ResearchPad - clonorchiasis https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Familial assimilation in transmission of raw-freshwater fish-eating practice leading to clonorchiasis]]> https://www.researchpad.co/article/elastic_article_15763 Clonorchiasis is caused by the ingestion of raw freshwater fish, which contains the infective larvae of Clonorchis sinensis. It is highly endemic in Asia, where about 15 million people are afflicted. To establish sustainable control strategy, the transmission of raw-eating practice needs to be illuminated. In this study, we conducted a survey in school students from four clonorchiasis endemic provinces in China, covering 23,222 students aged 9–18. The characteristics of raw-eating practice, impact of parents’ raw-eating practice on children, interaction of spouses’ practice was explored. It is demonstrated that raw-eating practice presents familial clustering, which is higher in those families with older children and with boys. Raw-eating practice in children is highly influenced by their parents’ raw-eating practice especially when both parents do. Additionally, there exists interaction between spouses’ raw-eating practice. The impact of husband’s raw-eating practice on his wife is higher than that of wife’s raw-eating practice on her husband. Familial assimilation dominates the transmission of raw-freshwater eating-practice, including the assimilation from parents to their children and that between spouses. This finding indicates the adoption of sustainable strategy against clonorchiasis through blocking raw-freshwater fish-eating practice.

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<![CDATA[Amino acids serve as an important energy source for adult flukes of <i>Clonorchis sinensis</i>]]> https://www.researchpad.co/article/elastic_article_13829 Clonorchiasis, closely related to cholangiocarcinoma and hepatocellular carcinoma, has led to a negative socioeconomic impact in global areas especially some Asian endemic regions. Owing to the emergence of drug resistance and hypersensitivity reactions after the massive and repeated use of praziquantel as well as the lack of effective vaccines, searching for new strategies that prevent and treat clonorchiasis has become an urgent matter. Clonorchis sinensis, the causative agent of clonorchiasis, long-term inhabits the microaerobic and limited-glucose environment of the bile ducts. Adequate nutrients are essential for adult flukes to resist the adverse condition and survive in the crowed habitat. Studies on energy metabolism of adult flukes are beneficial for further exploring host-parasite interactions and developing novel anti-parasitic drugs. Our results suggest that gluconeogenesis probably plays a vital role in energy metabolism of Clonorchis sinensis and exogenous amino acids might be an essential energy source for adult flukes to successfully survive in the host. Our foundational study opens a new avenue for explaining energy metabolism of Clonorchis sinensis and provides a valuable strategy that the gluconeogenesis pathway will be a potential and novel target for the prevention and treatment of clonorchiasis.

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<![CDATA[Developmental Transcriptomic Features of the Carcinogenic Liver Fluke, Clonorchis sinensis]]> https://www.researchpad.co/article/5989d9f0ab0ee8fa60b6e20a

Clonorchis sinensis is the causative agent of the life-threatening disease endemic to China, Korea, and Vietnam. It is estimated that about 15 million people are infected with this fluke. C. sinensis provokes inflammation, epithelial hyperplasia, and periductal fibrosis in bile ducts, and may cause cholangiocarcinoma in chronically infected individuals. Accumulation of a large amount of biological information about the adult stage of this liver fluke in recent years has advanced our understanding of the pathological interplay between this parasite and its hosts. However, no developmental gene expression profiles of C. sinensis have been published. In this study, we generated gene expression profiles of three developmental stages of C. sinensis by analyzing expressed sequence tags (ESTs). Complementary DNA libraries were constructed from the adult, metacercaria, and egg developmental stages of C. sinensis. A total of 52,745 ESTs were generated and assembled into 12,830 C. sinensis assembled EST sequences, and then these assemblies were further categorized into groups according to biological functions and developmental stages. Most of the genes that were differentially expressed in the different stages were consistent with the biological and physical features of the particular developmental stage; high energy metabolism, motility and reproduction genes were differentially expressed in adults, minimal metabolism and final host adaptation genes were differentially expressed in metacercariae, and embryonic genes were differentially expressed in eggs. The higher expression of glucose transporters, proteases, and antioxidant enzymes in the adults accounts for active uptake of nutrients and defense against host immune attacks. The types of ion channels present in C. sinensis are consistent with its parasitic nature and phylogenetic placement in the tree of life. We anticipate that the transcriptomic information on essential regulators of development, bile chemotaxis, and physico-metabolic pathways in C. sinensis that presented in this study will guide further studies to identify novel drug targets and diagnostic antigens.

