Evaluation of the efficacy of emodepside plus praziquantel topical solution against ascarid infections (Toxocara cati or Toxascaris leonina) in cats.

Eleven controlled studies were conducted in the United States and Europe to evaluate the efficacy of a topical solution of emodepside (3 mg/kg)+praziquantel (12 mg/kg) (Profender, Bayer AG, Leverkusen, Germany) against infection with various stages of the ascarid nematodes Toxocara cati and Toxascaris leonina. Infections were induced by administration of larvated ascarid eggs, and stage-specific efficacy was evaluated by treating cats at scheduled intervals post-inoculation. All studies featured random allocation to treatment groups, placebo-treated control animals and assessment of outcome measures by masked personnel. The product (emodepside+praziquantel topical solution) was 100% effective against mature adults and immature adult T. cati. In addition, it was 96.8% effective against third stage larvae and at least 99.4% effective against fourth stage larvae of T. cati, respectively. Efficacy against mature, immature adult and L4 stages of T. leonina exceeded 93.4%, but regulatory "adequacy of infection" criteria were not met in some studies. No adverse reactions to treatment were noted in cats treated with the emodepside+praziquantel topical solution.

Efficacy of a topically administered combination of emodepside and praziquantel against mature and immature Ancylostoma tubaeforme in domestic cats.

This paper reports the efficacy of emodepside/praziquantel spot-on (Profender), Bayer AG, Leverkusen, Germany), a novel broad-spectrum anthelmintic for dermal application, against L4 larvae and immature adult and adult stages of Ancylostoma tubaeforme in cats. The formulation contains 2.14% (w/w) emodepside and 8.58% (w/v) praziquantel, with emodepside being active against gastrointestinal nematodes and praziquantel against cestodes. Five randomized, blinded and controlled laboratory studies demonstrated 100% efficacy of emodepside/praziquantel spot-on against mature A. tubaeforme and an efficacy of >95% and >97%, respectively, against L4 larvae and immature adults (based on worm counts after necropsy) at approximately the minimum proposed dose rate in cats of 3.0 mg emodepside and 12.0 mg praziquantel/kg body weight. No adverse reactions to the treatment were observed. It is concluded that emodepside/praziquantel spot-on is an effective and safe treatment against infections with mature and immature A. tubaeforme. Emodepside/praziquantel spot-on will considerably facilitate the treatment of cats against nematodes and cestodes compared with orally administered preparations.

Evaluation of the efficacy of emodepside+praziquantel topical solution against cestode (Dipylidium caninum, Taenia taeniaeformis, and Echinococcus multilocularis) infections in cats.

Emodepside+praziquantel topical solution was developed to provide broad-spectrum anthelmintic activity against gastrointestinal parasites in cats. Eight controlled studies were conducted to evaluate the efficacy of a topical solution of emodepside (3 mg/kg) and praziquantel (12 mg/kg) (Profender, BayerAG, Leverkusen, Germany) against feline infections with three species of cestodes. Studies featured naturally acquired infections of Dipylidium caninum or Taenia taeniaeformis, or experimental infections with Echinococcus multilocularis that were placebo-controlled, randomized and blinded. Cats were euthanatized and necropsied between 2 and 11 days after treatment, depending on the target parasite. The efficacy of emodepside+praziquantel topical solution was 100% against D. caninum and T. taeniaeformis, and 98.5- 100% against E. multilocularis. No significant systemic or local adverse reactions to treatment were noted in cats that received the combination. Topical treatment of cats with emodepside+praziquantel topical solution was safe and highly effective against cestode infections.

Antiparasitic agents. 3. Synthesis and anthelmintic activities of novel 2-pyridinyl-5-isothiocyanatobenzimidazoles.

The preparation and anthelmintic activities of a series of 2-pyridinyl-5-isothiocyanatobenzimidazoles are described. In the primary oral mouse screen, six derivatives showed 100% taeniacidal activity at 0.2% in diet. The most active member in this series, 1c, is potentially an effective gastrointestinal nematocide in sheep at 50 mg/kg po.

Antiparasitic agents. 5. Synthesis and anthelmintic activities of novel 2-heteroaromatic-substituted isothiocyanatobenzoxazoles and benzothiazoles.

