The prevention of attachment and the detachment effects of a novel combination of fipronil, amitraz and (S)-methoprene for Rhipicephalus sanguineus and Dermacentor variabilis on dogs.

A novel combination of fipronil, amitraz and (S)-methoprene (CERTIFECT™, Merial Limited, GA, USA) was evaluated for the prevention of attachment of ticks and its ability to cause detachment of ticks. For the two prevention of attachment studies, 20 purpose-bred beagles were allocated each to two equal groups based on pretreatment tick counts (treated and untreated). Each dog was exposed to 50 adult Rhipicephalus sanguineus and Dermacentor variabilis weekly starting 24h after treatment. In study 1 infestations with R. sanguineus were discontinued after Day 7 but continued to Day 28 for D. variabilis in both studies. Counts of ticks by species were made 2, 4 and 24h after exposure to ticks. Ticks not attaching to dogs were evaluated for viability. For the evaluation of detachment study, 16 purpose-bred beagles were allocated each to two equal groups based on pretreatment tick counts (treated and untreated). Each dog was infested with 50 unfed R. sanguineus and D. variabilis adults on Day -2. Ticks were thumb counted without removal on all dogs on Day -1, and at 4, 12, and 24h after treatment. Ticks were counted and removed at 48 h after treatment. Dogs treated with the novel combination had significantly (p<0.05) lower total numbers of attached R. sanguineus and D. variabilis than untreated controls at 4h through Day 7. For R. sanguineus, percent reduction of attachment at 24h after infestation through Day 29 ranged from 94.5% to 100%. For D. variabilis, the percent reduction of attachment at 24h through Day 22 was above 98.0%. These studies demonstrate that novel combination can disrupt attachment of R. sanguineus and D. variabilis for up to 28 days following treatment. Of those ticks that are exposed to the treatment, even if they do not attach to the dog and remain in the environment, greater than 90% (p<0.05) die within 24h for 2-3 weeks following treatment. Also, for those dogs infested with ticks at the time of treatment, the novel combination causes significant detachment (p<.05) starting at 12h and reaching 98.9% by 48 h after treatment. This product provides an effective means for controlling ticks infesting dogs and limiting the spread of tick transmitted diseases. Additionally, the mortality of ticks exposed to CERTIFECT will reduce infestation of the dog's environment.

Efficacy of a novel topical combination of fipronil, amitraz and (S)-methoprene for treatment and control of induced infestations of brown dog ticks (Rhipicephalus sanguineus) on dogs.

Four laboratory studies were conducted to demonstrate that a single topical dose of a novel spot-on combination containing fipronil, amitraz and (S)-methoprene (CERTIFECT™, Merial Limited, GA, USA) is efficacious against the brown dog tick, Rhipicephalus sanguineus. In each study, 6-8 male and 6-8 female purpose-bred, laboratory mongrels, terrier cross or Beagles were randomly assigned to one of two study groups (treated and untreated), based on pre-treatment parasite counts. Starting on the day before treatment, each dog was infested weekly with 50 ticks. Ticks were thumb counted at various time points after treatment and weekly infestations starting as early as 6h and continued at 12, 18 and 24h depending on the study. Ticks were removed and counted at 48 h after treatment and weekly infestations. CERTIFECT provided rapid and excellent control of pre-existing and newly acquired infestations of R. sanguineus with efficacy as high as 93% within the first 12h after a single topical treatment. Excellent control (>96%) of R. sanguineus as early as 18 h, following post treatment infestations was maintained for at least 35 days.

Efficacy of a novel topical combination of fipronil, amitraz and (S)-methoprene for treatment and control of induced infestations with four North American tick species (Dermacentor variabilis, Ixodes scapularis, Amblyomma americanum and Amblyomma maculatum) on dogs.

Five laboratory studies were conducted to confirm that a single topical dose of the novel combination of fipronil, amitraz and (S)-methoprene, CERTIFECT™ (Merial Limited, GA, USA), is efficacious for the rapid control of pre-existing infestations and the prevention of new infestations with Ixodes scapularis, Dermacentor variabilis, Amblyomma americanum and Amblyomma maculatum for at least 28 days on dogs. In each study, 8 male and 8 female purpose-bred, laboratory beagles were randomly assigned to one of two study groups (treated and untreated). Starting on the day before treatment, each dog was infested weekly with about 30 or 50 ticks, depending on the study. Treatment with the novel combination rapidly eliminated pre-existing infestations and controlled weekly re-infestations for at least 28 days. Pre-existing infestations with all four tick species were rapidly and effectively reduced, with post-treatment therapeutic efficacies ranging from 91.7 to 99.5% within 18-48 h post treatment. Amblyomma maculatum numbers were significantly (p<0.05) reduced on treated dogs from the first tick counts as early as 6h post-treatment. All subsequent infestations with each of the 4 tick species were quickly disrupted, with prophylactic efficacies greater than 90% within 18-48 h post-infestation for at least a full month. Because the combination of fipronil, amitraz and (S)-methoprene quickly starts disrupting and killing ixodid ticks within hours of treatment, with similar high levels of efficacy maintained for at least 28 days in these and other studies, the authors conclude that a single topical treatment with CERTIFECT may prevent the transmission of most infectious agents carried by ixodid ticks for at least one month.

