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Schwabenheim, Germany

Meesters R.J.W.,University of Los Andes, Colombia | Hooff G.P.,MSD Animal Health Innovation GmbH

Dried blood spots have become a popular method in a variety of micro blood-sampling techniques in the life sciences sector, consequently competing with the field of conventional, invasive blood sampling by venepuncture. Dried blood spots are widely applied in numerous bioanalytical assays and have gained a significant role in the screening of inherited metabolic diseases, in PK and PD modeling; in the treatment and diagnosis of infectious diseases; and in therapeutic drug monitoring. Recent technological developments such as automation, online extraction, mass spectrometric direct analysis and also conventional dried blood spot bioanalysis, as well as future developments in dried blood spot bioanalysis are highlighted and presented in this article. © 2013 Future Science Ltd. Source

Olsen A.S.,University of Southern Denmark | Warrass R.,MSD Animal Health Innovation GmbH | Douthwaite S.,University of Southern Denmark
Journal of Antimicrobial Chemotherapy

Objectives: To determine how resistance to macrolides is conferred in field isolates of Pasteurella multocida and Mannheimia haemolytica that lack previously identified resistance determinants for rRNA methylation, efflux and macrolide-modifying enzymes. Methods: Isolates of P. multocida and M. haemolytica identified as being highly resistant (MICs >64 mg/L) to the macrolides erythromycin, gamithromycin, tilmicosin, tildipirosin and tulathromycin were screened by multiplex PCR for the previously identified resistance genes erm(42), msr(E) and mph(E). Strains lacking these determinants were analysed by genome sequencing and primer extension on the rRNAs. Results: Macrolide resistance in one M. haemolytica isolate was conferred by the 23S rRNA mutation A2058G; resistance in three P. multocida isolates were caused by mutations at the neighbouring nucleotide A2059G. In each strain, all six copies of the rrn operons encoded the respective mutations. There were no mutations in the ribosomal protein genes rplD or rplV, and no other macrolide resistance mechanism was evident. Conclusions: High-level macrolide resistance can arise from 23S rRNA mutations in P. multocida and M. haemolytica despite their multiple copies of rrn. Selective pressures from exposure to different macrolide or lincosamide drugs presumably resulted in consolidation of either the A2058G or the A2059G mutation. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. Source

Walther F.M.,Merck Animal Health | Allan M.J.,MSD Animal Health Innovation GmbH | Roepke R.K.A.,MSD Animal Health Innovation GmbH
Parasites and Vectors

Background: Fluralaner is a novel systemic ectoparasiticide for cats providing immediate and persistent flea- and tick-control after a single topical dose. Emodepsid and praziquantel are routinely used to control intestinal worm infections in cats. The safety of concurrent use of fluralaner and a commercially available emodepsid-praziquantel combination topical solution was investigated using topical administrations at the maximum recommended dose rates. Findings: Few mild and transient clinical findings like erythema at the administration site and single incidences of salivation or vomiting were observed. All of which were consistent with the individual product leaflets. There were no findings suggesting an increased safety risk associated with the concurrent treatment of cats with fluralaner and emodepsid-praziquantel. Conclusions: Concurrent treatment with fluralaner, emodepsid and praziquantel is well tolerated in cats. © 2016 The Author(s). Source

Taenzler J.,MSD Animal Health Innovation GmbH | Liebenberg J.,ClinVet International | Roepke R.K.A.,MSD Animal Health Innovation GmbH | Heckeroth A.R.,MSD Animal Health Innovation GmbH
Parasites and Vectors

Background: The preventive effect of fluralaner chewable tablets (Bravecto™) against transmission of Babesia canis by Dermacentor reticulatus ticks was evaluated. Methods: Sixteen dogs, tested negative for B. canis by PCR and IFAT, were allocated to two study groups. On day 0, dogs in one group (n=8) were treated once orally with a fluralaner chewable tablet according to label recommendations and dogs in the control group (n=8) remained untreated. On days 2, 28, 56, 70 and 84, dogs were infested with 50 (±4) B. canis infected D. reticulatus ticks with tick in situ thumb counts 48 ± 4 h post-infestation. Prior to each infestation, the D. reticulatus ticks were confirmed to harbour B. canis by PCR analysis. On day 90, ticks were counted and removed from all dogs. Efficacy against ticks was calculated for each assessment time point. After treatment, all dogs were physically examined in conjunction with blood collection for PCR every 7 days, blood samples for IFAT were collected every 14 days and the dog's rectal body temperature was measured thrice weekly. From dogs displaying symptoms of babesiosis or were PCR positive, a blood smear was taken, and, if positive, dogs were rescue treated and replaced with a replacement dog. The preventive effect was evaluated by comparing infected dogs in the treated group with infected dogs in the untreated control group. Results: All control dogs became infected with B. canis, as confirmed by PCR and IFAT. None of the 8 treated dogs became infected with B. canis, as IFAT and PCR were negative throughout the study until day 112. Fluralaner chewable tablet was 100 % effective against ticks on days 4, 30, 58, and 90 and an efficacy of 99.6 % and 99.2 % was achieved on day 72 and day 86 after treatment, respectively. Over the 12-week study duration, a 100 % preventive effect against B. canis transmission was demonstrated. Conclusions: A single oral administration of fluralaner chewable tablets effectively prevented the transmission of B. canis by infected D. reticulatus ticks over a 12-week period. © 2015 Taenzler et al. Source

Williams H.,MSD Animal Health Innovation GmbH | Young D.R.,Young Veterinary Research Services | Qureshi T.,490 Franklin Circle | Zoller H.,MSD Animal Health Innovation GmbH | Heckeroth A.R.,MSD Animal Health Innovation GmbH
Parasites and Vectors

Background: Fluralaner, a novel isoxazoline, has both acaricidal and insecticidal activity through potent blockage of GABA- and L-glutamate-gated chloride channels. This study investigated the in vitro and in vivo effects of fluralaner exposure on flea (Ctenocephalides felis) reproduction. Methods. Blood spiked with sub-insecticidal fluralaner concentrations (between 0.09 and 50.0 ng/mL) was fed to fleas for 10 days using a membrane system. Cessation of reproduction in exposed fleas was assessed using flea survival, egg hatchability, and control of oviposition, pupae, and flea emergence. Fluralaner efficacy for in vivo Ctenocephalides (C.) felis control on dogs was assessed using a simulated flea-infested home environment. During a pre-treatment period, dogs were infested twice on days -28 and -21 with 100 adult unfed fleas to establish a thriving population by day 0 of the study. On day 0, one group of dogs was treated with fluralaner (Bravecto™; n = 10), while another group served as negative control (n = 10). Following treatment, dogs were infested three times with 50 fleas on days 22, 50 and 78 to simulate new infestations. Live flea counts were conducted weekly on all dogs for 12 weeks starting 1 day before treatment. Results: Fluralaner potently inhibited flea reproduction capacity in vitro. Oviposition ceased completely at concentrations as low as 25.0 ng/mL. While no ovicidal effect was observed, fluralaner exerted a larvicidal effect at exceptionally low concentrations (6.25 ng/mL). In the simulated flea-infested home environment, flea-control efficacy on fluralaner-treated dogs was >99% at every time point measured for 12 weeks. No adverse events were observed in fluralaner-treated dogs. Conclusions: Fluralaner completely controls egg laying, larval development and flea reproduction even at sub-insecticidal concentrations. Oral treatment of dogs with fluralaner is highly effective for eliminating fleas in a simulated flea-infested home environment. © 2014 Williams et al.; licensee BioMed Central Ltd. Source

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