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In the past decade significant advances in our understanding of liver fluke biology have been made through in-depth interrogation and analysis of evolving Fasciola hepatica and Fasciola gigantica omics datasets. This information is crucial for developing novel control strategies, particularly vaccines necessitated by the global spread of anthelmintic resistance. Distilling them down to a manageable number of testable vaccines requires combined rational, empirical, and collaborative approaches. Despite a lack of clear outstanding vaccine candidate(s), we must continue to identify salient parasite-host interacting molecules, likely in the secretory products, tegument, or extracellular vesicles, and perform robust trials especially in livestock, using present and emerging vaccinology technologies to discover that elusive liver fluke vaccine. Omics tools are bringing this prospect ever closer.

Fascioliasis is a zoonotic disease caused by Fasciola hepatica or F. gigantica. There are two phases of Fasciola infection. In the acute phase, the patient has a wide spectrum of clinical manifestations while the later phase of infection is usually related to inflammatory changes in the bile duct and the mechanical effects of the worm, which can lead to biliary obstruction. The presence of Fasciola inside the biliary system has rarely been reported in the literature. In this report, we presented a case of bile duct obstruction in a 36-year-old male patient undergoing cholecystectomy for gallstones and with a history of worsening jaundice for one month. Extensive laboratory testing failed to clarify the cause of jaundice. Three living liver flukes were subsequently retrieved from the right hepatic duct and later confirmed as F. gigantica by morphology and internal transcribed spacer (ITS2) sequence analysis.

Fasciolosis is one of the most important causes of reduction in milk production, growth and fertility in cattle and causes considerable economic losses generated by liver seizures in slaughterhouses. The objective of this study was to determine the occurrence of livers seized byFasciola hepaticain the Lorenzo Gonzales bovine slaughterhouse in Sagua la Grande municipality in Villa Clara province, Cuba. A retrospective observational analysis of the seizures of livers by F. hepatica in the period 2016-2020 was carried out. The prevalence, seasonality, trend and enzootic channels of the occurrence of livers seizures due to fasciolosis in slaughtered cattle were determined. In addition, the annual economic losses as a consequence of fasciolosis seizures were estimated. The sanitary impact of seizures due to fasciolosis showed a prevalence of 18.93%, which is a reflection of the epizootic situation of the units of origin. Losses due to liver seizures as a consequence of F. hepatica infestation amounted to 1 088 532 cup in the five-year period evaluated. The trend in the incidence of F. hepatica seizures is decreasing and shows a marked seasonal pattern in the months of March, April, May, June, October, November and December. The usual expected behavior of F. hepatica seizures of livers in the Sagua bovine slaughterhouse for a period of five years shows a wide range of monthly occurrences.

Hepatic trematodes, such as Fasciola hepatica and Fascioloides magna, have variable distribution throughout the United States. F. magna is endemic in the upper midwestern United States, and F. magna infections are diagnosed frequently in weaned calves and adult beef cattle at the North Dakota State University Veterinary Diagnostic Laboratory (NDSU-VDL). Rarely, liver fluke infestation has also been observed in much younger calves, including aborted fetuses. We describe here, in 2 fetal and 7 neonatal beef calves submitted to the NDSU-VDL between 2011 and 2020, parasitic migration tracts in livers, consisting of regionally extensive, random, linear tracts of fibrosis admixed with black porphyrin pigment, along with foci of necrosis and hemorrhage, and mixed inflammatory cells, which were caused presumptively by F. magna infection. Samples were not available from our 9 cases for PCR assay and sequencing, but we did confirm F. magna within liver samples collected from regional cattle in 2020 and 2021. Fetal and neonatal trematodosis was often concurrent with other common causes of fetal abortion and neonatal calf loss in our cases; however, based on the prepatent period of F. magna, fetal and neonatal beef calf trematode infestations occurred in utero.

Protein phosphorylation plays key roles in a variety of essential cellular processes. Fasciola gigantica is a tropical liver fluke causing hepatobiliary disease fascioliasis, leading to human health threats and heavy economic losses. Although the genome and protein kinases of F. gigantica provided new insights to understand the molecular biology and etiology of this parasite, there is scant knowledge of protein phosphorylation events in F. gigantica. In this study, we characterized the global phosphoproteomics of adult F. gigantica by phosphopeptide enrichment-based LC–MS/MS, a high-throughput analysis to maximize the detection of a large repertoire of phosphoproteins and phosphosites. A total of 1030 phosphopeptides with 1244 phosphosites representing 635 F. gigantica phosphoproteins were identified. The phosphoproteins were involved in a wide variety of biological processes including cellular, metabolic, and single-organism processes. Meanwhile, these proteins were found predominantly in cellular components like membranes and organelles with molecular functions of binding (51.3%) and catalytic activity (40.6%). The KEGG annotation inferred that the most enriched pathways of the phosphoproteins included tight junction, spliceosome, and RNA transport (each one contains 15 identified proteins). Combining the reports in other protozoa and helminths, the phosphoproteins identified in this work play roles in metabolic regulation and signal transduction. To our knowledge, this work performed the first global phosphoproteomics analysis of adult F. gigantica, which provides valuable information for development of intervention strategies for fascioliasis. Supplementary Information The online version contains supplementary material available at 10.1007/s00436-021-07422-2.

Liver fluke (Fasciola hepatica) is a parasite of herbivores including wildlife. Macropods, such as Eastern grey kangaroo (Macropus giganteus) and Common wallaroo (Osphranter robustus), are frequently observed sharing grazing sites with domestic livestock. The impact of Macropods, as reservoirs of infection, on livestock production and risks to cross-species transmission are largely unknown. In Phase 1 of this study, liver and faecal samples were collected from 245 Macropods (181 Eastern grey kangaroos, 64 Common wallaroos) cohabiting livestock farms (n = 7) in the Northern Tablelands regions of New South Wales. Total fluke (TFC) and fluke eggs (FEC) were counted in the liver and faeces, respectively, to assess prevalence. Faecal antigens were also measured using the commercial Bio-X Diagnostic Monoscreen AgELISA Fasciola hepatica kit (cELISA) to assess suitability as a diagnostic tool. In Phase 2, Macropod faecal samples were collected from 60 livestock farms to conduct FEC and assess prevalence by region. Liver fluke was prevalent in 22% of Eastern grey kangaroo and 20% of Common wallaroos with prevalence as high as 45% in the Eastern grey kangaroo. Fluke burdens ranged from 1 to 122 flukes (mean = 9 flukes) with a FEC range of 0–195 eggs per gram (epg) of faeces (mean = 18 epg). Evidence of dead and live flukes trapped within fibrotic capsules confirms the ability of Macropods to resolve infections. cELISA proved highly specific (100%) and sensitive (98%) in liver fluke detection however fibrotic capsules observed in the liver may reduce the correlation of coproantigens with fluke burden. Phase 2 revealed that 27% of livestock farms had Macropods infected with liver fluke. Overall, this study confirmed Eastern grey kangaroo and Common wallaroo are susceptible hosts and potential reservoirs for liver fluke and, monitoring infections in Macropods would assist in livestock disease management., Graphical abstract Image 1, Highlights • Eastern grey kangaroo and Common wallaroo harbouring liver fluke in north eastern Australia. • Macropods with liver fluke may limit effectiveness of integrated parasite management strategies for liver fluke control. • Monitoring Macropod populations within liver fluke endemic regions may assist livestock disease management.

