The disease burden and its distribution characteristics of clonorchiasis in Guangdong Province, Southern China.

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.

Effects of fish-human transmission and different life stages of fish on Clonorchiasis: A novel mathematical model.

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 R0=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.

Exploration of the Amino Acid Metabolic Profiling and Pathway in Clonorchis sinensis-Infected Rats Revealed by the Targeted Metabolomic Analysis.

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 ß-alanine metabolism were significantly altered in clonorchiasis. There were no significant correlations between 14 significant differential AAs and interleukin (IL)-1ß. 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; ß-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.

The Parasitism and Tumors Carcinogenesis: A Review Subject.

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.

Natural variables separate the endemic areas of Clonorchis sinensis and Opisthorchis viverrini along a continuous, straight zone in Southeast Asia.

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.

High-resolution mapping of age- and gender-specific risk of Clonorchis sinensis infection risk in Guangdong, China: a geostatistical modeling study.

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.

Effectiveness of health education in improving knowledge, attitude and practice related to foodborne zoonotic trematodes in Vietnam, with a particular focus on Clonorchis sinensis.

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.

Clonorchiasis and opisthorchiasis: epidemiology, transmission, clinical features, morbidity, diagnosis, treatment, and control.

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.

[Effect of information-knowledge-attitude-practice theory-based health education on clonorchiasis control among community residents and primary school students in Zhongshan City].

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 (χ2 = 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 (χ2 = 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 (χ2 = 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 (χ2 = 16.04 to 62.65, all P values < 0.05). The frequency of eating raw freshwater fish (χ2 = 32.85, P < 0.05), fish congee (χ2 = 7.02, P < 0.05) and fish fillet hot pot (χ2 = 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 (χ2 = 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.

Genome-wide exploration reveals distinctive northern and southern variants of Clonorchis sinensis in the Far East.

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.

Effect of information-knowledge-attitude-practice theory-based health education on clonorchiasis control among community residents and primary school students in Zhongshan City / 中国血吸虫病防治杂志

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 (χ2 = 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 (χ2 = 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 (χ2 = 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 (χ2 = 16.04 to 62.65, all P values < 0.05). The frequency of eating raw freshwater fish (χ2 = 32.85, P < 0.05), fish congee (χ2 = 7.02, P < 0.05) and fish fillet hot pot (χ2 = 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 (χ2 = 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.

Risk factors for clonorchiasis: a Meta-analysis / 中国热带医学

@#Abstract: 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 semi-raw 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.

An Innovative Test for the Rapid Detection of Specific IgG Antibodies in Human Whole-Blood for the Diagnosis of Opisthorchis viverrini Infection.

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.

Mapping of the Complement C9 Binding Region on Clonorchis sinensis Paramyosin.

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 flanking731Leu-780 Leu 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.

Relationship between Clonorchis sinensis Infection and Cholangiocarcinoma in Korea.

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.

Current status of Clonorchis sinensis and clonorchiasis in Korea: epidemiological perspectives integrating the data from human and intermediate hosts.

Clonorchis sinensis is a carcinogenic liver fluke that causes clonorchiasis in humans. Clonorchiasis is prevalent in East Asian countries, and approximately 15­20 million individuals are estimated to be infected with this fluke globally. This review highlights the current status of C. sinensis and clonorchiasis in Korea from the epidemiological perspective involving the analysis of humans and intermediate hosts. Despite the recent decline in C. sinensis infection rate in Korea, C. sinensis infections remain endemic in 5 major river basins (Han-gang, Geum-gang, Seomjin-gang, Yeongsan-gang and Nakdong-gang; gang means river) with a high incidence of cholangiocarcinoma. A noticeable pattern involves increasing mild infections among patients diagnosed positive for C. sinensis eggs. The infection rate of C. sinensis metacercariae in the second intermediate host, freshwater fish, is also maintained at a substantial level. Thus, the One Health approach integrating different sectors and disciplines is recommended to accelerate and sustain control of C. sinensis, thereby leading to successful eradication. Health promotion via information dissemination and health education should be extended to prevent the consumption of raw freshwater fish by residents living in high-risk areas.

Epidemiological characterization of Clonorchis sinensis infection in humans and freshwater fish in Guangxi, China.

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.

Serum metabolic profiling of rats infected with Clonorchis sinensis using LC-MS/MS method.

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.

Clonorchis sinensis Reinfection Rate and Reinfection Determinants: A Prospective Cohort Study in Hengxian County, Guangxi, China.

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.