Efficacy of milbemycin oxime/afoxolaner chewable tablets (NEXGARD SPECTRA®) against Capillaria aerophila and Capillaria boehmi in naturally infected dogs

BACKGROUND: Capillaria aerophila and Capillaria boehmi parasitize the respiratory system of wild and domestic carnivores. Capillaria aerophila inhabits the trachea and bronchi of dogs and cats, while C. boehmi affects the nasal cavities and sinuses of dogs. In dogs the infection may be subclinical or characterized by varying respiratory distress.METHODS: The present study evaluated the efficacyof an oral formulation containing milbemycin oxime and afoxolaner (NEXGARD SPECTRA) in dogs naturally infected with C. aerophila and/or C. boehmi from three enzootic areas of Italy. Dogs were enrolled pending fecal examination and molecular confirmation of respiratory capillarioses. Dogs were allocated in two groups: Group 1 (G1, 25 dogs), treated with a negative control product with no anthelmintic activity (afoxolaner, NEXGARD), and Group 2 (G2, 26 dogs), treated with NEXGARD SPECTRA. At the day of treatment administration (Day 0), all dogs were clinically examined. Dogs were again subjected to clinical and fecal examinations at Days 28 (±4) and 56 (±2). The primary criterion for treatment efficacy was the reduction of fecal Capillaria egg counts in G2 compared with G1. The regression of/recovery from baseline clinical signs was considered as a further efficacy criterion.RESULTS: Percentage reduction of fecal Capillaria egg counts in the NEXGARD SPECTRA group compared to the control group was >97% on Day 28 and 100% on Day 56, respectively (p<0.05 for both time points). Twelve of the 13 dogs in the NEXGARD SPECTRA group with respiratory signs prior to treatment were free of clinical signs at the end of the study. Conversely, the six control group dogs with respiratory signs prior to treatment remained symptomatic.CONCLUSIONS: Results of the present study showed that NEXGARD SPECTRA was safe and highly efficacious in the reduction of C. aerophila and C. boehmi eggs after one treatment with a complete reduction of the egg output after the second administration associated with a recovery from respiratory signs

Prevention of the transmission of

This experimental study aimed to determine the efficacy of Afoxolaner (NexGard®) to prevent Babesia rossi transmission by Haemaphysalis elliptica ticks on dogs. The study included three groups of seven dogs each. Groups 1 and 2 remained untreated, whereas group 3 dogs received NexGard® on Day 0. All dogs were infested by 50 Haemaphysalis elliptica adult ticks: Group 1 on Day 2, Group 2 on Day 28 and Group 3 on Days 2 and 28. The ticks were originally nymphs having fed on B. rossi infected donor dogs. Their infection rate, assessed by PCR, was 12.8% at Day 2 and 6% at Day 28. On Days 0, 7, 14, 21, 28, 35, 42, 49 and 56, and in case of suspicion of babesiosis, blood samples were collected for blood smears, PCR and ELISA. The B. rossi infection rate in the untreated group 1 was 100% (6/6, as one dog was inadvertently treated on Day 15 and removed from statistical analysis). The infection rate was 57.1% (4/7) in group 2, and 0% (0/7) in the afoxolaner treated group 3 at all time-points until the end of the study on Day 56. After tick removal and count 144 h after each infestation, the control groups had an arithmetic mean of ticks of 23.8 (group 1) and 26.8 (group 2). No tick was recovered from any treated dogs. This study demonstrated that NexGard® protected dogs against infection by B. rossi for at least 28 days

Assessment of the efficacy of a topical combination of fipronil-permethrin (Frontline Tri-Act®/Frontect®) against egg laying and adult emergence of the cat flea (Ctenocephalides felis) in dogs

