Efficacy against nematode infections and safety of afoxolaner plus milbemycin oxime chewable tablets in domestic dogs under field conditions in Europe.

Afoxolaner (AFX) plus milbemycin oxime (MO) combination chewable tablets (NexGard Spectra®, Merial) were evaluated for safety and efficacy against naturally acquired nematode infections in domestic dogs in a multi-centre, positive control, blinded field study using a randomized block design based on the order of presentation for allocation. In total, 408 dogs confirmed positive for naturally acquired infections of intestinal nematodes by pre-treatment faecal examination were studied in ten countries in Europe (Albania, Austria, Bulgaria, France, Germany, Hungary, Italy, Lithuania, Romania and Slovakia). Pre-treatment faecal examination revealed Toxocara, Toxascaris, hookworm, Trichuris and/or Capillaria nematode infections in 134, 30, 223, 155 and 14 dogs, respectively. Dogs were allocated to one of two treatment groups in a ratio of 1, AFX + MO chewables (≥2.5 mg AFX + ≥0.5 mg MO per kg body weight, according to dose bands; 207 dogs), and 1, MO plus praziquantel (PRZ) chewables (Milbemax®, Novartis; ≥0.5 mg MO + ≥5 mg PRZ per kg body weight, according to the manufacturer's instructions; 201 dogs) and treated once. For evaluation of efficacy based on reduction of faecal nematode egg counts, two faecal samples, one collected prior to treatment and one collected 9 to 21 days after treatment, were examined using modified McMaster techniques. For evaluation of systemic safety, dogs were examined by a veterinarian before treatment administration and at study end, and dog owners observed the health status of their dogs until the end of the study and reported any abnormal observation. For dogs treated with AFX + MO chewables, the efficacy was 99.7, 99.7, 97.2, 99.7 and 99.7 % for Toxocara, Toxascaris, hookworm, Trichuris and Capillaria, respectively; and the efficacy was 99.5, 99.4, 94.3, 99.9 and 98.0 %, respectively, for the MO + PRZ-treated dogs (p ≤ 0.002 for all nematodes and both treatments). For Toxocara, hookworm and Trichuris, non-inferiority analysis demonstrated that the efficacy of AFX + MO chewable tablets was equal to or better than that of MO + PRZ. In spite that both treatments were ≥98 % efficacious against Toxascaris and Capillaria, a hypothesis of non-inferiority for both genera could not be established due to the low number of dogs infected with these parasites. No treatment-related adverse experiences were observed throughout the study. For both treatments, all dogs were given a systemic safety score of 'excellent' apart from one dog in each treatment group which received a score of 'acceptable'. AFX + MO combination chewables were shown to be safe and demonstrated a high level of efficacy when administered once to dogs infected with a broad range of parasitic nematodes under field conditions.

Monthly administrations of milbemycin oxime plus afoxolaner chewable tablets to prevent Angiostrongylus vasorum infection in dogs.

BACKGROUND: Infection of dogs with the cardiopulmonary nematode Angiostrongylus vasorum may result in severe clinical disease therefore adequate prevention is necessary. A randomized, negative control, blinded study was conducted to evaluate the efficacy in the prevention of canine A. vasorum infection after monthly administrations of NexGard Spectra®, a novel chewable tablet formulation combining the insecticide and acaricide afoxolaner and the anthelmintic milbemycin oxime, in a multiple challenge (trickle infection) model. METHODS: Twenty beagle dogs were challenged orally with doses of approximately 32-43 third-stage larvae of A. vasorum once every other week on seven occasions (Study Days -7, 7, 21, 35, 49, 63 and 77). Ten dogs were administered NexGard Spectra® as close as possible to the minimum recommended dose of afoxolaner and milbemycin oxime, i.e. 2.5 mg/kg body weight and 0.5 mg/kg body weight, respectively, four times at monthly intervals (Study Days 0, 28, 56 and 84) while the remaining ten dogs served as untreated controls. For parasite recovery and count, dogs were euthanized humanely and necropsied six to eight days following the last treatment (Study Days 90-92). Beginning six weeks after first inoculation, faeces were collected on a bi-weekly basis and examined for first-stage larvae of A. vasorum. RESULTS: Untreated dogs harboured 39-95 adult A. vasorum (geometric mean, 66.4), while zero to 24 adult A. vasorum were recovered from the treated dogs (geometric mean, 3.4; P < 0.0001). Thus, efficacy of NexGard Spectra® administered at monthly intervals against incoming A. vasorum was 94.9 %. Compared to the untreated controls, larval excretion of the treated dogs was reduced by 99.9 % (P < 0.0001). CONCLUSION: Results of this study demonstrate that NexGard Spectra®, when administered at monthly intervals, can effectively prevent canine A. vasorum infection.