Fasciolosis caused by the liver flukes Fasciola hepatica and Fasciola gigantica is one of the most important neglected parasitic diseases of humans and animals. The ability of the parasites to infect and multiply in their intermediate snail hosts, and their adaptation to a wide variety of mammalian definitive hosts contribute to their high transmissibility and distribution. Within the mammalian host, the trauma caused by the immature flukes burrowing through the liver parenchyma is associated with most of the pathogenesis. Similarly, the feeding activity and the physical presence of large flukes in the bile ducts can lead to anaemia, inflammation, obstruction and cholangitis. The high frequency of non-synonymous polymorphisms found in Fasciola spp. genes allows for adaptation and invasion of a broad range of hosts. This is also facilitated by parasite's excretory-secretory (ES) molecules that mediate physiological changes that allows their establishment within the host. ES contains cathepsin peptidases that aid parasite invasion by degrading collagen and fibronectin. In the bile ducts, cathepsin-L is critical to haemoglobin digestion during feeding activities. Other molecules (peroxiredoxin, cathepsin-L and Kunitz-type inhibitor) stimulate a strong immune response polarised towards a Treg/Th2 phenotype that favours fluke's survival. Helminth defence molecule, fatty acid binding proteins, Fasciola-specific glycans and miRNAs modulate host pro-inflammatory responses, while antioxidant scavenger enzymes work in an orchestrated way to deter host oxidant-mediated damage. Combining these strategies Fasciola spp. survive for decades within their mammalian host, where they reproduce and spread to become one of the most widespread zoonotic worm parasites in the world.

The aim of the present study was to determine the effective dose of fosfatriclaben through a field study in sheep naturally infected with F. hepatica. Thirty crossbred sheep positive for fluke eggs were selected for inclusion in the trial. On day 0, 5 groups of 6 animals each were formed for treatments: group 1 (G1), G2, and G3 received fosfatriclaben at 4, 6, and 8 mg/kg/IM, respectively. G4 received triclabendazole at 10 mg/kg/PO, and G5 was the untreated control group. Fecal samples of the sheep were analyzed to count the number of fluke eggs to evaluate the percentage of egg reduction. Twenty-one days after treatment, all sheep were humanely euthanized to extract the flukes from the bile ducts. They were counted to assess the percentage of fluke reduction. Fosfatriclaben reduced fluke eggs by 99.6, 99.6, and 100% and flukes by 94.3, 100, and 100%, respectively. Triclabendazole reduced fluke eggs by 95.2% and flukes by 100%. The fosfatriclaben injectable prodrug showed a high fasciolicidal efficacy similar to triclabendazole, with advantages over its predecessor, since only half the dose as compared to triclabendazole was required to remove eggs and flukes in the sheep that were studied.

Background Fasciola hepatica is an important pathogen that causes liver fluke disease in definitive hosts such as livestock animals and humans. Various excretory/secretory products have been used in serological diagnosis and vaccination studies targeting fasciolosis. There are no commercial vaccines against fasciolosis yet. Bioinformatic analysis based on computational methods have lower cost and provide faster output compared to conventional vaccine antigen discovery techniques. The aim of this study was to predict B- and T-cell specific epitopes of four excretory/secretory antigens (Kunitz-type serine protease inhibitor, cathepsin L1, helminth defense molecule, and glutathione S-transferase) of Fasciola hepatica and to construct a multiepitope vaccine candidate against fasciolosis. Methods and Results Initially, nonallergic and the highest antigenic B- and T- cell epitopes were selected and then, physico-chemical parameters, secondary and tertiary structures of designed multiepitope vaccine candidate were predicted. Tertiary structure was refined and validated using online bioinformatic tools. Linear and discontinuous B-cell epitopes and disulfide bonds were determined. Finally, molecular docking analysis for MHC-I and MHC-II receptors was performed. Conclusion This multi-epitope vaccine candidate antigen, with high immunological properties, can be considered as a promising vaccine candidate for animal experiments and wet lab studies.

Fresh vegetables are an important part of a healthy diet. Consumed raw, they could be agents of transmission of intestinal parasites. The frequency and variability of parasites eggs on thirty-two samples each of lettuce, tomato and cucumber form irrigated vegetable farms in Bamako, Kati, Baguineda, Samanko, Sikasso and Niono were evaluated. The parasite load was assessed using Uga et al. method, which consist the counting of parasite eggs and cysts in 100 g of vegetable. The overall prevalence of parasitic contamination of vegetables was 20.83% of which 41.66% for lettuce and 16.66% for tomato. Cucumber was free of parasites eggs. Parasites found on the vegetables were Entamoeba coli and Trichomonas intestinalis (24.19% each), Ascaris lumbricoides (13.25%), Giardia intestinalis (12.9%), Balantidium coli (11.29%), Entamoeba histolitica (7.26%), Fasciola hepatica (3.23%), Trichinella spiralis (1.61%), Ancylostoma duodenale and Schistosoma intercalatum (1.04% each). The frequency of parasites on lettuce was 83.33% each in Bamako and Niono; 50% in Kati; 16.66% each in Baguineda and Samanko and 0% in Sikasso. Consumption of vegetables contaminated by parasites can cause a health risk for consumers. Key words: Parasitic contamination, lettuce, tomato, cucumber, health risk.

Rumen fluke (Calicophoron daubneyi) has emerged as a prominent parasite of ruminants in Europe over the past decades. Epidemiological questions remain regarding this observed increase in prevalence as well as the prospect for future paramphistomosis risk. This study aimed to identify factors associated with the temporal−spatial prevalence of rumen fluke as measured by veterinary surveillance in a temperate region using zero-inflated negative binomial mixed modelling. Modelling revealed that summer rainfall, raindays and sunshine hours and mean winter temperature as significant positively associated climate variables for rumen fluke prevalence over space and time (P< 0.05). Rumen fluke prevalence was also higher in counties with higher cattle/sheep densities and was positively associated with rumen fluke case rates in the previous years (P< 0.05). Equivalent models for fasciolosis prevalence revealed no significant association with winter temperature and sunshine hours, (P> 0.05). These results confirm a strong association between rainfall and the prevalence of both fluke species in a temperate environment, likely due to the role ofGalba truncatulaas their intermediate snail host. It also highlights the potential added importance of winter temperature and sunshine hours in rumen fluke epidemiology when compared to liver fluke.

