Rumen (Calicophoron/Paramphistomum spp.) and Liver Flukes (Fasciola hepatica) in Cattle—Prevalence, Distribution, and Impact of Management Factors in Germany

This study was carried out to determine the prevalence of rumen flukes on German cattle farms via the sedimentation technique, and to identify the rumen fluke species occurring in Germany. Additionally, the prevalence of patent Fasciola hepatica infections was determined. Furthermore, a short questionnaire was answered by the farmers. A prevalence of 5.5% and 9.5% was detected for rumen flukes and liver flukes, respectively. Coinfections occurred on 2.1% of farms. In northern Germany, the rumen fluke prevalence was higher than in southern Germany, while for liver fluke the distribution was reversed. Rumen flukes were mostly identified as Calicophoron daubneyi, but in four cases, sequencing revealed Paramphistomum leydeni for the first time in Germany. Grazing and feeding of fresh grass, as well as organic farming, were significantly associated with rumen and liver fluke occurrence. In contrast, suckler cow husbandry only had an influence on the occurrence of rumen flukes, but not liver flukes. Trematode eggs could be detected in both, farms with and without deworming. Since there were only a few studies about Paramphistomidosis in Germany, more attention should be paid to these parasitic diseases for animal welfare and animal health reasons.

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Characterisation of two calmodulin-like proteins from the liver fluke, Fasciola hepatica

Biological Chemistry ◽

10.1515/bc.2007.076 ◽

2007 ◽

Vol 388 (6) ◽

pp. 593-599 ◽

Cited By ~ 16

Author(s):

Sean L. Russell ◽

Neil V. McFerran ◽

Elizabeth M. Hoey ◽

Alan Trudgett ◽

David J. Timson

Keyword(s):

Metal Binding ◽

Metal Ion ◽

Liver Fluke ◽

Fasciola Hepatica ◽

Expression Vectors ◽

Metal Ion Binding ◽

Ion Sensing ◽

Calcium Magnesium ◽

Ion Binding Sites ◽

Liver Flukes

Abstract Calmodulin is a calcium ion-sensing signalling protein found in eukaryotics. Two calmodulin-like gene sequences were identified in an EST library from adult liver flukes. One codes for a protein (FhCaM1) homologous to mammalian calmodulins (98% identity), whereas the other protein (FhCaM2) has only 41% identity. These genes were cloned into expression vectors and the recombinant proteins were expressed in Escherichia coli. Gel shift assays showed that both proteins bind to calcium, magnesium and zinc ions. Homology models have been built for both proteins. As expected, FhCaM1 has a highly similar structure to other calmodulins. Although FhCaM2 has a similar fold, its surface charge is higher than FhCaM1. One of the potential metal ion-binding sites has lower metal-ion co-ordination capability, while another has an adjacent lysine residue, both of which may decrease the metal-binding affinity. These differences may reflect a specialised role for FhCaM2 in the liver fluke.

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In vitro and in vivo trematode models for chemotherapeutic studies

Parasitology ◽

10.1017/s0031182009991739 ◽

2009 ◽

Vol 137 (3) ◽

pp. 589-603 ◽

Cited By ~ 100

Author(s):

J. KEISER

Keyword(s):

Liver Fluke ◽

Fasciola Hepatica ◽

State Of The Art ◽

Parasitic Diseases ◽

Current State ◽

Food Borne ◽

Essential Components ◽

Discovery Pipeline

SUMMARYSchistosomiasis and food-borne trematodiases are chronic parasitic diseases affecting millions of people mostly in the developing world. Additional drugs should be developed as only few drugs are available for treatment and drug resistance might emerge. In vitro and in vivo whole parasite screens represent essential components of the trematodicidal drug discovery cascade. This review describes the current state-of-the-art of in vitro and in vivo screening systems of the blood fluke Schistosoma mansoni, the liver fluke Fasciola hepatica and the intestinal fluke Echinostoma caproni. Examples of in vitro and in vivo evaluation of compounds for activity are presented. To boost the discovery pipeline for these diseases there is a need to develop validated, robust high-throughput in vitro systems with simple readouts.

