Hormonal modulation of reproduction in Polistes fuscatus social wasps: Dual functions in both ovary development and sexual receptivity.

Hormones are often major regulators of complex behaviors, such as mating and reproduction. In insects, juvenile hormone (JH) is integral to many components of reproductive physiology and behavior, but its role in female sexual receptivity is not well understood. To investigate the influence of JH on receptivity, we utilized the social wasp Polistes fuscatus. In Polistes, mating behavior is temporally separated from other components of reproduction, which allows for examination of the physiology and behavior of mating, disentangled from fertilization and egg-laying. We reared virgin gynes (reproductive females) in the lab and divided them into four groups, in which gynes received multiple topical treatments of either 20 µg, 10 µg, 5 µg, or 0 µg of the JH analog methoprene. Gynes were then placed in petri dishes with 2 unrelated males and we recorded attempted and successful mating. Additionally, we measured gyne ovarian development and survival in each group. We found that methoprene increased both sexual receptivity and ovarian development, but was associated with a decrease in long-term survival. Receptivity increased linearly as methoprene treatment increased, but the effect of methoprene on ovarian development was independent of dose. These results demonstrate the importance of JH in sexual receptivity and mating behavior. We argue that the relatively understudied Polistes gyne has potential as a model for mating and reproduction, and for the internal and external regulation of this complex behavior.

Efficacy of a new topical formulation of selamectin plus sarolaner for the control of fleas and ticks infesting cats in Japan.

The efficacy of a single application of a new topical formulation containing selamectin plus sarolaner (Revolution® Plus / Stronghold® Plus, Zoetis) was evaluated against fleas and ticks infesting cats enrolled as veterinary patients in two field studies conducted in Japan and against Haemaphysalis longicornis ticks on cats in a laboratory study. In the laboratory study, sixteen cats were ranked based on pre-treatment tick counts and allocated randomly to treatment on Day 0 with either selamectin plus sarolaner or placebo. Cats were infested with adult H. longicornis on Days -2, 5, 12, 19, 26 and 33. Efficacy relative to placebo was based on live attached tick counts conducted 48 h after treatment and subsequent re-infestations. Selamectin plus sarolaner reduced live, attached H. longicornis counts by 96.4% within 48 h of treatment, and by ≥91.7% within 48 h of weekly re-infestation for 35 days, based on arithmetic means. In the field studies, 67 client-owned cats harboring six or more live fleas and 63 cats harboring four or more live attached ticks were enrolled to evaluate selamectin plus sarolaner for efficacy and safety compared with a registered product. Cats were allocated randomly to treatment with selamectin plus sarolaner or fipronil plus (S)-methoprene based on order of presentation. Treatment was administered once on Day 0 and efficacy was assessed by parasite counts conducted on Days 14 and 30 compared to the pre-treatment count. In the flea field study, live flea counts on Days 14 and 30 were reduced by 99.5% and 99.9% in the selamectin plus sarolaner group, and by 97.6% and 98.6% in the fipronil plus (S)-methoprene group, based on least squares mean percentage reductions. Clinical signs typically associated with flea allergy dermatitis improved following treatment. In the tick field study, live tick counts on Days 14 and 30 were reduced by 97.5% and 97.7% in the selamectin plus sarolaner group, and by 91.5% and 93.4% in the fipronil plus (S)-methoprene group, based on least squares mean percentage reductions. Selamectin plus sarolaner was determined to be non-inferior to fipronil plus (S)-methoprene in both field studies. There were no treatment-related adverse events in any study. A single topical dose of Revolution® Plus / Stronghold® Plus providing a minimum dosage of 6.0 mg/kg selamectin and 1.0 mg/kg sarolaner was confirmed to be effective against H. longicornis ticks on cats for one month and safe and effective in the treatment of fleas and ticks on cats enrolled as veterinary patients in Japan.

Does juvenile hormone prompt oxidative stress in male damselflies?