Efficacy of oral afoxolaner plus milbemycin oxime chewables against induced infestations with Dermacentor reticulatus in dogs.

The efficacy of afoxolaner plus milbemycin oxime (AFX + MO) combination chewables (NexGard Spectra®, Merial) and AFX single-entity chewables (NexGard®, Merial) against induced infestations with Dermacentor reticulatus ticks was evaluated in dogs. Thirty dogs were assigned to blocks of three animals each based on pre-allocation tick counts and were randomly allocated to one of three groups: untreated (control), treated with a combination of AFX + MO chewables to be as close as possible to the minimum effective dose of AFX + MO (2.5 + 0.5 mg per kg body weight), and treated with a combination of NexGard® chewables to be as close as possible to the minimum effective dose of AFX (2.5 mg per kg body weight). Treatments were administered orally once on day 0. Starting 2 days before treatment administration, each dog was infested with approximately 50 ticks weekly for six consecutive weeks. Live ticks were counted at ∼48 h post-treatment (removal count) and at ∼48 h (in situ counts) and ∼72 h (removal counts) following each post-treatment infestation. Treatment with both AFX + MO and NexGard® chewables rapidly eliminated the existing tick infestations (100 % efficacy) within 2 days following treatment administration. Weekly re-infestations were controlled for a minimum of 5 weeks with the efficacy ranging from 92.2 to 99.7 % based on ∼48 h post-treatment in situ counts and between 99.0 and 100 % based on ∼72 h post-treatment removal counts (p < 0.0001 at each occasion). This study demonstrated a high efficacy of both AFX + MO chewable and NexGard® chewable treatments against infestations of dogs with D. reticulatus ticks for at least 5 weeks. In addition, this study indicated no interference between the two compounds with respect to the acaricidal activity provided by AFX.

Second family with the Boston-type craniosynostosis syndrome: novel mutation and expansion of the clinical spectrum.

Craniosynostosis, caused by early fusion of one or more cranial sutures, can affect the coronal or lambdoid sutures, or include premature fusion of the sagittal (scaphocephaly) or metopic suture (trigonocephaly). Often occurring as isolated finding, their co-existence in a craniosynostosis syndrome is infrequent. We describe a four-generation family with variable expression of a craniosynostosis phenotype with scaphocephaly and a particularly severe trigonocephaly. Molecular analysis revealed a missense mutation in the MSX2-associated with the Boston-type craniosynostosis syndrome-affecting the same amino-acid residue as in the original Boston family. Besides unique features such as the cranial sutures involved, minor limb abnormalities and incomplete penetrance, our patients share with the original family autosomal dominant inheritance and the presence of multiple endocranial erosions on CT imaging. Though these findings appear to be important diagnostic clues for MSX2-related craniosynostosis, it is noteworthy that the first affected generation in this family presented merely with isolated sagittal or unicoronal craniosynostosis and cutaneous syndactyly. Molecular analysis of MSX2 should therefore be considered in patients with isolated scaphocephaly/unicoronal synostosis, especially in the presence of a family history for craniosynostosis or syndactyly.

Effect of topical application of fipronil in cats with flea allergic dermatitis.

OBJECTIVE: To determine whether topical application of a 10% fipronil solution would control signs of flea allergic dermatitis in cats housed under natural conditions. DESIGN: Multicenter open clinical trial. ANIMALS: 42 client-owned cats with flea allergic dermatitis. PROCEDURES: Study cats along with all other cats and dogs living in the same houses were treated with 10% fipronil solution topically on days 0, 30, and 60. Flea counts and clinical assessments were performed on study cats on days 0, 14, 30, 60, and 90. RESULTS: Percentage reductions in geometric mean flea counts on days 14, 30, 60, and 90, compared with day-0 geometric mean count, were 75, 73, 85, and 94%, respectively. Pruritus score was significantly improved at each examination after day 0, and pruritus was reduced or eliminated in 31 of 40 (78%) cats at the final examination. Similarly, scores for severity of miliary dermatitis and alopecia were significantly improved at each examination, except for alopecia score on day 14. Overall treatment efficacy, assessed on day 90, was excellent for 28 (70%) cats, good for 6 (15%), moderate for 3 (7.5%), and poor for 3 (7.5%). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that monthly topical application of fipronil is effective for treatment of flea allergic dermatitis in cats housed under natural conditions.

