Comparative speed of kill provided by lotilaner (Credelio™), sarolaner (Simparica Trio™), and afoxolaner (NexGard™) to control Amblyomma americanum infestations on dogs.

BACKGROUND: Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products. METHODS: Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days - 7, - 2, 21, and 28, and tick counts were performed on day - 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons. RESULTS: On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) (P < 0.001) and afoxolaner (6.3%) (P < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different (P < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) (P = 0.020) and afoxolaner (9.0%) (P = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% (P < 0.001) and afoxolaner (0.0%) (P < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24-48 h earlier for lotilaner compared with sarolaner or afoxolaner. CONCLUSIONS: Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner's speed of tick kill is sustained throughout the dosing period.

Efficacy of a combination of esafoxolaner, eprinomectin and praziquantel (NexGard® Combo) against Thelazia callipaeda in naturally infected cats.

This clinical study assessed the efficacy of a topical combination of esafoxolaner, eprinomectin and praziquantel (NexGard® Combo) in treating cats naturally infected with the eyeworm Thelazia callipaeda (Nematoda, Thelaziidae). On Study Day (SD) 0, sixteen client-owned cats with eyeworm infection were allocated to an untreated control group (G1, 8 cats) or to a NexGard® Combo treated group (G2, 8 cats) and subjected to ocular examination. Cats in G2 received the treatment as per label recommendations. On SD 7 and 14 (±1), cats were examined for the presence of eyeworms and clinical signs. On SD 14, eyeworms were collected and counted. On SD 7 and 14, all cats in G1 were still infected with eyeworms, while G2 cats were free from eyeworms on SD 7 and 14, demonstrating 100% efficacy (p < 0.0001). All collected eyeworms were morphologically and molecularly confirmed to be T. callipaeda. On SD 0, fifteen out of the sixteen cats (7 in G1 and 8 in G2) displayed inflammatory ocular signs. On SD 7, all eight untreated cats and seven treated cats displayed inflammatory ocular signs. On SD 14, five out of eight G2 treated cats had recovered, while the eight untreated cats still displayed inflammatory ocular signs. The treatment significantly reduced lacrimation and conjunctivitis (p = 0.0001). No adverse reactions occurred. This clinical study provides evidence that NexGard® Combo is highly safe and effective for the treatment of T. callipaeda infection in cats under field conditions.

Title: Efficacité d'une association d'esafoxolaner, d'éprinomectine et de praziquantel (NexGard® Combo) contre Thelazia callipaeda chez le chat naturellement infecté. Abstract: Cette étude clinique a évalué l'efficacité d'une association topique d'esafoxolaner, d'éprinomectine et de praziquantel (NexGard® Combo) dans le traitement des chats naturellement infectés par le ver oculaire Thelazia callipaeda (Nematoda, Thelaziidae). Au jour d'étude (JE) 0, seize chats appartenant à des clients et atteints d'une infection par le ver oculaire ont été attribués à un groupe témoin non traité (G1, 8 chats) ou à un groupe traité NexGard® Combo (G2, 8 chats) et soumis à un examen oculaire. Les chats du groupe G2 ont reçu le traitement conformément aux recommandations de l'étiquette. Aux JE 7 et 14 (±1), les chats ont été examinés pour détecter la présence de vers oculaires et de signes cliniques. Au JE 14, les vers oculaires ont été collectés et comptés. Aux JE 7 et 14, tous les chats du G1 étaient toujours infectés par des vers oculaires, tandis que les chats du G2 étaient exempts de vers oculaires aux JE 7 et 14, démontrant une efficacité de 100 % (p < 0,0001). Tous les vers oculaires collectés ont été confirmés morphologiquement et moléculairement comme étant T. callipaeda. Au JE 0, quinze chats sur seize (7 en G1 et 8 en G2) présentaient des signes oculaires inflammatoires. Au JE 7, les huit chats non traités et les sept chats traités présentaient des signes oculaires inflammatoires. Au JE 14, cinq des huit chats traités par G2 s'étaient rétablis tandis que les huit chats non traités présentaient toujours des signes oculaires inflammatoires. Le traitement a réduit de manière significative le larmoiement et la conjonctivite (p = 0,0001). Aucun effet indésirable n'est survenu. Cette étude clinique indique que NexGard® Combo est hautement sûr et efficace pour le traitement de l'infection à T. callipaeda chez les chats dans des conditions de terrain.

Efficacy of afoxolaner or the combination of afoxolaner with milbemycin oxime against Otodectes cynotis in naturally infested dogs.

