Efficacy of a topical combination of esafoxolaner, eprinomectin and praziquantel against Amblyomma maculatum infestations in cats.

Amblyomma maculatum, the Gulf Coast tick, infests a wide range of vertebrate species including livestock, dogs, cats, and humans. It is a species of significant veterinary and public health importance, especially as a vector of diseases, for instance American canine hepatozoonosis or tidewater spotted fever. An experimental study was conducted to evaluate the efficacy of NexGard® Combo, a topical endectoparasiticide product for cats combining eprinomectin, praziquantel and esafoxolaner, against induced infestations of A. maculatum in cats. This Good Clinical Practice (GCP) study used a randomized, negative controlled, masked design. Ten cats were allocated to an untreated group and ten to a treated group, dosed once on Day 0 at the minimum label dose. On Days -2, 7, 14, 21, 28, 35, and 42, cats were infested with ~50 unfed adult A. maculatum. On Days 3, 10, 17, 24, 31, 38, and 45, i.e., 72 h after treatment and subsequent infestations, ticks were removed, counted and the numbers of live attached tick in each group were used for efficacy calculations. At each time-point, all untreated cats were adequately infested, demonstrating a vigorous tick population and an adequate study model. The curative efficacy after a single application against existing tick infestation, 72 h after treatment, was 98.7%. The preventive efficacy, 72 h after weekly infestations, over the following five weeks ranged from 93.8% to 99.4%.

Title: Efficacité d'une association topique d'esafoxolaner, d'éprinomectine et de praziquantel contre les infestations par Amblyomma maculatum chez le chat. Abstract: Amblyomma maculatum, la tique de la Gulf Coast, infeste un large éventail d'espèces de vertébrés, notamment le bétail, les chiens, les chats et les humains. Il s'agit d'une espèce d'importance significative en médecine vétérinaire et en santé publique, notamment en tant que vecteur de maladies, par exemple l'hépatozoonose canine américaine ou la fièvre pourprée des marées. Une étude expérimentale a été menée pour évaluer l'efficacité de NexGard® Combo, un produit endectoparasiticide topique pour chats associant éprinomectine, praziquantel et esafoxolaner, contre les infestations par A. maculatum provoquées chez le chat. Cette étude de bonnes pratiques cliniques (BPC) a utilisé une conception randomisée, contrôlée négativement et masquée. Dix chats ont été répartis dans un groupe non traité et dix chats dans un groupe traité, traités une fois au jour 0 à la dose minimale indiquée sur l'étiquette. Aux jours −2, 7, 14, 21, 28, 35 et 42, les chats ont été infestés par environ 50 A. maculatum adultes non nourris. Les jours 3, 10, 17, 24, 31, 38 et 45, c'est-à-dire 72 heures après le traitement et les infestations ultérieures, les tiques ont été retirées, comptées et le nombre de tiques vivantes attachées dans chaque groupe a été utilisé pour les calculs d'efficacité. À chaque instant, tous les chats non traités étaient correctement infestés, démontrant une population de tiques vigoureuse et un modèle d'étude adéquat. L'efficacité curative après une seule application contre une infestation de tiques existante, 72 heures après le traitement, était de 98,7%. L'efficacité préventive, 72 heures après les infestations hebdomadaires, au cours des cinq semaines suivantes, variait entre 93,8% et 99,4%.

Efficacy of a topical formulation containing eprinomectin, esafoxolaner and praziquantel (NexGard® Combo) in the treatment of natural respiratory capillariosis of cats.

