Klemens Krieger

Evaluation of the efficacy and safety of imidacloprid 10% plus moxidectin 2.5% spot–on in the treatment of generalized demodicosis in dogs: results of a European field study

Efficacy and safety of the test product imidacloprid 10%+moxidectin 2.5% spot on (Advocate®, Advantage multi®) in the treatment of canine generalized demodicosis were evaluated in a multi–centre, controlled, randomized, blinded field study in Albania, France, and Germany. The study was conducted according to a non–inferiority design to demonstrate that the efficacy of the test product is not inferior to that of a control product containing milbemycin oxime (Interceptor, tablets for oral application). Of the 72 dogs enrolled, all of which expressed clinical signs of generalized demodicosis, 63 completed the study. Of these, 30 dogs were treated 2–4 times, at 4–week intervals, with the test product at the recommended dose of at least 0.1 ml/kg body weight. Thirty–three dogs were treated daily for two to four periods of 4 weeks with the control product according to label instructions (0.5–1 or 1–2 mg/kg body weight). Presence of mites in deep skin scrapings and clinical improvement were assessed 3–6 times at each inspection at 4–week intervals. Treatment was discontinued in dogs negative for mites on two subsequent examinations 4weeks apart or at the last examination on day 84. At the end of the trial, dogs in both groups showed a similar clinical improvement. No Demodex mites were detected in 26 of 30 dogs treated with imidacloprid/moxidectin and in 29 of 33 dogs treated with milbemycin oxime. Statistical evaluation confirmed that the efficacy of the test product in the treatment of generalized canine demodicosis was not inferior to that of milbemycin oxime.

Efficacy and safety of imidacloprid 10% plus moxidectin 2.5% spot-on in the treatment of sarcoptic mange and otoacariosis in dogs: results af a European field study

Efficacy and safety of treatment with imidacloprid 10%+moxidectin 2.5% spot-on (Advocate®, Advantage multi®; Bayer AG, Leverkusen, Germany) were tested in dogs naturally infested with Sarcoptes scabiei or Otodectes cynotis in a multi–centre, controlled, randomized, blinded field study conducted in France, Germany, Albania and the UK. The study was performed according to a non–inferiority design to demonstrate that the efficacy of imidacloprid/moxidectin spot–on was not inferior to that of a control product containing selamectin (Stronghold spot–on; Pfizer). All Sarcoptes–infested dogs were topically treated twice (days 0 and 28) with the dosage recommended by the respective manufacturer (27 dogs with imidacloprid/moxidectin, 26 with selamectin). All Otodectes–infested dogs were treated on day 0 (35 dogs with imidacloprid/moxidectin, 34 with selamectin), and only those still positive on day 28 received a second treatment. Parasitological cure rate in Sarcoptes–infested dogs was 100% for both treatments, while parasitological cures rates in the Otodectes–infested dogs at day 28 and day 56 were 68.6 and 85.7% with imidacloprid/moxidectin, and 64.7 and 88.2% with Stronghold. Non–inferiority of Advocate was confirmed statistically. Clinical assessment of skin lesion scores at day 56 showed that with either product >96% of the dogs treated against sarcoptic mange were improved or cured, the difference between the groups being non–significant. On the basis of a final clinical assessment of lesion scores, 80% of the dogs treated with imidacloprid/moxidectin against otoacariosis and 85.3% of those treated with selamectin were rated cured or improved. Only three mild, possibly drug–relatedBadverse reactions were observed among alI treated animals (two in the imidacloprid/moxidectin group, one in the selamectin group). It is concluded that imidacloprid/moxidectin spot–on is an effective and safe treatment for sarcoptic mange and otoacariosis in the dog.

