Repellent efficacy of a new combination of fipronil and permethrin against Lutzomyia longipalpis.

BACKGROUND: Lutzomyia longipalpis is the main vector of Leishmania infantum, the agent of canine and human visceral leishmaniosis in the Americas. Considering that the dog is the main domestic host of the parasite, repellent treatment is a measure that might contribute to the prevention of canine visceral leishmaniosis. The repellent efficacy of a single treatment of a new spot-on topical combination of fipronil and permethrin (Frontline Tri-Act®, Merial, now part of Boehringer-Ingelheim) to repel Lu. longipalpis sand flies was evaluated. METHODS: Sixteen healthy Beagle dogs, eight females and eight males, weighing 8.4-14.4 kg, and 2 to 4 years-old were included in the study. Animals were blocked on decreasing body weight and randomly allocated within the blocks to one of two treatment groups of eight animals each. Dogs in Group 1 were untreated and Dogs in Group 2 were treated with a combination containing 67.6 mg/ml fipronil + 504.8 mg/ml permethrin (Frontline Tri-Act®) once on Day 0. Sand fly exposures were performed on Days 1, 14, 21 and 30 with Lu. longipalpis female sand flies. After 65 (± 15 min), sand flies were assessed for engorgement status. RESULTS: The percent repellency of the treated group compared to the untreated control group was 95.7, 94.3, 81.7 and 72.2% for exposure days 1, 14, 21 and 30, respectively. The two treatment groups were significantly different for all exposure days (P ≤ 0.016 for days 1, 14, 21 and 30). No adverse reactions were observed during the study. CONCLUSION: A single topical administration of a new combination of fipronil and permethrin demonstrated a significant repellent effect against Lu. longipalpis bites as soon as it was applied on the dogs and its repellent efficacy lasted for 4 weeks with results greater than 80% for 3 weeks. The results suggest that in endemic areas the regular application of the new combination could contribute to protect dogs from Leishmania infection and therefore serve as an additional tool for the prevention of canine visceral leishmaniosis.

Efficacy of a topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel (Broadline(®)) against naturally acquired infections with cestodes of the genus Joyeuxiella in cats.

Cats are host to dipylidiid cestodes of the genera Diplopylidium, Dipylidium and Joyeuxiella. Broadline(®), a topical broad-spectrum combination parasiticide containing fipronil (8.3 % w/v), (S)-methoprene (10 % w/v), eprinomectin (0.4 % w/v) and the cestocide praziquantel (8.3 % w/v), has previously been shown to be efficacious against Dipylidium caninum and Diplopylidium spp. in cats. To evaluate its efficacy against Joyeuxiella species, a blinded clinical efficacy study was conducted according to GCP. All cats had evidence for naturally acquired dipylidiid cestode infection as confirmed by pre-treatment examination. Cats were allocated randomly to two groups of 13 cats each based on bodyweight: Control (untreated) and Broadline(®) at 0.12 mL/kg bodyweight administered once topically. Based on the comparison of helminth counts in the treated and untreated cats seven days post treatment, Broadline(®) demonstrated >99 % efficacy (p < 0.01) against mature J. fuhrmanni and J. pasqualei, with 11 and 13 of the untreated cats harbouring 1 to 102 or 2 to 95 cestodes, respectively. In addition, parasite counts indicated 95.9 % efficacy (p = 0.006) against the rictularoid nematode Pterygodermatites cahirensis.

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., 2.5 mg/kg body weight and 0.5 mg/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.

Repellent and insecticidal efficacy of a new combination of fipronil and permethrin against stable flies (Stomoxys calcitrans).