In invertebrates, it has recently been reported that secondary sexual characteristics (SSCs) reflect the antioxidant defense of their bearers, but it is not known what physiological link maintains the honesty of those signals. Here, we used the damselfly Hetaerina americana to test whether juvenile hormone plays such a role. First, we analyzed whether oxidative damage is a real threat in natural damselfly populations by examining the accumulation of oxidized guanines as a function of age in males. Then, we injected paraquat (a pro-oxidant agent) and added the juvenile hormone analog methoprene (JHa) to the experimental group and the JHa vehicle (acetone) to the control group, to determine whether JHa increases the levels of pro-oxidants and antioxidants. We found that DNA oxidation increased with age, and that levels of hydrogen peroxide and superoxide dismutase, but not catalase or glutathione, were elevated in the JHa group compared with the control group. We propose that juvenile hormone is a mediator of the relationship between SSCs and antioxidant capacity and, based on the literature, we know that JHa suppresses the immune response. We therefore suggest that juvenile hormone is a molecular mediator of the general health of males, which is reflected in their SSCs.

Evaluation of an 11.2% spinetoram topical spot-on solution for the control of experimental and natural flea (Ctenocephalides felis) infestations on cats in Europe.

Spinetoram is the newest member the spinosyn-class of natural products to be commercialized for flea control on cats in the United States under the tradename Cheristin® for cats. This report describes results from two laboratory studies and a multi-center clinical field trial designed to confirm the efficacy of a topical spot-on solution containing spinetoram (11.2% w/w, 130 mg/mL) against European strains of the cat flea, Ctenocephalides felis. In the laboratory studies, cats were allocated to one of two treatment groups of eight animals each: negative control (mineral oil) or spinetoram, both applied as a topical spot-on at the base of the skull on Day 0. Cats were infested with ∼100 newly emerged, unfed adult fleas on Days -2 or -1, 7, 14, 21, 28 and 35. To calculate efficacy, fleas were counted and removed 48 h after treatment, and 48 h after each subsequent infestation through week 5. Spinetoram treatments provided 100% efficacy through at least day 16 and ≥ 97% efficacy (arithmetic mean) for one month. For the field trial, 23 clinics from Northern and Southern Europe participated in the study that compared the effectiveness and safety of spinetoram and fipronil/(S)-methoprene treatments over a period of two months. There were 258 and 248 evaluable efficacy cases for month 1 and month 2, respectively, with 300 total evaluable cases for safety. Treatments were administered on Day 0 and again on Day 30 (±3 days). The effectiveness of treatments was calculated based on reduction in live flea counts on Days 14, 30, 44 and 60 (±3 days) relative to flea counts obtained on Day 0. Efficacy (geometric mean percent flea reduction) on Days 14, 30, 44 and 60 was 97.0%, 95.0%, 99.3% and 99.1% for spinetoram, respectively, and 86.1%, 80.9%, 92.4% and 92.3% for fipronil/(S)-methoprene, respectively. Spinetoram was deemed non-inferior at all intervals and superior to fipronil/(S)-methoprene at Days 30 and 60. Clinical signs of flea allergy dermatitis (FAD) were markedly improved following spinetoram treatment, as demonstrated through statistically significant reductions in severity of FAD scores for most of the clinical signs when compared to fipronil/(S)-methoprene treatment. There was a lower overall adverse event incidence rate for spinetoram (5.1%) versus fipronil/(S)-methoprene treatment (11.5%).

Aerosol Dispersal Patterns and Resulting Effects on Tribolium confusum (Coleoptera: Tenebrionidae) Adults.