Feline pulmonary capillariosis is a significant disorder due to its distribution and clinical impact. This study evaluated the safety and efficacy of two administrations 28 days apart of a topical solution containing esafoxolaner, eprinomectin and praziquantel (NexGard® Combo) in treating Eucoleus aerophilus (syn. Capillaria aerophila) infection in naturally infected cats. Cats were allocated to two groups: G1 cats (n = 23) received two treatments at study days (SDs) 0 and 28 (±2) and were evaluated for 6 weeks, and G2 cats (n = 17) served as a negative control for 6 weeks and were then treated twice on SDs 42 (±2) and 70 (±2), allowing for an additional 6-week assessment of efficacy. Each cat was subjected to McMaster coproscopy at SDs -7/0, 28 (±2) and 42 (±2) for both groups, 70 (±2) and 84 (±2) only for G2. Clinical examination and chest radiographic images were performed at SDs 0, 28 (±2) and 42 (±2) for G1 and G2, 70 (±2) and 84 (±2) only for G2. The comparison of EPG (eggs per gram of feces), clinical (CS), and radiographic scores (RS) at each time-point was used as a criterion. The efficacy based on the EPG reduction was 99.5% (G1) and 100% (G2) after two administrations of NexGard® Combo 2 weeks apart. At SD 0, no significant differences for CS and RS were recorded between G1 and G2, while a significant reduction (p < 0.05) was observed post-treatment for CS, RS, oculo-nasal discharge, auscultation noises, and cough. Two doses of NexGard® Combo 28 days apart stopped egg shedding and significantly improved clinical alterations in cats infected by E. aerophilus.

Title: Efficacité d'une formulation topique contenant de l'éprinomectine, de l'esafoxolaner et du praziquantel (NexGard® Combo) dans le traitement de la capillariose respiratoire naturelle du chat. Abstract: La capillariose pulmonaire féline est un trouble important, de par sa répartition et son impact clinique. Cette étude a évalué l'innocuité et l'efficacité de deux administrations à 28 jours d'intervalle d'une solution topique contenant de l'esafoxolaner, de l'éprinomectine et du praziquantel (NexGard® Combo) dans le traitement de l'infection à Eucoleus aerophilus (syn. Capillaria aerophila) chez des chats naturellement infectés. Les chats ont été répartis en deux groupes : les chats G1 (n = 23) ont reçu deux traitements aux jours d'étude (JE) 0 et 28 (±2) et ont été évalués pendant 6 semaines et les chats G2 (n = 17) ont servi de contrôle négatif pendant 6 semaines, puis ont été traités deux fois aux JE 42 (±2) et 70 (±2), permettant une évaluation supplémentaire de l'efficacité sur 6 semaines. Chaque chat a été soumis à une coproscopie McMaster aux JE −7/0, 28 (±2) et 42 (±2) pour les deux groupes, 70 (±2) et 84 (±2) uniquement pour G2. L'examen clinique et les images radiographiques thoraciques ont été réalisés aux JE 0, 28 (±2) et 42 (±2) pour G1 et G2, 70 (±2) et 84 (±2) uniquement pour G2. La comparaison des nombres d'œufs par gramme de matières fécales (OPG), score clinique (SC) et score radiographique (SR) à chaque point ont été utilisées comme critères d'efficacité. L'efficacité basée sur la réduction de OPG était de 99,5 % (G1) et de 100 % (G2) après deux administrations de NexGard Combo à deux semaines d'intervalle. À JE 0, aucune différence significative pour SC et SR n'a été enregistrée entre G1 et G2, tandis qu'une réduction significative (p < 0,05) a été observée après le traitement pour SC, SR, écoulements oculo-nasaux, bruits d'auscultation et toux. Deux doses de NexGard® Combo à 28 jours d'intervalle arrêtent l'excrétion des œufs et améliorent considérablement les altérations cliniques chez les chats infectés par E. aerophilus.

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 a topical formulation containing esafoxolaner, eprinomectin and praziquantel (NexGard Combo®) against natural infestations with the cat louse, Felicola subrostratus under field conditions.