BACKGROUND: A laboratory study was conducted to assess the repellent and insecticidal efficacy of a new combination of fipronil and permethrin (Frontline Tri- Act/Frontect Merial) against Stomoxys calcitrans (stable flies). METHODS: Sixteen dogs were allocated to two treatment groups. Eight dogs were treated with a new topical spot-on formulation containing 6.76% w/v fipronil + 50.48% w/v permethrin on Day 0 and eight dogs served as untreated controls. Each dog was exposed to approximately 100 stable flies on Days 1, 7, 14, 21, 28 and 35. After a one-hour exposure period, live flies were carefully aspirated into a vial, anesthetized with CO2 and crushed to determine feeding status (fed or unfed). Any dead flies remaining on the dog or in the cage were crushed to determine feeding status and counted as fed or unfed. Repellency was defined as the percent reduction in the number of fed flies in the treated group as compared to the untreated control group, and insecticidal efficacy was defined as the reduction in the number of live flies at the end of each exposure period in the treated group as compared to the control group. RESULTS: Percent repellency was ≥96.6% through Day 28, and 88.7% on Day 35. Percent insecticidal efficacy was ≥ 98.3% through Day 35. CONCLUSIONS: A single topical administration of a new combination of fipronil and permethrin provides protection (repellency and insecticidal efficacy) from S. calcitrans on dogs for at least 5 weeks.

Repellent and insecticidal efficacy of a new combination of fipronil and permethrin against three mosquito species (Aedes albopictus, Aedes aegypti and Culex pipiens) on dogs.

BACKGROUND: Three laboratory studies were conducted to assess the repellent and insecticidal efficacy of a combination of fipronil and permethrin (Frontline Tri- Act/Frontect) against three mosquito species (Aedes albopictus, Aedes aegypti and Culex pipiens) on dogs. METHODS: In each study, 16 healthy adult dogs were allocated to two groups. Eight dogs were treated with the new topical spot-on combination of fipronil and permethrin on Day 0 and the other eight dogs served as untreated controls. Each dog was exposed to mosquitoes on Days 1, 7, 14, 21 and 28 (and also on Day 35 in the A. aegypti study). After a 1-h exposure period, all mosquitoes were counted and categorized as live or dead and fed or non-fed. Live mosquitoes were kept in an insectary and observed for mortality counts 4, 24 and 48 h post-exposure (PE) for Aedes spp. and 24 and 48 h PE for C. pipiens. Repellency and insecticidal efficacies were defined as the percent reduction in the number of fed and live mosquitoes, respectively, in the treated group as compared to the untreated control group. RESULTS: Repellency against A. albopictus was ≥93.4% through Day 21 and 86.9% on Day 28. It was ≥91.0% through Day 35 against A. aegypti and ≥90.4% through Day 28 against C. pipiens. Insecticidal efficacy against A. albopictus was ≥97.1% at 24 h PE from Day 7 to Day 28. It was ≥98.0% for the first 3 weeks and still 75.7% on Day 35 against A. aegypti at 24 h PE. For C. pipiens, insecticidal efficacy ranged from 93.8% (Day 7) to 30.9% (Day 28) at 48 h PE. CONCLUSIONS: A single topical administration of the combination of fipronil and permethrin provides repellency against mosquitoes on dogs for at least 4 weeks. The product may therefore significantly reduce the potential for the transmission of vector-borne pathogens through the inhibition of mosquito feeding, as well as the discomfort associated with mosquito bites. Moreover, mosquito mortality was induced by contact with the treated dogs, which could aid in the control of mosquitoes, and hence the control of mosquito-borne diseases, in the local vicinity of treated dogs.

Efficacy against nematode and cestode infections and safety of a novel topical fipronil, (S)-methoprene, eprinomectin and praziquantel combination product in domestic cats under field conditions in Europe.

