Efficacy Of Afoxolaner Research Articles

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 Afoxolaner Alone or in Combination with Milbemycin Oxime against <i>Rhipicephalus sanguineus</i> Lato Sensu in Naturally Infested Dogs in Colombia

The brown dog tick (Rhipicephalus sanguineus lato sensu) is the tick that most affects dogs worldwide and is therefore the main blood pathogen vector in dogs. The efficacy of afoxolaner 2.7 to 7.1 mg/kg NexGard® (group A) and afoxolaner plus milbemycin oxime 2.5 to 5.4 mg/kg and 0.5 to 1.1 mg/kg respectively NexGard Spectra® (Group B) against R. sanguineus, was evaluated in naturally infected sheltered dogs under high challenging conditions in four different areas of Colombia (Antioquia, Córdoba, Santander, and Meta). Tick counts (alive, dead, attached, and unattached) were performed on treated dogs, the average was calculated for the different areas to evaluate the efficacy of each treatment at six different times post-treatment (24 h, 48 h, 7 d, 14 d, 21 d, 30 d). None of the dogs showed adverse events related to the treatments. The average tick number pre-treatment was 68 in group A and 78.3 for group B indicating a strong natural infection of the dogs and their environment. Efficacy after 24 h against R. sanguineus was always above 90% with ≥97.4% for NexGard® and ≥93.7% for NexGard Spectra®. Consistent results were observed along all the observation periods with final efficacies (day 30) of ≥99.8% and 98.3% for NexGard® and NexGard Spectra®, respectively. In conclusion, both NexGard® and Nexgard Spectra® provided a curative effect and sustained efficacy against Rhipicephalus sanguineus for at least 30 days in highly contaminated shelter environments.

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

BackgroundLeishmania 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.MethodsAll 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.ResultsThe 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%).ConclusionsAfoxolaner 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.Graphical abstract

Efficacy of afoxolaner (NexGard®) on the treatment of myiasis caused by the New World screwworm fly Cochliomyia hominivorax (Diptera: Calliphoridae) in naturally infested dogs.

New World screwworm (NWS) myiasis is an infestation by Cochliomyia hominivorax larvae that consume the living tissue of warm-blooded animals, including humans. Domestic dogs are among the potential hosts of these flies that lay their eggs on the edges of wounds. NWS myiasis cases can be fatal if untreated. Treatment with parasiticides must be fast-acting, long-lasting and show 100% efficacy, since open wounds can be reinfested. Afoxolaner is a molecule from the isoxazoline family with proven ectoparasiticide action against fleas, ticks and mites in dogs. Fourteen healthy client-owned dogs, naturally infested by C. hominivorax larvae, were treated with afoxolaner (NexGard®) as per label recommendations, providing at least the minimum dosage of 2.5mg/kg. Maggot infestations were classified as light (fewer than 10 larvae), mild (from 10 to 20 larvae) or severe (more than 20 larvae), according to the number of larvae found in the wound and/or collected from the ground after treatment. Twenty-four hours post-treatment, infested lesions were carefully inspected and collected larvae were counted and classified as live or dead. All maggots were identified as second and third instar larvae of C. hominivorax and were found dead within 24h after treatment, demonstrating 100% larvicidal efficacy against C. hominivorax.

Efficacy of afoxolaner in the flea control in experimentally infested cats.

The aim of this study was to evaluate the efficacy of a single dose of oral afoxolaner in controlling fleas in cats. Fourteen cats were used. The cats were given identification numbers, housed individually, artificially infested with Ctenocephalides felis felis, and treated (or not) with afoxolaner. Were divided into a treatment group and a control group (n = 7/group), on the basis of the fleas count hours after an infestation applied on Day (one-by-one allocation after ordering by count). At the start of the experimental protocol (designated day 0), the treated group received afoxolaner in a single dose of 2.5 mg/kg and the control group animals received a placebo. All animals were infested with 100 C. felis felis fleas two days before day 0, as well as on days 5, 12, 19, 26, 33, 40, 47, 54, and 63, parasite loads being evaluated at 48 h after each infestation. The efficacy of afoxolaner was 100% on day 2 and remained above 98% until day 42, decreasing to 95.3% by day 63. The findings confirm that a single dose of oral afoxolaner was effective in controlling C. felis felis in cats, and there were no observed adverse events.

