moxidectin and Parasitic-Diseases--Animal

Topics: Animals; Animals, Wild; Anthelmintics; Macrolides; Mammals; Parasitic Diseases, Animal

The avermectins and, to a lesser extent, the milbemycins, have revolutionized antiparasitic and antipest control over the last decade. Both avermectins and milbemycins have macrocyclic lactone structures that are superimposable, they are produced by the same genus of soil dwelling organisms, they have the same mode of action, they exert this action against the same nematode/acarine/insect spectrum of targets, and they show the same mechanism-based toxicity in mammals. Reports suggesting that milbemycins have a different mode of action from avermectins with implications that there will be no mutual resistance to the groups have been shown to be false. Contributing to the belief that there were differences in mode of action between the two groups are the vague definitions of resistance presently in use which rely on the ability of the parasite to survive treatment at the manufacturer's recommended use level. More appropriately, drug resistance should be defined as 'a change in gene frequency of a population, produced by drug selection, which renders the minimal, effective dosage previously used to kill a defined portion (e.g. 95%) of the population no longer equally effective'. This type of definition would allow us to detect changes in susceptibility of a population earlier and is essential when comparing different chemicals to determine if there is mutual resistance to them. It is concluded that much effort has been expended by pharmaceutical, government, and academic scientists searching for broad-spectrum second generation avermectin and milbemycin products, but none has exceeded the original avermectin in any fundamental way. The newer avermectin and milbemycin compounds that have appeared claim niches in the market place based on emphasis of certain narrow parts of the overall spectrum. Consequently, there are no second generation avermectins and milbemycins at present and all newer compounds from this mode of action class are viewed as siblings of the first generation.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Antiprotozoal Agents; Dog Diseases; Dogs; Helminthiasis; Helminthiasis, Animal; Ivermectin; Macrolides; Molecular Structure; Parasitic Diseases; Parasitic Diseases, Animal; Sheep; Sheep Diseases; Structure-Activity Relationship

Topics: Agriculture; Animals; Anti-Bacterial Agents; Antiparasitic Agents; Biodegradation, Environmental; Ecology; Environmental Pollution; Feces; Ivermectin; Macrolides; Parasitic Diseases; Parasitic Diseases, Animal

The use of anthelmintics introduced over the past 25 years is discussed. The spectrum of action, efficacy, and toxicity of benzimidazoles, ivermectin, milbemycin, praziquantel, and epsiprantel are considered.

Topics: Animals; Anthelmintics; Anti-Bacterial Agents; Anticestodal Agents; Benzimidazoles; Cat Diseases; Cats; Dog Diseases; Dogs; Fenbendazole; Forecasting; Gastrointestinal Diseases; Ivermectin; Lactones; Macrolides; Mebendazole; Parasitic Diseases; Parasitic Diseases, Animal; Praziquantel