Aerosol application of insecticides as part of an integrated pest management program is becoming more widely adopted in food facilities such as flour mills. However, the method of application and the complex structural features within a facility can impact how insecticide particles travel and settle on surfaces and therefore impact the consistency in efficacy obtained. Here we investigated how the location from which an aerosol insecticide is released impacts the spatial pattern of aerosol deposition, using efficacy against Tribolium confusum Jacquelin du Val (Coleoptera: Tenebrionidae), the confused flour beetle, as a model insects. Concrete bioassay arenas containing T. confusum adults and flour were exposed to two commercial aerosol formulations, pyrethrin + pyriproxyfen and pyrethrin + methoprene, and observed for initial adult knockdown and subsequent mortality. Aerosols were applied from one of three static locations or a fourth application comprised of multiple aerosol release points. The aerosol release position had a significant effect on T. confusum adult knockdown and mortality; both ranged from 0 to 100% depending on bioassay arena location. The multiple aerosol release positions tended to have more bioassay arenas with higher knockdown and mortality, and had a more consistent impact across all arena locations, yet there were still areas on the mill floor where little adult beetle efficacy was observed. The effect of each aerosol on T. confusum adults is a culmination of how the aerosol was applied, the distance the aerosol particles traveled, and the complexity of a milling facility.

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.

Synergism of the IGRs Methoprene and Pyriproxyfen Against Larval Cat Fleas (Siphonaptera: Pulicidae).

Insect growth regulators (IGRs) methoprene and pyriproxyfen are widely used as topical treatments to pets or applied to the indoor environment to control cat fleas, Ctenocephalides felis (Bouché). The toxicity of methoprene, pyriproxyfen, and combinations of both IGRs to cat flea larvae was determined. The LC50 of methoprene and pyriproxyfen applied to larval rearing medium was 0.39 and 0.19 ppm, respectively. Combinations of methoprene:pyriproxyfen in ratios of 1:1, 5:1, 10:1, and 20:1 produced LC50s of 0.06, 0.09, 0.19, and 0.13 ppm, respectively. The pyriproxyfen synergized the activity of methoprene as indicated by the combination indices (CI). The ratio of methoprene:pyriproxyfen (40:1) provided an LC50 of 0.42 ppm and the pyriproxyfen was not synergistic. Combinations of pyriproxyfen:methoprene in ratios of 5:1, 10:1, and 20:1 provided LC50s of 0.14, 0.20, 0.20 ppm, respectively, and the methoprene did not synergize the activity of pyriproxyfen. The dose-reduction indices (DRIs) indicated that the concentrations of IGRs in the combinations of methoprene:pyriproxyfen (ratios of 20:1 or less) could be reduced by at least one-third of the amount required by methoprene alone to provide similar larval mortality. Combinations of methoprene and pyriproxyfen may be effective in increasing the residual activity on pets and assist in reducing the likelihood of insecticide resistance developing to IGRs.

Efficacy of a topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel (Broadline(®)) against naturally acquired infections with cestodes of the genus Joyeuxiella in cats.

Cats are host to dipylidiid cestodes of the genera Diplopylidium, Dipylidium and Joyeuxiella. Broadline(®), a topical broad-spectrum combination parasiticide containing fipronil (8.3 % w/v), (S)-methoprene (10 % w/v), eprinomectin (0.4 % w/v) and the cestocide praziquantel (8.3 % w/v), has previously been shown to be efficacious against Dipylidium caninum and Diplopylidium spp. in cats. To evaluate its efficacy against Joyeuxiella species, a blinded clinical efficacy study was conducted according to GCP. All cats had evidence for naturally acquired dipylidiid cestode infection as confirmed by pre-treatment examination. Cats were allocated randomly to two groups of 13 cats each based on bodyweight: Control (untreated) and Broadline(®) at 0.12 mL/kg bodyweight administered once topically. Based on the comparison of helminth counts in the treated and untreated cats seven days post treatment, Broadline(®) demonstrated >99 % efficacy (p < 0.01) against mature J. fuhrmanni and J. pasqualei, with 11 and 13 of the untreated cats harbouring 1 to 102 or 2 to 95 cestodes, respectively. In addition, parasite counts indicated 95.9 % efficacy (p = 0.006) against the rictularoid nematode Pterygodermatites cahirensis.