Otodectes cynotis, commonly known as "the ear mite," is a highly contagious ectoparasite and a significant cause of otitis externa in canines. The objective of the current study was to determine the efficacy of the isoxazoline afoxolaner (Nexgard®), and the combination of afoxolaner with milbemycin oxime (Nexgard Spectra®), in dogs naturally infested with O. cynotis. In total, 32 infested client-owned dogs from two different sites in Greece were included. The animals were randomly divided into four equal groups based on their infestation score. Group 1 served as the negative control, group 2 received one oral administration of Nexgard (Day 0), group 3 received two monthly oral administrations of Nexgard (Days 0, 30), and group 4 received two monthly oral administrations of Nexgard Spectra (Days 0, 30), according to label instructions. Otoscopic examinations for mites and observations on debris/cerumen in the ears were carried out on Days 0, 15, 30, and 45. A quantitative assessment of ear mites by ear duct flushing and live mite counts was performed on Day 45. The results demonstrated that a single oral dose of afoxolaner and two monthly doses of afoxolaner or afoxolaner with milbemycin oxime resulted in a 99.9% reduction in live mite counts compared to the untreated control group by Day 45. Additionally, treated dogs showed improved clinical symptoms, such as ear cerumen/debris decrease, while untreated dogs experienced worsening symptoms over the study duration. No adverse events were reported. Overall, these results support the use of afoxolaner-based products to treat O. cynotis infestation in dogs.

Efficacy of two endectoparasiticide products combining fipronil and (S)-methoprene or esafoxolaner with eprinomectin and praziquantel against fleas and intestinal helminths in cats naturally infested in Brazil.

Eprinomectin and praziquantel, nematodicide and cestodicide compounds, are both combined with the insecticide and acaricide compounds fipronil and (S)-methoprene in Frontline® Protect/Broadline®, or esafoxolaner in NexGard® Combo. These topical feline endectoparasiticide products were tested for efficacy against fleas and intestinal helminths in a field trial in Brazil. Flea- and/or helminth-infested domestic cats were treated twice at a monthly interval following label instructions: 160 cats with Frontline® Protect/Broadline® and 165 cats with NexGard® Combo. The flea and intestinal helminth infestations were evaluated using comb counts and copromicroscopy, respectively before first treatment for baseline value, then 9 and 30 days after each treatment for fleas, and 9 days after each treatment for helminths. Multiparasitism was very frequent at baseline, as amongst the 325 included cats, 295, 280, 86 and 93 cats were at least infested with Ctenocephalides fleas, Ancylostoma, Toxocara and Dipylidium caninum, respectively. Efficacies were calculated by comparing the geometric means at baseline and at post-treatment timepoints for each parasite genus/species. Inclusive of both products and of all evaluation timepoints, the Ctenocephalides, Ancylostoma, Toxocara and D. caninum efficacies were at least 98.3%, 99.8%, 99.8% and 96.3%, respectively. No adverse reactions were observed, except for a few instances of mild, transient, and self-resolving hypersalivation occurring on the day of treatment in both groups. This field trial demonstrated high-level efficacy of Frontline® Protect/Broadline® and NexGard® Combo against major parasites of cats in Brazil.

TITLE: Efficacité de deux produits endectoparasiticides associant fipronil et (S)-méthoprène ou esafoxolaner à l'éprinomectine et au praziquantel contre les puces et les helminthes intestinaux chez les chats naturellement infestés au Brésil. ABSTRACT: L'éprinomectine et le praziquantel, composés nématodicides et cestodicides, sont tous les deux associés aux composés insecticides et acaricides fipronil et (S)-méthoprène dans Frontline® Protect/Broadline®, ou esafoxolaner dans NexGard® Combo. Ces produits endectoparasiticides félins topiques ont été testés pour leur efficacité contre les puces et les helminthes intestinaux lors d'un essai sur le terrain au Brésil. Des chats domestiques infestés de puces et/ou d'helminthes ont été traités deux fois à intervalle d'un mois en suivant les instructions d'utilisation, 160 chats avec Frontline® Protect/Broadline® et 165 chats avec NexGard® Combo. Les infestations par les puces et les helminthes intestinaux ont été évaluées en utilisant respectivement par comptage au peigne et par copromicroscopie, avant le premier traitement pour la valeur de base, puis 9 et 30 jours après chaque traitement pour les puces, et 9 jours après chaque traitement pour les helminthes. Le multiparasitisme était très fréquent à l'inclusion puisque parmi les 325 chats inclus, 295, 280, 86 et 93 chats étaient au moins infestés respectivement par les puces Ctenocephalides, ou Ancylostoma, Toxocara et Dipylidium caninum. Les efficacités ont été calculées en comparant les moyennes géométriques au départ et aux points d'évaluation post-traitement pour chaque genre/espèce de parasite. En incluant les deux produits et tous les points temporels d'évaluation, les efficacités contre Ctenocephalides, Ancylostoma, Toxocara et D. caninum étaient respectivement d'au moins 98,3 %, 99,8 %, 99,8 % et 96,3 %. Aucun effet indésirable n'a été observé à l'exception de quelques cas d'hypersalivation légère, transitoire et auto-résolvante survenant le jour d'un traitement dans les deux groupes. Cet essai sur le terrain a démontré une efficacité de haut niveau de Frontline® Protect / Broadline® et NexGard® Combo contre les principaux parasites des chats au Brésil.