Felicola subrostratus is the only species of louse affecting domestic cats. Although it is considered a rare ectoparasite of pet cats, it occurs mainly in stray or shelter animals and is sometimes associated with intense pruritus and secondary bacterial infections. The aim of the present study was to evaluate the efficacy of a single dose of the topical formulation of esafoxolaner, eprinomectin and praziquantel (NexGard Combo®, Boehringer Ingelheim) in cats for the treatment of naturally acquired chewing lice infestation in a multi-site, positive-control, blinded clinical field study. Thirty-one domestic cats presenting natural F. subrostratus infestation were included in the study. The animals had not been treated with any ectoparasiticide within the previous 60 days. After inclusion, each cat was randomly assigned to one of the two groups: group 1, 14 cats treated with NexGard Combo® or group 2, 17 cats treated with Frontline Combo®. A clinical evaluation was performed at days 0 (inclusion), 14 and 30 and consisted in scoring the skin lesions and symptoms and scoring the presence of lice. On day 30, all cats from both groups scored 0 for the presence of live lice and no dead lice were found, demonstrating 100% efficacy. The clinical scores significantly improved from day 0 to day 30 in both groups. During the 30 days of surveillance, no reinfestations due to the hatching of eggs were observed and none of the cats had any adverse reactions. Esafoxolaner demonstrated high efficacy for the treatment of F. subrostratus infestation.

Title: Efficacité d'une formulation topique contenant de l'esafoxolaner, de l'éprinomectine et du praziquantel (NexGard Combo®) contre les infestations naturelles par le pou du chat, Felicola subrostratus, dans des conditions de terrain. Abstract: Felicola subrostratus est la seule espèce de pou affectant les chats domestiques. Bien que ce pou soit rare comme ectoparasite chez les chats de compagnie, il infeste principalement les animaux errants ou en refuge et est parfois associé à un prurit intense et à des infections bactériennes secondaires. Le but de la présente étude était d'évaluer l'efficacité d'une dose unique de la formulation topique d'esafoxolaner, d'éprinomectine et de praziquantel (NexGard Combo®, Boehringer Ingelheim) chez le chat pour le traitement de l'infestation naturelle par les poux broyeurs dans une étude de terrain multi-sites, randomisée, avec un contrôle positif. Trente et un chats domestiques présentant une infestation naturelle par F. subrostratus ont été inclus dans l'étude. Les animaux n'avaient été traités avec aucun ectoparasiticide au cours des 60 jours précédents. Après inclusion, chaque chat a été assigné au hasard à l'un des deux groupes : groupe 1, 14 chats traités avec NexGard Combo®, ou groupe 2, 17 chats traités avec Frontline Combo®. Une évaluation clinique a été réalisée aux jours 0 (inclusion), 14 et 30 et a consisté à un score clinique des lésions et symptômes cutanés et à noter la présence de poux. Au jour 30, tous les chats des deux groupes ont obtenu un score de 0 pour la présence de poux vivants et aucun pou mort n'a été trouvé, démontrant une efficacité de 100 %. Les scores cliniques se sont significativement améliorés du jour 0 au jour 30 dans les deux groupes. Au cours des 30 jours de surveillance, aucune réinfestation due à l'éclosion des œufs n'a été observée et aucun des chats n'a présenté d'effet indésirable. L'esafoxolaner a démontré une efficacité élevée pour le traitement de l'infestation par F. subrostratus.

Efficacy of a topical product combining esafoxolaner, eprinomectin and praziquantel against bedbug (Cimex lectularius) experimental infestations in cats.

Bedbugs (Cimex lectularius) are a persistent nuisance pest for humans and their home environment, and may also opportunistically feed on other mammals, including household pets like dogs and cats. NexGard® Combo is a topical endectoparasiticide product for cats combining esafoxolaner, an isoxazoline compound with insecticidal and acaricidal properties, the nematocide eprinomectin and the cestocide praziquantel. The insecticidal efficacy of this product was evaluated in cats experimentally infested with C. lectularius in a blinded, negative controlled and randomized study. Two groups of 7 cats were formed: an untreated control group, and a NexGard® Combo group treated once on Day 0 at the label dose. Cats were then challenged weekly, each with twenty unfed adult C. lectularius, on Days 1, 7, 14, 21 and 28. After close contact with the cat's skin for 15 min, live fed C. lectularius were collected and incubated for 96 h. The weekly efficacy evaluations were based on a comparison of the number of surviving bedbugs in the control and the treated group after 48, 72 and 96 h of incubation. The model was demonstrated to be robust as in the control group the average feeding rate after the 15-minute challenge was 94%, and as 96% of incubated bed bugs were alive after 96 hours of incubation. Significant live bedbug reductions were demonstrated in the Nexgard® Combo treated group: after 96 h of incubation, the reductions ranged from 80.6 to 88.0% during the Day 1 to Day 21 period, and dropped to 58% at Day 28.