Efficacy of a proprietary formulation of fipronil/(S)-methoprene/cyphenothrin against Ixodes scapularis tick infestations on dogs.

BACKGROUND: Efficacy of FRONTLINE TRITAK For Dogs (fipronil/(S)-methoprene/cyphenothrin, Merial, Inc., Duluth, GA) against Ixodes scapularis was evaluated in two separate, but concurrent laboratory studies. METHODS: One day after topical treatment with placebo or active, dogs (n = 24) were infested with 50 unfed adult Ixodes scapularis ticks, with repeat infestations on Days 7, 14, 21 and 28. The number of live ticks was counted at 6 hours post-infestation in the first study (n = 12) and at 24 hours post-infestation in the second study (n = 12). RESULTS: Observed efficacies in study 1 were 93-99% at 6 hour assessments on Day 1 through Day 28 and in the second study, 98-100% at 24 hour assessments, occurring on Day 2 through Day 29. CONCLUSIONS: A single dose of FRONTLINE TRITAK For Dogs (fipronil/(S)-methoprene/cyphenothrin) (0.67 ml or 1.34 ml) prevented the establishment of a new infestation following treatment, as well as the repeated weekly re-infestations with Ixodes scapularis ticks, for 4 weeks.

Comparative Speed of Kill, Repellent (anti-feeding) and Acaricidal Efficacy of an Imidacloprid/Flumethrin Collar (Seresto®) and a Fipronil/(S)-Methoprene/Eprinomectin/Praziquantel Spot-on (Broadline®) against Ixodes ricinus (Linné, 1758) on Cats.

Speed of kill, repellent (anti-feeding) and acaricidal efficacy of an imidacloprid 10 % (w/w) /flumethrin 4.5 % (w/w) collar (Seresto(®), Bayer) and a spot-on formulation of fipronil 8.3 % (w/v) /(S)-methoprene 10 % (w/v) /eprinomectin 0.4 % (w/v) /praziquantel 8.3 % (w/v) (Broadline(®), Merial) against artificiallyinduced infestations with Ixodes ricinus on cats, were assessed in a parallel group design, randomised, controlled study. Twenty-four cats were included and randomly allocated to treatment groups or a non-treated control group. Starting on Day (D) 7 after treatment until D28, cats were each infested with 50 I. ricinus at weekly intervals. Ticks were counted in situ on the cats at 6, 12 and 24 h and upon removal 48 h after each infestation. Based on arithmetic means, Seresto(®) proved to be 100 % effective against adult I. ricinus at all assessment times (6, 12, 24 and 48 h after infestation) throughout the month-long study. Broadline(®) was 0 % to 16.7 % effective at 6 h, 26.8 % to 50.0 % effective at 12 h, while at 24 h after infestation efficacy peaked at 81.5 % on D15 declining to 31.5 % on D29. Based on the 48 h tick counts, the efficacy of Broadline(®) peaked at 100 % on D16 after treatment and decreased to 83.2 % by D30. The Seresto(®) collar provided significantly faster speed of kill and better persistent acaricidal effectiveness against Ixodes ricinus on cats compared to Broadline(®) spot-on. The additional repellent (anti-feeding) effect of Seresto(®) prevents parasites from taking a blood meal and thereby reduces the risk of vector-borne disease pathogen transmission.

Efficacy of Broadline® spot-on against Aelurostrongylus abstrusus and Troglostrongylus brevior lungworms in naturally infected cats from Italy.