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Adenomatous Cholecystitis in Cattle with Chronic Fascioliasis

Veterinary Pathology ◽

10.1177/030098587401100502 ◽

1974 ◽

Vol 11 (5) ◽

pp. 407-416 ◽

Cited By ~ 1

Author(s):

A. H. Cheema

Keyword(s):

Liver Fluke ◽

Fasciola Hepatica ◽

Inflammatory Cells ◽

Fasciola Gigantica ◽

Clinical Effects ◽

Fibrous Stroma ◽

Submucosal Glands ◽

Glandular Structures ◽

Mitotic Figures ◽

Liver Flukes

Gall bladders from 80 mature cattle infested with liver flukes were shrunken; their walls were thickened; and mucosa was raised into rugose folds, nodules and papillary projections. All contained thick bile and mature liver flukes, predominantly Fasciola gigantica and to a lesser extent Fasciola hepatica. There was an adenomatous proliferation of the lining epithelium as well as of submucosal glands forming numerous tubuloalveolar structures and cysts lined with a uniform layer of columnar epithelium. Fibrous stroma was more than normal, and there was a mild to heavy infiltration by inflammatory cells. Some bladders had many enterochromaffin cells in the epithelium lining the glandular structures. Mitotic figures were rare, and there was no evidence of malignancy. The condition is inflammatory and hyperplastic and is believed to be common in cattle infested with liver fluke. The clinical effects of this condition have not been studied.

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Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola

10.1101/606772 ◽

2019 ◽

Author(s):

Maria João Gouveia ◽

Maria Y. Pakharukova ◽

Banchob Sripa ◽

Gabriel Rinaldi ◽

Paul J. Brindley ◽

...

Keyword(s):

Dna Adducts ◽

Liver Fluke ◽

Helminth Infection ◽

Fasciola Hepatica ◽

Clonorchis Sinensis ◽

Opisthorchis Viverrini ◽

International Agency ◽

Fresh Water Fish ◽

Liver Flukes ◽

Group 1

AbstractChronic infections with the flatworm parasites Opisthorchis viverrini, Clonorchis sinensis and Schistosoma haematobium are classified as group 1 biological carcinogens, i.e. definitive causes of cancer. In addition, we reported findings that support the inclusion of Opisthorchis felineus in this list of biological carcinogens. By contrast, infections with close phylogenetic relatives including Fasciola hepatica have not been associated with carcinogenesis. Earlier reports revealed of oxysterol metabolites of Opisthorchis liver fluke origin conjugated with DNA bases, suggesting that the generation of these DNA-adducts may underlie the mutagenicity and carcinogenicity of the infection with these food-borne pathogens. Here we employed liquid chromatography-mass spectrometry (LC-MS/MS) to investigate, compare and contrast spectrograms of soluble extracts from F. hepatica adult worms from bile ducts of cattle with those from O. viverrini and O. felineus from experimentally-infected hamsters. F. hepatica displayed a complex spectrophotometric profile. F. hepatica and Opisthorchis spp. shared several common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of these Opisthorchis species included far fewer compounds than F. hepatica. These findings support the postulate that oxysterol-like metabolites of parasite origin can initiate carcinogenesis and they point to a molecular basis for the inconsistencies among major groups of liver flukes concerning infection-induced malignancy.Author SummarySeveral species of trematodes are parasites of the human hepatobiliary tract. Infection with two of these flukes, Clonorchis sinsensis and Opisthorchis viverrini, fresh water fish-borne parasites that occur in East Asia is classified as group 1 carcinogens by the International Agency for Research on Cancer (IARC), i.e. definitive causes of cancer in humans. By contrast, infection with a different liver fluke, Fasciola hepatica, does not lead to malignant transformation of the biliary tract. Given the close phylogeny of all three parasites, this difference in carcinogenicity is intriguing and, if explained, likely of value in novel therapeutic approaches. The importance of the current findings is informative because they present a mass spectrometric analysis and catalog of the similarities and differences between fluke of the genus Opisthorchis and F. hepatica, potentially identifying carcinogenic metabolites of liver fluke origin. These metabolites can be expected to provide deeper understanding of helminth infection induced malignancy.

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Profiling G protein-coupled receptors of Fasciola hepatica identifies orphan rhodopsins unique to phylum Platyhelminthes

10.1101/207316 ◽

2017 ◽

Author(s):

Paul McVeigh ◽

Erin McCammick ◽

Paul McCusker ◽

Duncan Wells ◽

Jane Hodgkinson ◽

...

