Liver fluke infection of livestock causes economic losses of over US$ 3 billion worldwide per annum. The disease is increasing in livestock worldwide and is a re-emerging human disease. There are currently no commercial vaccines, and only one drug with significant efficacy against adult worms and juveniles. A liver fluke vaccine is deemed essential as short-lived chemotherapy, which is prone to resistance, is an unsustainable option in both developed and developing countries. Protein superfamilies have provided a number of leading liver fluke vaccine candidates. A new form of glutathione transferase (GST) family, Sigma class GST, closely related to a leading Schistosome vaccine candidate (Sm28), has previously been revealed by proteomics in the liver fluke but not functionally characterised. In this manuscript we show that a purified recombinant form of the F. hepatica Sigma class GST possesses prostaglandin synthase activity and influences activity of host immune cells. Immunocytochemistry and western blotting have shown the protein is present near the surface of the fluke and expressed in eggs and newly excysted juveniles, and present in the excretory/secretory fraction of adults. We have assessed the potential to use F. hepatica Sigma class GST as a vaccine in a goat-based vaccine trial. No significant reduction of worm burden was found but we show significant reduction in the pathology normally associated with liver fluke infection. We have shown that F. hepatica Sigma class GST has likely multi-functional roles in the host-parasite interaction from general detoxification and bile acid sequestration to PGD synthase activity. Combating neglected parasitic diseases is of paramount importance to improve the health of human populations and/or their domestic animals. Uncovering key roles in host-parasite interactions may support the vaccine potential portfolio of a parasite protein. Fasciola hepatica causes global disease in humans and their livestock but no commercial vaccines are available. Members of the Sigma class glutathione transferase (GST) family have long been highlighted as vaccine candidates towards parasitic flatworms. To this end, a Sigma class GST is currently undergoing phase II clinical trials to protect against infection from the schistosomes. In this study we characterise the protein from F. hepatica following four work pathways that 1) confirm its designation as a Sigma class GST using substrate profiling, 2) assess prostaglandin synthase activity and its effect on host immune cells, 3) localise the Sigma GST within adult fluke and between ontogenic stages and 4) measure its potential as a vaccine candidate. The work presented here shows F. hepatica Sigma class GST to have key host-parasite roles and we suggest, warrants further investigation for inclusion into vaccine formulations.

Internal parasites are one of the main causes of health threats in livestock production, especially in extensive livestock farming. Despite the environmental toxic effects (loss of dung beetles, biodiversity, and other issues) and resistance phenomenon derived from their prolonged use, anti-parasitic chemical pharmaceuticals are frequently used, even in organic farming. Such a situation within the context of climate change requires urgent exploration of alternative compounds to solve these problems and apparent conflicts between organic farming objectives regarding the environment, public health, and animal health. This review is focused on some plants (Artemisia spp., Cichorium intybus L., Ericaceae family, Hedysarum coronarium L., Lotus spp., Onobrychis viciifolia Scop.) that are well known for their antiparasitic effect, are voluntarily grazed and ingested, and can be spontaneously found or cultivated in southern Europe and other regions with a Mediterranean climate. The differences found between effectiveness, parasite species affected, in vitro/in vivo experiments, and active compounds are explored. A total of 87 papers where antiparasitic activity of those plants have been studied are included in this review; 75% studied the effect on ruminant parasites, where gastrointestinal nematodes were the parasite group most studied (70%), and these included natural (31%) and experimental (37%) infections.