The synthesis and antiparasitic properties of 22 isothiocyanato-2-pyridinylbenzoxazoles and benzothiazoles are described; the preparation and anthelmintic activities of 14 isothiocyanato-2-thienyl-, -furyl-, and -pyrrolylbenzoxazoles are outlined. In mice experimentally infected with Nematospiroides dubius (nematode) and Hymenolepis nana (tapeworm), three derivatives, i.e., 5-isothiocyanato-2-(2-furyl)benzoxazole (34), 5-isothiocyanato-2-(5-methyl-2-furyl)benzoxazole (35), and 5-isothiocyanato-2-(1-methyl-1H-2-pyrroly)benzoxazole (37), show 100% nematocidal activity and two, i.e., 5- and 6-isothiocyanato-2-(3-pyridinyl)benzoxazole (5) and 5- and 6-isothiocyanato-2-(3-pyridinyl)benzthiazole (21), show 10% taeniacidal activity at 0.2% in the diet. Two derivatives (5 and 21) show good nematocidal activity in sheep. Maximum activity requires 3-pyridinyl derivatives for both the benzoxazole and benzothiazole series.

Antiparasitic agents. 6. Synthesis and anthelmintic activities of novel isothiocyanatophenyl-1,2,4-oxadiazoles.

The syntheses and anthelmintic activities of 31 3- and 5-(isothiocyanatophenyl)-1,2,4-oxadiazoles are reported. In the primary anthelmintic screen, 3-(4-isothiocyanatophenyl)-1,2,4-oxadiazole (39) showed 100% nematocidal activity and 3-(2-furanyl)-5-(4-isothiocyanatophenyl)-1,2,4-oxadiazole (63), 3-(2-furanyl)-5-(2-chloro-4-isothiocyanatophenyl)-1,2,4-oxadiazole (64), and 3-(2-furanyl)-5-(4-chloro-3-isothiocyanatophenyl)-1,2,4-oxadiazole (66) showed 100% taeniacidal activity when administered orally to mice. The two most active members of this series, 39 and 63, were active against the gastrointestinal nematodes of sheep at 100 mg/kg. In addition, 39 was also found to be active against hookworms in dogs at a single, oral dose of 200 mg/kg.

Separation and biologic activities of individual components of S15-1, a streptothricin class antibiotic.

A method is described for isolation of gram quantities of the components of the streptothricin complex S15-1 utilizing CM Sephadex column chromatography eluted with 10% acetic acid as an eluant followed by gradient elution with 10% acetic acid containing 0.02 N approximately 0.03 N HCI. Streptothricins F and E, as well as an unidentified component C1, have been isolated and their comparative biological activities determined. Streptothricins F and E were comparable in taeniacidal activity in mice infected with Hymenolepis nana ia feeding either one at 0.05% in the diet removed 92 approximately 100% of the adult tapeworms. The unidentified component C1 was inactive at the levels tested. In contrast, component C1 was the most active in antimicrobial activity against Bacillus subtilis and in inhibiting the urease activity of proteus mirabilis. In the former test, the ratios of activity were; 1:7:30 for F:E:C1 and in the latter; 1:2:4 for F:E:C1.

Persistent efficacy of doramectin against experimental challenge with Ostertagia ostertagi in cattle.

Two studies were conducted in North America to evaluate the persistent efficacy of doramectin injectable solution against experimental challenge with infective larvae of Ostertagia ostertagi. In both studies, four groups of 10 randomly-assigned calves, negative for trichostrongyle-type eggs on fecal examination, were treated subcutaneously in the midline of the neck with saline (1 ml 50 kg-1) on Day 0 or doramectin (200 micrograms kg-1 = 1 ml 50 kg-1) on Day 0, 7, or 14. Two additional calves from the same pool of animals were randomly assigned as larval-viability monitors and received no treatment. Beginning on Day 14 and continuing through Day 28, the 40 treated calves each were given approximately 1000 infective larvae of O. ostertagi by gavage daily; the two larval-viability monitors were inoculated in a similar manner with approximately 30,000 larvae as a single dose on Day 28. Animals were slaughtered on Day 42 in one study and on Days 42, 43, or 46 in the second. The abomasum from each calf was harvested and processed for worm recovery. A 2% aliquot of abomasal contents plus wash was examined for worm quantification and identification. Geometric mean O. ostertagi burdens were calculated from the log (O. ostertagi count + 1) and were used to estimate percentage reduction. In both studies, doramectin injectable solution was > or = 99.6% efficacious in reducing infection resulting from challenge with infective larvae of O. ostertagi for at least 21 days posttreatment; by 28 days posttreatment, efficacy was 87.3% in one study and 99.7% in the other.