Efficacy of a novel combination of fipronil, amitraz and (S)-methoprene for treatment and control of tick species infesting dogs in Europe.

Four studies were conducted to show the effectiveness of a novel combination of fipronil, amitraz and (S)-methoprene in a spot-on formulation (CERTIFECT™, Merial Limited, GA, USA) for the therapeutic and preventive control of Ixodid tick species affecting dogs in Europe: Ixodes ricinus, Dermacentor reticulatus and Rhipicephalus sanguineus. In each, untreated control dogs were compared to others treated with the novel combination. All dogs were infested with 50 adult, unfed ticks prior to treatment and at 7-day intervals after treatment. Ticks on all dogs were counted at 18, 24 and 48 h after treatment (therapeutic efficacy) or infestation (preventive efficacy). Therapeutic efficacy of fipronil, amitraz and (S)-methoprene was excellent as shown by significant (p<0.05) and greater than 97% and up to 100% reductions in the 48 h tick counts and significant (p<0.05) detachment/death of ticks evident at 18-24h after treatment for all three tick species. Preventive efficacy was demonstrated by significant (p<0.05) and greater than 93% and up to 100% reductions in tick counts at 48 h after repeat infestations out to 35 days after treatment for I. ricinus and out to 42 days after treatment for D. reticulatus and R. sanguineus. The time to substantial disruption of establishment of new tick infestations after treatment was less than 18-24h and was maintained for up to 28 days after treatment of I. ricinus and D. reticulatus infestations, and 4h to at most 18 h and maintained up to 35 days after treatment of R. sanguineus. Similar preventive efficacy profiles for each of the Ixodid species tested suggest that CERTIFECT kills all Ixodid species starting 4h after contact as demonstrated for R. sanguineus.

The ability of a topical novel combination of fipronil, amitraz and (S)-methoprene to protect dogs from Borrelia burgdorferi and Anaplasma phagocytophilum infections transmitted by Ixodes scapularis.

Healthy, purpose-bred laboratory beagle dogs that had not been exposed to ticks and were seronegative for Borrelia burgdorferi and Anaplasma phagocytophilum were randomly assigned to four groups of eight dogs each. Control group 1 was not treated. Groups 2, 3 and 4 were treated with a single topical application of a new formulation of fipronil, amitraz and (S)-methoprene (CERTIFECT™, Merial Limited, GA, USA) at 28, 21 or 14 days prior to tick infestation, respectively. Each dog was infested with 25 female and 25 male field-collected adult Ixodes scapularis ticks that had infection rates of 66% for B. burgdorferi sensu stricto and 23% for A. phagocytophilum, as determined by polymerase chain reaction. Two and five days after tick infestation, control dogs had an average of 9.5 and 13.9 attached adult female ticks, respectively, whilst the 24 treated dogs remained tick-free aside from a single tick on the 2nd day after infestation. Serial serological tests demonstrated that the ticks successfully infected 8/8 control dogs with B. burgdorferi and co-infected 6/8 with A. phagocytophilum. B. burgdorferi infection also was confirmed in most control dogs by culture (6/8) and PCR (7/8) of skin biopsies. In contrast, CERTIFECT protected all 24 treated dogs against infection by both B. burgdorferi and A. phagocytophilum, as demonstrated by their negative serological tests throughout the study and the absence of any positive skin biopsy culture or PCR in these dogs.

Efficacy of fipronil, amitraz and (S)-methoprene combination spot-on for dogs against adult dog fleas (Ctenocephalides canis, Curtis, 1826).

A novel spot-on formulation combining fipronil, amitraz and (S)-methoprene (CERTIFECT™, Merial Limited, GA, USA) was evaluated in adult Beagle dogs in a study to determine its adulticidal efficacy against the dog flea (Ctenocephalides canis, Curtis, 1826). Sixteen dogs were randomly allocated to treatment groups: 8 dogs served as untreated controls, and 8 dogs were treated once. Treatment consisted of applying a new combination formulation to deliver at least 6.7mg fipronil/kg body weight (bw), 8.0mg amitraz/kg bw, and 6.0mg (S)-methoprene/kg bw. The combination was designed to enhance the efficacy against ticks of the original fipronil/(S)-methoprene combination. Each dog was infested with 100 adult unfed dog fleas within 24h prior to treatment and then at weekly intervals for 8 weeks after treatment. At 24h after treatment or after each subsequent infestation, each dog was combed thoroughly to remove live fleas to be counted. A single treatment with CERTIFECT provided excellent knock-down of fleas within 24h after treatment and controlled re-infestations for up to 7 weeks (efficacy ≥96.5%, p<0.05).