Vector-Borne Diseases - constant challenge for practicing veterinarians: recommendations from the CVBD World Forum

The human-animal bond has been a fundamental feature of mankinds history for millennia. The first, and strongest of these, mans relationship with the dog, is believed to pre-date even agriculture, going back as far as 30,000 years. It remains at least as powerful today. Fed by the changing nature of the interactions between people and their dogs worldwide and the increasing tendency towards close domesticity, the health of dogs has never played a more important role in family life. Thanks to developments in scientific understanding and diagnostic techniques, as well as changing priorities of pet owners, veterinarians are now able, and indeed expected, to play a fundamental role in the prevention and treatment of canine disease, including canine vector-borne diseases (CVBDs).The CVBDs represent a varied and complex group of diseases, including anaplasmosis, babesiosis, bartonellosis, borreliosis, dirofilariosis, ehrlichiosis, leishmaniosis, rickettsiosis and thelaziosis, with new syndromes being uncovered every year. Many of these diseases can cause serious, even life-threatening clinical conditions in dogs, with a number having zoonotic potential, affecting the human population.Today, CVBDs pose a growing global threat as they continue their spread far from their traditional geographical and temporal restraints as a result of changes in both climatic conditions and pet dog travel patterns, exposing new populations to previously unknown infectious agents and posing unprecedented challenges to veterinarians.In response to this growing threat, the CVBD World Forum, a multidisciplinary group of experts in CVBDs from around the world which meets on an annual basis, gathered in Nice (France) in 2011 to share the latest research on CVBDs and discuss the best approaches to managing these diseases around the world.As a result of these discussions, we, the members of the CVBD Forum have developed the following recommendations to veterinarians for the management of CVBDs.

A Novel High-Resolution Melt PCR Assay Discriminates Anaplasma phagocytophilum and “Candidatus Neoehrlichia mikurensis”

ABSTRACT “Candidatus Neoehrlichia mikurensis” (Anaplasmataceae) is an emerging pathogen transmitted by Ixodes ticks. Conventional PCR and the newly developed high-resolution melt PCR were used to detect and discriminate “Candidatus Neoehrlichia mikurensis” and Anaplasma phagocytophilum. Both bacterial species were frequently found in Ixodes ricinus and Ixodes hexagonus but virtually absent from Dermacentor reticulatus. In rodents, “Candidatus N. mikurensis” was significantly more prevalent than A. phagocytophilum, whereas in cats, only A. phagocytophilum was found.

Pathogens in ticks collected from dogs in Berlin/Brandenburg, Germany

BackgroundTick-borne diseases are a major health risk for humans and dogs. In addition to collection and analysis of questing ticks, analysis of host-associated ticks for the presence of pathogens is a valuable method to gain insight into transmission patterns of tick-borne diseases.MethodsTicks were collected from dogs living in the Berlin/Brandenburg area. The three tick species Ixodes ricinus, Ixodes hexagonus and Dermacentor reticulatus were examined for the presence of Babesia spp., Borrelia spp., Rickettsia spp. and Anaplasmataceae. Conventional PCR followed by sequencing was used for pathogen detection and characterization.ResultsBabesia spp. were found in 2.5% and 3% of I. ricinus and I. hexagonus, respectively. Sequencing revealed the presence of Babesia microti, Babesia capreoli and Babesia venatorum. D. reticulatus were free of Babesia canis. Rickettsia spp. were detected in 61% of I. ricinus, 44% of I. hexagonus and 39% of D. reticulatus. Specifically detected were Rickettsia raoulti in D. reticulatus and I. hexagonus, Rickettsia helvetica in I. ricinus and I. hexagonus and Rickettsia monacensis in I. hexagonus. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis have been reported previously in I. ricinus (6.5% and 4.3%, respectively) and I. hexagonus (3.9% and 5.9%). Borrelia spp. were found in 11.6% of I. ricinus and 11.2% of I. hexagonus. Subsequent genospecies analysis revealed Borrelia afzelii, Borrelia garinii, Borrelia burgdorferi sensu stricto and Borrelia miyamotoi. Simultanous presence of more than one pathogen was found in 20% of I. ricinus and in 59% of I. hexagonus whereas the total frequency of any pathogen was 65% in I. ricinus, 59% in I. hexagonus and 64% in D. reticulatus. Ticks in which A. phagocytophilum was detected had a significantly increased risk of also containing Rickettsia. Ticks harbouring a pathogen had significantly higher scutal indices than ticks without presence of any pathogen.ConclusionsFrequencies of potential human or canine pathogens in ticks were considerable and DNA of all four groups of pathogens was detected. Differences in scutal indices might suggest that pathogens are frequently taken up by ticks when feeding on dogs in Berlin/Brandenburg.