Safety and efficacy of the combined monthly use of spot-on fipronil 6.76% w/v / permethrin 50.48% w/v (Frontline Tri-Act®) and chewable tablets of afoxolaner 1.9% w/w / milbemycin oxime 0.4% w/w (NexGard Spectra®) in dogs was evaluated in a field study over a period of 6 months.. Forty-one healthy dogs living in highly endemic area for canine leishmaniosis and other canine vector borne diseases (VBD) were included in the study at the beginning of the Leishmania transmission season. Sixteen dogs were pet dogs living each in a single household; twenty-five dogs were hunting dogs living in three kennels. At inclusion, the dogs were ELISA (rapid test) negative for antibodies to Anaplasma, Borrelia, Ehrlichia, and for antigens of Dirofilaria. The dogs were also negative for blood microfilariae at the Knott's test, and no clinical or haematological abnormalities were observed. Of the included dogs, six hunting, apparently healthy, dogs were ELISA (rapid test) positive to Leishmania, and some were naturally infected by gastrointestinal nematodes (58.5%) and/or infested by fleas (58.5%) and ticks (9.8%). All the included dogs were treated at Days 0, 28, 56, 84, 112 and 140, and followed-up for efficacy until the study end (Day 168).. No adverse events related to the two products, nor skin reactions, general signs, or changes in the haematological profile, were observed during the study. At Day 14, anthelminthic efficacy was 100% for Toxocara canis, Toxascaris leonina and Capillaria aerophila, while few hunting dogs were still shedding eggs of Trichuris vulpis (1/25 hunting dog) and Ancylostomatidae (9/25 hunting dogs). All pet dogs were nematode free at the end of the study. Hunting dogs were free of roundworms and whipworms. Twenty-four hours after the first treatment, 95.8% of the ectoparasite infested dogs were free from fleas and ticks. Ectoparasites were significantly controlled during the 6-month study period, with 100% efficacy on both fleas and ticks from Day 56 to Day 168. Blood and serum samples collected on Day 168 were tested for vector-borne pathogens using same methods of the inclusion and no new seroconversions or circulating blood microfilariae were observed.. Concomitant use of Frontline Tri-Act® and NexGard Spectra® in dogs for six months was well tolerated. The combination was effective in controlling fleas, ticks, gastro-intestinal nematodes, and neither new seroconversion to the tested vector-borne pathogens nor blood microfilariae were detected in treated dogs at the end of the study.

Topics: Animals; Dog Diseases; Dogs; Drug Combinations; Female; Insect Vectors; Insecticides; Isoxazoles; Macrolides; Male; Naphthalenes; Parasitic Diseases, Animal; Permethrin; Pyrazoles

The activity of moxidectin was evaluated in 1988 and 1989 against natural infections of internal parasites in 20 critical tests (n = 20 equids) and three controlled tests (n = 20 equids). Two formulations, injectable administered intramuscularly (i.m.) or intraorally (i.o.) and gel i.o., were given at dose rates of 0.2, 0.3 or 0.4 mg kg-1 body weight. For the critical tests (all three dose rates evaluated), removals of second instar Gasterophilus intestinalis were 93-100%, except (89%) for the injectable formulation (i.m.) at 0.2 mg kg-1. Removals of third instar G. intestinalis were 88-100% for the injectable formulation given i.m. or i.o. and 93-100% for the gel formulation, except (53%) for one batch (0.4 mg kg-1). Activity was 100% for third instar Gasterophilus nasalis, Parascaris equorum, Strongylus vulgaris and Strongylus edentatus. For Oxyuris equi, removals were 91-100%, except (27%) for one batch of the injectable formulation given i.o. at 0.3 mg kg-1. There was apparent activity against migrating S. vulgaris and S. edentatus at various dose rates and routes of administration for both formulations. At necropsy, there were local reactions observed at the injection site of three equids. In the controlled tests, dose rates were 0.2 or 0.4 mg kg-1. Removal of third instar G. intestinalis was highest for the injectable formulation given i.m. All formulations and dose rates were highly effective against S. vulgaris and S. edentatus, but variable and incomplete against O. equi. Removal was excellent on Habronema muscae and on migrating S. vulgaris and S. edentatus, although incomplete on S. vulgaris. Gasterophilus nasalis third instars and P. equorum were present in low numbers in some non-treated equids, but none were recovered from treated equids. Toxicosis was not evident.

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Female; Gels; Horse Diseases; Horses; Injections, Intramuscular; Intestinal Diseases, Parasitic; Macrolides; Male; Parasitic Diseases; Parasitic Diseases, Animal

Topics: Animals; Anthelmintics; Drug Resistance; Humans; Macrolides; Parasitic Diseases, Animal; Sheep; Sheep Diseases; United Kingdom