Title: Efficacité d'une formulation topique associant esafoxolaner, éprinomectine et praziquantel contre les infestations expérimentales par les punaises de lit (Cimex lectularius) chez le chat. Abstract: Les punaises de lit (Cimex lectularius) sont une nuisance persistante pour les humains et leur environnement domestique, et peuvent également se nourrir de manière opportuniste d'autres mammifères, y compris les animaux domestiques comme les chiens et les chats. NexGard® Combo est une formulation topique endectoparasiticide pour chats associant l'esafoxolaner, un composé d'isoxazoline à propriétés insecticides et acaricides, le nématodicide éprinomectine et le cestodicide praziquantel. L'efficacité insecticide de ce produit a été évaluée chez des chats infestés expérimentalement par C. lectularius dans une étude en aveugle et randomisée avec contrôle négatif. Deux groupes de 7 chats ont été formés, un groupe témoin non traité et un groupe traité par NexGard® Combo une fois au jour 0 à la dose indiquée sur l'étiquette. Les chats ont ensuite été testés chaque semaine, chacun avec vingt C. lectularius adultes non nourris, les jours 1, 7, 14, 21 et 28. Après un contact étroit avec la peau du chat pendant 15 minutes, les C. lectularius nourris et vivants ont été collectés et incubés pendant 96 heures. Les évaluations hebdomadaires d'efficacité ont été basées sur une comparaison du nombre de punaises de lit survivantes entre le groupe témoin et le groupe traité après 48, 72 et 96 heures d'incubation. Le modèle s'est avéré robuste car dans le groupe témoin, le taux d'alimentation moyen après 15 minutes de contact était de 94 % et 96 % des punaises de lit incubées étaient vivantes après 96 heures d'incubation. Des réductions significatives du nombre de punaises de lit vivantes ont été démontrées dans le groupe traité par Nexgard® Combo : après 96 heures d'incubation, les réductions variaient de 80,6 à 88,0 % pendant la période du jour 1 au jour 21 et ont chuté à 58 % au jour 28.

Laboratory breeding of two Phortica species (Diptera: Drosophilidae), vectors of the zoonotic eyeworm Thelazia callipaeda.

BACKGROUND: Some species of drosophilid flies belonging to the genus Phortica feed on ocular secretions of mammals, acting as biological vectors of the zoonotic eyeworm Thelazia callipaeda. This study describes an effective breeding protocol of Phortica variegata and Phortica oldenbergi in insectary conditions. METHODS: Alive gravid flies of P. oldenbergi, P. variegata and Phortica semivirgo were field collected in wooded areas of Lazio region (Italy) and allowed to oviposit singularly to obtain isofamilies. Flies were maintained in ovipots (200 ml) with a plaster-covered bottom to maintain high humidity level inside. Adult feeding was guaranteed by fresh apples and a liquid dietary supplement containing sodium chloride and mucin proteins, while larval development was obtained by Drosophila-like agar feeding medium. The breeding performances of two media were compared: a standard one based on cornmeal flour and an enriched medium based on chestnut flour. All conditions were kept in a climatic chamber with a photoperiod of 14:10 h light:dark, 26 ± 2 °C and 80 ± 10% RH. RESULTS: From a total of 130 field-collected Phortica spp., three generations (i.e. F1 = 783, F2 = 109, F3 = 6) were obtained. Phortica oldenbergi was the species with highest breeding performance, being the only species reaching F3. Chestnut-based feeding medium allowed higher adult production and survival probability in both P. oldenbergi and P. variegata. Adult production/female was promising in both species (P. oldenbergi: 13.5 F1/f; P. variegata: 4.5 F1/f). CONCLUSIONS: This standardized breeding protocol, based on controlled climatic parameters and fly densities, together with the introduction of an enriched chestnut-based feeding medium, allowed to investigate aspects of life history traits of Phortica spp. involved in the transmission of T. callipaeda. Obtaining F3 generation of these species for the first time paved the road for the establishment of stable colonies, an essential requirement for future studies on these vectors in controlled conditions.