Significant disease burden is caused by infections with human liver flukes, including Clonorchis sinensis, Opisthorchis viverrini and O. felineus. Epidemiology is characterized by high burden in the male than the female, and in the elder than the younger. Chemotherapy is the mainstream for morbidity control, but it could not prevent re-infection. Meanwhile, behavioral change on the dietary habit of ingesting raw freshwater fish is challenging. In this opinion, we argue why it is important to educate children for sustainable control of liver fluke infections. Then, the design, development and key messages of an educational cartoon for preventing liver fluke infections is introduced. Technical focuses are emphasized based on a pilot using the education cartoon for preventing clonorchiasis in China. Finally, how to further develop and verify this education strategy is discussed. Graphical Abstract

Fasciola hepatica, one of the agents that causes fasciolosis, modulates the host immune system to allow parasite survival in the host. F. hepatica expresses carbohydrate-containing glycoconjugates that are decoded by C-type lectin receptors, such as Dectin-1, mannose receptor, DC-SIGN and MGL, that are mainly present on myeloid antigen presenting cells (APCs) and can mediate immunoregulatory properties on T cells. In particular, Macrophage Gal/GalNAc lectin 2 (MGL2) expands modified Th2 immune responses, while suppressing Th1 polarization, upon recognition of GalNAc-glycosylated parasite components. In this study, by using MGL2-DTR transgenic mice that encode human diphtheria toxin receptor in MGL2+ cells, we demonstrate the role of peritoneal APCs during F. hepatica infection in favoring parasite survival. This process might be mediated by the induction of splenic Tregs in vivo, since the depletion of MGL2+ cells conferred mice with partial resistance to the infection and abrogated the increase of CD4+/CD25+ FoxP3+ Tregs induced by the parasite. Therefore, MGL2+ cells are critical determinants of F. hepatica infection and could constitute immune checkpoints to control parasite infection.

In this study, an inventory of the types of rodents in the study area was conducted, and a survey of internal parasites was done for the most important types of rodents prevalent in Sohag region during the year 2020. The results showed that four types of climbing rodents were present. Those rodents were the white-bellied rat (the most dominant in the region), the gray-bellied climber rat, field rat and brown Norwegian rat. The results showed the absence of many species. By studying the internal parasites of the most common species in the study area. we found 3 trematodes (Echinostoma liei Jeyarasasingam &Heyneman,1972, Schistosoma mansoni (Bilharzia), and Fasciola hepatica Linnaeus,1758),two nematodes (Angiostrongylus cantoniensis Chen,1935, and Trichuris sp.) and one cestode (Hymenolepis sp.) of the white-bellied climbing rat Rattus rattus frugivorus, which is the dominant species in this study.

The upshot of γ-irradiated Fasciola hepatica infection on the activity of plasma glutamate dehydrogenase (GLDH) and γ-glutamyl transpeptidase (GGT) was evaluated in 36 sheep infected with a single dose of 30, 60, 120, and 240 grays and those kept as negative and positive control over 17 weeks. During this period, serum and faecal samples, as well as body weight gains, were taken at weekly intervals. Furthermore, the effects of the irradiation dose (500) for oral vaccination and on the recovery of adult flukes were assessed following primary infection. Eggs were first detected in the faeces of infected sheep on week 8 post-infection. The parasite viability was severely affected by doses of γ-irradiation of 120 Gy or 240 Gy. In the aforementioned doses, relatively low numbers of mature flukes of about 60 (17.1%) and 38 (10.8%) were recovered than the control group, respectively. The sensitized lambs also showed less hepatic damage compared with the controls as indicated by lower levels of the serum enzyme glutamate dehydrogenase and γ- glutamyl transferase significant body weight loss was observed between weeks 6 and 8 post-infection followed by a steady increase of the mean weight of infected animals across time. In conclusion, vaccination of sheep with γ irradiated metacercariae of F. hepatica appeared to affect the number and development of the fluke population resulting in reduced hepatic damage during migration, reduced fecundity after patency, as measured by worm and egg counts, levels of serum glutamate dehydrogenase and γ- glutamyl transferase.

In the present study, we describe the proliferative response and the IFN - y, IL-10, IL-4 cytokine expression profiles in peripheral blood, and IgG production, after the experimental infection of Santa Inês sheep with 250 Fasciola hepatica metacercariae that were evaluated at 60 and 210 days post-infection(dpi). The cytokine expression profile at 60 dpi was characterized by the production of IFN - y, and IL-10, which is indicative of an initial mixed Th1/Th2 response. The modulation of the response occurred at 210 dpi with a predominance of IL-10 and IL-4 over IFN - y. Mononuclear cells from peripheral blood stimulated with F. hepatica antigen exhibited proliferative capacity at 60 dpi, whereas the response was consistent with modulation from Th1 to Th2 in the chronic phase. The IgG antibody response was more marked at 60 days than at 210 dpi, confirming the mixed-response profile. The late modulation of the T lymphocyte response in association with the predominance of IL-10 and IL-4 at 210 dpi suggests the involvement of these cytokines after the establishment of the parasites in the bile ducts. The transition from a mixed to a regulatory response in the chronic phase was also accompanied by a reduced number of eggs per gram of feces. No presente estudo, observou-se a resposta proliferativa e os perfis de expressão de citocinas IFN - y, IL-10, IL-4 no sangue periférico, e a produção de IgG, aos 60 e 210 dias após infecção (dpi) experimental de ovinos Santa Inês com 250 metacercárias de Fasciola hepatica. O perfil de expressão de citocinas aos 60 dpi foi caracterizado pela produção de IFN - y e IL-10, o que é indicativo de uma resposta mista inicial Th1/Th2. A modulação da resposta ocorreu aos 210 dpi, com predominância de IL-10 e IL-4 sobre IFN - y. As células mononucleares do sangue periférico estimuladas com antígeno total de F. hepatica adulta exibiram capacidade proliferativa aos 60 dpi, enquanto a resposta foi consistente com uma modulação de Th1 para Th2 na fase crônica. A resposta do anticorpo IgG foi maior aos 60 dpi do que aos 210 dpi. A modulação tardia da resposta dos linfócitos T em associação com a predominância de IL-10 e IL-4 aos 210 dpi sugere o envolvimento dessas citocinas após o estabelecimento dos parasitos nos ductos biliares. A transição de uma resposta mista para uma resposta com pefil regulador na fase crônica também foi acompanhada por redução dos ovos por grama de fezes.

The objective of this study was to evaluate the effectiveness of the main anthelmintics used for the control of trematodes in cattle in an endemic area in the humid Mexican tropics. A diagnostic study was carried out in nine cattle farms to determine the prevalence of flukes through faecal examination. Only three farms with more than 20 cows positive to trematodes were chosen to determine the effectiveness of commercial anthelmintics (triclabendazole, TCBZ; ivermectin + closantel, (IVM + CLOS); IVM + clorsulon, (CLORS); nitroxynil, NITROX). The prevalence of Fasciola hepatica was 27.1% and 29.6% of paramphistomes. The faecal egg count of trematodes ranged from 0.0 to 12.2 eggs per gram of faeces. The highest effectiveness against F. hepatica was 96.7%, and 92.7% against paramphistomes. NITROX was the most effective in the control of trematodes, while other products, such as IVM + CLORS and TCBZ obtained values lower than 90%, which puts sustainable trematode control at risk. The presence of trematodes was observed on most farms, although the prevalence per herd was highly variable, which indicates that the trematodes F. hepatica and paramphistomes are endemic to the region and a suitable management programme is suggested to control infections caused by these parasites.