The increasing reports of Aelurostrongylus abstrusus infection and the new information on Troglostrongylus brevior have spurred the interest of the scientific community towards the research of pharmaceutical compounds effective against both pathogens. A novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel (Broadline®, Merial) has been released for the treatment of a variety of feline parasitic infections. The present study reports the efficacy of this spot-on in treating cats naturally infected by feline lungworms. Client owned cats (n=191) were enrolled from three geographical areas of Italy and faecal samples were examined by floatation and Baermann techniques. Twenty-three individuals were positive for L1 of A. abstrusus (n=18) or T. brevior (n=3) or for both species (n=2) and they were topically treated with Broadline®. Seventeen of them were also concomitantly infected by other parasites. Four weeks after treatment, faecal samples were collected and examined to assess the efficacy of a single administration of the product. Based on lungworm larvae counts, the efficacy of the treatment was 90.5% or 100% for A. abstrusus or T. brevior, respectively. Cats released significantly lower amounts of lungworm larvae after treatment compared to pre-treatment (p<0.0001). All but three cats were negative for other nematodes after treatment and all cats recovered from respiratory signs. Results of this study indicate that a single administration of the topical combination fipronil, (S)-methoprene, eprinomectin and praziquantel is effective and safe for the treatment of A. abstrusus and/or T. brevior infections in cats living under field conditions.

One-month comparative efficacy of three topical ectoparasiticides against adult brown dog ticks (Rhipicephalus sanguineus sensu lato) on mixed-bred dogs in controlled environment.

This study was designed to compare the therapeutic and residual efficacy for 1 month of three topical ectoparasiticides on mixed-bred dogs against the brown dog tick, Rhipicephalus sanguineus. Adult dogs (n = 32, 10.8-18.4 kg BW) were allocated to 4 groups (n = 8) and infested with 50 adult ticks on days -8, -2, 7, 14, 21, and 28. Within each group, dogs were treated topically on day 0 with a control solution (CS), Vectra 3D (DPP), Frontline Plus (FM), or K9 Advantix (IP). Ticks were enumerated on dogs 24 h after treatment and each subsequent tick infestation by in situ thumb count assessment without removal and at 48 h by combing and removal. Acaricidal efficacy was calculated using arithmetic means for all 24 and 48 h tick count assessments. From 42 to 56% of the total, infested ticks were found on dogs 48 h post-challenge in the CS group. Therapeutic efficacy for all treatments ranged from 45.5 to 64.6% after 48 h of infestation. Residual efficacy after FM treatment was consistently lower compared to DPP or IP treatments at the 24 h assessments on days 8, 22, 23, and 29. Residual efficacy measured at this last time point was 94.8% for DPP, 83.1% for IP, and 46.9% for FM. This study demonstrates that permethrin-based formulations (DPP and IP) provided a quicker onset of residual protection against brown dog ticks compared to FM. Although DPP and IP are both permethrin-based formulations, DPP exhibited consistently higher residual acaricidal efficacies and was the only treatment that provided >90% protection for 1 month at 24 h post challenge.

Therapeutic efficacy of Broadline against notoedric mange in cats.

The efficacy of a novel topical combination of fipronil 8.3% w/v, (S)-methoprene 10 % w/v, eprinomectin 0.4% w/v, and praziquantel 8.3% w/v (Broadline, Merial) was evaluated in 18 cats naturally infested by Notoedres cati in a controlled, blinded clinical efficacy study. Cats were blocked on pretreatment bodyweight and randomly allocated to two groups of nine cats each. One group served as control (untreated) and one group was treated once topically with Broadline according to the label instructions. Skin scrapings (three scrapings per animal per occasion) were collected prior to treatment and every other week for 8 weeks thereafter and examined for live N. cati mites. In addition, lesions were evaluated at each sampling to monitor the clinical recovery. Based on live mite counts, efficacy against N. cati of a single topical administration with Broadline was >99%, and all treated cats recovered from clinical signs of notoedric mange. No treatment-related adverse events were observed.

Preventive efficacy of a topical combination of fipronil--(S)-methoprene--eprinomectin--praziquantel against ear mite (Otodectes cynotis) infestation of cats through a natural infestation model.