This study was conducted to assess the prevention of egg laying and the inhibition of the emergence of the cat flea (Ctenocephalides felis) resulting from the application of a combination of fipronil and permethrin (Frontline Tri-Act®/Frontect®, Merial) on dogs. Sixteen healthy dogs were included after pre-treatment live flea counts and randomly allocated to two groups. Eight dogs served as untreated controls and 8 dogs were treated on Day 0 and Day 30 with topical application of fipronil/permethrin at the minimum dose of 6.76 mg/kg fipronil and 50.48 mg/kg permethrin. On days −2, 7, 21, 28, 42 and 56, each dog was infested with 100 fleas. Flea eggs were collected from each dog in individual trays from 12 to 36 h after treatment or each flea re-infestation. All fleas were removed by combing and counted 36 h after treatment or infestations. The collected eggs were counted and incubated for 28 days for larval development and adult emergence assessment. The curative efficacy of Frontline Tri-Act®/Frontect® against adult fleas 36 h after treatment was 95.3% and the efficacy remained 100% after subsequent flea infestations for 8 weeks. Compared to the control group, the treatment reduced egg laying by 84.5% within 36 h after first treatment and was 99.9%, 100%, 100%, 100%, 100% on collection days 7, 21, 29, 43 and 57, respectively. Frontline Tri-Act®/Frontect® reduced by 28.7% the emergence of new adult fleas from eggs laid during the 48 h of pre-treatment infestation. The inhibition of adult emergence from incubated flea eggs could not be assessed after flea re-infestation in the treated group as no eggs were collected

Assessment of the efficacy of a topical combination of fipronil-permethrin (Frontline Tri-Act

This study was conducted to assess the prevention of egg laying and the inhibition of the emergence of the cat flea (Ctenocephalides felis) resulting from the application of a combination of fipronil and permethrin (Frontline Tri-Act®/Frontect®, Merial) on dogs. Sixteen healthy dogs were included after pre-treatment live flea counts and randomly allocated to two groups. Eight dogs served as untreated controls and 8 dogs were treated on Day 0 and Day 30 with topical application of fipronil/permethrin at the minimum dose of 6.76 mg/kg fipronil and 50.48 mg/kg permethrin. On days −2, 7, 21, 28, 42 and 56, each dog was infested with 100 fleas. Flea eggs were collected from each dog in individual trays from 12 to 36 h after treatment or each flea re-infestation. All fleas were removed by combing and counted 36 h after treatment or infestations. The collected eggs were counted and incubated for 28 days for larval development and adult emergence assessment. The curative efficacy of Frontline Tri-Act®/Frontect® against adult fleas 36 h after treatment was 95.3% and the efficacy remained 100% after subsequent flea infestations for 8 weeks. Compared to the control group, the treatment reduced egg laying by 84.5% within 36 h after first treatment and was 99.9%, 100%, 100%, 100%, 100% on collection days 7, 21, 29, 43 and 57, respectively. Frontline Tri-Act®/Frontect® reduced by 28.7% the emergence of new adult fleas from eggs laid during the 48 h of pre-treatment infestation. The inhibition of adult emergence from incubated flea eggs could not be assessed after flea re-infestation in the treated group as no eggs were collected

Immediate efficacy and persistent speed of kill of a novel oral formulation of afoxolaner (NexGardTM) against induced infestations with Ixodes ricinus ticks.

Ticks are hematophageous arthropods that transmit a wide spectrum of pathogens to human and animals. The ability of an acaricidal product to kill ticks quickly provides an important added benefit, especially as protecting dogs from tick bites remains the best preventive measure against tick-borne diseases. The speed of kill of afoxolaner in a novel soft chewable formulation (NexGardTM) against induced infestations with Ixodes ricinus adult ticks was evaluated during a full-month negative controlled and blinded study following a single oral administration.[br/] 12 healthy beagle dogs were included and randomly allocated to 2 groups of six dogs each. One Group was a negative control while the other group was treated with an oral formulation of afoxolaner on Day 0. Tick infestations with 40 (±5) female and 10 male adult unfed I. ricinus were performed on Days -1, 7, 14, 21 and 28. To evaluate immediate efficacy, the number of live ticks were thumb counted at 12 and 24 hours post treatment. To evaluate the persistent speed of kill following further infestations, ticks were thumb counted 12 and 24 hours post infestations. Ticks were removed 24 hours post treatment or infestation.[br/] Afoxolaner starts to kill the pre-existing tick infestations rapidly with an immediate efficacy of 93.4% and 100% respectively at 12 h and 24 h post treatment. The persistent speed of kill of afoxolaner was significant (p < 0,05), as compared with untreated controls, at 12 hours after infestations at D7 and D21. Efficacy at 12 h was 76.6%, 41.9%, 36.9% and 38.5% at D7, D14, D21 and D28 respectively. Efficacy at 24 h ranged from 91% to 100% for the entire month.[br/] This study demonstrated that besides the excellent acaricidal efficacy of afoxolaner after single oral administration, the product has a rapid speed of kill against one of the most important European tick species and controlled the weekly re-infestations for 28 days post treatment