We conducted a retrospective cohort study of children who had chronic fascioliasis in the highlands of Peru to determine triclabendazole treatment efficacy. Children passing Fasciola eggs in stool were offered directly observed triclabendazole treatment (>1 doses of 10 mg/kg). Parasitologic cure was evaluated by using microscopy of stool 1–4 months after each treatment. A total of 146 children who had chronic fascioliasis participated in the study; 53% were female, and the mean ± SD age was 10.4 ± 3.1 years. After the first treatment, 55% of the children achieved parasitologic cure. Cure rates decreased after the second (38%), third (30%), and fourth (23%) treatments; 17 children (11.6%) did not achieve cure after 4 treatments. Higher baseline egg counts and lower socioeconomic status were associated with triclabendazole treatment failure. Decreased triclabendazole efficacy in disease-endemic communities threatens control efforts. Further research on triclabendazole resistance and new drugs to overcome it are urgently needed.

The helminth parasites

Fascioliasis is a parasitic foodborne disease caused by the liver flukes,For this purpose, the secondary, tertiary, and quaternary structure of FhCatL1 protein were also predicted and analyzed using the SWISS-MODEL server. Validation of the modeled structures was performed by Ramachandran plots. The antigenic epitopes of the protein were predicted by IEDB server.Our findings revealed the low similarity of FhCatL1 with mammalian CatL1, lacking signal peptides or transmembrane domain, and the presence of 33 phosphorylation sites. Also, the containment of FhCatL1 for many topological, physico-chemical, immunological properties that favored its function of solubility and interaction with the immune components were reported. In addition, the earlier worldwide reports documented the high efficacy of FhCatL1 as a diagnostic and vaccine antigen in different animals. Altogether, FhCatL1 is considered an excellent candidate for using in commercialized diagnostic assays or vaccine products against fascioliasis in different animal species. Our assessment also included FgCatL1 and reported very similar findings and outputs to those of FhCatL1.

Exogenous bioactive peptides are considered promising for the wound healing therapy in humans. In this regard, parasitic trematodes proteins may potentially become a new perspective agents. Foodborne trematode Opisthorchis felineus is widespread in Europe and has the ability to stimulate proliferation of bile duct epithelium. In this study, we investigated skin wound healing potential of O. felineus proteins in mouse model. C57Bl/6 mice were inflicted with superficial wounds with 8 mm diameter. Experimental groups included several non-specific controls and specific treatment groups (excretory-secretory product and lysate). After 10 days of the experiment, the percentage of wound healing in the specific treatment groups significantly exceeded the control values. We also found that wound treatment with excretory-secretory product and worm lysate resulted in: (i) inflammation reducing, (ii) vascular response modulating, (iii) type 1 collagen deposition promoting dermal ECM remodeling. An additional proteomic analysis of excretory-secretory product and worm lysate samples was revealed 111 common proteins. The obtained data indicate a high wound-healing potential of liver fluke proteins and open prospects for further research as new therapeutic approaches.

Clonorchis sinensis, a liver fluke parasite, infects humans through ingestion of raw or undercooked fish, crabs, or crayfish in endemic areas where the parasite is found. Clonorchis sinensis infects the liver, gallbladder, and bile duct in humans, causing Clonorichiasis. Although the majority of patients are asymptomatic, long-lasting infections may cause severe disease. Without treatment, human infection may persist for the parasite's lifespan (25-30 years). Pathologic diagnosis can be challenging as sampling may demonstrate limited cellularity with minuscule eggs that may be overlooked. Here, we report a rare case of liver fluke eggs diagnosed in bile duct brush cytology.

Calicophoron daubneyi (rumen fluke) is an emerging parasitic infection of livestock across Europe. Despite increasing in prevalence, little is known about the level of awareness of rumen fluke or current control practices used by UK farmers. Fasciola hepatica (liver fluke) is a common parasitic infection of cattle and sheep in the UK. Co-infections with these parasites can present in sheep and cattle, but the only drug with reported efficacy against rumen fluke is oxyclozanide. Between December 2019 and March 2020, 451 sheep and/or cattle farmers completed an online questionnaire, capturing their awareness and current means of control for liver fluke and rumen fluke. Most respondents (70%) were aware of rumen fluke, with 14% recording its presence on their farms and 18% having previously treated for rumen fluke. Almost all respondents (99%) were aware of liver fluke and higher numbers of respondents reported its presence on farm (67%) with 88% having previously treated for liver fluke. Respondents who were aware of rumen fluke said they were concerned about the parasite (81%), although rumen fluke was less of a concern than liver fluke (p 0.05). Of respondents who reported rumen fluke presence on their farm, 42% cited incorrect diagnostic methods, including those traditionally used to detect liver fluke. Respondents were more likely to treat annually for liver fluke, as opposed to rumen fluke (p 0.05). The most frequently used drug for the treatment of liver fluke infection was triclabendazole (53% sheep treatments, 34% cattle treatments) and only a minority of farmers treated with a product effective against rumen fluke (oxyclozanide; 42% cattle treatments, 35% sheep treatments). A small proportion of farmers stated that they used a non-flukicide drug to treat sheep for liver fluke infection (1.6% sheep treatments). These results demonstrate a broad awareness of liver and rumen fluke in sheep and cattle, but reveal confusion amongst farmers about their diagnosis and treatment, highlighting the need to provide best practice advice to the livestock industry for the control of both parasites.

Background Glutamate carboxypeptidase 2 (GCP2) belongs to the M28B metalloprotease subfamily encompassing a variety of zinc-dependent exopeptidases that can be found in many eukaryotes, including unicellular organisms. Limited information exists on the physiological functions of GCP2 orthologs in mammalian tissues outside of the brain and intestine, and such data are completely absent for non-mammalian species. Here, we investigate GCP2 orthologs found in trematodes, not only as putative instrumental molecules for defining their basal function(s) but also as drug targets. Methods Identified genes encoding M28B proteases Schistosoma mansoni and Fasciola hepatica genomes were analyzed and annotated. Homology modeling was used to create three-dimensional models of SmM28B and FhM28B proteins using published X-ray structures as the template. For S. mansoni, RT-qPCR was used to evaluate gene expression profiles, and, by RNAi, we exploited the possible impact of knockdown on the viability of worms. Enzymes from both parasite species were cloned for recombinant expression. Polyclonal antibodies raised against purified recombinant enzymes and RNA probes were used for localization studies in both parasite species. Results Single genes encoding M28B metalloproteases were identified in the genomes of S. mansoni and F. hepatica. Homology models revealed the conserved three-dimensional fold as well as the organization of the di-zinc active site. Putative peptidase activities of purified recombinant proteins were assayed using peptidic libraries, yet no specific substrate was identified, pointing towards the likely stringent substrate specificity of the enzymes. The orthologs were found to be localized in reproductive, digestive, nervous, and sensory organs as well as parenchymal cells. Knockdown of gene expression by RNAi silencing revealed that the genes studied were non-essential for trematode survival under laboratory conditions, reflecting similar findings for GCP2 KO mice. Conclusions Our study offers the first insight to our knowledge into M28B protease orthologs found in trematodes. Conservation of their three-dimensional structure, as well as tissue expression pattern, suggests that trematode GCP2 orthologs may have functions similar to their mammalian counterparts and can thus serve as valuable models for future studies aimed at clarifying the physiological role(s) of GCP2 and related subfamily proteases. Graphical Abstract