A novel topical combination product (BROADLINE(®), Merial) composed of fipronil, (S)-methoprene, eprinomectin and praziquantel was evaluated for safety and efficacy against nematode and cestode infections in domestic cats. The study comprised a multi-centre, positive control, blinded, field study, using a randomized block design based on order of presentation for allocation. In total 196 client-owned cats, confirmed as positive for naturally acquired infections of nematodes and/or cestodes by pre-treatment faecal examination, were studied in seven countries in Europe. Pre-treatment faecal examination revealed the presence of Toxocara, hookworm, Capillaria and/or spirurid nematode infections in 129, 73, 33 or 1 cat(s), respectively; infections with taeniid and Dipylidium cestodes were demonstrated in 39 and 17 cats, respectively. Cats were allocated randomly to one of two treatments in a ratio of 2, topical fipronil (8.3%, w/v), (S)-methoprene (10%, w/v), eprinomectin (0.4%, w/v) and praziquantel (8.3%, w/v) (BROADLINE(®), Merial; 130 cats); and 1, topical PROFENDER(®) Spot-On (Bayer; 66 cats) and treated once on Day 0. For evaluation of efficacy, two faecal samples were collected, one prior to treatment (Day -4 ± 4 days) and one at the end of the study (Day 14 ± 5 days). These were examined for fecal forms of nematode and cestode parasites. For evaluation of safety, cats were examined by a veterinarian before treatment and at the end of the study, and cat owners recorded the health status of their cats daily until the end of the study. For cats treated with Broadline(®), the efficacy was >99.9%, 100%, and 99.6% for Toxocara, hookworms, and Capillaria, respectively; and the efficacy was >99.9%, >99.9%, and 98.5%, respectively, for the cats treated with Profender(®) (p<0.001 for all nematodes and both treatments). Efficacy was 100% for both cestodes for both treatments (p<0.001). No treatment related adverse experiences were observed throughout the study. For both treatments, every cat that completed the study was given a safety score of 'excellent' for both local and systemic evaluations. The topical combination product of fipronil, (S)-methoprene, eprinomectin and praziquantel was shown to have an excellent safety profile and demonstrated high levels of efficacy when administered once as topical solution to cats infected with nematodes and cestodes under field conditions.

Efficacy of a novel topical fipronil, (S)-methoprene, eprinomectin and praziquantel combination against naturally acquired intestinal nematode and cestode infections in cats.

The efficacy of a novel topical combination formulation of fipronil, (S)-methoprene, eprinomectin and praziquantel against naturally acquired intestinal nematode and cestode infections in cats was evaluated in seven negative control, blinded studies. Cats were selected based on a pre-treatment faecal examination indicating a patent infection with at least hookworms (two studies), Toxocara ascarids (one study), taeniid cestodes (two studies) or Dipylidium cestodes (two studies). In each study, cats were assigned randomly to blocks of two animals each, based on decreasing pre-treatment body weight and were randomly allocated to one of two groups of six to 12 cats: untreated (control) or treated with topical fipronil (8.3%, w/v), (S)-methoprene (10%, w/v), eprinomectin (0.4%, w/v) and praziquantel (8.3%, w/v) (BROADLINE(®), Merial) at 0.12 mL/kg body weight (providing a minimum of 10mg fipronil+12 mg S-methoprene+0.5mg eprinomectin+10mg praziquantel per kg body weight). The topical treatment was administered directly on the skin in the midline of the neck in a single spot once on Day 0. For parasite recovery and count, cats were euthanized humanely and necropsied seven or ten days after treatment. A single treatment with the novel topical combination product provided 91% efficacy against Ancylostoma braziliense, ≥ 99% efficacy against Ancylostoma tubaeforme, and >97% efficacy against Toxocara cati. Similarly, excellent efficacy was established against Taenia taeniaeformis, Dipylidium caninum and Diplopylidium spp. as demonstrated by >97% and up to 100% reductions of cestode counts in the treated cats when compared to the untreated controls (P<0.01). All cats accepted the treatment well based on health observations post-treatment and daily health observations. No adverse experiences or other health problems were observed throughout the studies. The results of this series of controlled studies demonstrated high efficacy and excellent acceptability of the novel topical combination formulation of fipronil, (S)-methoprene, eprinomectin and praziquantel against a broad range of feline intestinal nematode and cestode infections.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel against induced infections of Ancylostoma spp. nematodes of cats.