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<![CDATA[The Global Burden of Disease Study 2010: Interpretation and Implications for the Neglected Tropical Diseases]]> https://www.researchpad.co/article/5989da7eab0ee8fa60b999d9 ]]> <![CDATA[A Research Agenda for Helminth Diseases of Humans: Diagnostics for Control and Elimination Programmes]]> https://www.researchpad.co/article/5989db07ab0ee8fa60bc89fa

Diagnostic tools appropriate for undertaking interventions to control helminth infections are key to their success. Many diagnostic tests for helminth infection have unsatisfactory performance characteristics and are not well suited for use in the parasite control programmes that are being increasingly implemented. Although the application of modern laboratory research techniques to improve diagnostics for helminth infection has resulted in some technical advances, uptake has not been uniform. Frequently, pilot or proof of concept studies of promising diagnostic technologies have not been followed by much needed product development, and in many settings diagnosis continues to rely on insensitive and unsatisfactory parasitological or serodiagnostic techniques. In contrast, PCR-based xenomonitoring of arthropod vectors, and use of parasite recombinant proteins as reagents for serodiagnostic tests, have resulted in critical advances in the control of specific helminth parasites. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR) was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, the diagnostic technologies relevant to control of helminth infections, either available or in development, are reviewed. Critical gaps are identified and opportunities to improve needed technologies are discussed.

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<![CDATA[Production and Deformation of Clonorchis sinensis Eggs during In Vitro Maintenance]]> https://www.researchpad.co/article/5989da59ab0ee8fa60b8f7c9

Clonorchis sinensis is a carcinogenic human liver fluke. The present study monitored eggs produced by long-term maintained adult worms of C. sinensis to confirm their egg productivity in vitro. The worms from infected rabbits were incubated in vitro in 1× Locke’s solution and broth media (RPMI-1640, DMEM and IMDM). Numbers of expelled eggs were counted sequentially and their morphological changes were monitored by microscopy after 1, 30, 60, and 90 days of cultivation. On the 1–3 days of cultivation, the eggs counted maximum 4,756±202 eggs/worm/day in IMDM medium. The number of eggs gradually decreased less than 1,000 at 7–14 days and below 100 at 21days but continued to pass eggs after 56 days in all media. Length of the eggs were reduced about 1 µm at 30 days, and the length/width ratio was maintained around 1.8 at 30 days but decreased to 1.7 at 60 days and 1.5 at 90 days. Faust-Meleney index (FMI) decreased as the cultivation duration increased and lowest FMI (5662.9±974.7) observed in IMDM media at day 90 (P = 0.001). Microscopic findings of the eggs recognized the miracidium in most of eggs at 60 days but not in those at 90 days. Instead, the eggs contained dark granules or vacuoles in the deformed shell at 90 days. Scanning electron microscopy revealed partial loss of wrinkles on the deformed egg surface and prominent abopercular knob. Eggs viability decreased as the cultivation progressed and showed significant positive correlation with FMI and length/width ratio. In conclusion, the cultivated worms pass only the eggs which are preformed in their uterus before cultivation. One gravid C. sinensis contains about 37,000 eggs in its uterus and produces about 4,000 eggs every day. The deformed eggs with FMI less than 7,000 and length/width ratio lower than 1.7 are non-viable.

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<![CDATA[Efficacy and Safety of Praziquantel, Tribendimidine and Mebendazole in Patients with Co-infection of Clonorchis sinensis and Other Helminths]]> https://www.researchpad.co/article/5989dadaab0ee8fa60bb9748

Background

Both tribendimidine and mebendazole are broad-spectrum drugs for anti-intestinal nematodes. We aim to assess the efficacy and safety of tribendimidine and mebendazole in patients with co-infection of Clonorchis sinensis and other helminths.

Method

We performed a randomized open-label trial in Qiyang, People's Republic of China. Eligible participants were randomly assigned to one of four groups: (i) a single dose of 400 mg tribendimidine, (ii) 200 mg tribendimidine twice daily, (iii) 75 mg/kg praziquantel divided in four doses within 2 days, and (iv) a single dose of 400 mg mebendazole. Cure rates and egg reduction rates were assessed, and adverse events were monitored after treatments. Uncured patients accepted the second treatment with the same drugs after the first treatment.