Background Clonorchis sinensis requires bile acid transporters as this fluke inhabits bile juice-filled biliary ducts, which provide an extreme environment. Clonorchis sinensis sodium-bile acid co-transporter (CsSBAT) is indispensable for the fluke’s survival in the final host, as it circulates taurocholate and prevents bile toxicity in the fluke; hence, it is recognized as a useful drug target. Methodology and principal findings In the present study, using structure-based virtual screening approach, we presented inhibitor candidates targeting a bile acid-binding pocket of CsSBAT. CsSBAT models were built using tertiary structure modeling based on a bile acid transporter template (PDB ID: 3zuy and 4n7x) and were applied into AutoDock Vina for competitive docking simulation. First, potential compounds were identified from PubChem (holding more than 100,000 compounds) by applying three criteria: i) interacting more favorably with CsSBAT than with a human homolog, ii) intimate interaction to the inward- and outward-facing conformational states, iii) binding with CsSBAT preferably to natural bile acids. Second, two compounds were identified following the Lipinski’s rule of five. Third, other two compounds of molecular weight higher than 500 Da (Mr > 500 Da) were presumed to efficiently block the transporter via a feasible rational screening strategy. Of these candidates, compound 9806452 exhibited the least hepatotoxicity that may enhance drug-likeness properties. Conclusions It is proposed that compound 9806452 act as a potential inhibitor toward CsSBAT and further studies are warranted for drug development process against clonorchiasis.

Background Fascioliasis is a significant vector-borne disease that has emerged in numerous tropical and subtropical countries causing severe health problems. Egypt is one of the fascioliasis endemic regions; however, the current situation in Upper Egypt is understudied, with only sporadic human cases or outbreaks. This study aims to highlight the sociodemographic characteristics of human fascioliasis in a newly emerged endemic area in Upper Egypt, along with risk factors analysis and the molecular characteristics of the fasciolid population in humans, animals, and lymnaeid snails. Methodology/Principal findings The study reported Fasciola infection in patients and their close relatives by analyzing the risk of human infection. Morphological and molecular characterization was performed on lymnaeid snails. Multigene sequencing was also used to characterize fasciolids from human cases, cattle, and pooled snail samples. The study identified asymptomatic Fasciola infection among family members and identified the presence of peridomestic animals as a significant risk factor for infection. This is the first genetic evidence that Radix auricularia exists as the snail intermediate host in Egypt. Conclusions/Significance This study revealed that Assiut Governorate in Upper Egypt is a high-risk area for human fascioliasis that requires additional control measures. Fasciola hepatica was the main causative agent infecting humans and snail vectors in this newly emerged endemic area. In addition, this is the first report of R. auricularia as the snail intermediate host transmitting fascioliasis in Upper Egypt. Further research is required to clarify the widespread distribution of Fasciola in Egypt’s various animal hosts. This provides insight into the mode of transmission, epidemiological criteria, and genetic diversity of fasciolid populations in Upper Egypt.\

Fascioliasis has been reported from many countries across the globe. Acute phase of liver fluke is characterised by fever, abdominal pain and peripheral blood eosinophilia while the chronic phase is marked by chronic inflammation involving biliary tract. It is commonly diagnosed by a radiologist due to characteristic branching abscesses seen on CT scan, highly suggestive of liver fluke. Diagnosis is made by demonstration of eggs on direct microscopic examination of duodenal aspirate or bile. Screening of family members is recommended once diagnosis is has been made. Triclabendazole is the drug of choice for treatment.

Fascioliasis is a parasitic infection caused by liver flukes. Although several cases have been reported in Korea, phylogenetic analysis of isolates is lacking. In this study, a 66-year-old woman with right upper quadrant (RUQ) abdominal pain was diagnosed as fascioliasis involving abdominal muscle by imaging study. She received praziquantel treatment, but symptoms were not improved. Lateral movement of the abscess lesion was followed. Trematode parasite was surgically removed from the patient’s rectus abdominis muscle. The fluke was identified as Fasciola hepatica based on sequence analysis of 18S rDNA. To determine the phylogenetic position of this Fasciola strain (named Korean Fasciola 1; KF1), the cox1 gene (273 bp) was analyzed and compared with the genes of 17 F. hepatica strains isolated from cows, sheep, goats, and humans from various countries. Phylogenetic analysis showed that KF1 was closely related with the isolates from China goat.

Fasciola hepatica is highly prevalent in the highlands of Peru. School-age children have the greatest risk of infection. Mass treatment of at-risk populations has been proposed to control the infection and prevent complications. However, the decreasing effectiveness of triclabendazole raises concerns regarding this strategy. Previous studies reported aggregation of Fasciola infection among family members. This study aimed to determine the risk of fascioliasis among household members living with Fasciola-infected children identified through school-based testing. We conducted a cross-sectional study including adult members of households where children with and without fascioliasis were identified. Demographic, epidemiological, and socioeconomic information was collected. One blood sample was drawn to test for Fasciola antibodies, and three stool samples were collected for microscopy for Fasciola ova. We tested 326 adults from 213 households. Of these adult subjects, chronic fascioliasis (24 of 326, 7.4%) was the most common helminth infection. Thirty-nine subjects (12.7%) tested positive for Fasciola antibodies. Combining microscopy and serum antibody tests, 13.2% (43 of 326) had evidence of Fasciola infection. One third (104 of 326, 31.9%) of the participants lived with at least one child infected with Fasciola hepatica. Adults with fascioliasis were four times more likely to live with an infected child. Poverty and diet were associated with increased risk of Fasciola infection. Adults with fascioliasis were significantly more likely to live with Fasciola-infected children.

espanolEste estudiose llevo a cabo para establecer la prevalencia e identificar los factores de riesgo asociados con las infestaciones por trematodos en ganado lechero Holstein en el valle de Paipa, Boyaca. Las muestras fecales recogidas de 100 bovinos seleccionados aleatoriamente se examinaron utilizando una tecnica de sedimentacion simple para el recuento diferencial de huevos de trematodos. Se buscaron huevos de tres grupos de trematodos: Fasciola hepatica, Paramphistomum spp., y Cotylophorum spp. La prevalencia especifica de trematodos para cada grupo fue del 12, 9 y 4%, respectivamente. Se observo una superposicion sustancial en el recuento de F. hepatica y Paramphistomum spp. La prevalencia de los tres trematodos identificados en este estudio se asocio significativamente (P EnglishThis studywas carried out to establish the prevalence and identify the risk factors asso-ciated with trematode infestations in Holstein dairy cattle in the Paipa-Boyaca valley. Fecal samples collected from 100 randomly selected cattle were examined using a simple sedimentation technique for differential trematode egg count. Eggs were sought from three groups of trematodes: Fasciola hepatica, Paramphistomum spp., and Cotylophorum spp. The specific prevalence was 12, 9 and 4%, respectively. Substantial overlap was observed in the count of F. hepatica and Paramphistomum spp. The prevalence of the three flukes identified in this study was significantly associated (P

