Evaluation and comparison of a flumethrin-imidacloprid collar and repeated monthly treatments of fipronil/(s)-methoprene to control flea, Ctenocephalides f. felis, infestations on cats for eight months.

BACKGROUND: This controlled laboratory study was designed to evaluate the efficacy of the 10 % imidacloprid/4.5 % flumethrin collar (Seresto®, Bayer Animal Health) against fleas (Ctenocephalides f. felis) on cats, when compared to fipronil (9.8 %w/w)/(s)-methoprene (11.8 % w/w) topical spot-on formulation (Frontline® Plus for Cats and Kittens, Merial). METHODS: Thirty cats were randomized into three groups of ten animals based on pre-treatment flea counts: Group 1: imidacloprid/flumethrin collar; Group 2: fipronil/(s)-methoprene topical spot-on and Group 3: non-treated controls. The imidacloprid/flumethrin collars were applied one time on Day 0, while the fipronil/(s)-methoprene spot-on was administered every 30 days from Day 0 through Day 210. Cats were infested with 100 fleas on study days 0, 7, 14, 29, 59, 89, 119, 149, 179, 209 and 239. All flea counts were conducted by combing to remove fleas on post-treatment days 2, 8, 15, 30, 60, 90, 120, 150, 180, 210 and 240. RESULTS: The efficacy of the imidacloprid/flumethrin collar ranged from 98.2 to 100 % for eight months. The efficacy of fipronil/(s)-methoprene spot-on ranged from 68.2 to 99.9 %. Efficacy was < 85 % for fipronil/(s)-methoprene on Days 90, 150 and 210. The flea counts in both treatment groups were significantly fewer than those in the non-treated control group at every post-treatment study day (P < 0.0001). In addition, there were significantly fewer fleas in the imidacloprid/flumethrin collar group when compared to the fipronil/(s)-methoprene group on Days 90, 150 and 210 (P < 0.0001). CONCLUSIONS: This study demonstrated that the imidacloprid/flumethrin collar (Seresto®, Bayer Animal Health) maintained excellent ( > 98.2 %) efficacy against fleas on cats for the entire 8 month study. Monthly applications of fipronil/(s)-methoprene (Frontline® Plus for Cats and Kittens, Merial) generally had high, but variable (68.2 to 99.9 %) efficacy over the course of the eight month study. Based on the very high residual efficacy achieved by the imidacloprid/flumethrin collar in this study, veterinarians should expect that this collar will control and eliminate existing flea infestations on cats and in their in-home premises as long as every flea infested host is treated.

Field comparison of tolerance of a collar containing 10.0% imidacloprid/4.5% flumethrin (Seresto) and a placebo collar placed on cats.

OBJECTIVES: A collar containing 10.0% imidacloprid/4.5% flumethrin (Seresto; Bayer Animal Health) controls flea and tick infestations for 8 months and is effective in preventing transmission of Bartonella henselae and Cytauxzoon felis among cats. The purpose of this study was to compare tolerance of client-owned cats for the 10.0% imidacloprid/4.5% flumethrin collar or a physically identical placebo collar. METHODS: A total of 96 client-owned cats were enrolled in the study. Cats that were systemically ill, of hairless breed or declawed in all four limbs were excluded. Cats were randomized by household to wear a placebo collar for 14 days followed by the 10.0% imidacloprid/4.5% flumethrin collar for 14 days or the 10.0% imidacloprid/4.5% flumethrin collar for 28 days. Examinations by a veterinarian were performed on days 0, 14 and 28. Owners recorded daily systemic and local health observations. RESULTS: All but two cats, including one that entrapped the mandible in the collar and one that developed local pyodermatitis (10.0% imidacloprid/4.5% flumethrin collar), completed the 28 day study. The majority of the local lesions or licking associated with the collars occurred in the first 14 days, and licking (but not skin lesions) was more common in cats wearing the 10.0% imidacloprid/4.5% flumethrin collars. No local lesions were reported for placebo cats after switching to the 10.0% imidacloprid/4.5% flumethrin collar, and only one cat wearing the 10.0% imidacloprid/4.5% flumethrin collar had reports of licking after day 14. Housing status, single or multiple cat household, and whether a collar had been worn previously were not associated with side effects. CONCLUSIONS AND RELEVANCE: Adverse events detected for cats wearing 10.0% imidacloprid/4.5% flumethrin collars were similar to those for cats wearing placebo collars and to cats wearing identification collars in a separate study. The data suggest that most cats originally intolerant of collars become receptive over time.

Comparative Efficacy of an Imidacloprid/Flumethrin Collar (Seresto®) and an Oral Afoxolaner Chewable (NexGard®) against Tick (Dermacentor variabilis and Amblyomma americanum) Infestations on Dogs: a Randomised Controlled Trial.

