Age, period, and cohort effects of Clonorchis sinensis infection prevalence in the Republic of Korea: Insights and projections.

BACKGROUND: With decades of containment efforts, the prevalence of C. sinensis infection in Korea has shown a declining trend. However, well-tailored intervention assessments remain challenging, particularly when considering the potential impacts of cohort variations in raw freshwater fish consumption behavior, a major transmission route to humans, on this observed decline. METHODOLOGY: We applied an age-period-cohort modeling approach to nationally representative C. sinensis infection prevalence data from 1981-2012 in Korea to assess age, period, and cohort effects on its secular trend and to project the age-stratified prevalence up to 2023. PRINCIPAL FINDINGS: Our analysis suggests that both cohort and period effects have substantially contributed to the declining prevalence of C. sinensis infection in Korea. Age-stratified projections up to 2023 suggest a decline in prevalence across all age groups, while those aged over 40 are anticipated to maintain prevalences above the elimination threshold of 1%. CONCLUSIONS: Our study highlights the importance of incorporating cohort effects into intervention assessments aimed at controlling C. sinensis infection. The effectiveness of interventions remains evident in Korea despite adjusting for the cohort effect. This approach, applicable to other endemic countries, would provide valuable insights for intervention assessments and inform future public health planning to eliminate C. sinensis infection.

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.

Liver Flukes: Clonorchis and Opisthorchis.

Clonorchis sinensis, Opisthorchis viverrini and O. felineus are liver flukes of human and animal pathogens occurring across much of Europe and Asia. Nevertheless, they are often underestimated compared to other, better known neglected diseases in spite of the fact that many millions of people are infected and hundreds of millions are at risk. This is possibly because of the chronic nature of the infection and disease and that it takes several decades prior to a life-threatening pathology to develop. Several studies in the past decade have provided more information on the molecular biology of the liver flukes which clearly lead to better understanding of parasite biology, systematics and population genetics. Clonorchiasis and opisthorchiasis are characterized by a chronic infection that induces hepatobiliary inflammation, especially periductal fibrosis, which can be detected by ultrasonography. These chronic inflammations eventually lead to cholangiocarcinoma (CCA), a usually fatal bile duct cancer that develops in some infected individuals. In Thailand alone, opisthorchiasis-associated CCA kills up to 20,000 people every year and is therefore of substantial public health importance. Its socioeconomic impacts on impoverished families and communities are considerable. To reduce hepatobiliary morbidity and CCA, the primary intervention measures focus on control and elimination of the liver fluke. Accurate diagnosis of liver fluke infections in both human and other mammalian, snail and fish intermediate hosts is important for achieving these goals. While the short-term goal of liver fluke control can be achieved by praziquantel chemotherapy, a comprehensive health education package targeting school children is believed to be more beneficial for a long-term goal/solution. It is recommended that transdisciplinary research or multisectoral control approach including one health and/or eco health intervention strategy should be applied to combat the liver flukes and hence contribute to reduction of CCA in endemic areas.

Prevalence estimates of Opisthorchis viverrini and Clonorchis sinensis infection in the Greater Mekong subregion: a systematic review and meta-analysis.