La fasciolosis es una zoonosis provocada por el parásito Fasciola hepatica Linnaeus, 1758, éste para poder desarrollar su ciclo biológico, necesita de un hospedero intermediario (molusco gasterópodo, Lymnaeidae), y un hospedero definitivo (mamíferos, incluyendo al hombre). Esta enfermedad, ha causado pérdidas económicas anuales de $ 200 M en el mundo. El objetivo de la presente investigación fue identificar la prevalencia de F. hepatica en los centros de rastro bovino, determinar las pérdidas económicas, e identificar las características agroecológica en donde se desarrollan los hospederos intermediarios, en la provincia de Imbabura, Ecuador. Se identificó una prevalencia de F. hepatica, de 10,9%, donde el Cantón Otavalo presentó 190 muestras positivas (19,7%), considerándose el punto con mayor prevalencia dentro del estudio. Los bovinos positivos fueron, 102 machos (26,9%) y 277 hembras (73,1%), los cuales pertenecen al biotipo Mestizo (53,5%), Holstein (42%) y Normando (4,5 %), siendo el 78,6% mayores a dos años y 21,4% menores a dos años. Se presentó una pérdida económica anual de $ 69.547,5 dólares americanos. Los 20 biotopos muestreados, se mantuvieron dentro de los valores promedio; distancia del centro poblado 0,7 km, área de 42,8 m2; 31 moluscos por biotopo, pH del suelo 7,1; profundidad del agua 2,3 cm; altitud de 2.019 a 2.772 msnm; temperatura de 20 °C y humedad relativa de 74%. Los moluscos se ubicaron en acequias (55%), charcos (25%), pantanos (10%), riachuelos y el suelo (5%), con presencia de kikuyo (Pennisetum clandestinum Hochst. Ex Chiov, 1903) y totora (Schoenoplectus californicus C. A. Mey., 1850) como especies dominantes. La provincia de Imbabura posee una prevalencia moderada en cuanto a epidemiología por parte de fasciolosis, se confirma que estas zonas presentan un ecosistema apto para el desarrollo del ciclo biológico de la fasciolosis.

Calicophoron daubneyi is the primary rumen fluke (RF) found in Europe in ruminants and infection is more common in cattle than in sheep. The incidence of RF has appeared to increase greatly throughout Europe in the last 10-15 years, with outbreaks of clinical paramphistomosis confirmed in ruminants in many countries, including Great Britain and Ireland. Clinical disease, due to immature stages developing in the small intestine, appears infrequently but can occur, usually in the autumn or winter within weeks of beginning to graze wet pasture. Although disease due to adult RF has not been proven, subclinical production losses have been attributed to adult RF infection by some researchers. As the intermediate host for RF and the liver fluke (Fasciola hepatica) is the mud snail (Galba truncatula), similar habitats and environmental conditions favour both parasites. There may, however, be differences in parasite development and interactions within both the final and intermediate hosts. No anthelminthic product is licensed for treatment of ruminants for RF in the UK. However, oxyclozanide, licensed for the treatment of adult F. hepatica infection, has been shown to have activity, but it may be more effective against the adult than the immature stages. The future prevalence of RF due to climate change and limited treatment options is unpredictable. Infection and clinical disease could become more common and RF is worthy of further research.

The tropical liver fluke Fasciola gigantica affects livestock and humans in many Asian countries, large parts of Africa, and parts of Europe. Despite the public health and economic impacts of F. gigantica, understanding of F. gigantica biology and how the complex lifecycle of this liver fluke is transcriptionally regulated remain unknown. Here, we tested the hypothesis that the regulatory small non-coding RNAs (sncRNAs), microRNAs (miRNAs) and tRNA-derived fragments (tRFs) play roles in the adaptation of F. gigantica to its intermediate and definitive hosts. We sequenced sncRNAs of eight lifecycle stages of F. gigantica. In total, 56 miRNAs from 33 conserved families and four Fasciola-specific miRNAs were identified. Expression analysis of miRNAs suggested clear stage-related patterns. By leveraging the existing transcriptomic data, we predicted a miRNA-based regulation of metabolism, transport, growth and developmental processes. Also, by comparing miRNA complement of F. gigantica with that of Fasciola hepatica, we detected a high level of conservation and identified differences in some miRNAs, which can be used to distinguish the two species. Moreover, we found that tRFs at each lifecycle stage were predominantly derived by tRNA-Lys and tRNA-Gly at 5' half sites, but relatively high expression was related to the buffalo-infecting stages. Taken together, we provided a comprehensive overview of the dynamic transcriptional changes of small RNAs that occur during the developmental stages of F. gigantica. This global analysis of F. gigantica lifecycle stages revealed new roles of miRNAs and tRFs in parasite development and will facilitate future research into understanding of fasciolosis pathobiology.

22 páginas, 8 figuras, The trematode Fasciola hepatica is the most widespread causative agent of fasciolosis, a parasitic disease that mainly affects humans and ruminants worldwide. During F. hepatica infection, newly excysted juveniles (FhNEJ) emerge in the duodenum of the mammalian host and migrate towards their definitive location, the intra-hepatic biliary ducts. Understanding how F. hepatica traverses the intestinal wall and migrates towards the liver is pivotal for the development of more successful strategies against fasciolosis. The central enzyme of the mammalian fibrinolytic system is plasmin, a serine protease whose functions are exploited by a number of parasite species owing to its broad spectrum of substrates, including components of tissue extracellular matrices. The aim of the present work is to understand whether FhNEJ co-opt the functions of their host fibrinolytic system as a mechanism to facilitate trans-intestinal migration., This work was supported by the JIN project ‘ULYSSES’ (RTI2018-093463-J-100 to J.G.M.) funded by the Ministerio de Ciencia, Innovación y Universidades (MCIU), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER, UE). IRNASA-CSIC group acknowledges funding received from Project “CLU-2019-05 - IRNASA-CSIC Unit of Excellence”, funded by the Junta de Castilla y León cofunded by the European Union (FEDER “Europe drives our growth”) and funding from the Programme for strengthening research structures "Stairway to excellence" internationalisation aid, cofunded by the Junta de Castilla y León and the European Regional Development Fund. M.S.L.acknowledges the financial support of the Spanish Ministry of Science and Innovation (Project PID2019-108782RB-C22). J.S. and D.B.R. acknowledge the support of the Junta de Castilla y León for their Predoctoral contracts. J.G.M. is supported by the ‘Ramón y Cajal’ program (RYC2020-030575-I) of the Ministerio de Ciencia e Innovación. Valencia centre collaboration funded by: CIBER-Consorcio Centro de Investigación Biomédica en Red- (CB21/13/00056), Instituto de Salud Carlos III, Ministry of Science and Innovation and European Union – NextGenerationEU; the Red de Investigación de Centros de Enfermedades Tropicales - RICET (RD16/0027/0023) of the PN de I+D+I, ISCIII-Subdirección General de Redes y Centros de Investigación Cooperativa RETICS, Ministry of Health and Consumption, Madrid; the PROMETEO Program, Programa de Ayudas para Grupos de Investigación de Excelencia (2021/004), Generalitat Valenciana, Valencia, Spain. The proteomics laboratory where LC-MS/MS analysis was performed is a member of Proteored, PRB3 and is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by the Instituto de Salud Carlos III (ISCIII) and the European Regional Development Fund (ERDF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