Efficacy of a Single Oral Administration of Afoxolaner Alone or in Combination with Milbemycin Oxime against <i>Ixodes hexagonus</i> Ticks in Dogs

The efficacy of afoxolaner (NexGard® and NexGard Spectra®, Boehringer-Ingelheim), administered once orally at the minimum recommended dose, was assessed in dogs experimentally infested with Ixodes hexagonus ticks. The study was a blinded, negative controlled clinical efficacy study using a randomized block design. Twenty-four Beagle dogs, 12 females and 12 males were enrolled. Dogs were randomly allocated either to the negative control group, or to one of the two treated groups. Infestations were performed with 50 adult I. hexagonus ticks on Days-2, 7 and 28. On Day 0, dogs in groups 2 and 3 were treated with NexGard® (afoxolaner) or NexGard Spectra® (afoxolaner + milbemycin oxime), respectively. Tick counts were conducted 48 hours after treatment (Day 2) and 48 hours after each subsequent infestation (Days 9 and 30). In both treated groups, afoxolaner was 100% effective against existing infestations (p < 0.0001). Regarding the re-infestations, the efficacy of afoxolaner was 100% on Day 9 for both products, 96.5% and 100% on Day 30 for NexGard® and NexGard Spectra® respectively. NexGard® and NexGard Spectra® chewable tablets administered once orally at the minimum recommended dose were highly effective against I. hexagonus infestations for the 4 weeks duration of the study.

Prevention of the transmission of Babesia rossi by Haemaphysalis elliptica in dogs treated with Nexgard®.

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

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

BackgroundA 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.MethodsClient-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.ResultsTreatments 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.ConclusionsThis 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.

Efficacy of Afoxolaner in Six Cases of Canine Demodicosis

Efficacy of Afoxolaner in Six Cases of Canine Demodicosis

Efficacy of afoxolaner plus milbemycin oxime chewable tablets (NexGard Spectra®, Merial) against adult Ancylostoma ceylanicum hookworm, in dogs

A fixed-combination chewable tablet incorporating afoxolaner plus milbemycin oxime (NexGard Spectra®, Merial) was tested in purpose-bred Beagle dogs for efficacy against adult Ancylostoma ceylanicum hookworms. Sixteen dogs were inoculated each by oral administration of approximately 500 infective larvae of A. ceylanicum. Seventeen days after inoculation, the dogs were weighed and allocated randomly to be treated with afoxolaner plus milbemycin oxime chewable tablets or to remain untreated. Commercial chewable tablets of different strength were combined to deliver doses as close as possible to the minimum effective dose of 2.5mg afoxolaner plus 0.5mg milbemycin oxime per kg body weight. Parasites were recovered and counted for determination of efficacy seven days after treatment.All eight dogs that had been left untreated were harboring adult A. ceylanicum (geometric mean, 317.8; range, 210–428) while only one and nine A. ceylanicum were recovered from two of the eight dogs treated with afoxolaner plus milbemycin oxime chewable tablets (geometric mean, 0.5; p<0.0001). Thus, 99.9% efficacy against induced infection of A. ceylanicum was obtained by the use of oral NexGard Spectra® at the minimum effective dose. Treatment with afoxolaner plus milbemycin oxime chewable tablets was well accepted and safe.

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 (≥2.5mg AFX + ≥0.5mg MO per kg body weight, according to dose bands; 207 dogs), and 1, MO plus praziquantel (PRZ) chewables (Milbemax®, Novartis; ≥0.5mg MO + ≥5mg 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 21days 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.

Efficacy of oral afoxolaner plus milbemycin oxime chewables against induced gastrointestinal nematode infections in dogs

The efficacy of oral afoxolaner plus milbemycin oxime combination chewables against induced gastrointestinal nematode infections in dogs was evaluated in six separate studies. Two studies were performed to evaluate the efficacy of the product against Toxocara canis, two studies evaluated the efficacy against Toxascaris leonina, one study evaluated the efficacy against Ancylostoma braziliense, and one study evaluated the efficacy against Ancylostoma caninum. In the A. caninum study, the efficacy of milbemycin oxime alone and afoxolaner alone was also evaluated. Dogs in all studies were inoculated with infective eggs or larvae and confirmed to have patent infections based on a fecal examination prior to allocation to study group and treatment.Each study utilized a randomized block design with blocks based on pre-treatment body weight. All dogs were assigned to blocks based on body weight, and then each dog within a block was randomly assigned to treatment group. There were two groups of 10 dogs each in the T. canis, T. leonina, and A. braziliense studies: 1) an untreated (control) group and 2) a group treated with afoxolaner plus milbemycin oxime chewables (NexGard Spectra®, Merial). This group was treated at a dose as close as possible to the minimum effective dose of afoxolaner and milbemycin oxime (2.5mg+0.5mg per kg body weight, respectively) once on Day 0 using whole chews. There were four groups of 10 dogs each in the A. caninum study: 1) untreated (control), 2) NexGard Spectra® as described above, 3) milbemycin oxime alone (dose of at least 0.5mg per kg of body weight) and 4) afoxalaner alone (dose of at least 2.5mg per kg body weight). For parasite recovery and counts, dogs were euthanized humanely and necropsied seven days after treatment.The efficacy of the afoxolaner plus milbemycin oxime combination was ≥98% against T. canis, ≥95.8% against T. leonina, and 90.2% against A. braziliense. Efficacy of the combination against A. caninum was 99.7%, while the efficacy of milbemycin oxime alone was 99.6% and the efficacy of afoxolaner alone was 2.1%. Dogs treated with afoxolaner plus milbemycin oxime chewables had significantly (p≤0.0002) fewer nematodes than the untreated controls in all studies. There were no adverse events or other health problems that were related to treatment with Nexgard Spectra® in these studies.The results of these controlled studies demonstrate the high efficacy of the afoxolaner plus milbemycin oxime chewables against a broad range of canine intestinal nematode infections.