BACKGROUND: Opisthorchiasis and clonorchiasis, caused by Opisthorchis viverrini and Clonorchis sinensis, respectively, are significant yet neglected foodborne trematodiases in the Great Mekong Subregion (GMS). Despite the reporting of the prevalence of these human liver flukes in the region over the past decades, there has been a lack of a comprehensive and systematic consolidation of this data. Therefore, we aimed to conduct a thorough systematic review and meta-analysis to synthesize and analyze time-trend prevalence estimates of both O. viverrini and C. sinensis across the GMS for the past 30 years. METHODS: This study undertakes a systematic review using a comprehensive search for published articles in PubMed, EMBASE, Scopus, Cochrane and Thai Journal Online databases until early 2023. The pooled prevalence of O. viverrini and C. sinensis infection was analyzed through a random-effects meta-analysis, with meta-regression analysis used to quantify associations with study characteristics. Sub-group analysis was conducted, whenever comparison data were available, to assess the risk of O. viverrini and C. sinensis infection in each GMS country. Heterogeneity among studies was assessed using the Q statistic and quantified by using the I 2 Index. RESULTS: From a total of 2997 articles, 155 articles comprising 218 datasets and 751,108 participants were included for review. The GMS prevalence of O. viverrini was 21.11% [45,083/260,237; 95% confidence interval (CI): 17.74-24.47%]. Pooled prevalence estimates were highly observed in Laos (34.06%, 95% CI: 26.85-41.26%), followed by Thailand (18.19%, 95% CI: 13.86-22.51%), and Cambodia (10.48%, 95% CI: 5.52-15.45%). Myanmar and Vietnam had limited data sources for calculation. Clonorchis sinensis infection in GMS was 25.33% (95% CI: 18.32-32.34%), with Guangxi, China, exhibiting the highest prevalence rates at 26.89% (95% CI: 18.34-35.43%), while Vietnam had a prevalence rate of 20.30% (95% CI: 9.13-31.47%). O. viverrini prevalence decreased significantly over time, whereas C. sinensis infection appeared to be stable consistently over time in both China and Vietnam. CONCLUSIONS: This comprehensive study, drawing from the largest datasets to date, offers an in-depth systematic prevalence review of human liver flukes in the Greater Mekong Subregion. It underscores the imperative for systematic surveillance, data collection, and the implementation of intervention and control measures for these infectious diseases of poverty.

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.

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.

Spatio-temporal disparities of Clonorchis sinensis infection in animal hosts in China: a systematic review and meta-analysis.

BACKGROUND: Clonorchis sinensis, one of the most important food-borne zoonotic trematodes, remains prevalent in China. Understanding its infection status in animals is crucial for controlling human clonorchiasis. Here we conducted a systematic review and meta-analysis to focus on the spatio-temporal disparities of C. sinensis infection in animals in China. METHODS: Data on C. sinensis prevalence in snails, the second intermediate hosts, or animal reservoirs in China were extracted from electronic databases including PubMed, Embase, Web of Science, Chinese Wanfang database, CNKI, VIP, and China Biomedical Literature database. A random-effects meta-analysis model was utilized to estimate the pooled prevalence in each of the above animal hosts. Subgroup analysis and multivariable meta-regression were performed to explore potential sources of heterogeneity across studies and compare the temporal disparity of infection rates between high and low epidemic areas. Scatter plots were used to depict the biogeographical characteristics of regions reporting C. sinensis infection in animals. RESULTS: The overall pooled prevalence of C. sinensis was 0.9% (95% CI: 0.6-1.2%) in snails, 14.2% (12.7-15.7%) in the second intermediate host, and 14.3% (11.4-17.6%) in animal reservoirs. Prevalence in low epidemic areas (with human prevalence < 1%) decreased from 0.6% (0.2-1.2%) before 1990 to 0.0% (0.0-3.6%) after 2010 in snails (P = 0.0499), from 20.3% (15.6-25.3%) to 8.8% (5.6-12.6%) in the second intermediate hosts (P = 0.0002), and from 18.3% (12.7-24.7%) to 4.7% (1.0-10.4%) in animal reservoirs. However, no similar decrease in prevalence was observed in high epidemic areas (with human prevalence ≥ 1.0%). C. sinensis infections were predominantly reported in areas with altitudes below 2346 m and annual cumulative precipitation above 345 mm and were mostly concentrated in eastern China. CONCLUSIONS: There are spatio-temporal disparities in the animal infections of C. sinensis in different areas of China. Animal infections are primarily concentrated in regions with low altitude and high precipitation. The results suggest that implementing One Health-based comprehensive measures targeting both humans and animals, especially in high epidemic areas, is essential for successful eradication of C. sinensis in China.

Current status and progress in the omics of Clonorchis sinensis.