espanolLas enfermedades causadas por parasitos disminuyen las actividades productivas y reproductivas en los animales nativos y mas aun en los animales destinados al consumo humano, como el ganado bovino, una de estas enfermedades es la fasciolosis, causada por Fasciola hepatica, cuya prevalencia se estima entre 23.5 a 33 %en areas muy humedas con temperaturas que varian entre 15.5 ± 1.1 a 34.1 ± 2.1 oC., a altitudes que fluctuaron entre 300 y 2400 msnm. El objetivo de este estudio fue determinar los cambios fisiopatologicos (analisis histologico y obtener el numero de duelas en parenquima hepatico, perfil metabolico y enzimatico y conteo diferencial de leucocitos) en bovinos criollos en diferentes areas zoogeograficas en Mexico; se tomaron muestras de sangre y tejido hepatico de 7892 animales criollos. La prevalencia de fasciolosis fue de 48.9%; enmacrohistopatologia: se detectaron obstrucciones hepaticas, un aumento en el diametro y engrosamiento de los conductos biliares (colangiohepatitis),una disminucion en el grosor de los lobulos hepaticos izquierdo y ventral, y en casos cronicos, se observo cirrosis hepatica; a nivel histologico: se observo perdida de la morfologia celular y presencia de huevos deF. hepatica,depositados en el parenquima hepatico y en los conductos sanguineos y biliares. Se detecto que el dano hepatico era directamente proporcional al numero de trematodos encontrados y que estos tambien causaron alteraciones en los componentes bioquimicos sanguineos. Los parametros bioquimicos en sangre estuvieron alterados de manera muysignificativa (P EnglishDiseases caused by parasites reduce productive and reproductive activities in native animals and evenmore so in animals destined for human consumption, such as cattle, one of these diseases is fasciolosis, caused byFasciola hepatica, whose prevalence is estimated between 23.5 to 33 %in very humid areas with temperatures thatvary between 15.5 ± 1.1 to 34.1 ± 2.1 oC., At altitudes that fluctuated between 300 and 2400 masl. The objective of thisstudy was to determine the pathophysiological changes (histological analysis and obtain the number of flukes inliver parenchyma, metabolic andenzymatic profile anddifferential leukocyte count) increole cattle indifferentzoogeographic areas in Mexico; blood and liver tissue samples were taken from7 892 Creole animals. Results: theprevalence of fasciolosis was 48.9 %; in macro histopathology: hepatic obstructions were detected, an increase in thediameter and thickening of the bile ducts (cholangiohepatitis), a decrease in the thickness of the left and ventralhepatic lobes, and in chronic cases, liver cirrhosis was observed; at the histological level: loss of cell morphology andthe presence ofF. hepaticaeggs were observed, deposited in the liver parenchyma and in the blood and bile ducts. Itwas found that liver damage was directly proportional to the number of flukes found and that these also causedalterations in blood biochemical components. The biochemical parameters in blood were altered in a very significantway (P

Fascioliasis is caused in Venezuela by the trematode Fasciola hepatica, affecting herbivorous and human. The Venezuelan Andean region is endemic for bovine fascioliasis and its presence in humans is not known. The objective of this work was to detected positive cases of bovine and human fascioliasis by coprological and immunological techniques and determine the possible risk factors, in eight cattle farms of a Venezuelan Andean rural area. We studied 143 samples of feces and sera of bovines, and 34 samples of feces and sera of humans. Feces were examined by several coprologic techniques, while sera were evaluated by ELISA using two antigens: crude extract (CE) and surface proteins (SP) of F. hepatica, which were previously standardized and validated. The frequency of fascioliasis in bovines was 21% by coprology, and 49.7% by SP-ELISA. The human detection was 0% by coprology, and 29.4% by SP-ELISA. There were statistical significative differences between cattle farms, regarding to the positive results by coprology and by SP-ELISA. About the possible risk factors, statistical association was found only with the presence of snails near or in the farms and consumption of non-channeled water (river, ditch or spring), both for cattle and for humans. The results showed that the studied area is endemic for bovine fascioliasis, the human has been in contact with F. hepatica and there are risk factors for the transmission of the parasite in the studied farms.

Fascioliasis is a zoonotic disease caused by Fasciola hepatica that infects mainly cattle, sheep, and goats. Humans can be infected by water or aquatic plants contaminated with metacercariae. The authors encountered two cases of F. hepatica infection. One patient reported abdominal discomfort with marked eosinophilia. The other patient had chest discomfort with marked eosinophilia. The abdominal CT images revealed hypodense lesions in the liver. The ultrasonography-guided liver biopsy findings in both patients were indicative of parasitic infections. Serological tests confirmed the definite diagnoses. Both patients were treated with a single dose of triclabendazole, which is the treatment of choice for fascioliasis. These findings suggest that a diagnosis of fascioliasis, particularly in the acute phase, should be considered in patients with abdominal pain, marked eosinophilia, and hypodense hepatic lesions on CT.

The glycogen content in parasites, determined by spectrophotometric method, can be used as an additional criterion for assessing the effectiveness of anthelmintic drugs. In this study, the effect of albendazole and triclabendazole, drugs from the benzimidazole group, on the glycogen levels of adult Fasciola hepatica was investigated in Wistar rat model. Re-administration of anthelmintics resulted in a more significant effect on the carbohydrate and energy metabolism of Fasciola by 48 h, as evident by the lowest glycogen content during the experiment: 0.019 ± 0.003 mg/mg (triclabendazole) and 0.021 ± 0.004 mg/mg (albendazole) as compared to the control 0.045 ± 0.001 mg/mg at 22 ± 1°C. A decrease in the glycogen levels in flukes after therapy was significant (P 0.05). This study shows the degree to which flukes are susceptible to anthelmintics and can be useful in the development and evaluation of treatment regimens against F. hepatica and related parasites.

The threats posed by a range of viral and bacterial zoonotic diseases inevitably receive renewed attention in the wake of global pandemic events due to their overt and devastating impacts on human health and the economy. Parasitic zoonoses, however, many of which affect millions of people each day, are frequently ignored. In the case of fasciolosis, caused by infection with Fasciola hepatica or Fasciola gigantica, this oversight has allowed for the expansion of areas of parasite sympatry and thus increased the incidence of hybridization and possible introgression between the two species. Here we highlight how an increased demand for animal-derived protein, combined with a lack of appropriate tools for detection of these events, is changing the status quo of these zoonotic parasites., Highlights Increased demand for animal-derived protein from Fasciola hepatica-endemic countries has led to a growing number of reports of hybridization between F. hepatica and Fasciola gigantica in Southeast Asia. Hybridization and eventual introgression have been reported in a range of protozoan, helminth, and arthropod parasites and act as important drivers of evolutionary change and adaptation. Introgression between Fasciola spp. remains unproven but has potentially serious human and animal health consequences as seen in other parasites. New tools for the characterization of hybridization and introgression events between Fasciola spp. are needed.

