Acaricide resistance status of livestock ticks from East and West Africa and in vivo efficacy of acaricides to control them.

Through a collaborative effort across six Sub-Saharan African countries, using recognized international assessment techniques, 23 stocks of three tick species (Rhipicephalus microplus, Rhipicephalus appendiculatus and Amblyomma variegatum) of economic importance for rural small holder farming communities from East and West Africa were collected from cattle, and evaluated in in vitro larval packet tests (LPT). The results demonstrated medium to high resistance to chlorfenvinphos and amitraz across species. Rhipicephalus microplus demonstrated high level alpha-cypermethrin and cypermethrin resistance. Stocks of A. variegatum (West Africa) and R. appendiculatus (Uganda) demonstrated medium level ivermectin resistance. The four least susceptible stocks (East and West African R. microplus, A. variegatum and R. appendiculatus) were taken into in vivo controlled cattle studies where fipronil was found effective against West and East African R. microplus isolates although persistent efficacy failed to reach 90%. Cymiazole and cypermethrin, and ivermectin based acaricides were partially effective against R. microplus without persistent efficacy. Flumethrin spray-on killed A. variegatum within 72 h for up to 10 days posttreatment, however product application was directly to tick attachment sites, which may be impractical under field conditions. A flumethrin pour-on formulation on goats provided persistent efficacy against A. variegatum for up to one-month. Therapeutic control was achieved against R. appendiculatus through weekly spraying cattle with flumethrin, amitraz or combined cymiazole and cypermethrin. A fipronil pour-on product offered four-week residual control against R. appendiculatus (with slow onset of action). Few studies have assessed and directly compared acaricidal activity in vitro and in vivo. There was some discordance between efficacy indicated by LPT and in vivo results. This observation calls for more research into accurate and affordable assessment methods for acaricide resistance. No single active or product was effective against all three tick species, emphasising the need for the development of alternative integrated tick management solutions.

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.

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.

World Association for the Advancement of Veterinary Parasitology (WAAVP) second edition: Guideline for evaluating the efficacy of parasiticides against ectoparasites of ruminants.

This second edition guideline was prepared to assist in the planning, conduct and interpretation of studies to assess the efficacy of parasiticides against ectoparasites of ruminants. It provides updated information on the selection of animals, dosage determination, dosage confirmation and field studies, record keeping and result interpretation. This guideline is intended to assist investigators on how to conduct specific studies, to provide specific information for registration authorities involved in the decision-making process, to assist in the approval and registration of new ectoparasiticides, and to facilitate the worldwide adoption of standard procedures.

World Association for the Advancement of Veterinary Parasitology (W.A.A.V.P.) guidelines for studies evaluating the efficacy of parasiticides in reducing the risk of vector-borne pathogen transmission in dogs and cats.

These guidelines are intended to provide an in-depth review of current knowledge and assist the planning and implementation of studies for evaluating the efficacy of parasiticides in reducing transmission of vector-borne pathogens (VBPs) to dogs and cats. At present, the prevention of VBP transmission in companion animals is generally achieved through the administration of products that can repel or rapidly kill arthropods, thus preventing or interrupting feeding before transmission occurs. The present guidelines complement existing guidelines, which focus on efficacy assessment of parasiticides for the treatment, prevention and control of flea and tick infestations, but also give guidance for studies focused on other vectors (i.e. mosquitoes and phlebotomine sand flies). The efficacy of parasiticides in reducing VBP transmission can be evaluated through laboratory or field studies. As such, the present guidelines provide recommendations for these studies, representing a tool for researchers, pharmaceutical companies and authorities involved in the research, development and registration of products with claims for reducing VBP transmission in dogs and cats, respecting the overall principles of the 3Rs (replacement, reduction and refinement). Gaps in our current understanding of VBP transmission times are herein highlighted and the need for further basic research on related topics is briefly discussed.

An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni.

Two economically and biomedically important platyhelminth species, Fasciola hepatica (liver fluke) and Schistosoma mansoni (blood fluke), are responsible for the neglected tropical diseases (NTDs) fasciolosis and schistosomiasis. Due to the absence of prophylactic vaccines, these NTDs are principally managed by the single class chemotherapies triclabendazole (F. hepatica) and praziquantel (S. mansoni). Unfortunately, liver fluke resistance to triclabendazole has been widely reported and blood fluke insensitivity/resistance to praziquantel has been observed in both laboratory settings as well as in endemic communities. Therefore, the identification of new anthelmintics is necessary for the sustainable control of these NTDs in both animal and human populations. Here, continuing our work with phytochemicals, we isolated ten triterpenoids from the mature bark of Abies species and assessed their anthelmintic activities against F. hepatica and S. mansoni larval and adult lifecycle stages. Full 1H and 13C NMR-mediated structural elucidation of the two most active triterpenoids revealed that a tetracyclic steroid-like nucleus core and a lactone side chain are associated with the observed anthelmintic effects. When compared to representative mammalian cell lines (MDBK and HepG2), the most potent triterpenoid (700015; anthelmintic EC50s range from 0.7 µM-15.6 µM) displayed anthelmintic selectivity (selectivity indices for F. hepatica: 13 for newly excysted juveniles, 46 for immature flukes, 2 for mature flukes; selectivity indices for S. mansoni: 14 for schistosomula, 9 for immature flukes, 4 for adult males and 3 for adult females) and induced severe disruption of surface membranes in both liver and blood flukes. S. mansoni egg production, a process responsible for pathology in schistosomiasis, was also severely inhibited by 700015. Together, our results describe the structural elucidation of a novel broad acting anthelmintic triterpenoid and support further investigations developing this compound into more potent analogues for the control of both fasciolosis and schistosomiasis.