Field Evaluation of the Efficacy and Safety of Emodepside plus Praziquantel Tablets (Profender® Tablets for Dogs) against Naturally Acquired Nematode and Cestode Infections in Dogs

A controlled, blinded and randomised multicentre field study evaluated the efficacy and safety of a new anthelmintic tablet formulation containing emodepside plus praziquantel (Profender® tablets for dogs) in the treatment of gastrointestinal nematode and cestode infections in dogs in France, Germany, Portugal and Slovakia. Dogs positive for nematodes and/or cestodes (demonstrated by faecal egg counts and/or the presence of proglottids) were treated with emodepside plus praziquantel tablets (n = 239) or the reference product containing milbemycin oxime and praziquantel (Milbemax® [n = 115]) at the recommended dose rate. Two faecal samples collected between 7 and 13 days after treatment were evaluated for proglottids, nematode and cestode eggs. No suspected adverse drug reactions were observed in the study. The following parasite species were identified: Trichuris vulpis, Toxocara canis, Toxascaris leonina, Uncinaria stenocephala, Ancylostoma caninum, Dipylidium caninum, Taeniidae and Mesocestoides spp. Geometric mean nematode egg counts in dogs treated with emodepside plus prazi quantel tablets were reduced by 99.9 % compared with a reduction of 99.6 % for the reference product. Statistical analysis demonstrated noninferiority of investigational versus reference product (p = 0.0342). None of the dogs treated with emodepside plus praziquantel or reference product remained positive for cestodes after treatment. The study demonstrated that emodepside plus praziquantel tablets are safe and highly efficacious against a broad spectrum of nematodes and cestodes under field conditions.

A NOVEL APPROACH TO FLEA CONTROL ON CATS, USING PYRIPROXYFEN

Pyriproxyfen is a new insect growth regulator with potent activity against developing stages of the cat flea, Ctenocephalides felis. To determine its duration of action after application as a spot-on topical treatment, 20 cats were allocated to two groups. One group acted as untreated controls, and each cat in the other was given a single dose of 1 mg/kg pyriproxyfen. Each cat was infected with fleas at weekly intervals and caged. Eggs were collected and their viability determined as a measure of the effect of the agent on adult fleas. The effect of the transfer of pyriproxyfen from each cat to its immediate surroundings was monitored by observing the development of fertile flea eggs placed on samples of blanket taken from each cage. Results from untreated control cats showed that the experimental conditions were favourable for the lifecycle of the flea. Flea reproduction on treated cats was inhibited completely for seven weeks and substantially for at least a further two weeks. Blankets used by cats treated up to two weeks previously prevented flea development entirely and substantial control was still achieved up to four weeks after treatment.

Field evaluation of the efficacy and safety of emodepside/praziquantel spot–on solution against naturally acquired nematode and cestode infections in domestic cats

Two controlled, blinded and randomized multi–site clinical field studies evaluated the efficacy and safety of emodepside/praziquantel spot–on in the treatment of gastrointestinal nematode and cestode infections in cats. In a study conducted in Europe, faecal egg count reductions of >98% for all nematode eggs and eggs of Toxocara cati, respectively, were observed in cats treated with emodepside/praziquantel spot–on (Profender®, Bayer AG, Leverkusen, Germany). For a positivecontrol product containing selamectin (Stronghold) reductions of >95% were observed. A 100% reduction of faecal eggs and proglottids was observed in cats treated with emodepside/praziquantel spot–on that were infected with cestodes. In a study conducted in North America, cats were treated with either emodepside/praziquantel spot–on plus a placebo tablet or a combination of two control products containing, respectively, selamectin (Revolution) and epsiprantel (Cestex). Faecal egg count reduction for eggs of T. cati was >99% for both treatments. For faecal eggs and proglottids of Dipylidium caninum reductions of >99 and >97% were recorded for cats treated with emodepside/praziquantel spot–on and the control group, respectively. No adverse reactions were observed in the European study, and only mild ones of short duration in a few cats from both treatment groups of the North American study. The two studies demonstrated that emodepside/praziquantel spot–on is highly efficacious and safe under field conditions.