This randomised controlled laboratory study demonstrated the residual speed of efficacy of an imidacloprid/flumethrin collar (Seresto(®), Bayer) for the control of ticks (Dermacentor variabilis, Amblyomma americanum) at 6 and 12 hours postinfestation on dogs when compared to oral afoxolaner (NexGard(®), Merial). Dogs were randomised by pre-treatment tick counts: Group 1) imidacloprid 10 % (w/w) / flumethrin 4.5 % (w/w) collar, 2) afoxolaner chewable (dosage 3.1 - 6.2 mg/kg), and 3) non-treated controls. Ticks (50/species/dog) were infested on days 3, 14, 21, and 28; live (attached and non-attached) and dead attached ticks were counted 6 and 12 hours later. Efficacy against live D. variabilis at 6 hours for Group 1 was 95 - 100 % and for Group 2 was 38 - 48 %; efficacy at 12 hours for Group 1 was 97 - 100 % and for Group 2 was 27 - 59 %. Efficacy against A. americanum at 6 hours for Group 1 was 94 - 100 % and for Group 2 was < 0 - 38 %; efficacy at 12 hours for Group 1 was 98 - 100 % and for Group 2 was 1 - 40 %. Live and total (total live and dead attached) tick counts in Group 1 against both tick species were significantly lower (p ≤ 0.05) than Group 2 and 3 at all time points. The number of live or total ticks on Group 2 dogs was never significantly lower when compared to the respective number of ticks on Group 3 (controls). This study demonstrated that an imidacloprid/flumethrin collar was highly efficacious (94 - 100 %) at repelling and killing ticks on dogs at 6 and 12 hours post-infestation and was more efficacious than afoxolaner on all challenge days.

Comparative Efficacy of an Imidacloprid/Flumethrin Collar (Seresto®) and an Oral Fluralaner Chewable Tablet (Bravecto®) against Tick (Dermacentor variabilis and Amblyomma americanum) Infestations on Dogs: a Randomised Controlled Trial.

This controlled laboratory study demonstrated the residual speed of efficacy of an imidacloprid/flumethrin collar (Seresto(®), Bayer) for the control of ticks (Dermacentor variabilis, Amblyomma americanum) at 6 and 12 hours post-infestation on dogs when compared to oral fluralaner (Bravecto(®), Merck). Dogs were randomised by pre-treatment tick counts: Group 1) imidacloprid 10 % (w/w)/flumethrin 4.5 % (w/w) collar, 2) fluralaner (dosage 25.1 - 49.4 mg/kg), and 3) non-treated controls. Ticks (50/species/dog) were infested on days 3, 14, 21, 28, 42, and 56 followed by 50 D. variabilis on days 70 and 84. Live and dead attached ticks were counted 6 and 12 hours later. Efficacy against both species at 6 and 12 hours for Group 1 was 94 - 100 %. Efficacy for Group 2 against both species at 6 hours was 4 - 69 %; efficacy at 12 hours was 8 - 100 %. Live (attached and non-attached) tick counts at 6 hours in Group 1 were significantly lower (p ≤ 0.05) than counts in Group 2 and 3 on all days. At 12 hours, live counts were significantly lower (p ≤ 0.05) in Group 1 than Group 2 for D. variabilis from days 56 - 84 and for A. americanum from days 28 - 56. There were significantly fewer (p ≤ 0.05) total ticks (total live and dead attached) on dogs in Group 1 compared to Group 2 and 3 at all time points. This study demonstrated that an imidacloprid/flumethrin collar was highly efficacious (94 - 100 %) at repelling and killing ticks on dogs at 6 and 12 hours post-infestation and was more efficacious than fluralaner as early as 6 hours post-infestation on all challenge days.

A flea and tick collar containing 10% imidacloprid and 4.5% flumethrin prevents flea transmission of Bartonella henselae in cats.

BACKGROUND: Bartonella henselae is transmitted amongst cats by Ctenocephalides felis and is associated with multiple clinical syndromes in cats and people. In a previous study, monthly spot-on administration of 10% imidacloprid/1% moxidectin was shown to block transmission of B. henselae amongst cats experimentally exposed to infected C. felis. The purpose of this study was to determine whether application of a flea and tick collar containing 10% imidacloprid and 4.5% flumethrin would lessen C. felis transmission of B. henselae amongst cats for 8 months. METHODS: Specific pathogen free cats (n = 19) were housed in three adjoining enclosures that were separated by mesh to allow C. felis to pass among groups but prevent cats in different enclosures from contacting one another. One group of 4 cats was inoculated intravenously with B. henselae and after infection was confirmed in all cats based on positive PCR assay results, the cats were housed in the middle enclosure. The B. henselae infected cat group was flanked by a group of 8 cats that had the collar placed and maintained for the duration of the study and a group of 7 cats that were not treated. Ctenocephalides felis (50 males and 50 females) raised in an insectary were placed on each of the 4 cats in the B. henselae infected group monthly for 7 applications and then every 2 weeks for 4 applications starting the day the collar was applied. Blood was collected from all cats weekly for Bartonella spp. PCR, serology and culture. RESULTS: While side-effects associated with the collars were not noted, persistent fever necessitating enrofloxacin therapy occurred in two of the untreated cats. While B. henselae infection was ultimately confirmed in 4 of 7 of the untreated cats, none of the cats with collars became infected (P = 0.026). CONCLUSIONS: In this study design, use of a collar containing 10% imidacloprid and 4.5% flumethrin was well tolerated and prevented C. felis transmission of B. henselae amongst cats for 8 months.