Keyword(s):

G Protein ◽

Liver Fluke ◽

Fasciola Hepatica ◽

Animal Health ◽

Neuromuscular Control ◽

Egg Laying ◽

G Protein Coupled Receptors ◽

High Confidence ◽

Parasitic Worm ◽

G Protein Coupled

AbstractG protein-coupled receptors (GPCRs) are established drug targets. Despite their considerable appeal as targets for next-generation anthelmintics, poor understanding of their diversity and function in parasitic helminths has thwarted progress towards GPCR-targeted anti-parasite drugs. This study facilitates GPCR research in the liver fluke, Fasciola hepatica, by generating the first profile of GPCRs from the F. hepatica genome. Our dataset describes 146 high confidence GPCRs, representing the largest cohort of GPCRs, and the most complete set of in silico ligand-receptor predictions, yet reported in any parasitic helminth. All GPCRs fall within the established GRAFS nomenclature; comprising three glutamate, 135 rhodopsin, two adhesion, five frizzled and one smoothened GPCR. Stringent annotation pipelines identified 18 highly diverged rhodopsins in F. hepatica that maintained core rhodopsin signatures, but lacked significant similarity with non-flatworm sequences, providing a new sub-group of potential flukicide targets. These facilitated identification of a larger cohort of 76 related sequences from available flatworm genomes, representing new members of existing groups of flatworm-specific rhodopsins. These receptors imply flatworm specific GPCR functions, and/or co-evolution with unique flatworm ligands, and could facilitate development of exquisitely selective anthelminthics. Ligand binding domain sequence conservation relative to deorphanised rhodopsins enabled high confidence ligand-receptor matching of seventeen receptors activated by acetylcholine, neuropeptide F/Y, octopamine or serotonin. RNA-Seq analyses showed expression of 101 GPCRs across various developmental stages, with the majority expressed most highly in the pathogenic intra-mammalian juvenile parasites. These data identify a broad complement of GPCRs in F. hepatica, including rhodopsins likely to have key functions in neuromuscular control and sensory perception, as well as frizzled and adhesion families implicated, in other species, in growth, development and reproduction. This catalogue of liver fluke GPCRs provides a platform for new avenues into our understanding of flatworm biology and anthelmintic discovery.Author SummaryFasciola spp. liver fluke are important veterinary pathogens with impacts on human and animal health, and food security, around the world. Liver fluke have developed resistance to most of the drugs used to treat them (flukicides). Since no vaccines exist, we need to develop new flukicides as a matter of urgency. Most anthelmintic drugs used to treat parasitic worm infections operate by impeding the functioning of their nerve and muscle. In flatworms, most nervous signals are received by a type of receptor called a G protein-coupled receptor (GPCR). Since GPCRs control important parasite functions (e.g. movement, egg-laying, feeding), they represent appealing targets for new flukicides, but have not yet been targeted as such. This work exploited the F. hepatica genome to determine the quantity and diversity of GPCRs in liver fluke. We found more GPCRs in the Fasciola genome than have been reported in any other parasitic worm. These findings provide a foundation that for researchers to determine the functions of these receptors, and which molecules/ligands they are activated by. These data will pave the way to exploring the potential of F. hepatica GPCRs as targets for new flukicides.

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Helminth infection-induced carcinogenesis: spectrometric insights from the liver flukes, Opisthorchis and Fasciola

Experimental Results ◽

10.1017/exp.2020.38 ◽

2020 ◽

Vol 1 ◽

Author(s):

Maria João Gouveia ◽

Maria Y. Pakharukova ◽

Gabriel Rinaldi ◽

Viatcheslav A. Mordvinov ◽

Paul J. Brindley ◽

...

Keyword(s):

Dna Adducts ◽

Molecular Basis ◽

Liver Fluke ◽

Helminth Infection ◽

Fasciola Hepatica ◽

Dna Bases ◽

Liquid Chromatography Mass Spectrometry ◽

Food Borne ◽

Liver Flukes ◽

Compare And Contrast

AbstractEarlier reports revealed oxysterol metabolites of Opisthorchis spp. liver fluke origin conjugated with DNA bases, suggesting that the generation of these DNA-adducts may underlie the mutagenicity and carcinogenicity of the infection with these food-borne pathogens. Here, we employed liquid chromatography-mass spectrometry to investigate, compare and contrast spectrograms of soluble extracts from Fasciola hepatica adult worms from bile ducts of cattle with those from O. viverrini and O.felineus from experimentally infected hamsters. F. hepatica and Opisthorchis spp. shared common compounds including oxysterol-like metabolites, bile acids and DNA-adducts, but the spectrometric profiles of F. hepatica included far fewer compounds than Opisthorchis species. These findings support the postulate that parasitic oxysterol-like metabolites could be related to carcinogenesis associated to infection and they point to a molecular basis for the differences among major groups of liver flukes concerning infection-induced malignancy.

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Equines as reservoirs of human fascioliasis: transmission capacity, epidemiology and pathogenicity in Fasciola hepatica-infected mules

Journal of Helminthology ◽

10.1017/s0022149x20000693 ◽

2020 ◽

Vol 94 ◽

Cited By ~ 1

Author(s):

R. Mera y Sierra ◽

G. Neira ◽

M.D. Bargues ◽

P.F. Cuervo ◽

P. Artigas ◽

...