Efficacy of afoxolaner for the treatment of ear mite infestation under field conditions.

Otodectes cynotis is a commonly occurring surface mite that can be easily transmitted between suitable hosts, including dogs, causing otocariosis. The activity of the systemic insecticide afoxolaner against O. cynotis has been tested once under experimental conditions, showing a high efficacy. The present study aimed to i) assess the efficacy of two consecutive monthly oral administrations of afoxolaner (NexGard®) against O. cynotis in naturally infested dogs under field conditions and ii) evaluate its impact in reducing bacteria or fungal secondary infections. Dogs, positive for O. cynotis (n = 20), were included in the study and allocated in two groups of ten animals each (G1, control group, and G2, treated group). The first group of ear mite-infested dogs was treated with a placebo, while afoxolaner was administered orally to the second group of dogs at Day 0 (D0) and Day 30 (D30), following label instructions. Otoscopic assessments, deep-swab method and swab samples were performed on all dogs (Days 0, 30, 42) to evaluate the presence or absence of live mites and their number throughout the study, as well as to conduct bacterial and fungal assessments. No adverse events likely related were recorded throughout the study. By Day 42 (D42), all dog's ears were flushed to recover ear mites. All treated dogs became negative, as well as two dogs of the control group. The treatment efficacy of afoxolaner was 100 % based on the arithmetic means of the live mite counts. The clinical scores did not change significantly in the control group, whereas they significantly improved in the treated one from D0 to D30 (p-value = 5.47 10-5). No live mites were present in the afoxolaner-treated group at D42 (p-value = 0.00073). In this field study, two oral administrations of afoxolaner at the recommended dose allowed a complete cure of the infestation. Bacterial and Malassezia pachydermatis infections were detected in both groups, although no significant trend was associated to the ear mite treatment.

Efficacy of afoxolaner (NexGard®) in preventing the transmission of Leishmania infantum and Dirofilaria immitis to sheltered dogs in a highly endemic area.

BACKGROUND: Leishmania infantum and Dirofilaria immitis are among the most important canine vector-borne pathogens (CVBPs) of zoonotic concern in Europe. In endemic areas for both of these CVBPs, the use of systemic ectoparasiticides, such as afoxolaner (NexGard®; Boehringer Ingelheim Animal Health), may have the potential for controlling these infections. The aim of this study was to assess, for the first time, the insecticidal efficacy of NexGard® in decreasing the transmission of D. immitis and L. infantum to sheltered dogs living in a hyperendemic area, compared to the year before treatment, as well as its impact on the abundance of mosquito and sand fly populations. METHODS: All dogs (n = 179) enrolled in the study were divided into two groups based on their infection status at enrollment: a non-infected group (G1) and an infected group (G2; infected with D. immitis, L. infantum or both). The study was conducted from March 2020 to March 2021. In order to exclude all animals infected with L. infantum and D. immitis before March 2020 (sampling time: T0), dogs in G1 were sampled in June (T1; i.e. T0 + 90 days) and in October 2020 (T2; i.e. T0 + 210 days). From March to September 2020, all animals (G1 and G2) were weighed and treated monthly with NexGard®. Animals in G1 were tested for the last time in March 2021 (T3; i.e. T0 + 330 days) for assessing post-treatment incidence rate of infection and prevention efficacy. RESULTS: The post-treatment incidence of D. immitis was 3.7% (1/27; 95% confidence interval [CI]: 0.2-18.1) and that of L. infantum was 3.6% (3/83; 95% CI: 1.0-10.1). Considering the annual incidence in 2019 and 2020, the protective efficacy against D. immitis and L. infantum infections was 94.2 and 64%, respectively. Of the female mosquitoes collected (n = 146), only one pool out of 50 tested positive for D. immitis DNA, whereas out of 1252 female Sergentomya minuta specimens collected, only four tested positive for L. infantum (0.3%). CONCLUSIONS: Afoxolaner is efficacious in decreasing the rate of transmission of both D. immitis and L. infantum; however, comparison of the pre- and post-treatment period demonstrated that there was a significant difference only in the seasonal incidences of D. immitis infection. Preventive measures are recommended throughout the year in endemic areas to reduce the risk of pathogen transmission to animals and humans.