Efficacy of selamectin against experimentally induced and naturally acquired ascarid (Toxocara canis and Toxascaris leonina) infections in dogs.

The efficacy of selamectin against adult ascarids was evaluated in eight controlled and masked studies in dogs. Three laboratory studies evaluated selamectin against experimentally induced infections of Toxocara canis; three laboratory studies evaluated selamectin against naturally acquired infections of T. canis; one laboratory study evaluated selamectin against naturally acquired infections of both T. canis and Toxascaris leonina; one field study evaluated selamectin against naturally acquired infections of ascarids (T. canis and/or T. leonina) in dogs presented as veterinary patients. Selamectin was administered topically to the skin of dogs in unit doses designed to deliver a minimum of 6mgkg(-1) (range, 6-12mgkg(-1)). In all studies, dogs were allocated randomly to treatment assignments (selamectin or vehicle control in laboratory studies: selamectin or reference product in the field study) on the basis of pretreatment fecal egg counts. For induced infections, there were significant reductions in geometric mean numbers of adult T. canis after a single application of selamectin (93.9-98.1%, P=0.0001), after two monthly applications (> or =88.3%, P< or =0.0001), and after three monthly applications (100%, P< or =0.0002). In the natural infection laboratory studies, when selamectin was administered twice at an interval of 30 days, the percentage reductions in geometric mean numbers of adult T. canis at necropsy were 84.6, 91.3, and 97.9%, and when selamectin was administered on days 0, 14, and 30, the percentage reductions were 91.1 and 97.6%. Geometric mean fecal T. canis egg counts were reduced by > or =92.9% (P< or =0.0067) at the end of the studies. In the field study, geometric mean fecal ascarid egg counts were reduced by 89.5 and 95. 5% (P=0.0001) for 14 and 30 days, respectively, after a single treatment with selamectin, and by 94.0% (P=0.0001) 30 days after the second treatment with selamectin. These reductions compared favorably with the egg count reductions from dogs treated with a reference product containing praziquantel, pyrantel embonate, and febantel. There were no adverse drug experiences or treatment-related mortalities during any of the studies. Selamectin, when administered topically in a unit dose providing a minimum dosage of 6mgkg(-1), was safe and effective against adult T. canis and T. leonina and in reducing the fecal excretion of T. canis eggs in dogs.

Taeniacidal efficacy of SQ 21,704 in dogs by various types of oral administration and in comparison with niclosamide and bunamidine hydrochloride.

The streptothrinin antibiotics SQ 21,704 was evaluated against naturally occurring Taenia pisiformis and Dipylidium caninum infections in dogs when they were given at a dose level of 37.5 mg/kg of body weight in four different rations: loaf-type canned meat; chunk-type canned meat; dry (gravy-type) meal; and dry (pelleted) meal. The SQ 21,704 was 100% efficacious against both T pisiformis and D caninum infections when given with the chunk, gravy, and pelleted rations. When given with the loaf-type canned meat, it was 100% effective against T pisiformis and 60% efficacious against D caninum. The SQ 21,704 was effective against both tapeworm species when given orally as a liquid at a dose level of 37.5 mg/kg, formulated as an aqueous suspension containing 94 mg of activity per milliter. The SQ 21,704 was also tested in dogs when given orally in gelatin capsules at a dose level of 37.5 mg/kg without fasting, and was 100% efficacious against both tapeworm species. The results of a comparative taeniacidal study demonstrated that SQ 21,704 was 100% effective in removing both T pisiformis and D caninum when administered orally at a dose level of 37.5 mg/kg, whereas niclosamide and bunamidine hydrochloride were only partially effective at their recommended dose levels. One of five dogs treated with niclosamide at a dose level of 157 mg/kg was positive at necropsy, giving an orally efficacy of 80%. Three of five dogs treated with bunamidine hydrochloride at a dose level of 49 mg/kg were positive at necropsy, giving an overall efficacy of 40%.

