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Summary Fasciola hepatica is a trematode parasite with a global distribution, which is responsible for considerable disease and production losses in a range of food producing species. It is also identified by WHO as a re‐emerging neglected tropical disease associated with endemic and epidemic outbreaks of disease in human populations. In Europe, F. hepatica is mostly associated with disease in sheep, cattle and goats. This study reviews the most recent advances in our understanding of the transmission, diagnosis, epidemiology and the economic impact of fasciolosis. We also focus on the impact of the spread of resistance to anthelmintics used to control F. hepatica and consider how vaccines might be developed and applied in the context of the immune‐modulation driven by the parasite. Several major research gaps are identified which, when addressed, will contribute to providing focussed and where possible, bespoke, advice for farmers on how to integrate stock management and diagnosis with vaccination and/or targeted treatment to more effectively control the parasite in the face of increasing the prevalence of infection and spread of anthelmintic resistance that are likely to be exacerbated by climate change.

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BackgroundPersistence of gastrointestinal nematode (GIN) infection and the related control methods have major impacts on the sheep industry worldwide. Based on the information generated with the Illumina OvineSNP50 BeadChip (50 K chip), this study aims at confirming quantitative trait loci (QTL) that were previously identified by microsatellite-based genome scans and identifying new QTL and allelic variants that are associated with indicator traits of parasite resistance in adult sheep. We used a commercial half-sib population of 518 Spanish Churra ewes with available data for fecal egg counts (FEC) and serum levels of immunoglobulin A (IgA) to perform different genome scan QTL mapping analyses based on classical linkage analysis (LA), a combined linkage disequilibrium and linkage analysis (LDLA) and a genome-wide association study (GWAS).ResultsFor the FEC and IgA traits, we detected a total of three 5 % chromosome-wise significant QTL by LA and 63 significant regions by LDLA, of which 13 reached the 5 % genome-wise significance level. The GWAS also revealed 10 significant SNPs associated with IgAt, although no significant associations were found for LFEC. Some of the significant QTL for LFEC that were detected by LA and LDLA on OAR6 overlapped with a highly significant QTL that was previously detected in a different half-sib population of Churra sheep. In addition, several new QTL and SNP associations were identified, some of which show correspondence with effects that were reported for different populations of young sheep. Other significant associations that did not coincide with previously reported associations could be related to the specific immune response of adult animals.DiscussionOur results replicate a FEC-related QTL located on OAR6 that was previously reported in Churra sheep and provide support for future research on the identification of the allelic variant that underlies this QTL. The small proportion of genetic variance explained by the detected QTL and the large number of functional candidate genes identified here are consistent with the hypothesis that GIN resistance/susceptibility is a complex trait that is not determined by individual genes acting alone but rather by complex multi-gene interactions. Future studies that combine genomic variation analysis and functional genomic information may help elucidate the biology of GIN disease resistance in sheep.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-016-0182-4) contains supplementary material, which is available to authorized users.

20 21In this study critical thresholds are defined for storm impacts along the Spanish coast of the 22Gulf of Cádiz. The thresholds correspond to the minimum wave and tide conditions 23 necessary to produce significant morphological changes on beaches and dunes and/or 24 damage on coastal infrastructure or human occupation. 25Threshold definition was performed by computing theoretical sea-level variations during 26 storms and comparing them with the topography of the study area and the location of 27 infrastructure at a local level. Specifically, the elevations of the berm, the dune foot and the 28 entrance of existing washovers were selected as threshold parameters. The total sea-level 29 variation generated by a storm event was estimated as the sum of the tidal level, the wind-30 induced setup, the barometric setup and the wave-associated sea-level variation (wave setup 31 and runup), assuming a minimum interaction between the different processes. These 32 components were calculated on the basis of parameterisations for significant wave height 33 Furthermore, records of real damage in coastal infrastructure caused by storms were 42 collected at a regional level from newspapers and other bibliographic sources and compared 43 with the hydrodynamic conditions that caused the damage. These were extracted from the 44 hindcast database of the HIPOCAS project, including parameters such as storm duration, 45 mean and maximum wave height and wave direction. Results show that the duration of the 46 storm is not critical in determining the occurrence of coastal damage in the regional study 47 area. This way, the threshold would be defined as a duration ≥30 hours, with moderate 48 average wave height (≥3.3 m) and high maximum wave height (≥4.1 m) approaching from 49 the 3rd and 4th quadrants, during mean or spring tide situation. 50The calculated thresholds constitute snapshots of risk conditions within a certain time 51 framework. Beach and nearshore zones are extremely dynamic, and also the characteristics 52 of occupation on the coast change over time, so critical storm thresholds will change 53 accordingly and therefore will need to be updated. representing the world's foremost coastal natural hazard in terms of property damage and 67 lives lost (Murty, 1988). Storm events can cause coastal erosion, coastal flooding, damage to 68 infrastructure and other undesirable effects, thus creating the need for scientific tools, such 69 as vulnerability maps, predictive techniques or warning systems, that can help to prevent 70 these negative consequences. The development of such tools requires an adequate 71 understanding of both the hydrodynamic processes acting during a storm, and the coastal 72 response to this hydrodynamic forcing. 73In general terms the impact of storms on the coast is determined by the cumulative effect of 74 large-, meso-and local-scale processes. Barotropic forcing is the main large-scale process 75 affecting short-term sea-level variations. The spatial distribution of atmospheric pressure 76 ...