A study based on naturally infested cats was designed to evaluate the effectiveness of a single treatment with a topical formulation containing fipronil, (S)-methoprene, eprinomectin and praziquantel, for the prevention of Otodectes cynotis infestation in cats. Six treated cats and six untreated cats were housed with three chronically Otodectes cynotis-infested cats, respectively. The cats of each group were kept together in a 20-m(2) room for 1 month. Both clinical examination and ear mite counts were conducted on Day 28. All donor cats were confirmed to be chronically infested with Otodectes cynotis on Day -1 and Day 28. From untreated control cats, 129 live mites were recovered on Day 28 and all cats were found to be infested. In the treated group, three cats were found to be infested, with a total of five live mites recovered, the difference between the two groups being significant (p = 0.003). One treatment corresponded to 96% preventive efficacy at Day 28 based on ear mite counts. With regard to cerumen, the clinical score increased significantly for untreated cats between Day -1 and Day 28 (p = 0.00026) and not for treated cats (p = 0.30). The difference in cerumen abundance was significant between untreated and treated cats on Day 28 (p = 0.0035). Concerning the pruritic reflex in at least one ear, all cats were negative at inclusion. All six untreated cats became positive and showed a reflex on Day 28, whereas no treated cat showed ear pruritus (p = 0.00026).

Pharmacokinetics and metabolism of eprinomectin in cats when administered in a novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel.

Four studies were conducted to determine the pharmacokinetic characteristics and in vitro metabolism of eprinomectin, a semi-synthetic avermectin, in cats. Pharmacokinetic parameters including bioavailability of eprinomectin were determined in a parallel study design comprised of one group of eight cats which were treated once topically at 0.12 mL/kg bodyweight with BROADLINE(®), a novel combination product (fipronil 8.3% (w/v), (S)-methoprene 10% (w/v), eprinomectin 0.4% (w/v) and praziquantel 8.3% (w/v)), delivering a dose of 0.5mg eprinomectin per kg body weight, and a group of six cats which received 0.4% (w/v) eprinomectin at 0.4 mg/kg bodyweight once by intravenous injection. For cats treated by topical application, the average eprinomectin (B1a component) maximum plasma concentration (Cmax) was 20 ng/mL. The maximum concentrations were reached 24h after dosing in the majority of the animals (six of eight cats). The average terminal half-life was 114 h due to slow absorption ('flip-flop' kinetics). Following intravenous administration the average Cmax was 503 ng/mL at 5 min post-dose, and the mean elimination half-life was 23 h. Eprinomectin was widely distributed with a mean volume of distribution of 2,390 mL/kg, and the clearance rate was 81 mL/h/kg. Mean areas under the plasma concentration versus time curves extrapolated to infinity were 2,100 ngh/mL and 5,160 ngh/mL for the topical and intravenous doses, respectively. Topical eprinomectin was absorbed with an average absolute bioavailability of 31%. In a second parallel design study, the dose proportionality of eprinomectin after single topical administration of BROADLINE(®) was studied. Four groups of eight cats each were treated once topically with 0.5, 1, 2 or 5 times the minimum recommended dose of the combination, 0.12 mL/kg bodyweight. Based on comparison of areas under the plasma concentration versus time curves from the time of dosing to the last time point at which eprinomectin B1a was quantified, and Cmax, dose proportionality was established. In addition, the metabolic pathway of eprinomectin using cat liver microsomes, and plasma protein binding using cat, rat, and dog plasma were studied in vitro. Results of the analyses of eprinomectin B1a described here showed that it is metabolically stable and highly protein bound (>99%), and thus likely to be, as with other species, excreted mainly as unchanged parent drug in the feces of cats.

Efficacy against nematode and cestode infections and safety of a novel topical fipronil, (S)-methoprene, eprinomectin and praziquantel combination product in domestic cats under field conditions in Europe.