The indiscriminate and continuous use of anthelmintic drugs has promoted the selection of resistant parasites population, the presence of drug residues in food products, and heavy environmental contamination. The aim of the present study was to determine the presence of antiparasitic drug residues in 42-days old lamb serum and tissues, submitted to three endoparasite control programs: preventive treatment (PT) using moxidectin (MOX) at every 28days; selective treatment (FEC) using MOX when fecal egg count was greater than or equal to 700; and selective treatment (FMC), using MOX when FAMACHA/FMC score was 3 and above. For this purpose, MOX residues were quantified in serum, muscle, fat, liver and kidney. Lambs were slaughtered when reaching 30kg of body weight, and after a 28-day MOX withdrawal period. Before slaughter, blood was collected to determine the concentration of MOX in serum. Tissues and organ samples were collected at slaughter. The quantitation of MOX residues was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS). From the 756 tissue samples analyzed, only one sample of fat from the PT group showed residue levels (586.3μg/kg) above the maximum residue limit (MRL) of 500μg/kg. No treated lambs presented traces of MOX residues in fat and liver, suggesting possible environmental contamination. In conclusion, all weaned lambs, produced in continuous grazing and subjected to gastrointestinal parasite control programs via selective (FEC and FMC) or preventive (PT) treatment, displayed a low risk (<1%) of MOX residues above the MRL in muscle, fat, kidney, and liver.

Topics: Animals; Anthelmintics; Brazil; Drug Residues; Female; Macrolides; Male; Parasitic Diseases, Animal; Random Allocation; Sheep; Sheep Diseases; Time Factors; Tissue Distribution

Cydectin(®) 2% LA Solution for Injection for Sheep (Pfizer Animal Health) is a long-acting (LA) formulation of moxidectin for the treatment and prevention of mixed infections of gastro-intestinal nematodes, respiratory nematodes and certain arthropod parasites in sheep. To evaluate the duration of persistent efficacy against nasal bots (Oestrus ovis), a natural exposure study was conducted in Spain during the summer of 2011. One hundred and twenty nasal bot-free, Rasa Aragonesa sheep were randomly allocated to eight groups of 15 animals each. On Day 0, four groups were treated at the recommended dose rate of 1 mg moxidectin/kg bodyweight. Four groups remained untreated as negative controls. All animals were held in nasal bot-proof housing except for exposure to natural challenge when one group of treated sheep and one of group of control animals were transferred to a local pasture at either 0-20, 20-40, 40-60, or 60-80 days after treatment. Following challenge, sheep were scored for clinical signs of bot infestation, necropsied and the heads sectioned for larval recovery. Nasal bot larvae were retrieved from 7 to 11 control sheep following each exposure period indicating that adult bots were active throughout the study. In the first challenge up to 20 days after treatment, when sheep were slaughtered immediately after exposure, the majority of larvae were first instar (L1) and only 3 of the 15 control sheep were infested with second instars (L2). There was 100% efficacy against L2 and 38.1% reduction in the number of live L1 in the treated sheep but mean counts were not significantly different between treatment and control groups (P ≥ 0.05). For the subsequent exposure periods 20-80 days after treatment (necropsies 7-9 days after challenge), 6-10 sheep were infested with L1 and 9-11 control sheep were infested with L2 and third instars (L3). There was negligible efficacy against L1, but treatment with moxidectin resulted in 100% control of L2 and L3. These results are consistent with the biology of nasal bots and control with a systemic agent, as the slower growing L1 have limited feeding and are therefore less susceptible to systemic parasiticides. The study demonstrated that the persistent efficacy of this long-acting injectable formulation of moxidectin protects against the development of active O. ovis infestations for at least 80 days after treatment.

Topics: Animals; Delayed-Action Preparations; Diptera; Female; Injections; Insecticides; Larva; Macrolides; Myiasis; Nose; Parasitic Diseases, Animal; Random Allocation; Sheep; Sheep Diseases; Spain; Treatment Outcome

Topics: Animals; Anthelmintics; Drug Resistance; Drug Therapy, Combination; Fascioliasis; Macrolides; Parasitic Diseases, Animal; Sheep; Sheep Diseases

Topics: Animals; Anthelmintics; Drug Combinations; Drug Resistance; Macrolides; Parasitic Diseases, Animal