The effects of ponazuril on development of apicomplexans in vitro.

We examined the effects of 5 microg/ml ponazuril treatment on developing tachyzoites of Neospora caninum and merozoites of Sarcocystis neurona to better determine the mode of action of this anticoccidial drug. Both parasites develop asexually by endogenesis. Neospora caninum was selected for study because it develops by endodyogeny, which results in two tachyzoites being produced internally, and S. neurona was selected because it develops by endopolygeny which results in many merozoites being produced internally. Ponazuril inhibited development of N. caninum after approximately 48 h post-exposure. Treated tachyzoites of N. caninum developed vacuoles and underwent degeneration. Ponazuril also inhibited development of merozoites of S. neurona. Treated merozoites and maturing schizonts of S. neurona developed vacuoles and underwent degeneration. The ability of S. neurona schizonts to undergo cytokinesis was inhibited. Our results are discussed in relation to previous ultrastructural research on endogenesis of tachyzoites of Toxoplasma gondii undergoing endodyogeny which indicated that ponazuril induced multinucleate stage formation and inhibited cytokinesis. Ponazuril is believed to act on the apicoplast and our study demonstrates that this agent may express its inhibitory effects in different phenotypic manners on different apicomplexan parasites. The enzyme/enzyme systems that are the inhibitory target of ponazuril may be different in these apicomplexans, or the results of inhibition may affect different pathways downstream of its initial site of action in these parasites.

Efficacy of ponazuril in vitro and in preventing and treating Toxoplasma gondii infections in mice.

Toxoplasma gondii is an important apicomplexan parasite of humans and other warm-blooded animals. Ponazuril is a triazine anticoccidial recently approved for use in horses in the United States. We determined that ponazuril significantly inhibited T. gondii tachyzoite production (P < 0.05) at 5.0, 1.0, or 0.1 microg/ml in African green monkey kidney cells. We used outbred female CD-1 mice to determine the efficacy of ponazuril in preventing and treating acute toxoplasmosis. Each mouse was subcutaneously infected with 1,000 tachyzoites of the RH strain of T. gondii. Mice were weighed daily, and ponazuril was administered orally in a suspension. Mice given 10 or 20 mg/kg body weight ponazuril 1 day before infection and then daily for 10 days were completely protected against acute toxoplasmosis. Relapse did not occur after prophylactic treatments were stopped. Toxoplasma gondii DNA could not be detected in the brains of these mice using polymerase chain reaction (PCR). One hundred percent of mice treated with 10 or 20 mg/kg ponazuril at 3 days after infection and then daily for 10 days were protected from fatal toxoplasmosis. Sixty percent of mice treated with 10 mg/kg ponazuril at 6 days after infection and 100% of mice treated with 20 mg/kg or 50 mg ponazuril 6 days after infection and then daily for 10 days were protected from fatal toxoplasmosis. Relapse did not occur after treatments were stopped. Toxoplasma gondii DNA was detected in the brains of some, but not all, of these mice using PCR. The results demonstrate that ponazuril is effective in preventing and treating toxoplasmosis in mice. It should be further investigated as a safe and effective treatment for this disease in animals.

Mode of action of ponazuril against Toxoplasma gondii tachyzoites in cell culture.

Toxoplasma gondii is an important apicomplexan parasite of humans and other warm-blooded animals. Ponazuril is a triazine anticoccidial recently approved for use in horses in the United States. We investigated the mode of action of ponazuril against developing RH strain T. gondii tachyzoites in African green monkey kidney cells. Host cells were infected with 2.0 x 10(5) tachyzoites and treated with 5 microg/ml ponazuril. Cultures were fixed and examined by transmission electron microscopy 3 days after treatment. Ponazuril interfered with normal parasite division. This led to the presence of multinucleate schizonts stages. Up to six tachyzoites were observed partially budded from the surface of these schizonts. Large vacuoles developed in these schizonts and they eventually degenerated.