Efficacy of fipronil/(S)-methoprene/eprinomectin/praziquantel (Broadline®) against Thelazia callipaeda in naturally infected cats.

BACKGROUND: The present clinical field trial was conducted to assess the efficacy of a broad-spectrum parasiticide spot-on formulation containing eprinomectin (Broadline®) against Thelazia callipaeda eyeworm in naturally infected cats. METHODS: Fifteen privately owned cats harboring at least one live adult T. callipaeda were included in the study. Cats were randomly allocated to an untreated control group of seven cats or to a Broadline®-treated group of eight cats. Cats were treated on Day 0; ocular examinations were performed at inclusion and on Days 7 and 14; eyeworms were recovered and counted on Day 14. The primary efficacy assessment was based on group comparison of number of T. callipaeda on Day 14. RESULTS: Seven days after treatment, six of eight treated cats were negative for eyeworm infection per visual examination, and on Day 14 no eyeworms were found in the treated cats while the seven untreated cats were still infected (geometric mean: 1.97). All cats had inflammatory ocular signs at inclusion; on Day 14, five of eight treated cats had recovered while all untreated control cats were still symptomatic. All collected parasites were confirmed to be T. callipaeda by morphology and molecular characterization. CONCLUSIONS: A single treatment with Broadline® provided 100% efficacy against feline thelaziosis and improved related ocular inflammation signs.

Feline gastrointestinal parasitism in Greece: emergent zoonotic species and associated risk factors.

BACKGROUND: Feline gastrointestinal parasitism constitutes an issue of concern for veterinarians since parasites are widespread and affect animals' health and welfare. Furthermore, some of these pathogens have zoonotic potential. To provide detailed data on the current epizootiology of feline endoparasitism, a multicentric survey was conducted during 2016. METHODS: Faeces from 1150 cats were collected from all regions of Greece and examined by sedimentation and flotation techniques. Possible risk factors including gender, age, ownership status, living conditions and co-infections with other parasites were assessed using binary regression models for each one of the most prevalent parasites. RESULTS: The overall gastrointestinal parasite prevalence in cats was 50.7%. The study population consisted of cats of both sexes, different age groups, ownership status and living conditions. A total of 10 gastrointestinal parasitic species were detected and up to 5 different parasites were isolated in the same faecal sample. The most frequently identified parasites were Toxocara cati (n = 278; 24.2%), followed by Cystoisospora spp. (n = 189; 16.4%), Ancylostomatidae (n = 186; 16.2%), Aelurostrongylus abstrusus (n = 40; 3.5%), Giardia spp. (n = 26; 2.3%), Joyeuxiella pasqualei (n = 14; 1.2%), Capillaria aerophila (n = 8; 0.7%), Dipylidium caninum (n = 3; 0.2%), Toxascaris leonina (n = 2; 0.1%) and Troglostrongylus brevior (n = 2; 0.1%). The occurrence of co-infections was 11.6%. Concerning risk factors, the likelihood of T. cati infection was higher for female cats living outdoors and for cats being infected with Cystoisospora spp. In the same frame, young, stray, male and free of A. abstrusus cats were more likely to be infected with Cystoisospora spp. Correspondingly, stray, infected with Giardia spp. but free of Cystoisospora spp. cats were more likely to be infected with Ancylostomatidae. Regarding A. abstrusus infection, a higher probability was reported for cats living outdoors and for cats free of Cystoisospora spp., while Giardia spp. infections were more common in young and co-infected with Ancylostomatidae animals. CONCLUSIONS: The prevalence of parasitized cats in Greece was high and thus consideration should be paid to control the risk factors, to implement targeted preventive antiparasitic treatments and educate cat owners on the value of prevention for the health and welfare of their cats.

Preventive efficacy of NexGard Spectra® against Dipylidium caninum infection in dogs using a natural flea (Ctenocephalides felis) infestation model.