A novel topical combination product (BROADLINE(®), Merial) composed of fipronil, (S)-methoprene, eprinomectin and praziquantel was evaluated for safety and efficacy against nematode and cestode infections in domestic cats. The study comprised a multi-centre, positive control, blinded, field study, using a randomized block design based on order of presentation for allocation. In total 196 client-owned cats, confirmed as positive for naturally acquired infections of nematodes and/or cestodes by pre-treatment faecal examination, were studied in seven countries in Europe. Pre-treatment faecal examination revealed the presence of Toxocara, hookworm, Capillaria and/or spirurid nematode infections in 129, 73, 33 or 1 cat(s), respectively; infections with taeniid and Dipylidium cestodes were demonstrated in 39 and 17 cats, respectively. Cats were allocated randomly to one of two treatments in a ratio of 2, topical fipronil (8.3%, w/v), (S)-methoprene (10%, w/v), eprinomectin (0.4%, w/v) and praziquantel (8.3%, w/v) (BROADLINE(®), Merial; 130 cats); and 1, topical PROFENDER(®) Spot-On (Bayer; 66 cats) and treated once on Day 0. For evaluation of efficacy, two faecal samples were collected, one prior to treatment (Day -4 ± 4 days) and one at the end of the study (Day 14 ± 5 days). These were examined for fecal forms of nematode and cestode parasites. For evaluation of safety, cats were examined by a veterinarian before treatment and at the end of the study, and cat owners recorded the health status of their cats daily until the end of the study. For cats treated with Broadline(®), the efficacy was >99.9%, 100%, and 99.6% for Toxocara, hookworms, and Capillaria, respectively; and the efficacy was >99.9%, >99.9%, and 98.5%, respectively, for the cats treated with Profender(®) (p<0.001 for all nematodes and both treatments). Efficacy was 100% for both cestodes for both treatments (p<0.001). No treatment related adverse experiences were observed throughout the study. For both treatments, every cat that completed the study was given a safety score of 'excellent' for both local and systemic evaluations. The topical combination product of fipronil, (S)-methoprene, eprinomectin and praziquantel was shown to have an excellent safety profile and demonstrated high levels of efficacy when administered once as topical solution to cats infected with nematodes and cestodes under field conditions.

Efficacy of a novel topical fipronil, (S)-methoprene, eprinomectin and praziquantel combination against naturally acquired intestinal nematode and cestode infections in cats.

The efficacy of a novel topical combination formulation of fipronil, (S)-methoprene, eprinomectin and praziquantel against naturally acquired intestinal nematode and cestode infections in cats was evaluated in seven negative control, blinded studies. Cats were selected based on a pre-treatment faecal examination indicating a patent infection with at least hookworms (two studies), Toxocara ascarids (one study), taeniid cestodes (two studies) or Dipylidium cestodes (two studies). In each study, cats were assigned randomly to blocks of two animals each, based on decreasing pre-treatment body weight and were randomly allocated to one of two groups of six to 12 cats: untreated (control) or treated with topical fipronil (8.3%, w/v), (S)-methoprene (10%, w/v), eprinomectin (0.4%, w/v) and praziquantel (8.3%, w/v) (BROADLINE(®), Merial) at 0.12 mL/kg body weight (providing a minimum of 10mg fipronil+12 mg S-methoprene+0.5mg eprinomectin+10mg praziquantel per kg body weight). The topical treatment was administered directly on the skin in the midline of the neck in a single spot once on Day 0. For parasite recovery and count, cats were euthanized humanely and necropsied seven or ten days after treatment. A single treatment with the novel topical combination product provided 91% efficacy against Ancylostoma braziliense, ≥ 99% efficacy against Ancylostoma tubaeforme, and >97% efficacy against Toxocara cati. Similarly, excellent efficacy was established against Taenia taeniaeformis, Dipylidium caninum and Diplopylidium spp. as demonstrated by >97% and up to 100% reductions of cestode counts in the treated cats when compared to the untreated controls (P<0.01). All cats accepted the treatment well based on health observations post-treatment and daily health observations. No adverse experiences or other health problems were observed throughout the studies. The results of this series of controlled studies demonstrated high efficacy and excellent acceptability of the novel topical combination formulation of fipronil, (S)-methoprene, eprinomectin and praziquantel against a broad range of feline intestinal nematode and cestode infections.