Anticoccidial activity of lonomycin (SQ 12,525) in chicks.

Lonomycin (TM-481, SQ 12,525) at various concentrations in the feed was tested in controlled battery experiments against laboratory strains of single and mixed Eimeria species infections. The experimental results indicated that lonomycin at doses of .003125, .00625, or .0125% demonstrated a high degree of anticoccidial activity by preventing or reducing mortality, reducing fecal dropping scores, and allowing for normal or near-normal weight gains against single and mixed infections of 5 major pathogenic species, E. acervulina, E. brunetti, E. maxima, E. necatrix, and E. tenella. Lonomycin, at these same dosages, was highly effective against a recent field isolate obtained from a flock previously fed monensin. These studies involving 7 trials totaling 1,680 broiler chicks, have demonstrated that lonomycin at levels of .003125 to .0125% (dependent on species of Eimeria) in the feed is an effective aid in the control of avian coccidiosis in broiler chickens.

Evaluation of the speed of kill of fleas and ticks with Frontline Top Spot in dogs.

The speed of kill of a spot-on formulation of fipronil (Frontline Top Spot, Merial Limited, Duluth, GA) against adult cat fleas (Ctenocephalides felis) and brown dog ticks (Rhipicephalus sanguineus) was evaluated in dogs in a commercial laboratory setting. Forty dogs were allocated to 20 replicates of two based on sex and pretreatment flea counts. Within each replicate, dogs were randomly allocated to an untreated control group or to treatment with fipronil, administered topically as a spot-on per label instructions. The technical staff performing the flea and tick counts were unaware of treatment group assignments. Each dog was infested with approximately 100 unfed adult fleas on Day -8 or -6 and on Day -1. Each dog also was infested with approximately 50 unfed adult ticks on Day -1. Treatments were administered on Day 0 according to body weight. Flea and tick counts were performed on four randomly selected dogs from each treatment group at approximately 6, 12, 18, 24, and 48 hours after treatment. Flea and tick count reductions for dogs treated with fipronil were significant (P < .05), as compared with untreated controls, at 18, 24, and 48 hours after treatment. Controlled efficacy of fipronil against C. felis and R. sanguineus ranged from 94% to 100% at these evaluation times. This study demonstrated that the speed of kill of fipronil, applied topically as a spot-on, was 100% against C. felis fleas on dogs within 12 to 18 hours after treatment and 100% against R. sanguineus ticks between 24 and 48 hours after treatment.

Ivermectin and milbemycin oxime in experimental adult heartworm (Dirofilaria immitis) infection of dogs.

BACKGROUND: The US Food and Drug Administration reports an increase in the frequency of reports of lack of effectiveness claims for heartworm (HW) prevention products. HYPOTHESIS: At their labeled doses, single doses of commercially available HW prevention products are not completely effective against all field isolates of HW. ANIMALS: Forty-two HW-free dogs experimentally inoculated with a recent HW field isolate. METHODS: Placebo-controlled, blinded laboratory clinical trial. Dogs randomly allocated to 1 of 3 treatment groups with 14 dogs per group. Groups were untreated control or p.o. dosed with milbemycin oxime (MBO) or ivermectin (IVM). Dogs were inoculated with 50 HW third stage larvae 30 days before dosing and necropsy was performed on Day 123 after treatment to enumerate adult HW. RESULTS: Thirteen of 14 control dogs had adult HW detected at necropsy with a geometric mean worm count of 22.3. One HW was found in 1 dog in each of the MBO and IVM treatment groups. CONCLUSIONS AND CLINICAL IMPORTANCE: Two currently approved macrocyclic lactone HW preventives used at their labeled dose rates were <100% effective against a recent HW field isolate, supporting the hypothesis that the effectiveness of a single dose of these preventives can vary. This is important in guiding clients on expectations of product effectiveness.