Field Efficacy of a Mechanical Pump Spray Formulation Containing 0.25% Fipronil in the Treatment and Control of Flea Infestation and Associated Dermatological Signs in Dogs and Cats.

Abstract- Fipronil is a new insecticide and acaricide belonging to the phenylpyrazole family. Experimental studies have demonstrated the efficacy of a 0.25% fipronil mechanical pump spray formulation against fleas and ticks in both dogs and cats. Two multicentric clinical trials were set up to confirm the efficacy of this product under field conditions. The dog study was a positive control study. Flea infestation was qualitatively assessed at the initial visit (treatment date) and at the final visit (when reinfestation was observed or at the latest by 2 months after treatment). Sixty-one per cent and 21.5 per cent of dogs were free of fleas ("zero-flea stage") at the end of the second month post-treatment in the experimental and reference groups, respectively. The incidence of pruritus and dermatological lesions was reduced in the two groups but with significantly better results in the fipronil group. Sixty-one per cent of the cats treated with fipronil were also free of fleas at the end of the second month post-treatment. Pruritus was also significantly reduced. Résumé- Le fipronil est un nouvel insecticide appartenant à la famille des phénylpyrazolés. Des études expérimentales ont démontré l'efficacité d'une solution à 0,25% de fipronil en pulvérisation manuelle contre les puces et les tiques chez le chien et le chat. Deux études cliniques multicentriques ont été conduites pour confirmer l'efficacité de ce produit sur le terrain. L'étude chez le chien est une étude contrôlée positive. L'infestation par les puces a été déterminée qualitativement lors de la visite initiale (date du traitement), et lors de la visite finale (quand une réinfestation a été observée ou au moins 2 mois après le traitement). 61% et 21,5% des chiens étaient indemnes de puces (stade 0 puce) à la fin du second mois consécutif au traitement respectivement dans le groupe traité et dans le groupe de référence. Le prurit et les lésions dermatologiques étaient réduits dans les deux groupes, mais avec des résultats meilleurs dans le groupe fipronil. 61% des chats traités avec le fipronil étaient aussi indemnes de puces 2 mois après le traitement. Le prurit était également significativement réduit. [Postal, J.-M. R., Jeannin, P. C, Consalui, P.-J. Field efficiency of a mechanical pump spray formulation containing 0.25% fipronil in the treatment and control of flea infestation and associated dermatological signs in cats and dogs (Efficacité d'une solution à 0,25% de fipronil en pulvérisation manuelle dans le traitement et le contrôle d'une pullicose et des symptômes dermatologiques associés chez les chiens et les chats). Resumen- El fipronil es un nuevo insecticida y acaricida de la familia de los fenilpirazoles. Estudios expérimentales han demostrado la efectividad de une fórmula de fipronil al 0,25% en un pulverizador con sistema mecànico de bombeo contra pulgas y piojos en el perro y en el gato. Se diseñaron dos pruebas clinicas multicéntricas para confirmar la afectividad de este producto en condiciones de campo. El estudio en el perro fue la prueba control. Se realizó un examen cualtitativo sobre el grado de infestación por pulgas en la primera visita (fecha de tratamiento) y en la última visita (en caso de reinfestación o como máximo dos meses después del tratamiento). El sesenta y uno por ciento y el 21,5% de los perros estaba libre de pulgas ("estadio pulga-cero") al final del segundo mes después del tratamiento en los grupos experimental y de referencia, respectivamente. La incidencia de prurito y de lesiones dermatológicas se vieron reducidos en los dos grupos pero con resultados significativamente mejores en el grupo del fipronil. El sesenta y uno por ciento de los gatos tratados con fipronil estaban también fibres de pulgas al final del segundo mes después del tratamiento. El prurito se vió también significativamente disminuido. [Postal, J.-M. R., Jeannin, P. C, Consalui, P.-J. Field efficiency of a mechanical pump spray formulation containing 0.25% fipronil in the treatment and control of flea infestation and associated dermatological signs in cats and dogs (Efectividad en un estudio de campo de una fórmula para pulverizador con sistema mecànico de bombeo con un 0,25% de fipronil en el tratamiento y control de infestaciones por pulgas y problemas dermatológicos asociados en el perro y el gato).