The efficacy of a monthly oral endectocide product, NexGard Spectra® (Merial), a combination of afoxolaner and milbemycin oxime, was evaluated in a flea (Ctenocephalides felis) challenge model for the prevention of Dipylidium caninum tapeworm infection in dogs. The efficacy of treatment with NexGard Spectra® was assessed in 10 dogs following weekly flea infestation with metacestode naturally infected fleas and compared with that in 10 untreated control dogs. The 100 fleas deposited weekly on each dog were not removed until Day 35, allowing enough time for their ingestion. The microscopical analysis of 30 fleas from the flea batches before each weekly challenge demonstrated that 10-33% of the fleas were infected by D. caninum cysticercoid larvae. The arithmetic mean flea count recorded was 47.7 for the 10 untreated dogs and 0 for the 10 treated dogs at Day 35. Based on the daily collection of expelled D. caninum proglottids by dogs during the 70 days of the study, 70% (7/10) of the control dogs and 0% (0/10) of the treated dogs were infected with D. caninum (p < 0.0031). Through its efficacy against fleas, NexGard Spectra® treatment provided indirect prevention of D. caninum infestation. No treatment-related adverse events were observed in dogs during this study.

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.

Knock-down and speed of kill of a combination of fipronil and permethrin for the prevention of Ctenocephalides felis flea infestation in dogs.

BACKGROUND: A topical combination of fipronil + permethrin (Frontline Tri-Act/Frontect, Merial) has recently been developed to control fleas, ticks, mosquitoes, sandflies and stable flies on dogs. Two studies were conducted to assess its speed of kill and knock-down effect on Ctenocephalides felis fleas. The combination was compared to either fipronil alone or to a combination of permethrin, dinotefuran, and pyriproxyfen, METHODS: In each study, 18 dogs were randomly allocated to one of three groups: (Group 1: untreated dog; Group 2: treated once on D0 with the combination of fipronil and permethrin; Group 3: treated once on D0 either with fipronil alone (study 1) or with a combination of permethrin, dinetofuran and pyriproxyfen (study 2)). Each dog was infested with 100 unfed adult C. felis fleas on Days 2 (study 2), 7, 14, 21 and 28. Fleas were collected from dogs at 1 h and 12 h post- infestations (PI) (study 1) or at 2 h and 6 h PI (study 2) to assess efficacy and from collection pans underneath cages 1 h (study 1) or 5 min (study 2) PI to assess knock-down effect. RESULTS: All treated dogs had significantly (p ≤ 0.01) lower flea counts than untreated dogs at every time point in both studies. For a whole month, a significant knock-down effect against infesting fleas is obtained in five minutes PI with the combination of permethrin and fipronil. Complete efficacy (>95%) was achieved in 1 h (study 1) or 2 h (study 2) PI for 14 days and by 6 h PI for all challenges conducted throughout the month. Efficacy remains >85% at 2 h PI for the whole month. A significantly higher efficacy of the fipronil + permethrin combination compared to other treatments was demonstrated at the earliest time points for the month (1 h knock-down effect and insecticidal efficacy compared to fipronil alone; 5 min knock-down effect compared to the combination of permethrin + dinetofuran + pyriproxyfen). CONCLUSIONS: The rapid flea knock-down effect and speed of kill demonstrated by the spot on combination of fipronil + permethrin provide a reliable strategy against flea infestations in dogs.

Repellency and acaricidal efficacy of a new combination of fipronil and permethrin against Ixodes ricinus and Rhipicephalus sanguineus ticks on dogs.