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 efficacy of 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.

Efficacy of combination products containing sarolaner, moxidectin and pyrantel (Simparica Trio™) or afoxolaner and milbemycin (NexGard Spectra®) against induced infestations of Ixodes holocyclus in dogs.

BACKGROUND: The Australian paralysis tick, Ixodes holocyclus, causes tick paralysis in dogs and cats in the eastern coastal regions of Australia. Prevention is the best option to protect dogs against this potentially fatal disease and sarolaner provides rapid and sustained efficacy against I. holocyclus. In this laboratory study, the efficacy of two combination endectocides containing sarolaner + moxidectin + pyrantel (Simparica Trio™) and afoxolaner + milbemycin (NexGard Spectra®) was evaluated against an artificial infestation of I. holocyclus. METHODS: Twenty-four (n =24) foxhounds were randomly allocated to three treatment groups and artificially infested with 30 adult female viable ticks on Days - 1, 7, 14, 21, 28 and 35. On Day 0, dogs in each treatment group were treated with either Drontal® (control group), Simparica Trio™ at the label dose to provide minimum doses of sarolaner (1.2 mg/kg), moxidectin (24 µg/kg) and pyrantel (5 mg/kg) or NexGard Spectra® to provide minimum doses of afoxolaner (2.5 mg/kg) and milbemycin (0.5 mg/kg). Live tick counts were performed at 48 and 72 hours after treatment and after each re-infestation on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for control dogs based on geometric means. RESULTS: Against an existing infestation, efficacy of both Simparica Trio™ and NexGard Spectra® was 99.6% and 100% at 48 and 72 h time points, respectively (P = 1.000). Against subsequent weekly infestations, treatment with Simparica Trio™ and NexGard Spectra® resulted in efficacy of ≥ 97.7% and ≥ 95.5% (P ≥ 0.0911), respectively at the 48 h time point and at the 72 h time point, Simparica Trio™ and NexGard Spectra® resulted in efficacy of ≥ 99.0% and ≥ 98.4% (P ≥ 0.0511), respectively. There were no treatment-related adverse events in the study. CONCLUSIONS: Single doses of Simparica Trio™ and NexGard Spectra® were highly efficacious and provided comparable efficacy against the Australian paralysis tick, I. holocyclus for up to 35 days.

Assessment of the insecticidal activity of oral afoxolaner against Phlebotomus perniciosus in dogs.

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.

TITLE: Évaluation de l'activité insecticide de l'afoxolaner par voie orale contre Phlebotomus perniciosus chez le chien. ABSTRACT: Douze chiens en bonne santé ont été inclus dans cette étude d'efficacité en laboratoire. Six chiens ont été répartis au hasard en fonction de leur poids corporel dans un groupe témoin non traité et six dans un groupe traité par afoxolaner (NexGard®), administré par voie orale le jour 0 conformément aux instructions de l'étiquette. Les jours 1, 14 et 28, chaque chien a été exposé à 60 femelles à jeun et 10 mâles de Phlebotomus perniciosus pendant une heure. À la fin de chaque période d'exposition, les phlébotomes ont été évalués en termes de viabilité et de statut alimentaire. Il n'y avait pas de différence statistique dans la mortalité (0,0 à 5,4 %), ni dans le taux d'engorgement (61,6 à 78 %) entre le groupe témoin et le groupe traité lors de toutes les évaluations après une heure. Après la collecte, les phlébotomes vivants gorgés et non gorgés ont été conservés aux fins d'évaluation de la viabilité 48 et 72 heures après l'exposition. Dans le groupe témoin non traité, le pourcentage moyen de phlébotomes femelles gorgées et vivantes après l'exposition aux jours 1, 14 et 28 variait de 51 à 74 % à 48 heures et de 46 à 57 % à 72 heures, démontrant la robustesse du modèle au cours des 28 jours de l'étude. Un nombre significativement moins important de phlébotomes gorgés vivants ont été enregistrés dans le groupe traité par afoxolaner (p < 0,01). L'efficacité insecticide était de 100 %, 95,9 % et 75,2 % 48 heures après les expositions des jours 1, 14 et 28, respectivement, et 100 %, 100 % et 86,3 % à 72 heures après les expositions des jours 1, 14 et 28, respectivement. Une seule administration d'afoxolaner (NexGard®) par voie orale à un chien tue de manière significative les phlébotomes P. perniciosus 48 heures et 72 heures après la prise de sang pendant un mois.