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 + 0.5mg 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 (2.5mg per kg body weight). Treatments were administered orally once on day 0. Starting 2days before treatment administration, each dog was infested with approximately 50 ticks weekly for six consecutive weeks. Live ticks were counted at ∼48h post-treatment (removal count) and at ∼48h (in situ counts) and ∼72h (removal counts) following each post-treatment infestation. Treatment with both AFX + MO and NexGard® chewables rapidly eliminated the existing tick infestations (100% efficacy) within 2days following treatment administration. Weekly re-infestations were controlled for a minimum of 5weeks with the efficacy ranging from 92.2 to 99.7% based on ∼48h post-treatment in situ counts and between 99.0 and 100% based on ∼72h 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 5weeks. In addition, this study indicated no interference between the two compounds with respect to the acaricidal activity provided by AFX.

Efficacy of afoxolaner plus milbemycin oxime chewable tablets against naturally acquired intestinal nematodes in dogs

The efficacy of oral afoxolaner plus milbemycin oxime combination chewable tablets (NexGard Spectra®, Merial) against naturally acquired intestinal nematode infections in dogs was evaluated in six negative control, blinded studies including a total of 114 dogs. Dogs were selected based on a pre-treatment fecal examination indicating patent infections with hookworms (two studies), Toxocara or Toxascaris ascarids (one study each) or Trichuris whipworms (two studies).In each study, dogs were assigned to blocks of two animals each, based on decreasing pre-treatment body weight and were randomly allocated to one of two groups consisting of eight, nine or 10 dogs: untreated (control) or treated with the combination chewable tablet formulation. Chewable tablets were combined to provide doses of actives as close as possible to the minimum effective dose of afoxolaner and milbemycin oxime, i.e., 2.5mg/kg body weight and 0.5mg/kg body weight, respectively, once on Day 0. For parasite recovery and count, dogs were euthanized humanely and necropsied seven or eight days after treatment.A single treatment with afoxolaner plus milbemycin oxime chewable tablets provided 94.8% and 90.9% efficacy against adult Ancylostoma braziliense and A. caninum, respectively, 97.8% and 99.4% efficacy against adult Toxocara canis and Toxascaris leonina, respectively, and ≥98.3% efficacy against adult Trichuris vulpis. Compared to untreated controls, nematode counts of the treated dogs were significantly reduced (F-test; p<0.002). In addition, analysis of the pooled data across studies revealed that treatment with afoxolaner plus milbemycin oxime chewable tablets reduced adult Uncinaria stenocephala burdens by 74.9% (p=0.002). All dogs tolerated the treatment well based on clinical observations post-treatment and daily clinical observations. No adverse experiences or other clinical problems related to the treatment were observed throughout the studies.The results of this series of controlled studies demonstrated high efficacy and excellent acceptability and safety of the afoxolaner plus milbemycin oxime chewable tablets when administered for treatment of a broad range of canine intestinal nematode infections.

Efficacy of afoxolaner against Ixodes scapularis ticks in dogs

Efficacy of afoxolaner, a novel isoxazoline insecticide/acaricide, against Ixodes scapularis was evaluated in a laboratory study. One day prior to treatment, beagle dogs (n=16) were infested with 50 unfed wild adult ticks. Repeat infestations were performed weekly for four additional weeks. The number of live ticks remaining on each dog was determined 48h after treatment and after each subsequent infestation. A single oral treatment with a dose approaching the minimum effective dose of afoxolaner (2.5mg/kg) eliminated the pre-existing infestations of I. scapularis ticks and controlled weekly re-infestations, with efficacy between 98% and 100% recorded until Day 23 and 94% at Day 30.

Efficacy of afoxolaner against Dermacentor variabilis ticks in dogs

Efficacy of afoxolaner, a novel isoxazoline insecticide/acaricide, against Dermacentor variabilis ticks was confirmed in two laboratory studies. Each study utilized a controlled, randomized block design. One day prior to treatment, beagle dogs were infested with 50 unfed adult ticks. Repeat infestations were performed weekly for four weeks. The number of live ticks remaining on each dog was determined 48h after treatment and after each subsequent infestation. A single oral treatment with a dose approaching the minimum effective dose of afoxolaner (2.5mg/kg) eliminated the pre-existing infestations by D. variabilis ticks and controlled weekly re-infestations with 99.7–100% efficacy up to Day 23 and >97% efficacy at Day 30.