The synergistic action of imidacloprid and flumethrin and their release kinetics from collars applied for ectoparasite control in dogs and cats.

BackgroundThe control of tick and flea burdens in dogs and cats has become essential to the control of important and emerging vector borne diseases, some of which are zoonoses. Flea worry and flea bite hypersensitivity are additionally a significant disease entity in dogs and cats. Owner compliance in maintaining the pressure of control measures has been shown to be poor. For these reasons efforts are continuously being made to develop ectoparasiticides and application methods that are safe, effective and easy to apply for pet owners. A new polymer matrix collar has recently been developed which is registered for 8 months use in cats and dogs. The basic properties of this collar have been investigated in several in vitro and in vivo studies.MethodsThe effects of imidacloprid, flumethrin and the combination were evaluated in vitro by means of whole cell voltage clamp measurement experiments conducted on isolated neuron cells from Spodoptera frugiperda. The in vitro efficacy of the two compounds and the combination against three species of ticks and their life stages and fleas were evaluated in a dry surface glass vial assay. The kinetics of the compounds over time in the collar were evaluated by the change in mass of the collar and measurement of the surface concentrations and concentrations of the actives in the collar matrix by HPLC. Hair clipped from collar treated dogs and cats, collected at various time points, was used to assess the acaricidal efficacy of the actives ex vivo.ResultsAn in vitro isolated insect nerve model demonstrated the synergistic neurotoxic effects of the pyrethroid flumethrin and the neonicotinoid imidacloprid. An in vitro glass vial efficacy and mortality study against various life stages of the ticks Ixodes ricinus, Rhipicephalus sanguineus and Dermacentor reticulatus and against the flea (Ctenocephalides felis) demonstrated that the combination of these products was highly effective against these parasites. The release kinetics of these actives from a neck collar (compounded with 10% imidacloprid and 4.5% flumethrin) was extensively studied in dogs and cats under laboratory and field conditions. Acaricidal concentrations of the actives were found to be consistently released from the collar matrix for 8 months. None of the collar studies in dogs or cats were associated with any significant collar related adverse event.ConclusionHere we demonstrated the synergism between the pyrethroid flumethrin and the neonicotinoid imidacloprid, both provided in therapeutically relevant doses by a slow release collar matrix system over 8 months. This collar is therefore a convenient and safe tool for a long-term protection against ectoparasites.

European multicenter field trial on the efficacy and safety of a topical formulation of imidacloprid and permethrin (AdvantixTM) in dogs naturally infested with ticks and/or fleas

In a field trial 363 dogs naturally infested with ticks (n ≧ 1) and/or fleas (n ≧ 5) were enrolled at 23 centres in Germany, France and Italy. A total of 229 dogs were treated once with the test product, a topical formulation of imidacloprid 10% and permethrin 50%. 134 dogs were treated once with a registered control product, a topical fipronil 10% formulation, according to the label instructions. All dogs and cats living in the same household were treated with the control product. Cats living with the imidacloprid-permethrin treated dogs were treated with a mono imidacloprid formulation. Efficacy and safety of the products were assessed 2 days and 1,2,3 and 4 weeks after treatment by individual parasite counts and clinical examination. Continuous infestation pressure during the trial period was demonstrated by monitoring other dogs presented to the clinics. Efficacy calculations were based on geometric means of the individual parasite counts compared to pre-treatment infestation. The acute efficacy (day 2) of the imidacloprid permethrin combination vs. the control product was 91.1% vs. 89.7% against Ixodes. ricinus, 85.4% vs. 80.9% against Rhipicephalus spp. and 98.3% vs. 97.0% against Ctenocephalides spp. Residual efficacy (day 28) of the two products was 95.2% vs. 69.5% against I. ricinus, 98.5% vs. 89.4% against R.. spp. and 92.5% vs. 93.5% against C. spp. Results of the trial proved the safety of both products in treated dogs and in dogs and cats, living in the same household.