacerbate T cell exhaustion in patients with chronic hepatitis B. PD-1 and TIM-3 could be novel biomarkers for T cell exhaustion in patients with Clonorchis sinensis and chronic hepatitis B co-infection. Furthermore, it may be one possible reason for the weaker response to antiviral therapies and the chronicity of HBV infection in co-infected patients. We must realize the importance of C. sinensis treatment for HBV-infected patients. It might provide useful information for clinical doctors to choose the right treatment plans.

Objective: To evaluate the effect of information-knowledge-attitude-practice (IKAP) theory-based health education interventions on clonorchiasis control among community residents and primary school students in Torch High-tech Development Zone of Zhongshan City, so as to provide insights into formulation of clonorchiasis control strategies among different types of populations., Methods: Residents were randomly sampled from two communities and students from two primary schools using a random cluster sampling method in Torch High-tech Development Zone, Zhongshan City from 2019 to 2021, and health education pertaining to clonorchiasis control was performed based on the IKAP theory. The changes in the awareness of basic clonorchiasis control knowledge and belief, self-reported risk of Clonorchis sinensis infections and dietary behaviors were compared among community residents and primary school students before and after health education interventions., Results: The participants included 146 male and 151 female community residents and 158 male and 153 female primary school students, with no significant difference detected in gender distribution (χ 2 = 0.16, P > 0.05). The mean awareness of basic clonorchiasis control knowledge increased by 44.71% and 43.28% among primary school students and community residents 6 months following health education, and there were significant differences in the awareness of each item of basic clonorchiasis control knowledge before and after health education (χ 2 = 41.53 to 284.44, all P values < 0.05). The proportions of primary school students and community residents thinking very high and high risks of C. sinensis infections increased from 9.35% and 6.71% before health education to 22.15% and 37.75% after health education, but only the difference of the attitudes in community residents achieve statistical significance (χ 2 = 92.18, P < 0.05). The frequency of separation of raw and cooked foods with chopping board and knife significantly increased among community residents and primary school students following health education (χ 2 = 16.04 to 62.65, all P values < 0.05). The frequency of eating raw freshwater fish (χ 2 = 32.85, P < 0.05), fish congee (χ 2 = 7.02, P < 0.05) and fish fillet hot pot (χ 2 = 4.88, P < 0.05) significantly reduced among primary school students following health education, while only the frequency and proportions of eating raw freshwater fish have significantly reduced in community residents (χ 2 = 11.77, P < 0.05)., Conclusions: Health education interventions based on the IKAP theory are effective to increase the awareness of clonorchiasis control knowledge and improve dietary behaviors associated with C. sinensis infections among community residents and primary school students in Zhongshan City.

Background: Clonorchiasis, caused by the infection of Clonorchis sinensis (C. sinensis), is a kind of neglected tropical disease, but it is highly related to cholangiocarcinoma. It has been well known that NO from chronic inflammation responses are thought to be a major component of the damage and ultimate carcinogenesis ESPs such as nitric oxide synthase interacting protein (NOSIP) are thought to enhance the damage. The objective of this study was to identify the protein candidates interact with recombinant CsNOSIP (rCsNOSIP) and explore their role involved in CCA development or progression., Methods: We applied HuProt microarray containing 21,000 probe sets for a systematic identification of rCsNOSIP-binding proteins and grouped binding hits by gene function. Pull-down assays were used to confirm the interaction of rCsNOSIP with alveolar soft part sarcoma (ASPSCR-1) and sirtuins 5 (Sirt-5). ASPSCR-1/Sirt-5 over-expression and siRNA knockdown experiments were employed for obtain of ASPSCR-1/Sirt-5 high or low expression (ASP-oe/Sirt5-oe or ASP-si/Sirt5-si) cholangiocarcinoma cell line (CCLP-1) cells. Nitric oxide (NO) and reactive oxygen species assay (ROS) as well as cell proliferation and wound-healing assays were performed to observe the effect of rCsNOSIP on ASP-oe/Sirt5-oe or ASP-si/Sirt5-si CCLP-1 cells., Results: Seventy candidate proteins protein "hits" were detected as rCsNOSIP-binding proteins by HuProt microarray and bioinformatics analysis. Pull down assay showed that ASPSCR-1 and Sirt-5 could interact with rCsNOSIP. In addition, endotoxin-free-rCsNOSIP could increase the production of NO and ROS and promote the migration of CCLP-1 cells, while its effect on enhancing cell proliferation was not significant. Furthermore, ROS/NO production, proliferation, or migration were increased in ASP-si or Sirt5-si CCLP-1 cells but decreased in Asp-oe or Sirt5-oe CCLP-1 cells when stimulated with rCsNOSIP., Conclusions: Our findings suggest that CsNOSIP as a component of CsESPs might promote the development and invasion of CCA and Sirt5/ ASPSCR1 as host molecules might play a novel protective role against adverse stimulus during C. sinensis infection. This work supports the idea that CsESPs induce the occurrence and progression of CCA through ROS/RNS-induced oxidative and nitrative DNA damage., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Bian et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Clonorchiasis remains a non-negligible global zoonosis, causing serious socioeconomic burdens in endemic areas. Clonorchis sinensis infection typically elicits Th1/Th2 mixed immune responses during the course of biliary injury and periductal fibrosis. However, the molecular mechanism by which C. sinensis juvenile initially infects the host remains poorly understood., Methods: The BALB/c mouse model was established to study early infection (within 7 days) with C. sinensis juveniles. Liver pathology staining and observation as well as determination of biochemical enzymes, blood routine and cytokines in blood were conducted. Furthermore, analysis of liver transcriptome, proteome and metabolome changes was performed using multi-omics techniques. Statistical analyses were performed using Student's t-test., Results: Histopathological analysis revealed that liver injury, characterized by collagen deposition and inflammatory cell infiltration, occurred as early as 24 h of infection. Blood indicators including ALT, AST, WBC, CRP and IL-6 indicated that both liver injury and systemic inflammation worsened as the infection progressed. Proteomic data showed that apoptosis and junction-related pathways were enriched within 3 days of infection, indicating the occurrence of liver injury. Furthermore, proteomic and transcriptomic analysis jointly verified that the detoxification and antioxidant defense system was activated by enrichment of glutathione metabolism and cytochrome P450-related pathways in response to acute liver injury. Proteomic-based GO analysis demonstrated that biological processes such as cell deformation, proliferation, migration and wound healing occurred in the liver during the early infection. Correspondingly, transcriptomic results showed significant enrichment of cell cycle pathway on day 3 and 7. In addition, the KEGG analysis of multi-omics data demonstrated that numerous pathways related to immunity, inflammation, tumorigenesis and metabolism were enriched in the liver. Besides, metabolomic screening identified several metabolites that could promote inflammation and hepatobiliary periductal fibrosis, such as CA7S., Conclusions: This study revealed that acute inflammatory injury was rapidly triggered by initial infection by C. sinensis juveniles in the host, accompanied by the enrichment of detoxification, inflammation, fibrosis, tumor and metabolism-related pathways in the liver, which provides a new perspective for the early intervention and therapy of clonorchiasis., (© 2023. BioMed Central Ltd., part of Springer Nature.)