Efficacy of two formulations of afoxolaner (NexGard® and NexGard Spectra®) for the treatment of generalised demodicosis in dogs, in veterinary dermatology referral centers in Europe.

BACKGROUND: A multi-centre field trial was conducted to evaluate the efficacy of afoxolaner based chewables (NexGard® or NexGard Spectra®) for the treatment of generalised demodicosis caused by Demodex canis in dogs under field conditions in France, Italy and Poland. METHODS: Client-owned dogs, diagnosed positive for Demodex mites by pre-treatment skin scrapings and presenting clinical signs of generalised demodicosis were included. Dogs were orally treated with afoxolaner three times at monthly intervals. Of the 50 dogs enrolled, 48 completed the whole study. Efficacy of the treatments was assessed monthly by Demodex mite counts and physical examination with special regard to the severity and extension of skin lesions. RESULTS: Treatments were well tolerated in all dogs and resulted in a rapid reduction of mites, with all post-treatment mite counts significantly lower than baseline. The number of mites was reduced by 87.6%, 96.5% and 98.1% on Days 28, 56 and 84, respectively. In addition, the skin lesion severity and extent scores as well as the pruritus were all significantly lower at all post-treatment visits compared to the pre-treatment assessment. CONCLUSIONS: This clinical field study demonstrated that monthly administrations of afoxolaner in NexGard® or NexGard Spectra®, offered a convenient and reliable solution for the treatment of canine generalised demodicosis.

The sustained speed of kill of ticks (Rhipicephalus sanguineus) and fleas (Ctenocephalides felis felis) on dogs by a spot-on combination of fipronil and permethrin (Effitix®) compared with oral afoxolaner (NexGard®).

The rapid speed of kill of a spot-on, combination of fipronil-permethrin (Effitix®, Virbac) was shown against infestations of Rhipicephalus sanguineus and Ctenocephalides felis on dogs. Efficacy was determined against new infestations at weekly intervals for one month after treatment. Dogs were allocated randomly to either an untreated control or to a single administration, given on Day 0, of either topical fipronil-permethrin (6.7-13.4mg/kg and 60-120mg/kg, respectively) or oral afoxolaner (2.72-6.8mg/kg), based on pre-treatment, host-suitability flea counts. Dogs were infested with 50, unfed, adult R. sanguineus on Days 7, 14, 21 and 28, and with 100C. felis on Days 8, 15, 22 and 29. Tick counts were performed 0.5, 2, 6, 12 and 24h, and flea counts were performed 0.5 and 24h after each infestation. No treatment-related adverse reactions occurred. Dogs in the untreated group maintained viable infestations throughout the study. Following infestation, live tick and flea counts for dogs treated with fipronil-permethrin compared with untreated dogs were rapidly and significantly reduced with efficacy apparent at 0.5h after infestation. Flea efficacies (arithmetic mean counts) at 0.5h after infestation on Day 7 (Day 28) were significantly greater for fipronil-permethrin, 70% (34%) compared with 8% (18%) for afoxolaner (P≤0.05). Tick efficacies at 2h on Day 7 (Day 28) were 74% (63%) for fipronil-permethrin compared with 10% (0%) for afoxolaner (P≤0.05). Efficacies for tick repellency as indicated by counts of ticks off the dogs at 2h on Day 7 (Day 28) were greater for fipronil-permethrin, 32% (22%) compared with afoxolaner, 0% (0%) (P≤0.05). Anti-attachment efficacies at 12h were greater for fipronil-permethrin compared with afoxolaner. Tick efficacies at 24h, based on arithmetic (geometric) means, were significantly greater on Day 28 for fipronil-permethrin compared with afoxolaner (P≤0.05), 74% (87%) and 45% (60%), respectively, and were similar (P >0.05) on Days 7, 14 and 21. Flea efficacies, 24h after infestation were >98% and similar for both treated groups on all infestation days (P >0.05). The topically applied fipronil-permethrin containing ectoparasiticide Effitix® offers rapid efficacy against R. sanguineus and C. felis which persists for one month after a single administration in dogs. Afoxolaner is also effective although speed of kill is slower. The rapid and sustained speed of kill of both parasites by fipronil-permethrin should contribute to effective management not only of these parasites and their direct adverse effects including irritancy and allergy, but also to reducing the risk of transmitting infections.