Results

156 patients were eligible for the study. Results from the first treatment showed that the cure rates of single-dose tribendimidine and praziquantel against C. sinensis were 50% and 56.8%, respectively; the single-dose tribendimidine achieved the cure rate of 77.8% in the treatment for hookworm, which was significantly higher than that of praziquantel; Low cure rates were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura (28.6% and 23.1%). Results of the second treatment illustrated the cure rates of tribendimidine and praziquantel against C. sinensis were 78.1% and 75%, respectively. Most adverse events were mild and transient. Adverse events caused by tribendimidine were significantly less than praziquantel.

Conclusion

Single-dose tribendimidine showed similar efficacy against C. sinensis as praziquantel with less adverse events, and achieved significantly higher cure rate in the treatment for hookworm than those of praziquantel and mebendazole. Low cure rates, which were still higher than other drugs, were obtained in the treatment of single-dose tribendimidine against Ascaris lumbricoides and Trichuris trichiura.

Trial Registration

Controlled-Trials.com ISRCTN55086560

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<![CDATA[Application of a loop-mediated isothermal amplification (LAMP) assay targeting cox1 gene for the detection of Clonorchis sinensis in human fecal samples]]> https://www.researchpad.co/article/5ab08489463d7e2faeab8ab7

Background

Clonorchiasis is prevalent in the Far East, and a major health problem in endemic areas. Infected persons may experience, if not treated, serious complications such as bile stone formation, pyogenic cholangitis, and even cholangiocarcinoma. Early diagnosis and treatment are important to prevent serious complications and, therefore, the simple and reliable diagnostic method is necessary to control clonorchiasis in endemic areas, where resources for the diagnosis are limited.

Methodology/Principle findings

The loop-mediated isothermal amplification (LAMP) assay has been applied for the detection of Clonorchis sinensis DNA. Six primers targeting eight locations on the cytochrome c oxidase subunit 1 gene of C. sinensis were designed for species-specific amplification using the LAMP assay. The LAMP assay was sensitive enough to detect as little as 100 fg of C. sinensis genomic DNA and the detection limit in 100 mg of stool was as low as one egg. The assay was highly specific because no cross-reactivity was observed with the DNA of other helminths, protozoa or Escherichia coli. Then, LAMP assay was applied to human fecal samples collected from an endemic area of clonorchiasis in Korea. Using samples showing consistent results by both Kato-Katz method and real-time PCR as reference standards, the LAMP assay showed 97.1% (95% CI, 90.1–99.2) of sensitivity and 100% (95% CI, 92.9–100) of specificity. In stool samples with more than 100 eggs per gram of feces, the sensitivity achieved 100%.

Conclusions

To detect C. sinensis in human fecal samples, the LAMP assay was applied and achieved high sensitivity and specificity. The LAMP assay can be utilized in field laboratories as a powerful tool for diagnosis and epidemiological survey of clonorchiasis.

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<![CDATA[Disability Weight of Clonorchis sinensis Infection: Captured from Community Study and Model Simulation]]> https://www.researchpad.co/article/5989db48ab0ee8fa60bd932f

Background

Clonorchiasis is among the most neglected tropical diseases. It is caused by ingesting raw or undercooked fish or shrimp containing the larval of Clonorchis sinensis and mainly endemic in Southeast Asia including China, Korea and Vietnam. The global estimations for population at risk and infected are 601 million and 35 million, respectively. However, it is still not listed among the Global Burden of Disease (GBD) and no disability weight is available for it. Disability weight reflects the average degree of loss of life value due to certain chronic disease condition and ranges between 0 (complete health) and 1 (death). It is crucial parameter for calculating the morbidity part of any disease burden in terms of disability-adjusted life years (DALYs).

Methodology/Principal Findings

According to the probability and disability weight of single sequelae caused by C. sinensis infection, the overall disability weight could be captured through Monte Carlo simulation. The probability of single sequelae was gained from one community investigation, while the corresponding disability weight was searched from the literatures in evidence-based approach. The overall disability weights of the male and female were 0.101 and 0.050, respectively. The overall disability weights of the age group of 5–14, 15–29, 30–44, 45–59 and 60+ were 0.022, 0.052, 0.072, 0.094 and 0.118, respectively. There was some evidence showing that the disability weight and geometric mean of eggs per gram of feces (GMEPG) fitted a logarithmic equation.