Dung invertebrate colonization and degradation levels of faeces from cattle treated with endectocides were studied. Faeces of control and doramectin (DRM) (subcutaneous) and moxidectin (MXD) (subcutaneous and topical) treated animals were deposited on the field from 3 to 21 days post-treatment (pt). Pats were recovered after 6 to 42 days post-deposition (pd). Faecal weight, dry matter, arthropods number, and drugs concentrations were determined. Total arthropods number was higher in control (P<0.0001) than in the other groups from days 3 to 21 pt. Total number of insects recovered on days 3, 11, and 21 pt from control pats was significantly (P<0.001) higher than in treated-animal pats during all the trial. At day 21 pt, the insects' number in dung voided by DRM-treated cattle was (P<0.05) lower than in the other groups. Comparisons of dung degradation among treatments were inconclusive. A lower adverse effect was observed for MXD compared with DRM. No significant degradation of MXD or DRM was observed during the present trial.

Topics: Administration, Topical; Animals; Anthelmintics; Arthropods; Cattle; Cattle Diseases; Coleoptera; Diptera; Feces; Injections, Subcutaneous; Ivermectin; Macrolides; Male; Parasitic Diseases, Animal; Time Factors; Weather

Topics: Animals; Anti-Bacterial Agents; Antinematodal Agents; Fenbendazole; Horses; Macrolides; Parasite Egg Count; Parasitic Diseases, Animal

The present study was carried out to investigate whether the pharmacokinetics of avermectins or a milbemycin could explain their known or predicted efficacy in the horse. The avermectins, ivermectin (IVM) and doramectin (DRM), and the milbemycin, moxidectin (MXD), were each administered orally to horses at 200 microg/kg bwt. Blood and faecal samples were collected at predetermined times over 80 days (197 days for MXD) and 30 days, respectively, and plasma pharmacokinetics and faecal excretion determined. Maximum plasma concentrations (Cmax) (IVM: 21.4 ng/ml; DRM: 21.3 ng/ml; MXD: 30.1 ng/ml) were obtained at (tmax) 7.9 h (IVM), 8 h (DRM) and 7.9 h (MXD). The area under the concentration time curve (AUC) of MXD (92.8 ng x day/ml) was significantly larger than that of IVM (46.1 ng x day/ml) but not of DRM (53.3 ng x day/ml) and mean residence time of MXD (17.5 days) was significantly longer than that of either avermectin, while that of DRM (3 days) was significantly longer than that of IVM (2:3 days). The highest (dry weight) faecal concentrations (IVM: 19.5 microg/g; DRM: 20.5 microg/g; MXD: 16.6 microg/g) were detected at 24 h for all molecules and each compound was detected (> or = 0.05 microg/g) in faeces between 8 h and 8 days following administration. The avermectins and milbemycin with longer residence times may have extended prophylactic activity in horses and may be more effective against emerging and maturing cyathostomes during therapy. This will be dependent upon the relative potency of the drugs and should be confirmed in efficacy studies.

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Area Under Curve; Chromatography, High Pressure Liquid; Feces; Horse Diseases; Horses; Ivermectin; Macrolides; Parasitic Diseases, Animal; Treatment Outcome

A 3 m, video gastroscope was used to screen 47 horses suspected of being naturally infected with equine bot larvae. 17 of 47 (36.2%) candidate horses harbored Gasterophilus nasalis larvae in the proximal duodenum and 46 of 47 (97.9%) had G. intestinalis larvae in the stomach. All horses infected with G. nasalis had concurrent infections with G. intestinalis. 14 horses with dual infections were allocated randomly to two treatment groups. Seven horses in Group 1 received 2% moxidectin oral gel once at a dosage of 0.4 mg/kg bodyweight (BW), and seven horses in Group 2 were untreated controls. 14 days after treatment, all horses were necropsied and the stomach and proximal duodenum harvested from each. Bot larvae were recovered, identified to species and instar, and counted. At the label dosage, moxidectin oral gel was 100 and 97.6% effective (P < 0.05) against third-instar G. nasalis and G. intestinalis, respectively. In addition to demonstrating the boticidal efficacy of moxidectin, this trial illustrated that gastroscopy/duodenoscopy is a feasible method for confirming infections with different species of bot larvae in the horse.