Neglected Tropical Diseases (NTD) represent a serious threat to humans, especially for those living in poor or developing countries. Almost one-sixth of the world population is at risk of suffering from these diseases and many thousands die because of NTDs, to which we should add the sanitary, labor and social issues that hinder the economic development of these countries. Protozoan-borne diseases are responsible for more than one million deaths every year. Visceral leishmaniasis, Chagas disease or sleeping sickness are among the most lethal NTDs. Despite not being considered an NTD by the World Health Organization (WHO), malaria must be added to this sinister group. Malaria, caused by the apicomplexan parasite Plasmodium falciparum, is responsible for thousands of deaths each year. The treatment of this disease has been losing effectiveness year after year. Many of the medicines currently in use are obsolete due to their gradual loss of efficacy, their intrinsic toxicity and the emergence of drug resistance or a lack of adherence to treatment. Therefore, there is an urgent and global need for new drugs. Despite this, the scant interest shown by most of the stakeholders involved in the pharmaceutical industry makes our present therapeutic arsenal scarce, and until recently, the search for new drugs has not been seriously addressed. The sources of new drugs for these and other pathologies include natural products, synthetic molecules or repurposing drugs. The most frequent sources of natural products are microorganisms, e.g., bacteria, fungi, yeasts, algae and plants, which are able to synthesize many drugs that are currently in use (e.g. antimicrobials, antitumor, immunosuppressants, etc.). The marine environment is another well-established source of bioactive natural products, with recent applications against parasites, bacteria and other pathogens which affect humans and animals. Drug discovery techniques have rapidly advanced since the beginning of the millennium. The combination of novel techniques that include the genetic modification of pathogens, bioimaging and robotics has given rise to the standardization of High-Performance Screening platforms in the discovery of drugs. These advancements have accelerated the discovery of new chemical entities with antiparasitic effects. This review presents critical updates regarding the use of High-Throughput Screening (HTS) in the discovery of drugs for NTDs transmitted by protozoa, including malaria, and its application in the discovery of new drugs of marine origin.

To determine whether purified Ascaris suum haemoglobin (AsHb) is a suitable vaccine candidate for the control of Ascaris infections, pigs were vaccinated with AsHb in combination with QuilA adjuvant and challenged with A. suum eggs. The number of liver lesions and worms in the intestine was assessed on day 14, 28 and 56 post-infection (p.i.). No significant differences were found in the number of worms recovered between vaccinated and control pigs on any of these days. However, significantly more white spots were counted on the livers of vaccinated pigs on day 14 (+86%) and day 28 (+118%) p.i. compared with nonvaccinated controls. To investigate whether the increased immunoreactivity against the liver stage L3s in vaccinated pigs was triggered by and directed against AsHb, the transcription and expression of AsHb in this larval life stage was analysed by RT-PCR and immunoblotting. The results showed that neither the AsHb transcript nor protein was detectable in freshly hatched L3. However, the immunoblot analysis showed that vaccination with AsHb resulted in the production of antibodies binding to several other antigens of the L3, suggesting that these might be involved in the increased white spot development.

The liver fluke Fasciola hepatica is a worldwide distributed trematode parasite of great veterinary importance. In Spain, the prevalence of the infection is up to 56% in sheep. Its control is mainly based on the use of anthelmitics, although some resistant populations have been described. Genetic studies of the genus Fasciola have been focused on the 28S ribosomal deoxyribonucleic acid (rDNA) gene, with no intraspecific variations and a few interspecific nucleotide differences. We have designed a specific polymerase chain reaction to amplify and sequence a 510-bp-long fragment of the gene to characterize several F. hepatica ovine isolates from the northwest of Spain. All the isolates rendered the expected results on the agarose gel, while sequencing revealed some differences in the 34 site. The anthelmintic-resistant specimens showed the same nucleotide differing of the sensitive ones. Comparing to other studies, our results conclude that there are some genetic variations in F. hepatica (at the level of the 28S rDNA), including heterozygous specimens. In conclusion, a genetic heterogeneity has been found in the F. hepatica populations of ovine origin in the northwest of Spain, using an assay that could be useful for further epidemiology and characterization studies.