Clonorchis sinensis (C. sinensis) is a fish-borne trematode that inhabits the bile duct of mammals including humans, cats, dogs, rats, and so on. In the complex life cycle of C. sinensis, the worm develops successively in two intermediate hosts in fresh water and one definitive host. What's more, it undergoes eight developmental stages with a distinct morphology. Clonorchiasis, caused by C. sinensis infection, is an important food-borne parasitic disease and one of the most common zoonoses. C. sinensis infection could result in hyperplasia of the bile duct epithelium, obstructive jaundice, gall-stones, cholecystitis and cholangitis, even liver cirrhosis and cholangiocarcinoma. Thus, clonorchiasis is a serious public health problem in endemic areas. Integrated strategies should be adopted in the prevention and control of clonorchiasis due to the epidemiological characteristics. The recent advances in high-throughput technologies have made available the profiling of multiple layers of a biological system, genomics, transcriptomics, proteomics, and metabolomics. These data can help us to get more information about the development, physiology, metabolism, and reproduction of the parasite as well as pathogenesis and parasite-host interactions in clonorchiasis. In the present study, we summarized recent progresses in omics studies on C. sinensis providing insights into the studies and future directions on treating and preventing C. sinensis associated diseases.

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.

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.

[Clinical characteristics of biliary obstruction patients with Clonorchis sinensis infections].

OBJECTIVE: To analyze the clinical characteristics of biliary obstruction patients with Clonorchis sinensis infections, so as to provide insights into the clinical diagnosis and therapy of this comorbidity. METHODS: A total of 45 biliary obstruction patients with C. sinensis infections that were admitted to the Second Affiliated Hospital of Harbin Medical University from October 2012 to September 2019 were enrolled, and 45 patients with biliary obstruction alone at the hospital during the same study period were recruited as controls. Univariate analysis was performed to analyze the epidemiological characteristics, clinical manifestations, laboratory examination results and imaging manifestations related to C. sinensis infection, and the statistically significant univariate was used as an independent variable for multivariate logistic regression analysis. RESULTS: Compared with biliary obstruction alone, males (91.11% vs. 46.67%; χ2 = 20.737, P < 0.01) and rural areas (62.22% vs. 22.22%; χ2 = 14.757, P < 0.01) showed a significantly higher proportion in biliary obstruction patients with C. sinensis infections. The major clinical symptoms involved in had jaundice (45 cases, 100%) and abdominal pain (40 cases, 88.89%) in C. sinensis-infected patients. Logistic regression analysis showed that males [odds ratio (OR) = 10.717, 95% confidential interval (CI): (2.571, 44.662)] and drinking alcohol [OR = 4.474, 95% CI: (1.019, 19.642)] were risk factors for biliary obstruction patients with C. sinensis infections, while living in city [OR = 0.128, 95% CI: (0.038, 0.435)] was a protective factor. Additionally, in biliary obstruction patients with C. sinensis infections, lower total bilirubin (Z = -2.566, P <0.05) and direct bilirubin (Z = -3.454, P <0.05), higher indirect bilirubin (Z = -3.821, P < 0.05), thickening of the bile duct wall and dilatation of the intrahepatic bile duct were detected. CONCLUSIONS: A comprehensive diagnosis requires to be made based on clinical symptoms, laboratory and imaging examinations, in order to improve the diagnosis of biliary obstruction patients with C. sinensis infections.

Status of Helminthic Infections in Residents around River Basins in the Republic of Korea for 10 Years (2011-2020).

The positive rate of Clonorchis sinensis is the highest among intestinal parasites in the Republic of Korea (Korea). More than 1.2 million people were at risk of C. sinensis infection in Korea in 2012. An intensive control program is being implemented for residents of the 5 major river basins to reduce helminthic infections, including C. sinensis infection. This study evaluated the continuous intensive control program for parasitic diseases including clonorchiasis in areas near the 5 major river basins in Korea over the past 10 years (2011-2020). A total of 335,020 fecal samples (one sample per resident) prepared by the modified sedimentation technic were microscopically examined. Those who expelled helminth eggs were treated with anthelmintics through local health centers and re-examined 3 months later. The overall positive rate of helminths egg was 7.1%. The annual positive rates were dramatically decreased from 14.4% (2011) to 5.9% (2020). The egg positive rate was highest in C. sinensis (5.3%), followed by heterophyid flukes (1.5%) and Trichuris trichiura (0.2%). The prevalence of C. sinensis was significantly higher in males (7.6%) than in females (3.7%), and the highest in the 50-59 years (7.0%) age group. Our results are beneficial to establish prevention and control policies against helminthiases including clonorchiasis in endemic areas in this country.