Keyword(s):

High Altitude ◽

Disease Transmission ◽

Fasciola Hepatica ◽

Human Fascioliasis ◽

Infection Susceptibility ◽

Fluke Infection ◽

Endemic Areas ◽

Liver Flukes ◽

Liver Fluke Infection ◽

First Time

Abstract Fascioliasis is a zoonotic disease caused by liver flukes transmitted by freshwater lymnaeid snails. Donkey and horse reservoir roles have been highlighted in human endemic areas. Liver fluke infection in mules has received very limited research. Their role in disease transmission, epidemiological importance and Fasciola hepatica pathogenicity are studied for the first time. Prevalence was 39.5% in 81 mules from Aconcagua, and 24.4% in 127 from Uspallata, in high-altitude areas of Mendoza province, Argentina. A mean amount of 101,242 eggs/mule/day is estimated. Lymnaeids from Uspallata proved to belong to ribosomal DNA internal transcribed spacer (ITS) markers ITS-1 and ITS-2 combined haplotype 3C of Galba truncatula. These lymnaeids were experimentally susceptible to infection by egg miracidia from mules. Infectivity, number of cercariae/snail and shedding period fit the enhanced F. hepatica/G. truncatula transmission pattern at very high altitude. This indicates that the mule is able to maintain the F. hepatica cycle independently. Individual burdens of 20 and 97 flukes were found. Mule infection susceptibility is intermediate between donkey and horse, although closer to the latter. Anatomo-pathology and histopathology indicate that massive infection may cause mule death. Haematological value decreases of red blood cells, haemoglobin, leucocytes and lymphocytes indicate anaemia and strong immunosuppression. Strongly increased biochemical marker values indicate liver function alterations. The mule probably played a role in the past exchanges with Chile and Bolivia through Mendoza province. Evidence suggests that mules could contribute to the spread of both F. hepatica and G. truncatula to human fascioliasis-endemic areas in these countries.

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The excretory metabolism of the endoparasitic digenean Fasciola hepatica and its relationship to its respiratory metabolism

Parasitology ◽

10.1017/s0031182000077209 ◽

1970 ◽

Vol 60 (1) ◽

pp. 1-19 ◽

Cited By ~ 39

Author(s):

G. D. Moss

Keyword(s):

Lactic Acid ◽

Liver Fluke ◽

Fasciola Hepatica ◽

Hymenolepis Diminuta ◽

Respiratory Metabolism ◽

Sheep Liver Fluke ◽

Liver Flukes ◽

Meat Market ◽

Veterinary Officer

SUMMARYThe amounts of ammonia excreted by two endoparasitic flatworms have been compared and, weight for weight, the sheep liver fluke Fasciola hepatica produces ten times as much ammonia as the rat tapeworm Hymenolepis diminuta. This is thought to reflect a difference in diet, the fluke feeding mainly on the blood and tissue proteins of its host, and the tapeworm mainly on carbohydrates from the food materials in the gut of the host. However, the addition of glucose to the saline in which the flukes are cultured produces a marked decrease in the ammonia and an increase in the lactic acid excreted, suggesting that flukes are not obligatory protein feeders but that they may utilize carbohydrate when it is available. The relatively low production of lactic acid when proteins are being metabolized suggests that the flukes are producing an alternative end-product of respiratory metabolism. It is possible that this is the neutral lipid found in the excretory system of Fasciola and the possibility of an alternative metabolic pathway for the production of such lipid is discussed. The respiratory metabolism appears to be independent of oxygen, and the possible role of oxygen in other aspects of the metabolism of the fluke is discussed.I should like to express my sincere gratitude to Dr J. Llewellyn for his constant advice and encouragement during the course of this work and the preparation of the manuscript. I also thank Professor 0. E. Lowenstein, F.R.S., for allowing me the use of the facilities in his department during the tenure of an S.R.C. Research Studentship. Finally, my thanks are due to Mr E. Wilson, the Veterinary Officer at the Birmingham City Meat Market, for his constant co-operation in obtaining supplies of liver flukes.

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Developmental regulation and functional prediction of microRNAs in an expanded Fasciola hepatica miRNome

10.1101/2021.11.08.467689 ◽

2021 ◽

Author(s):

Caoimhe M Herron ◽

Anna O'Connor ◽

Emily Robb ◽

Erin McCammick ◽

Claire Hill ◽

...