The food-borne trematodes, Opisthorchis viverrini and Clonorchis sinensis, are classified as group 1 biological carcinogens: definitive causes of cancer. By contrast, infections with Fasciola hepatica, also a food-borne trematode of the phylum Platyhelminthes, are not carcinogenic. This review explores the premise that the differential activation of macrophages during infection with these food-borne trematodes is a major determinant of the pathological outcome of infection. Like most helminths, the latter stages of infection with all 3 flukes induce M2 macrophages, a phenotype that mediates the functional repair of tissue damaged by the feeding and migratory activities of the parasites. However, there is a critical difference in how the development of pro-inflammatory M1 macrophages is regulated during infection with these parasites. While the activation of the M1 macrophage phenotype is largely suppressed during the early stages of infection with F. hepatica, M1 macrophages predominate in the bile ducts following infection with O. viverrini and C. sinensis. The anti-microbial factors released by M1 macrophages create an environment conducive to mutagenesis, and hence the initiation of tumour formation. Subsequently, the tissue remodelling processes induced by the M2 macrophages promote the proliferation of mutated cells, and the expansion of cancerous tissue. This review will also explore the interactions between macrophages and parasite-derived signals, and their contributions to the stark differences in the innate immune responses to infection with these parasites.

Although a common pathogen in much of Asia, liver flukes are believed to be a rare cause of disease in the United States. In this series, we describe 3 patients diagnosed with Clonorchis sinensis during ERCP within 1 year at our institution.Three patients referred to a large community hospital underwent ERCP with direct visualization of a worm in the biliary tree and subsequent histopathologic confirmation.The patients had variable clinical presentations, and 2 had repeat negative stool studies for ova and parasites. Each patient had imaging studies showing abnormalities within the biliary tree, after which ERCP was performed with direct visualization and extraction of a wormlike structure. It was confirmed that all 3 patients had emigrated from China within the last decade. The epidemiologic data and the histopathologic characteristics of the fluke eggs in utero were consistent with a diagnosis of C sinensis.The diagnosis of clonorchiasis should remain on the differential diagnosis for patients with nonspecific biliary symptoms who have known risk factors for this uncommonly common pathogen.

The parasite

The foodborne liver trematode

Liver flukes, Fasciola spp., are veterinary and medically important parasites infecting numerous species of economically important animals in addition to humans on a global scale. The components of transforming growth factor beta (TGF-β) signalling are widely distributed throughout the animal kingdom and are considerably conserved. Through shared common signal transduction mechanisms, crosstalk of TGF-β signalling between a host and the parasite during infection is possible. Herein, we have identified and undertaken the molecular characterisation of a putative TGF-β homologue from the tropical liver fluke F. gigantica (FgTLM). A FgTLM cDNA was 3557 bp in length, it encoded for 620 amino acid polypeptide which consisted of 494 amino acids of prodomain and 126 amino acids comprising the mature protein. FgTLM displayed characteristic structures of mammalian TGF-β ligands that were unique to the inhibin-β chain, monomer of activin. A phylogenetic analysis revealed the high degree of conservation with TGF-β molecules from trematode species. Interestingly, the sequence of amino acid in the active domain of FgTLM was completely identical to FhTLM from F. hepatica. FgTLM expressed throughout the lifecycle of F. gigantica but was highly expressed in developmental active stages. The dynamics of expression of FgTLM during the developmental stages of F. gigantica was comparable to the pattern of TGF-β expression in F. hepatica. Our findings demonstrated that FgTLM exhibits a high level of similarity to FhTLM in the context of both amino acid sequence and the life stage expression patterns. These similarities underline the possibility that the FgTLM molecule might have the same properties and functions as FhTLM in biological processes of the immature parasites and host immune evasion. Consequently, the specific biological functions of FgTLM on either parasite or relevant hosts need to be defined experimentally.

Fascioliasis is an important parasitic zoonosis with an estimated annual economic loss at more than US$3 billion in animals and infection risk in more than 180 million people worldwide. Given the economic and public health significance of this trematode, a periodical evaluation of its prevalence and the associated risk factors as well as the evolutionary relatedness is needed. Here, 1560 cattle and 1630 goat livers were examined for the presence of adult Fasciola among animals slaughtered in slaughterhouses of at Assiut and Sohag Governorates, Upper Egypt. Molecular characterization and phylogenetic relationships were determined based on the second internal transcribed spacer (ITS-2) of nuclear ribosomal DNA (rDNA). The overall prevalence of fasciolosis was based on morphological identification of the recovered Fasciola adult worms and the prevalence was 5.1% and 3.5% among cattle and goats, respectively. Though the age, gender, and housing system significantly affected the disease in cattle, none of these variables had a significant impact on goat fasciolosis. Nonetheless, the sampled goats were found at increased risk of being infected with Fasciola hepatica as the age increases and when the winter season emerges. Phylogenetic analyses showed that both Fasciola gigantica and Fasciola hepatica sequenced in this study had a common ancestor and they fall in one clade with several previously reported Egyptian and worldwide fasciolae from animals and humans. This study demonstrates that the disease is currently circulating among animals in Assiut and Sohag Governorates that warrants the urgent need for application of the appropriate control measures as well as evaluating the possible ongoing zoonotic burden in people residing such areas.

The purpose of the research: is to conduct a comparative assessment of the infection of cattle with helminths and the structure of helminthic complexes in various natural provinces of Gorny Altai.Materials and methods. Coproovolarvoscopic examinations of about 2.4 thousand of cattle from various farms of the Altai Republic were carried out. Based on their results, the animal’s infection (the prevalence of infection, PI, %) with helminths in various natural provinces was characterized. The structural indices of various taxa of helminths (SI) have been calculated, which reflect their weight in the structure of the parasite complex.Results and discussion. Cattle in the Altai Republic are mostly infected with nematodes (51.4%). The indicators of the animal infection with trematodes and cestodes were significantly lower and amounted to 17.4 and 5.2% respectively. Nematodes dominate in the structure of animal helminthocenosis in various provinces. Their total SI varies from 66.8 to 76.8. The classes of trematodes and cestodes account for 8.8–26.3 and 4.5–14.4 respectively. The maximum SI was registered in Strongylata of the digestive tract (45.2), the subdominant position is occupied by trematodes: Dicrocelium sp. (SI – 13.2) and Fasciola hepatica (SI – 11.5). Moniezia sp. SI was quite low and amounted to 4.7.

The only drug effective against the infection caused byThe present review focuses on the evidence of TCBZ for the treatment of fascioliasis. For acute fascioliasis, there is a lack of studies to measure the presence of eggs of Fasciola in stool samples on the follow-up after initial TCBZ treatment. For chronic fascioliasis, WHO recommends a single oral dose of TCBZ 10 mg/kg whereas CDC recommends two doses of TCBZ 10 mg/kg 12 h apart. Incremental number of treatment failures have been documented worldwide. There are currently no therapeutic alternatives for the treatment of fascioliasis in humans.Most cases of human fascioliasis are successfully treated with TCBZ, but some continue excreting eggs in the stools despite 1-2 standard of care regimens of TCBZ. A precise regimen is unclear for those patients who fail the initial treatment with TCBZ. Further clinical trials are needed to address the possible TCBZ emerging resistance.