Systemic insecticide treatment of the canine reservoir of Trypanosoma cruzi induces high levels of lethality in Triatoma infestans, a principal vector of Chagas disease.

BACKGROUND: Despite large-scale reductions in Chagas disease prevalence across Central and South America, Trypanosoma cruzi infection remains a considerable public health problem in the Gran Chaco region where vector-borne transmission persists. In these communities, peridomestic animals are major blood-meal sources for triatomines, and household presence of infected dogs increases T. cruzi transmission risk for humans. To address the pressing need for field-friendly, complementary methods to reduce triatomine infestation and interrupt T. cruzi transmission, this study evaluated the systemic activity of three commercial, oral, single dose insecticides Fluralaner (Bravecto®), Afoxolaner (NexGard®) and Spinosad (Comfortis®) in canine feed-through assays against Triatoma infestans, the principal domestic vector species in the Southern Cone of South America. METHODS: Twelve healthy, outbred dogs were recruited from the Zoonosis Surveillance and Control Program in Santa Cruz, Bolivia, and randomized to three treatment groups, each containing one control and three treated dogs. Following oral drug administration, colony-reared second and third stage T. infestans instars were offered to feed on dogs for 30 min at 2, 7, 21, 34 and 51 days post-treatment. RESULTS: Eighty-five per cent (768/907) of T. infestans successfully blood-fed during bioassays, with significantly higher proportions of bugs becoming fully-engorged when exposed to Bravecto® treated dogs (P < 0.001) for reasons unknown. Exposure to Bravecto® or NexGard® induced 100% triatomine mortality in fully- or semi-engorged bugs within 5 days of feeding for the entire follow-up period. The lethality effect for Comfortis® was much lower (50-70%) and declined almost entirely after 51 days. Instead Comfortis® treatment resulted in substantial morbidity; of these, 30% fully recovered whereas 53% remained morbid after 120 h, the latter subsequently unable to feed 30 days later. CONCLUSIONS: A single oral dose of Fluralaner or Afoxolaner was safe and well tolerated, producing complete triatomine mortality on treated dogs over 7.3 weeks. While both drugs were highly efficacious, more bugs exposed to Fluralaner took complete blood-meals, and experienced rapid knock-down. Coupled with its longer residual activity, Fluralaner represents an ideal insecticide for development into a complementary, operationally-feasible, community-level method of reducing triatomine infestation and potentially controlling T. cruzi transmission, in the Gran Chaco region.

Comparative speed of kill of sarolaner (Simparica®) and afoxolaner (NexGard®) against induced infestations of Ixodes holocyclus on dogs.