Efficacy of oral afoxolaner plus milbemycin oxime chewable (NexGard Spectra®, Merial) to prevent heartworm disease in dogs after inoculation with third stage larvae of Dirofilaria immitis

The novel combination of afoxolaner plus milbemycin oxime, NexGard Spectra®, was evaluated against the migrating Dirofilaria immitis larvae in beagle dogs in two negative control, blinded laboratory studies. In each study, dogs were randomly allocated to an untreated control and a treated group of 10 dogs each. In each study, dogs were inoculated with third stage D. immitis larvae by subcutaneous injection (50 larvae in the first, 100 larvae in the second study). The larvae had grown into L3 stage in mosquitoes fed on blood obtained in the field from naturally infected dogs in Italy (Lombardy for the first, Sardinia for the second study). Thirty-one days after inoculation, each dog in the treated group was orally treated with NexGard Spectra® dosed as close as possible to the minimum effective dose (2.5 mg/kg Afoxolaner + 0.5 mg/kg milbemycin oxime). The control group remained untreated. All dogs were humanely euthanized and examined for adult D. immitis 146 or 147 days after inoculation. In the first study, seven of the ten untreated dogs were infected, harboring 1 to 5 adult D. immitis. In the second study, the ten untreated dogs were positive and harbored 22 to 46 adult D. immitis. In both studies all treated dogs remained free of heartworm infection as no D. immitis was recovered, demonstrating that the novel combination of afoxolaner plus milbemycin oxime was 100% effective in preventing heartworm disease in dogs

Assessment of the insecticidal activity of afoxolaner against Aedes aegypti in dogs treated with NexGard®

Twelve healthy dogs were studied in this parallel group, blinded, randomised, and negative controlled efficacy study. On Day -1, the 12 dogs included were ranked within sex in descending order of individual pre-treatment (Day -5) fed mosquito counts and randomly allocated by blocks of two dogs to the untreated control group or the afoxolaner-treated group. NexGard® (Merial, now part of Boehringer Ingelheim Animal Health) was administered orally on Day 0 in accordance with the European label instructions. On Days 1, 7, 14, 21 and 28, all dogs were exposed for a duration of 1 hour to 50 ± 5 unfed Aedes aegypti females. After each exposure, mosquitoes were collected after 1 hour and assessed for viability during collection and at 24 ± 2 hours. The arithmetic (and geometric) mean values of live fed mosquito counts at 24 hours after the exposure periods for the negative control group ranged from 33.7 (32.3) to 49.8 (49.7), indicating that this was a vigorous mosquito strain. There was no significant difference between control and treated groups in the number of live and fed mosquitoes at each 1 hour post-exposure collection time. Based on arithmetic and geometric mean values at 24 hours after each exposure, significantly fewer live fed mosquitoes were recorded in the treated group, compared to the negative control group, throughout the study (p < 0.001). The afoxolaner insecticidal efficacy against A. aegypti varied from 98% (Day 2) to 75.3% (Day 29) based on arithmetic means, and 98.7% (Day 2) to 89.8% (Day 29) based on geometric means

Assessment of the insecticidal activity of afoxolaner against Aedes aegypti in dogs treated with NexGard®