An electric-field representation of the harmonic XY model.

The two-dimensional harmonic XY (HXY) model is a spin model in which the classical spins interact via a piecewise parabolic potential. We argue that the HXY model should be regarded as the canonical classical lattice spin model of phase fluctuations in two-dimensional condensates, as it is the simplest model that guarantees the modular symmetry of the experimental systems. Here we formulate a lattice electric-field representation of the HXY model and contrast this with an analogous representation of the Villain model and the two-dimensional Coulomb gas with a purely rotational auxiliary field. We find that the HXY model is a spin-model analogue of a lattice electric-field model of the Coulomb gas with an auxiliary field, but with a temperature-dependent vacuum (electric) permittivity that encodes the coupling of the spin vortices to their background spin-wave medium. The spin vortices map to the Coulomb charges, while the spin-wave fluctuations correspond to auxiliary-field fluctuations. The coupling explains the striking differences in the high-temperature asymptotes of the specific heats of the HXY model and the Coulomb gas with an auxiliary field. Our results elucidate the propagation of effective long-range interactions throughout the HXY model (whose interactions are purely local) by the lattice electric fields. They also imply that global spin-twist excitations (topological-sector fluctuations) generated by local spin dynamics are ergodically excluded in the low-temperature phase. We discuss the relevance of these results to condensate physics.

Direct calculation of the critical Casimir force in a binary fluid.

We show that critical Casimir effects can be accessed through direct simulation of a model binary fluid passing through the demixing transition. We work in the semi-grand-canonical ensemble, in slab geometry, in which the Casimir force appears as the excess of the generalized pressure, P_{⊥}-nµ. The excesses of the perpendicular pressure, P_{⊥}, and of nµ, are individually of much larger amplitude. A critical pressure anisotropy is observed between forces parallel and perpendicular to the confinement direction, which collapses onto a universal scaling function closely related to that of the critical Casimir force.

Finite-size scaling of the magnetization probability density for the critical Ising model in slab geometry.

The magnetization probability density in d = 2 and 3 dimensional Ising models in slab geometry of volume [Formula: see text] is computed through Monte-Carlo simulation at the critical temperature and zero magnetic field. The finite-size scaling of this distribution and its dependence on the system aspect-ratio [Formula: see text]and boundary conditions are discussed. In the limiting case [Formula: see text] of a macroscopically large slab ([Formula: see text]) the distribution is found to scale as a Gaussian function for all tested system sizes and boundary conditions.

Classical topological order in kagome ice.

We examine the onset of classical topological order in a nearest neighbour kagome ice model. Using Monte Carlo simulations, we characterize the topological sectors of the ground state using a nonlocal cut measure which circumscribes the toroidal geometry of the simulation cell. We demonstrate that simulations which employ global loop updates that are allowed to wind around the periodic boundaries cause the topological sector to fluctuate, while restricted local loop updates freeze the simulation into one topological sector. The freezing into one topological sector can also be observed in the susceptibility of the real magnetic spin vectors projected onto the kagome plane. The ability of the susceptibility to distinguish between fluctuating and non-fluctuating topological sectors should motivate its use as a local probe of topological order in a variety of related systems.

Criterion for universality-class-independent critical fluctuations: example of the two-dimensional Ising model.

Order parameter fluctuations for the two-dimensional Ising model in the region of the critical temperature are presented. A locus of temperatures T(*) (L) and a locus of magnetic fields B(*) (L) are identified, for which the probability density function is similar to that for the two-dimensional XY model in the spin wave approximation. The characteristics of the fluctuations along these points are largely independent of universality class. We show that the largest range of fluctuations relative to the variance of the distribution occurs along these loci of points, rather than at the critical temperature itself and we discuss this observation in terms of intermittency. Our motivation is the identification of a generic form for fluctuations in correlated systems in accordance with recent experimental and numerical observations. We conclude that a universality-class-dependent form for the fluctuations is a particularity of critical phenomena related to the change in symmetry at a phase transition.