BACKGROUND: The Australian paralysis tick, Ixodes holocyclus, causes paralysis predominantly in dogs and cats in the Eastern coastal regions of Australia. Rapid onset of effect of a parasiticide is critical to minimize the deleterious effects of these tick infestations, especially tick paralysis caused by the salivary neurotoxin. The speed of kill of a novel orally administered isoxazoline parasiticide, sarolaner chewable tablets (Simparica®), against I. holocyclus on dogs was evaluated and compared with afoxolaner (NexGard®) for 5 weeks after a single oral dose. METHODS: Twenty-four (24) dogs were randomly allocated to treatment with either placebo, sarolaner (label dose of 2 to 4 mg/kg as per dosing table), or afoxolaner (label dose of 2.7 to 6.9 mg/kg) based on pre-treatment body weights. Following artificial infestation on Day -1, dogs were examined and live ticks counted at 8, 12, 24 and 48 h after treatment on Day 0, and at 12, 24 and 48 h after subsequent re-infestations on Days 7, 14, 21, 28 and 35. Efficacy was determined at each time point relative to counts for placebo dogs based on geometric means. RESULTS: At 8 and 12 h time points on Day 0, sarolaner-treated dogs had significantly lower geometric mean tick counts compared to the dogs treated with afoxolaner (P ≤ 0.0303). Efficacy of sarolaner against an existing infestation was 86.2 and 96.9% compared with that of afoxolaner which had efficacy of 21.3 and 85.0% at 8 and 12 h time points, respectively. Against subsequent weekly re-infestations at 12 h time points, treatment with sarolaner resulted in significantly lower geometric mean tick counts than afoxolaner-treated dogs on all days (P ≤ 0.0077) with the efficacy ranging from 60.2 to 92.2%, compared to 5.8 to 61.0% in the afoxolaner-treated dogs. Against subsequent weekly re-infestations at the 24 h time points on Days 22 and 36, efficacy of sarolaner was significantly higher at 99.2 and 97.9%, respectively, compared with afoxolaner which had efficacy of 92.4 and 91.9% (P ≤ 0.0356). At the 48 h time points following each of the five weekly re-infestations, the mean efficacy results of sarolaner and afoxolaner treated dogs were similar on most occasions. There were no adverse reactions to treatments. CONCLUSIONS: In this controlled laboratory evaluation, a single dose of sarolaner had a significantly faster speed of kill against an existing infestation of I. holocyclus, than afoxolaner at 8 and 12 h post-treatment. The rapid and consistent kill of ticks provided by sarolaner within 24 h after a single oral dose and following weekly re-infestations over 35 days suggests this treatment will provide highly effective, rapid and reliable control of ticks over the entire treatment interval, thereby minimizing the risk of tick paralysis in dogs.

Assessment of afoxolaner efficacy against Otodectes cynotis infestations of dogs.

BACKGROUND: The efficacy of a single 2.5 mg/kg dose of afoxolaner (NexGard®, Merial) against induced Otodectes cynotis infestations was assessed in eight afoxolaner-treated dogs, compared to eight untreated dogs. METHODS: After O. cynotis infestations were established and confirmed by otoscopic assessments in 16 dogs, all of the dogs were included in the study and allocated to two separate treatment groups. The first group of eight ear mite-infested dogs remained untreated, while afoxolaner was administered orally to the second group of dogs at the minimum recommended dose once on Day 0. Otoscopic assessments performed on all dogs (Days -7, -2, 14 and 28) confirmed the presence or absence of live mites throughout the study. No serious adverse events were recorded throughout the study, and no adverse events were likely related to the administration of NexGard. RESULTS: By Day 28, seven out of eight untreated dogs were still infested with ear mites, while only two out of eight afoxolaner-treated dogs were infested, with one and four ear mites, respectively. On Day 28, the reductions of mite counts in the afoxolaner-treated group versus those of the control dogs were 98.5% based on geometric means, and 99.4% based on arithmetic means. Significantly fewer (P < 0.05) live mites were present in the afoxolaner-treated group than the untreated group on Day 28. CONCLUSION: The results of this study demonstrated that a single oral administration of afoxolaner at the minimum recommended dose is highly effective (>98%) in treating dogs with induced O. cynotis infestations.

Ability of an oral formulation of afoxolaner to protect dogs from Borrelia burgdorferi infection transmitted by wild Ixodes scapularis ticks.

A randomized, blinded, negative controlled study was conducted to determine whether treatment with afoxolaner (NexGard®, Merial, Inc.) would prevent the transmission of Borrelia burgdorferi to dogs by wild caught Ixodes scapularis ticks. Twenty healthy dogs were randomly assigned to two groups of ten dogs each. Ten dogs were treated orally on Day 0 at a dose near the minimum recommended dose of afoxolaner of 2.5mg/kg (actual doses 2.5-3.1mg/kg) and ten control dogs were not treated. On Day 28, each dog was infested with approximately 50 adult unfed wild caught I. scapularis that had a 67% B. burgdorferi infection rate (determined by polymerase chain reaction). On Day 33, live ticks were counted and removed. No ticks were found on treated dogs while control dogs had an average of 21.4 ticks. To detect infection, the B. burgdorferi-specific C6 antibody SNAP® 4Dx® test (IDEXX) was performed on serum collected before infestation (all dogs seronegative on Days -6 and 27) and on Days 48, 63, 77 and 92. The ten treated dogs remained seronegative through the end of the study (Day 92), while nine out of the ten control dogs were infected, as demonstrated by their seroconversion to being positive for the presence of the B. burgdorferi-specific C6 antibody starting on Day 48. In this study, all dogs treated with NexGard® 28days prior to challenge with wild caught I. scapularis ticks were protected from B. burgdorferi infection, while nine out of the ten untreated control dogs were infected.