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.

Cost-effectiveness evaluation of different control strategies for Clonorchis sinensis infection in a high endemic area of China: A modelling study.

Clonorchiasis is an important food-borne parasitic disease caused by Clonorchis sinensis infection. The evaluation of long-term cost-effectiveness of control strategies is important for disease control and prevention. The present study aimed to assess the cost-effectiveness of the three recommended strategies (i.e., WHO, Chinese and Guangdong strategies) and different combinations of commonly used measures (i.e., preventive chemotherapy, information, education, and communication (IEC) and environmental improvement) on clonorchiasis. The study area, Fusha town in Guangdong Province, was a typical high endemic area in China. The analysis was based on a multi-group transmission model of C. sinensis infection. We set the intervention duration for 10 years and post-intervention period for 50 years. The corresponding costs and DALYs were estimated. Strategies with incremental cost-effectiveness ratios (ICERs) less than 1/5 of the willingness-to-pay threshold were identified as highly cost-effective strategies. The optimal control strategy was obtained using the next best comparator method. The ICERs of Guangdong strategy were $172 (95% CI: $143-$230) US for praziquantel and $106 (95% CI: $85-$143) US for albendazole, suggesting the highest cost-effectiveness among the three recommended strategies. For praziquantel, 470 sets of control strategies were identified as highly cost-effective strategies for achieving infection control (prevalence<5%). The optimal strategy consisted of chemotherapy targeted on at-risk population, IEC and environmental improvement, with coverages all being 100%, and with the ICER of $202 (95% CI: $168-$271) US. The results for transmission control (prevalence<1%) and albendazole were obtained with the same procedures. The findings may help to develop control policies for C. sinensis infection in high endemic areas. Moreover, the method adopted is applicable for assessment of optimal strategies in other endemic areas.

Infection Characteristics of Clonorchis sinensis Metacercariae in Fish from Republic of Korea.

The infection nature of Clonorchis sinensis metacercariae (CsMc) in freshwater fish hosts is closely related to the transmission of human clonorchiasis. This article reviewed the infection characteristics of CsMc in freshwater fish in the Republic of Korea (Korea). The status of CsMc infection was examined in a total of 17,792 cyprinid fish of 49 species in 9 water systems, which included Hantan-/Imjin-gang, Han-gang, Geum-gang, Mangyeong-gang, Yeongsan-gang, Tamjin-gang, Seomjin-gang, Nakdong-gang, and streams in the east coastal areas from 2010 to 2020. The infection status of CsMc was examined according to cyprinid fish species and water systems, after which analyzed by endemicity and susceptibility index. The high endemicity was shown in the cyprinid fish from 3 regions (6.1%) in the upper reaches of Nakdong-gang, such as Banbyeon-cheon (stream), Yongjeon-cheon, and Wi-cheon. The moderate levels were observed in fishes from 8 regions (16.3%), and low endemicity was shown in fishes from 20 regions (40.8%). No CsMc were detected in fish from 18 regions (36.7%). The susceptibility of CsMc in index fish, Puntungia herzi, was found to be a reliable index without examination of other fish species. CsMc infection rates were closely related to subfamily groups in the cyprinid fish hosts in a highly endemic area. In Korea, a total of 58 fish species in 10 families has been listed as the second intermediate hosts for C. sinensis. This review provides several novel features of CsMc infection and clarifies the species of second intermediate freshwater fish host in Korea.

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.

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.