Conclusion/Significance

The overall disability weights of C. sinensis infection are differential in different sex and age groups. The disability weight captured here may be referred for estimating the disease burden of C. sinensis infection.

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<![CDATA[Risk mapping of clonorchiasis in the People’s Republic of China: A systematic review and Bayesian geostatistical analysis]]> https://www.researchpad.co/article/5989db54ab0ee8fa60bdd10f

Background

Clonorchiasis, one of the most important food-borne trematodiases, affects more than 12 million people in the People’s Republic of China (P.R. China). Spatially explicit risk estimates of Clonorchis sinensis infection are needed in order to target control interventions.

Methodology

Georeferenced survey data pertaining to infection prevalence of C. sinensis in P.R. China from 2000 onwards were obtained via a systematic review in PubMed, ISI Web of Science, Chinese National Knowledge Internet, and Wanfang Data from January 1, 2000 until January 10, 2016, with no restriction of language or study design. Additional disease data were provided by the National Institute of Parasitic Diseases, Chinese Center for Diseases Control and Prevention in Shanghai. Environmental and socioeconomic proxies were extracted from remote-sensing and other data sources. Bayesian variable selection was carried out to identify the most important predictors of C. sinensis risk. Geostatistical models were applied to quantify the association between infection risk and the predictors of the disease, and to predict the risk of infection across P.R. China at high spatial resolution (over a grid with grid cell size of 5×5 km).

Principal findings

We obtained clonorchiasis survey data at 633 unique locations in P.R. China. We observed that the risk of C. sinensis infection increased over time, particularly from 2005 onwards. We estimate that around 14.8 million (95% Bayesian credible interval 13.8–15.8 million) people in P.R. China were infected with C. sinensis in 2010. Highly endemic areas (≥ 20%) were concentrated in southern and northeastern parts of the country. The provinces with the highest risk of infection and the largest number of infected people were Guangdong, Guangxi, and Heilongjiang.

Conclusions/Significance

Our results provide spatially relevant information for guiding clonorchiasis control interventions in P.R. China. The trend toward higher risk of C. sinensis infection in the recent past urges the Chinese government to pay more attention to the public health importance of clonorchiasis and to target interventions to high-risk areas.

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<![CDATA[A Combination of the Kato-Katz Methods and ELISA to Improve the Diagnosis of Clonorchiasis in an Endemic Area, China]]> https://www.researchpad.co/article/5989db14ab0ee8fa60bccdfd

Background

Examination of feces by light microscopy is widely used for specific parasitological diagnosis of clonorchiasis. However, the true incidence of infection is underestimated owing to the high missing diagnosis rate of this method. The enzyme-linked immunosorbent assay (ELISA) is widely used for the detection and control of clonorchiasis but the practicality of this method is unclear. The purpose of this study was to evaluate the effect of ELISA as a supplementary method for the diagnosis of clonorchiasis.

Methodology/Principal Findings

The present study recruited 2,359 clinically suspected patients from Heilongjiang Province, China. In all, 954 cases were identified as antibody-positive by immunoglobulin (IgG)-ELISA and 495 individuals were diagnosed as egg-positive by the Kato-Katz (KK) method. The seropositive and egg-negative individuals were re-examined by repeated egg counts and/or the number of KK slides and 18 (18.18%) cases were confirmed as clonorchiasis. The 40.44%, antibody-positive rate determined by IgG-ELISA was significantly higher (P<0.05) than the 21.75% egg-positive rate found by examination of feces. A Bayesian approach indicated that the prevalence of clonorchiasis in this region was 22.27% and that the sensitivity, specificity, positive predictive value and negative predictive value of IgG-ELISA were 98.7%, 76.53%, 54.66% and 99.52%, respectively. The agreement between the two methods was moderate (kappa value = 0.564). The clonorchiasis patients lived mainly along the Songhua River. The risk factors, except for ethnic factors, were estimated effectively by both methods.

Conclusions/Significance

The present study suggested that clonorchiasis was widely distributed in Heilongjiang Province, China. The missing diagnosis rate was high using the KK technique alone. The combination of immunological methods and parasitological techniques could improve diagnostic accuracy and reduce the missing diagnosis rate. ELISA used as an auxiliary diagnostic method was realistic and practical for a large-scale screening test, monitoring the prevalence and assessing the risk factors of clonorchiasis.

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