Twelve healthy dogs were studied in this parallel group, blinded, randomised, and negative controlled efficacy study. On Day -1, the 12 dogs included were ranked within sex in descending order of individual pre-treatment (Day -5) fed mosquito counts and randomly allocated by blocks of two dogs to the untreated control group or the afoxolaner-treated group. NexGard® (Merial, now part of Boehringer Ingelheim Animal Health) was administered orally on Day 0 in accordance with the European label instructions. On Days 1, 7, 14, 21 and 28, all dogs were exposed for a duration of 1 hour to 50 ± 5 unfed Aedes aegypti females. After each exposure, mosquitoes were collected after 1 hour and assessed for viability during collection and at 24 ± 2 hours. The arithmetic (and geometric) mean values of live fed mosquito counts at 24 hours after the exposure periods for the negative control group ranged from 33.7 (32.3) to 49.8 (49.7), indicating that this was a vigorous mosquito strain. There was no significant difference between control and treated groups in the number of live and fed mosquitoes at each 1 hour post-exposure collection time. Based on arithmetic and geometric mean values at 24 hours after each exposure, significantly fewer live fed mosquitoes were recorded in the treated group, compared to the negative control group, throughout the study (p < 0.001). The afoxolaner insecticidal efficacy against A. aegypti varied from 98% (Day 2) to 75.3% (Day 29) based on arithmetic means, and 98.7% (Day 2) to 89.8% (Day 29) based on geometric means

Assessment of the insecticidal activity of oral afoxolaner against

Twelve healthy dogs were included in this laboratory efficacy study. Six dogs were randomly allocated based on body weight to an untreated control group and six to an afoxolaner (NexGard®) treated group. In the treatment group, afoxolaner was administered orally on Day 0 in accordance with label instructions. On Days 1, 14 and 28, each dog was exposed to 60 unfed female and 10 male Phlebotomus perniciosus sandflies for 1 h. At the end of each exposure period, sandflies were counted and assessed for viability and feeding status. There was no statistical difference in mortality (0.0–5.4%), nor in feeding proportion (61.6–78%) between the control and the treated groups at all 1-h post-exposure assessments. After collection, live fed and unfed sandflies were kept for viability assessments at 48 and 72 h post-exposure. In the untreated control group, the average percentages of live, fed, female sandflies after exposure, on Days 1, 14 and 28, ranged from 51% to 74% at 48 h and from 46% to 57% at 72 h, demonstrating model robustness over the 28 days of the study. Significantly fewer live fed sandflies were recorded for the afoxolaner treated group (p < 0.01). The insecticidal efficacy was 100%, 95.9% and 75.2% at 48 h post Days 1, 14 and 28 exposures, respectively, and 100%, 100% and 86.3% at 72 h post Days 1, 14, and 28 exposures, respectively. A single administration of oral afoxolaner (NexGard®) to dogs significantly killed P. perniciosus sandflies 48 and 72 h after blood feeding for 1 month

Assessment of the insecticidal activity of afoxolaner against

Twelve healthy dogs were studied in this parallel group, blinded, randomised, and negative controlled efficacy study. On Day -1, the 12 dogs included were ranked within sex in descending order of individual pre-treatment (Day -5) fed mosquito counts and randomly allocated by blocks of two dogs to the untreated control group or the afoxolaner-treated group. NexGard® (Merial, now part of Boehringer Ingelheim Animal Health) was administered orally on Day 0 in accordance with the European label instructions. On Days 1, 7, 14, 21 and 28, all dogs were exposed for a duration of 1 hour to 50 ± 5 unfed Aedes aegypti females. After each exposure, mosquitoes were collected after 1 hour and assessed for viability during collection and at 24 ± 2 hours. The arithmetic (and geometric) mean values of live fed mosquito counts at 24 hours after the exposure periods for the negative control group ranged from 33.7 (32.3) to 49.8 (49.7), indicating that this was a vigorous mosquito strain. There was no significant difference between control and treated groups in the number of live and fed mosquitoes at each 1 hour post-exposure collection time. Based on arithmetic and geometric mean values at 24 hours after each exposure, significantly fewer live fed mosquitoes were recorded in the treated group, compared to the negative control group, throughout the study (p < 0.001). The afoxolaner insecticidal efficacy against A. aegypti varied from 98% (Day 2) to 75.3% (Day 29) based on arithmetic means, and 98.7% (Day 2) to 89.8% (Day 29) based on geometric means