Incidence of anthelmintic resistance in cattle farms in Northern Germany – first results

Anthelmintic resistance (AR) is an increasing problem worldwide especially for small ruminants and it is also rising in cattle. To maintain the efficacy of anthelmintics is an important objective. The current project aims at the investigation of the current efficacy of macrocyclic lactone anthelmintics for strongylid nematodes in first season grazing (FSG) calves in Northern Germany. On 8 participating farms in Northern Germany faecal egg count reduction tests (FECRT) with ivermectin (IVM) were performed. On 3 farms the efficacy of IVM was found to be ≤90% and on only 4 farms it was > 95% at 14 days post treatment (d.p.t.). Only 2 farms showed a reduction ≥ 95% at 21 d.p.t.. This survey reveals a rising problem of AR. The problem of drug resistance places the welfare of animals at risk. In organic farming, without a preventive treatment, livestock may harbour high worm counts. Therefore it is necessary to maintain powerful anthelmintic drugs to guarantee the welfare of animals that need salvage treatment. To investigate the AR problem in cattle more surveys with different anthelmintic drug classes are urgently needed

Structure and Activation Mechanism of the Drosophila Initiator Caspase Dronc

Activation of an initiator caspase is essential to the execution of apoptosis. The molecular mechanisms by which initiator caspases are activated remain poorly understood. Here we demonstrate that the autocatalytic cleavage of Dronc, an important initiator caspase in Drosophila, results in a drastic enhancement of its catalytic activity in vitro. The autocleaved Dronc forms a homodimer, whereas the uncleaved Dronc zymogen exists exclusively as a monomer. Thus the autocatalytic cleavage in Dronc induces its stable dimerization, which presumably allows the two adjacent monomers to mutually stabilize their active sites, leading to activation. Crystal structure of a prodomain-deleted Dronc zymogen, determined at 2.5 Å resolution, reveals an unproductive conformation at the active site, which is consistent with the observation that the zymogen remains catalytically inactive. This study revealed insights into mechanism of Dronc activation, and in conjunction with other observations, suggests diverse mechanisms for the activation of initiator caspases

Untersuchung zum Vorkommen von Anthelminthikaresistenzen in norddeutschen Rinderbeständen

Anthelmintic resistance has become a serious problem worldwide especially for small ruminants but it is also rising for cattle. The sustainability to maintain the efficacy of anthelmintics is an important objective. Furthermore, reduction of anthelmintic use is desired to assure safe and high quality food. Therefore targeted selective treatment (TST) systems should be developed. Through TST the use of anthelmintics can be reduced and selection pressure on sensible endoparasite isolates decreases. The current project aims at 1st the investigation of the current efficacy of macrocyclic lac-tone anthelmintics in first season grazing cattle in Northern Germany and 2nd to com-paratively investigate different approaches to TST such as body weight, body condition-ing scores (BCS) and egg output (EPG)

Efficacy of imidacloprid 10%/moxidectin 1% spot-on formulation (Advocate®) in the prevention and treatment of feline aelurostrongylosis

Background: In three randomized, controlled laboratory efficacy studies, the efficacy in the prevention of patent infections of a topical combination of imidacloprid 10%/moxidectin 1% (Advocate® spot-on formulation for cats, Bayer Animal Health GmbH) against larval stages and immature adults of Aelurostrongylus abstrusus, as well as the treatment efficacy of a single or three monthly treatments against adult A. abstrusus, were evaluated. Methods: Cats were experimentally inoculated with 300–800 third-stage larvae (L3). Each group comprised 8 animals and the treatment dose was 10 mg/kg bodyweight (bw) imidacloprid and 1 mg/kg bw moxidectin in each study. Prevention of the establishment of patent infections was evaluated by two treatments at a monthly interval at three different time points before and after challenge infection. Curative efficacy was tested by one or three treatments after the onset of patency. Worm counts at necropsy were used for efficacy calculations. Results: In Study 1, the control group had a geometric mean (GM) of 28.8 adult nematodes and the single treatment group had a GM of 3.4 (efficacy 88.3%). In Study 2, the control group had a GM of 14.3, the prevention group had a GM of 0 (efficacy 100%), while the treatment group had a GM of 0.1 (efficacy 99.4%). In Study 3, the GM worm burden in the control group was 32.6 compared to 0 in all three prevention groups (efficacy 100% for all of those groups). Conclusions: The monthly administration of Advocate® reliably eliminated early larval stages and thereby prevented lung damage from and patent infections with A. abstrusus in cats. Regarding treatment, a single application of Advocate® reduced the worm burden, but it did not sufficiently clear the infection. In contrast, three monthly treatments were safe and highly efficacious against A. abstrusus

Targeted Selective Treatment (TST) bei Rindern zur Reduzierung der Resistenzbildung bei Endoparasiten

Infektionen mit Endorparasiten, insbesondere mit Magen-Darm-Strogyliden (MDS), sind oft ein limitierender Faktor in der Entwicklung und Produktivität von erststömmrigen Rindern. Diese Infektionen haben somit große wirtschaftliche Bedeutung. Die bisher weitverbreitet durchgeführte strategische Entwurmung (planmäßiger Einsatz von Medikamenten) ganzer Herden sollte aus verschiedenen Gründen angepasst werden