Keyword(s):

Liver Fluke ◽

Fasciola Hepatica ◽

Developmental Regulation ◽

Life Stages ◽

Mirna Regulation ◽

Full Account ◽

Peripheral Blood Mononuclear ◽

Host Interactions ◽

Cathepsin Proteases ◽

First Time

The liver fluke, Fasciola hepatica, is a global burden on the wellbeing and productivity of farmed ruminants, and a zoonotic threat to human health. Despite the clear need for accelerated discovery of new drug and vaccine treatments for this pathogen, we still have a relatively limited understanding of liver fluke biology and host interactions. Noncoding RNAs, including micro (mi)RNAs, are key to transcriptional regulation in all eukaryotes, such that an understanding of miRNA biology can shed light on organismal function at a systems level. Four previous publications have reported up to 89 mature miRNA sequences from F. hepatica, but our data show that this does not represent a full account of this species miRNome. We have expanded on previous studies by sequencing, for the first time, miRNAs from multiple life stages (adult, newly excysted juvenile (NEJ), metacercariae and adult-derived extracellular vesicles (EVs)). These experiments detected an additional 61 high-confidence miRNAs, most of which have not been described in any other species, expanding the F. hepatica miRNome to 150 mature sequences. We used quantitative (q)PCR assays to provide the first developmental profile of miRNA expression across metacercariae, NEJ, adult and adult-derived Evs. The majority of miRNAs were expressed most highly in metacercariae, with at least six distinct expression clusters apparent across life stages. Intracellular miRNAs were functionally analysed to identify target mRNAs with inversely correlated expression in F. hepatica tissue transcriptomes, highlighting regulatory interactions with key virulence transcripts including cathepsin proteases, and neuromuscular genes that control parasite growth, development and motility. We also linked 28 adult-derived EV miRNAs with downregulation of 397 host genes in F. hepatica-infected transcriptomes from ruminant lymph node, peripheral blood mononuclear cell (PBMC) and liver tissue transcriptomes. These included genes involved in signal transduction, immune and metabolic pathways, adding to the evidence for miRNA-based immunosuppression during fasciolosis. These data expand our understanding of the F. hepatica miRNome, provide the first data on developmental miRNA regulation in this species, and provide a set of testable hypotheses for functional genomics interrogations of liver fluke miRNA biology.

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Epidemiology and economic loss of fasciolosis and dicrocoeliosis in Arak, Iran

Veterinary World ◽

10.14202/vetworld.2018.1648-1655 ◽

2018 ◽

pp. 1648-1655 ◽

Cited By ~ 5

Author(s):

Mohsen Arbabi ◽

Elnaz Nezami ◽

Hossein Hooshyar ◽

Mahdi Delavari

Keyword(s):

Liver Fluke ◽

Fasciola Hepatica ◽

Economic Loss ◽

Average Weight ◽

Parasitic Diseases ◽

Economic Perspective ◽

Financial Loss ◽

Variance Test ◽

Significance Level ◽

Financial Losses

Aim: Fasciolosis and dicrocoeliosis are important parasitic diseases worldwide, causing significant financial losses due to decrease in production and viscera condemnation in animals. We performed the current research to assess the epidemiology of these infections and determine their significance from an economic perspective in Arak, Iran. Materials and Methods: In total, we evaluated 118,463 sheep, 207,652 goats, and 43,675 cattle through necropsic analysis at the slaughterhouses. The average weight of sheep, goat, and cattle liver was 1000, 900, and 5000 g, respectively. The average price of liver in the market was 8 USD/kg. Moreover, the elimination of fundamental nutrients and vitamins was evaluated in infected livers. The prevalence of fasciolosis and dicrocoeliosis was determined. Analysis of variance test was applied for the statistical analysis, and the significance level was <0.05. Results: In total, Fasciola hepatica and Dicrocoelium dendriticum were detected in 0.56% (confidence interval CI, 0.54-0.59) and 0.77% (CI, 0.75-0.81) of the animals, respectively (p=0.1). The annual economic loss attributed to fasciolosis and dicrocoeliosis was 26698.4 and 30479.2 USD, respectively. The total economic loss was 10,880, 9079.2, and 10,520 dollars in sheep, cattle, and goats, respectively. On the other hand, financial loss resulting from fasciolosis was 7160, 6098.4, and 13,440 dollars in sheep, goats, and cattle, respectively. In addition, economic loss due to dicroceliasis was 10,880, 9079.2, and 10,520 dollars, respectively. Conclusion: Overall, fasciolosis and dicrocoeliosis in Iran always remain common in sheep, goats, and cattle that afford major economic loss of all the country also exist in Arak province. The present study could provide basic information for further examination of liver fluke infections in Iran.

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