Modified Hederagenin Derivatives Demonstrate Ex Vivo Anthelmintic Activity against Fasciola hepatica.

Infection with Fasciola hepatica (liver fluke) causes fasciolosis (or fascioliasis) and poses a considerable economic as well as welfare burden to both the agricultural and animal health sectors. Here, we explore the ex vivo anthelmintic potential of synthetic derivatives of hederagenin, isolated in bulk from Hedera helix. Thirty-six compounds were initially screened against F. hepatica newly excysted juveniles (NEJs) of the Italian strain. Eleven of these compounds were active against NEJs and were selected for further study, using adult F. hepatica derived from a local abattoir (provenance unknown). From these eleven compounds, six demonstrated activity and were further assessed against immature liver flukes of the Italian strain. Subsequently, the most active compounds (n = 5) were further evaluated in ex vivo dose response experiments against adult Italian strain liver flukes. Overall, MC042 was identified as the most active molecule and the EC50 obtained from immature and adult liver fluke assays (at 24 h post co-culture) are estimated as 1.07 µM and 13.02 µM, respectively. When compared to the in vitro cytotoxicity of MDBK bovine cell line, MC042 demonstrated the highest anthelmintic selectivity (44.37 for immature and 3.64 for adult flukes). These data indicate that modified hederagenins display properties suitable for further investigations as candidate flukicides.

A survey of gastrointestinal parasites in dogs illegally entering the UK (2015-2017).

Background: This study involving non-compliant, seized dogs entering the UK surveyed endoparasites detected in faecal samples. A focus was placed on taeniid infection as the detection of these tapeworms acts as a marker for failure of effective tapeworm treatment. Methods: Individual faecal samples taken from 65 dogs over a 24-month period were examined for helminth eggs, for protozoal oocysts and cysts, using a centrifugal flotation technique. Any sample presenting positive results for taeniid eggs had residual faeces examined using polymerase chain reaction to aid speciation of the tapeworm eggs. Additionally, a Baermann technique was used to assess faeces for lungworm larvae. Results: Patent endoparasite infection was detected in 27.7% of dog faecal samples. No sample was positive for lungworm larvae. Five dogs were co-infected with Isospora spp. and Toxocara canis. One dog sample was detected with taeniid eggs, identified as Taenia serialis. Conclusions: The taeniid-positive dog indicated that appropriate tapeworm treatment may not have occurred, reinforcing the risk to the UK of illegally imported dogs potentially introducing Echinococcus multilocularis infection.

Creation of a Pilot School Health Research Network in an English Education Infrastructure to Improve Adolescent Health and Well-Being: A Study Protocol.

Schools play a significant role in promoting health and well-being and the reciprocal links between health and educational attainment are well-evidenced. Despite recognition of the beneficial impact of school-based health improvement programmes, significant barriers to improving health and well-being within schools remain. This study pilots a School Health Research Network in the South West of England (SW-SHRN), a systems-based health intervention bringing together schools, academic health researchers and public health and/or education teams in local authorities to share knowledge and expertise to improve the health and well-being of young people. A maximum of 20 secondary schools will be recruited to the pilot SW-SHRN. All students in Years 8 (age 12-13) and 10 (age 14-15) will be invited to complete a health and well-being questionnaire, generating a cohort of approximately 5000 adolescents. School environment questionnaires will also be completed with each school to build a regional picture of existing school health policies and programmes. Each school will be provided with a report summarising data for their students benchmarked against data for all schools in the network. Quantitative analysis will model associations between health risk behaviours and mental health outcomes and a qualitative process evaluation will explore the feasibility and sustainability of the network. This study will create adolescent health data to help provide schools and local authorities with timely and robust information on the health and well-being of their students and help them to identify areas in which public health interventions may be required. SW-SHRN will also help public health professionals focus their resources in the areas most at need.

Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.

Control of liver fluke infections remains a significant challenge in the livestock sector due to widespread distribution of drug resistant parasite populations. In particular, increasing prevalence and economic losses due to infection with Fasciola hepatica is a direct result of drug resistance to the gold standard flukicide, triclabendazole. Sustainable control of this significant zoonotic pathogen, therefore, urgently requires the identification of new anthelmintics. Plants represent a source of molecules with potential flukicidal effects and, amongst their secondary metabolites, the diterpenoid abietic acids can be isolated in large quantities. In this study, nineteen (19) chemically modified abietic acid analogues (MC_X) were first evaluated for their anthelmintic activities against F. hepatica newly excysted juveniles (NEJs, from the laboratory-derived Italian strain); from this, 6 analogues were secondly evaluated for their anthelmintic activities against adult wild strain flukes. One analogue, MC010, was progressed further against 8-week immature- and 12-week mature Italian strain flukes. Here, MC010 demonstrated moderate activity against both of these intra-mammalian fluke stages (with an adult fluke EC50 = 12.97 µM at 72 h post culture). Overt mammalian cell toxicity of MC010 was inferred from the Madin-Darby bovine kidney (MDBK) cell line (CC50 = 17.52 µM at 24 h post culture) and demonstrated that medicinal chemistry improvements are necessary before abietic acid analogues could be considered as potential anthelmintics against liver fluke pathogens.