BACKGROUND: A blinded, controlled laboratory study was conducted to assess the repellency and acaricidal activity of a topical spot on formulation, a combination of fipronil and permethrin, against Ixodes ricinus and Rhipicephalus sanguineus ticks on dogs. METHODS: A group of 16 adult mixed breed dogs were randomly divided into treatment and control groups based on pre-treatment live tick counts. On Day 0, the topical spot on formulation of fipronil + permethrin (commercialized under the name Frontline Tri-Act®/Frontect®) was administered to dogs in the treatment group at the minimum recommended dose of 0.1 mL/kg, corresponding to 6.76 mg fipronil/kg and 50.48 mg/kg permethrin. Tick infestations were performed with I. ricinus (50 females, 50 males) and R. sanguineus (25 females, 25 males) on each dog on Days 2, 7, 14, 21, and 28. Dogs were sedated prior to exposure and confined to crates for approximately 4 h following tick challenge. Ticks were released next to the sedated dogs and tick counts were performed at 4 h and 24 h after the start of exposure for tick counts and removal. RESULTS: Repellency at 4 h against I. ricinus was 72.6, 96.3, 92.8, 89.0, and 88.7 % on Days 2, 7, 14, 21, and 28, respectively. Repellency was 100 % 24 h after exposures on Days 2, 7, and 14 and 99.6 % after exposures on Days 21 and 28. For R. sanguineus, repellency at 4 h was 78.0, 96.8, 91.5, 88.0, and 56.8 % on Days 2, 7, 14, 21, and 28, respectively. Repellency at 24 h was 98.6, 100, 98.7, 96.1, and 95.1 % for exposures on Days 2, 7, 14, 21, and 28, respectively. For I. ricinus, acaricidal efficacy recorded at 4 h was ≥ 91.1 % during the full month and was ≥ 99.5 % for the full month when counted at 24 h. Acaricidal efficacy against R. sanguineus was ≥ 94.7 % at 4 h from Day 2 to Day 21 and was 71.4 % on Day 28. Acaricidal efficacy at 24 h, was > 97.7 % during the month. Tick counts were statistically significantly reduced in treated dogs at all time-points during the study. CONCLUSIONS: A combination of fipronil and permethrin was highly effective at rapidly repelling and killing both I. ricinus and R. sanguineus ticks on dogs for at least 4 weeks, with a significant effect at 4 and 24 h after tick exposure.

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.

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).

Preventive efficacy of Frontline® Combo and Certifect® against Dipylidium caninum infestation of cats and dogs using a natural flea (Ctenocephalides felis) infestation model.

Two studies were performed to evaluate the effectiveness of two monthly topical anti-flea products for the prevention of Dipylidium caninum infestations in cats and dogs. A single treatment with Frontline(®) Combo spot-on for cats (fipronil-(S)-methoprene) and two successive monthly treatments of Certifect(®) for dogs (fipronil-amitraz-(S)-methoprene) were assessed for the prevention of D. caninum infestations following weekly challenges of treated cats or dogs with metacestode naturally-infected fleas. The rate of infestations using the model in cats versus dogs explains the choice of a 1-month trial in cats and a 2-month trial in dogs. The experimental flea-infection model resulted in a range of 22-53% of the fleas being infected by Dipylidium cysticercoids. The arithmetic mean flea counts recorded for the untreated cats ranged from 51.2 to 68. The geometric mean flea counts recorded for the Frontline Combo treated cats differed significantly (p < 0.05) from those of the untreated control cats on all assessment days. The arithmetic mean flea counts recorded for the untreated dogs ranged from 166.6 to 238.6. The geometric mean flea counts recorded for the Certifect treated dogs differed significantly (p < 0.001) from those of the untreated group on all assessment days. Frontline Combo treatment on cats provided ≥99.8% persistent anti-flea efficacy throughout the 30-day treatment period. In the dog study, the two Certifect treatments provided ≥97% persistent efficacy throughout the 60-day study. Based on the collection of expelled D. caninum proglottids by cats, 100% (6/6) of the control cats and 0% (0/6) of Frontline Combo treated cats were infested with D. caninum. Frontline Combo spot-on for cats was therefore 100% effective in preventing infection with D. caninum. In dogs, 7 out of the 8 control group dogs (87.5%) produced proglottids following infestation of infected fleas, whereas 0 out of 8 dogs (0%) in the treated group were infected. The infection rates of the two groups were significantly different. The percent effectiveness for the Certifect treatment group for the prevention of D. caninum infection was 100% during this 2-month trial. No treatment-related adverse events were observed in either cats or dogs during these studies.