Untersuchungen zur Wirksamkeit von Anthelminthika bei erstsömmrigen Rindern in Europa

Resistance to anthelmintics is a threat to several animal industries world wide. Nevertheless, the use of effective anthelmintics to control nematode infections in cattle still remains irreplaceable. Anthelmintic resistance in cattle has been reported in New Zealand, North and South America and England but so far not in Europe. To be able to determine the extent of anthelmintic resistance in nematodes of farm animals and to monitor the success of any resistance management requires reliable tests for the detection of anthelmintic resistance. One of the objectives of PARASOL, a European Framework 6 funded project, is to produce standard operating procedures for the running of a faecal egg count reduction test (FECRT). Standardized procedures for the FECRT have been developed and surveys with injectable ivermectin were then performed in Germany, Sweden and Belgium in 2006 and 2007. Additional tests using benzimidazoles were performed in Sweden and Germany in 2007. Furthermore, some of the refractory strains will be isolated to test whether the phenomena observed in the field was due to the evolution of anthelmintic resistance

A quantitative evaluation of the extent of fluralaner uptake by ticks (Ixodes ricinus, Ixodes scapularis) in fluralaner (Bravecto TM ) treated vs. untreated dogs using the parameters tick weight and coxal index

Background Fluralaner is a new antiparasitic drug that was recently introduced as Bravecto TM chewable tablets for the treatment of tick and flea infestations in dogs. Most marketed tick products exert their effect via topical application and contact exposure to the parasite. In contrast, Bravecto TM delivers its acaricidal activity through systemic exposure. Tick exposure to fluralaner occurs after attachment to orally treated dogs, which induces a tick-killing effect within 12 h. The fast onset of killing lasts over the entire treatment interval (12 weeks) and suggests that only marginal uptake by ticks is required to induce efficacy. Three laboratory studies were conducted to quantify the extent of uptake by comparison of ticks’ weight and coxal index obtained from Bravecto TM -treated and negative-control dogs. Methods Three studies were conducted using experimental tick infestation with either Ixodes ricinus or Ixodes scapularis after oral administration of fluralaner to dogs. All studies included a treated (Bravecto TM chewable tablets, MSD Animal Health) and a negative control group. Each study had a similar design for assessing vitality and weighing of ticks collected from dogs of both groups. Additionally, in one study the coxal index (I. ricinus) was calculated as a ratio of tick’s ventral coxal gap and dorsal width of scutum. Tick weight data and coxal indices from Bravecto TM -treated and negative-control groups were compared via statistical analysis. Results Ticks collected from Bravecto TM -treated dogs weighed significantly less (p ≤ 0.0108) than ticks collected from negative-control dogs, and their coxal index was also significantly lower (p < 0.0001). The difference in tick weights was demonstrated irrespective of the tick species investigated (I. ricinus, I. scapularis). At some assessments the mean tick weights of Bravecto TM -treated dogs were significantly lower than those of unfed pre-infestation (baseline) ticks. The demonstrated tick-killing efficacy was in the range of 94.6 – 100 %. Conclusions Tick weights and coxal indices confirm that a minimal uptake results in a sufficient exposure of ticks to fluralaner (Bravecto TM ) and consequently in a potent acaricidal effect

Substitutions in the redox-sensing PAS domain of the NifL regulatory protein define an inter-subunit pathway for redox signal transmission

The Per-ARNT-Sim (PAS) domain is a conserved a/ß fold present within a plethora of signalling proteins from all kingdoms of life. PAS domains are often dimeric and act as versatile sensory and interaction modules to propagate environmental signals to effector domains. The NifL regulatory protein from Azotobacter vinelandii senses the oxygen status of the cell via an FAD cofactor accommodated within the first of two amino-terminal tandem PAS domains, termed PAS1 and PAS2. The redox signal perceived at PAS1 is relayed to PAS2 resulting in conformational reorganization of NifL and consequent inhibition of NifA activity. We have identified mutations in the cofactor-binding cavity of PAS1 that prevent 'release' of the inhibitory signal upon oxidation of FAD. Substitutions of conserved ß-sheet residues on the distal surface of the FAD-binding cavity trap PAS1 in the inhibitory signalling state, irrespective of the redox state of the FAD group. In contrast, substitutions within the flanking A'a-helix that comprises part of the dimerization interface of PAS1 prevent transmission of the inhibitory signal. Taken together, these results suggest an inter-subunit pathway for redox signal transmission from PAS1 that propagates from core to the surface in a conformation-dependent manner requiring a flexible dimer interface

Entwicklung eines Serum- und Milch-ELISAs zum Nachweis der Infektion mit Magen-Darm-Strongyliden bei Ziegen

Grazing goats are naturally infected with gastrointestinal nematodes which are an important cause of diseases and economic losses. Targeted selective treatment (TST) is a possibility to avoid spreading of anthelmintic resistances and to reduce the use of anthelmintics. The aim of this study is the development of an goat-milk ELISA for the detection of infection with T. circumcincta in order to provide a monitoring tool for herd infection levels. Therefore a group of kids were artificially infected, blood and faecal samples were taken over a period of 10 weeks. Additional a herd of milk goats,kept on pasture at the experimental farm were used to obtain milk, blood and faecal samples regularly