Efficacy in cats of a novel topical combination of fipronil, (S)-methoprene, eprinomectin, praziquantel, against induced infestations of Echinococcus multilocularis.

Although foxes are the main reservoir of Echinococcus multilocularis, it is recognized that dogs and cats also may become infected. In cats the infection and egg production rates are usually low. Nevertheless, cats are a potential source of transmission of E. multilocularis. Due to the high human medical significance of E. multilocularis infection, it is important in endemic areas that owned cats are dewormed regularly. This paper presents the efficacy results of a new topical formulation, Broadline(®) (Merial) tested against E. multilocularis infection in cats. Two blinded laboratory studies were conducted to evaluate this novel topical combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel against E. multilocularis. In each study, purpose-bred cats were assigned randomly to two treatment groups of 10 cats each: one untreated control group and one group treated at the minimum therapeutic dose of 0.12 mL/kg bodyweight to deliver 10mg fipronil, 12 mg (S)-methoprene, 0.5mg eprinomectin and 10mg praziquantel/kg bodyweight. The cats were inoculated orally with E. multilocularis protoscolices, 22 or 23 days before treatment. Based on necropsy and intestinal worm count, 8 or 11 days after treatment, the two studies confirmed 100% efficacy of Broadline(®) against adult E. multilocularis.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel against induced infections of Ancylostoma spp. nematodes of cats.

Four studies were conducted to examine the efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel (BROADLINE(®), Merial) against Ancylostoma tubaeforme and Ancylostoma braziliense hookworms of cats. In each study, purpose-bred cats were randomly assigned to treatment groups of 10 or 12 cats per group. In three studies the cats were inoculated with A. tubaeforme and in one study with A. braziliense. The inoculations were undertaken on a schedule which resulted in the hookworms reaching the fourth larval stage in two of the studies, or the adult stage in four of the studies, by the day of treatment. In each study there was also an untreated control and 1 or 2 groups treated with the novel combination. In the two studies where efficacy against the fourth larval stage of A. tubaeforme was tested, the efficacy recorded was 100%. In the three studies where efficacy against the adult stage of A. tubaeforme was tested, efficacy of 100% was also confirmed. In the study where efficacy against the adult stage of A. braziliense was tested efficacy was 99.5%.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel against experimental infections of Toxascaris leonina in cats.

The efficacy of a novel topical fipronil, (S)-methoprene, eprinomectin and praziquantel combination product (BROADLINE(®), Merial) was evaluated against adult Toxascaris leonina ascarids in experimentally infected cats in two controlled studies under an identical protocol. For each study, 30 nematode-naive, purpose-bred European Short Hair cats were inoculated orally with approximately 300 larvated T. leonina eggs. Twenty-two and 24 cats, respectively, that were shown to be positive for Toxascaris eggs by pre-treatment faecal examination were subsequently included in the two studies. In each study, the animals were allocated randomly to an untreated (control) group or to a treatment group. The treatment was a novel topical combination: fipronil (8.3%, w/v), (S)-methoprene (10%, w/v), eprinomectin (0.4% w/v) and praziquantel (8.3% w/v). Treatment was applied on Day 0 at 0.12 mL/kg bodyweight. For parasite recovery and count, cats were euthanized humanely seven days after treatment and necropsied. All untreated cats harboured adult T. leonina (range, 1-31 nematodes). The treatment provided a high level of efficacy against adult T. leonina in both studies (95.8% and 98.1%, respectively p<0.001). All cats accepted the treatment well based on hourly post-treatment observations for 4h and daily observations thereafter. No adverse experiences or other health problems were observed throughout the studies. Thus the data indicate that this novel combination product will provide a safe and effective treatment against T. leonina in cats.