Effects of short-term light to heavy exercise on gastric ulcer development in horses and efficacy of omeprazole paste in preventing gastric ulceration.

OBJECTIVE: To determine the effects of 8 days of light to heavy exercise on gastric ulcer development in horses and determine the efficacy of omeprazole paste in preventing gastric ulceration. DESIGN: Randomized, controlled, multicenter clinical trial. ANIMALS: 102 horses with normal-appearing gastric mucosa on endoscopic examination that were in light to heavy training. PROCEDURES: Horses at 4 trial locations were allocated into replicates and sham dosed orally (empty syringe) or treated with a paste formulation of omeprazole (1 mg/kg [0.45 mg/ lb], PO) once daily for 8 days. Training regimens varied among locations and included early training for western performance events; walking, trotting, and cantering in a mechanical exerciser; and race training (2 locations). Prevalences of gastric ulceration at the completion of the 8-day treatment period were compared between groups. RESULTS: At the end of the 8-day treatment period, the proportion of omeprazole-treated horses free from gastric ulceration (88%) was significantly higher than the proportion of sham-dosed horses free from gastric ulceration (27%). CONCLUSIONS AND CLINICAL RELEVANCE: Results showed that horses in light to heavy training for as short as 8 days were at risk of developing gastric ulcers and that administration of omeprazole paste decreased the incidence of gastric ulcers.

Efficacy of omeprazole paste for prevention of gastric ulcers in horses in race training.

OBJECTIVE: To determine the minimal effective dosage of omeprazole oral paste for the prevention of naturally occurring ulcers in horses starting race training. DESIGN: Prospective study. ANIMALS: 175 horses. PROCEDURE: Horses in the dose selection portion of the study were sham dose treated or received 1 mg (0.45 mg/lb) or 2 mg (0.9 mg/lb) of omeprazole/kg, PO, every 24 hours for 28 days or 4 mg of omeprazole/kg (1.8 mg/lb; loading dose), PO, every 24 hours for 4 days, then 1 or 2 mg of omeprazole/kg, PO, every 24 hours for 24 days. Horses in the dose confirmation portion of the study were sham dose treated or received 1 mg of omeprazole/kg, PO, every 24 hours for 28 days. Gastric ulcer scores at the beginning and end of the study were compared. RESULTS: Sham-dose-treated horses had significantly higher ulcer scores than did horses treated with any of the omeprazole dosages evaluated. Among horses treated with omeprazole, there was no significant interaction of dose (1 or 2 mg/kg) and loading dose; therefore, the lowest effective dose (1 mg/kg) was evaluated in the dose confirmation portion of the study. In the dose confirmation study, 4 of 39 (10%) sham-dose-treated horses remained ulcer free, which was significantly different from the proportion of horses (31/38 [82%]) receiving 1 mg of omeprazole/kg that remained ulcer free. CONCLUSIONS AND CLINICAL RELEVANCE; Results indicated that omeprazole administered at a dosage of 1 mg/kg, PO, every 24 hours for 28 days was effective for prevention of gastric ulcers in horses starting race training.

Efficacy of omeprazole paste for prevention of recurrence of gastric ulcers in horses in race training.

OBJECTIVE: To determine whether omeprazole oral paste administered at a dosage of 0.5 or 1 mg/kg (0.23 or 0.45 mg/lb), PO, every 24 hours would effectively prevent the recurrence of gastric ulcers in horses in race training. DESIGN: Prospective study. ANIMALS: 135 horses. PROCEDURES: Horses with gastric ulcers were treated with omeprazole at a dosage of 4 mg/kg (1.8 mg/lb), PO, every 24 hours for 28 days. Horses in the dose selection portion of the study were sham dose treated or received 0.5 or 1 mg of omeprazole/kg, PO, every 24 hours for an additional 28 days. Horses in the dose confirmation portion of the study were sham dose treated or received 1 mg of omeprazole/kg, PO, every 24 hours for an additional 28 days. Gastric ulcers were scored before and after the preventive phase of the study (day 28 to day 56) via gastroscopy, and ulcer scores were compared. RESULTS: Sham-dose-treated horses and horses receiving 0.5 mg of omeprazole/kg had significantly higher ulcer scores than did horses receiving 1 mg of omeprazole/kg. There was a significant difference between the proportion of horses receiving 1 mg of omeprazole/kg (38/48 179%]) that remained ulcer free and the proportion of sham-dose-treated horses (7/44 [16%]) that remained ulcer free. CONCLUSIONS AND CLINICAL RELEVANCE: Omeprazole oral paste administered at a dosage of 1 mg/kg, PO, every 24 hours for 28 days was effective for prevention of recurrence of gastric ulcers in horses in race training.