Topics: Administration, Oral; Animals; Anti-Bacterial Agents; Digestive System; Diptera; Duodenum; Gastroscopy; Gels; Horse Diseases; Horses; Insecticides; Macrolides; Parasitic Diseases, Animal; Random Allocation; Stomach

The efficacy of moxidectin was evaluated in young ponies naturally infected with gastrointestinal parasites. Eight animals were treated orally with moxidectin at 0.4 mg/kg bodyweight and eight received only the vehicle. They were all necropsied two weeks later. Faecal samples were examined daily for egg counts and larval cultures. Parasites were recovered from total faecal samples collected daily and from the gastrointestinal tracts at necropsy. Moxidectin reduced the strongyle egg counts by > 99 per cent from three days after treatment but some individuals remained positive for 10 days. The drug had little or no ovicidal activity. As evaluated in the critical-controlled test, moxidectin was 99 to 100 per cent effective (P < 0.05) against luminal stages of parascaris equorum, Strongylus vulgaris, Triodontophorus species, Craterostomum acuticaudatum, 19 cyathostome species and Oxyuris equi. Adult S edentatus were also completely removed. Its efficacy against third stage larvae of Gasterophilus intestinalis was 95 per cent (P < 0.05). Luminal nematode stages were removed within a few days, and bots continued to be eliminated for at least two weeks after treatment. No activity was observed against Anoplocephala perforliata. As evaluated in the controlled test, moxidectin was 100 per cent effective against Habronema muscae (P < 0.05) and had a 76 per cent but not significant efficacy against encysted small strongyle larvae.

Topics: Administration, Oral; Animals; Anthelmintics; Anti-Bacterial Agents; Digestive System; Female; Horse Diseases; Horses; Macrolides; Male; Parasite Egg Count; Parasitic Diseases, Animal; Treatment Outcome

During the winter 1991-92, 42 reindeer hinds of the Kaamanen Experimental Reindeer Herd in Finnish Lapland, naturally infected with various parasites, were allocated to 3 groups. One group was an untreated control group and the other 2 groups received either moxidectin or ivermectin at a dose of 200 micrograms kg-1 subcutaneously. The efficacy of treatment was followed with monthly faecal examinations for nematode eggs and counting of warbles, Hypoderma tarandi larvae, and throat bots, Cephenemyia trompe larvae, from live animals in spring. The efficacy of moxidectin against warbles (92.8%) and throat bots (70.8%) did not match that of ivermectin, which was 100% against both species. Both moxidectin and ivermectin were effective against gastrointestinal trichostrongylid egg production over the December to May trial period indicating good efficacy against adult and inhibited trichostrongylids. Only non-significant differences were seen in weight development and calf birth weights between the groups. Because of its only moderate insecticidal efficacy, moxidectin cannot be recommended as an endectocide in reindeer.

Topics: Animals; Animals, Newborn; Anthelmintics; Anti-Bacterial Agents; Birth Weight; Capillaria; Feces; Female; Ivermectin; Macrolides; Parasite Egg Count; Parasitic Diseases, Animal; Pregnancy; Reindeer; Trichostrongyloidea; Weight Gain

Topics: Animals; Anti-Bacterial Agents; Antiprotozoal Agents; Cattle; Cattle Diseases; Ecosystem; Environmental Monitoring; Ivermectin; Macrolides; Parasitic Diseases; Parasitic Diseases, Animal; Safety

Topics: Animals; Anti-Bacterial Agents; Antiprotozoal Agents; Cattle; Cattle Diseases; Ecosystem; Environmental Monitoring; Ivermectin; Macrolides; Parasitic Diseases; Parasitic Diseases, Animal; Parasitology; Risk Assessment; Safety; Veterinary Medicine