Evaluation of the efficacy of monthly oral administration of afoxolaner plus milbemycin oxime (NexGard Spectra(®), Merial) in the prevention of adult Spirocerca lupi establishment in experimentally infected dogs.

The nematode Spirocerca lupi (Rudolphi, 1809) is widely distributed but mostly occurs sporadically with stable populations only in certain geographic areas. This helminth mainly infects dogs and wild canids. Primary pathology relates to migration of third stage larvae (L3) damaging the thoracic aorta and establishment of adults in nodules in the oesophagus. The objective of the present study was to evaluate the efficacy of milbemycin oxime in combination with afoxolaner (NexGard Spectra(®), Merial), administered monthly, in preventing establishment of adult worms after experimental infection. Two groups consisting of eight animals each were experimentally infected with 15 L3 on Days -28, -14 and -2, respectively (45 L3 per animal in total). Group 1 dogs served as untreated (negative) control, whereas animals in group 2 were treated with NexGard Spectra(®) at a minimum dose of 0.5mg/kg milbemycin oxime on Day 0 and from then onwards every 28 days up to Day 140 (six treatment occasions). Endoscopy was performed on Day 112 and for some animals also Day 140. Necropsy for worm recovery and nodule/lesion scoring was performed on Day 168. All eight animals in the control group (group 1) presented with 1-3 nodules and worm counts ranging from 9 to 41. Six animals in the NexGard Spectra(®) group presented with 1-4 nodules and worm counts ranging from 1 to 5. Significantly (p<0.05) fewer worms were collected from treated animals in the treated group (geometric mean 1.7) versus the negative control group (geometric mean 22.0) with 92.3% efficacy calculated. There was no significant (p>0.05) difference between groups with reference to number of nodules in the oesophagus. However, nodules in the control group were significantly (p<0.05) larger than those in the treated group. Number and size of lesions in the dorsal aorta did not differ statistically between groups 1 and 2. Because NexGard Spectra(®) was administered 28 days after onset of inoculation, migrating and developing L3 caused damage to the aorta wall of animals in the treated group. Milbemycin oxime (administered as NexGard Spectra(®)) demonstrated effectiveness in reducing infection with adult Spirocerca lupi worms in the oesophagus.

Comparative speed of efficacy against Ctenocephalides felis of two oral treatments for dogs containing either afoxolaner or fluralaner.

A study was designed to compare the efficacy of NexGard(®) and Bravecto™, 2 recently introduced oral ectoparasiticides containing isoxazolines, against fleas (Ctenocephalides felis) on dogs. Twenty-four healthy dogs, weighing 9.2 kg to 28.6 kg, were included in this parallel group design, randomized, and controlled efficacy study. On Day -1, the 24 dogs were allocated to 3 study groups: untreated control; Nexgard(®) treated and Bravecto™ treated. The treatments were administered on Days 0, 28 and 56 for Nexgard(®) (labelled for monthly administration), and once on Day 0 for Bravecto™ (labelled for a 12 week use). Flea infestations were performed weekly with 100 adult unfed C. felis on each dog from Days 42 to 84. Fleas were counted and re-applied at 6 and 12 h post-infestation and removed and counted 24 h post-infestation. The arithmetic mean flea count for the untreated group ranged from 62.9 to 77.6 at 24 h post-infestation, indicating vigorous flea challenges on all assessment days. Both the Nexgard(®) and Bravecto™ treated groups had statistically significantly (p<0.05) less fleas compared to the untreated group on all assessment time points and days. Significantly fewer fleas were recorded for NexGard(®) treated dogs compared to Bravecto™ treated dogs at 6 h post-infestation on Day 56, 63, 70, 77 and 84 and at 12 h post-infestation on Days 70 and 84. No statistically significant (p<0.05) differences were recorded between the treated groups at 24 h post-infestation. Efficacies recorded 6 h post-infestation for Nexgard(®) ranged from 62.8% (Day 49) to 97.3% (Day 56), and efficacies ranged from 94.1% (Day 49) to 100% (Days 42, 56, 70 and 84) at 12 h post-infestation. Efficacies recorded for Bravecto™ ranged from 45.1% (Day 84) to 97.8% (Day 42) at 6 h post-infestation, and from 64.7% (Day 84) to 100% (Days 42 and 56) at 12 h post-infestation. Efficacies observed at 24 h were 100% for both products during the study except 99.6% on Day 84 for Bravecto™.