Four studies were conducted to examine the efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel (BROADLINE(®), Merial) against Ancylostoma tubaeforme and Ancylostoma braziliense hookworms of cats. In each study, purpose-bred cats were randomly assigned to treatment groups of 10 or 12 cats per group. In three studies the cats were inoculated with A. tubaeforme and in one study with A. braziliense. The inoculations were undertaken on a schedule which resulted in the hookworms reaching the fourth larval stage in two of the studies, or the adult stage in four of the studies, by the day of treatment. In each study there was also an untreated control and 1 or 2 groups treated with the novel combination. In the two studies where efficacy against the fourth larval stage of A. tubaeforme was tested, the efficacy recorded was 100%. In the three studies where efficacy against the adult stage of A. tubaeforme was tested, efficacy of 100% was also confirmed. In the study where efficacy against the adult stage of A. braziliense was tested efficacy was 99.5%.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel against adult and larval stages of Toxocara cati in cats.

The efficacy of a novel topical combination of fipronil 8.3% (w/v), (S)-methoprene 10% (w/v), eprinomectin 0.4% (w/v), and praziquantel 8.3% (w/v) (BROADLINE(®), Merial) was evaluated against adult and larval Toxocara cati in four controlled studies. All studies included experimentally infected, purpose-bred, short-haired cats. In two studies, 22 or 20 cats harbouring patent infections as confirmed by pre-treatment faecal examination, were included. Within each study, cats were allocated to one of two groups: control or treated. In a further two studies, 30 cats were included in each; cats were allocated to one of three groups: control, treated when T. cati were expected to be either migrating third and/or fourth-stage larvae, or treated when T. cati were expected to be fourth-stage larvae. Cats allocated to the treated groups received a single topical application of the combination product at 0.12 mL/kg bodyweight (10mg fipronil+12 mg (S)-methoprene+0.5mg eprinomectin+10mg praziquantel per kg). For parasite recovery and count, cats were euthanized humanely at different intervals after treatment. In the studies targeting adult T. cati, ascarids were recovered from all controls (range 1-150) while only two worms were isolated from one treated cat. Thus, the efficacy of the novel combination was 99.4% and 100% against adult T. cati. For studies targeting larval T. cati, up to 21 worms were recovered from each of seven or eight of the control cats per study. No T. cati were recovered from the treated cats in two studies, corresponding to 100% efficacy against both, migrating third and/or fourth-stage larvae and luminal fourth-stage larvae. All cats accepted the treatment well and no adverse experiences or other health problems were observed throughout the studies.

Efficacy of a single dose of a novel topical combination product containing eprinomectin to prevent heartworm infection in cats.

Cats may be infected by heartworm, Dirofilaria immitis, through mosquito bites. They can develop severe heartworm disease when infective D. immitis larvae migrate and develop into adults in the pulmonary vasculature or other tissues. As there is no curative treatment for feline heartworm infection, the monthly administration of preventative treatment is recommended in endemic areas. Three controlled, blinded laboratory studies were conducted to evaluate the preventative efficacy of BROADLINE(®), a novel combination of fipronil, (S)-methoprene, eprinomectin, and praziquantel against D. immitis in cats. In each study, 28 cats were inoculated with approximately 100 (studies 1 and 2) or 40 (study 3) infective third stage D. immitis larvae by subcutaneous injection, thirty days prior to treatment. The larvae were from recent field isolates from naturally infected dogs from three distinct geographic areas (two in the USA and one in Europe). In each study, the cats were allocated randomly to two study groups of 14 cats each. The control group remained untreated. On Day 0, each cat in the treated group received one topical application of the novel topical formulation, delivering the minimum intended dose of 0.5mg of eprinomectin per kilogram of body weight. At 6 months after infection, all cats were humanely euthanized and examined for adult D. immitis. Across all three studies, 28 (68%) of the 41 untreated cats harbored one or more heartworms, while 100% of the 42 treated cats remained free of heartworm infection, demonstrating the 100% preventive efficacy of BROADLINE(®) against D. immitis in cats. The treatment was well tolerated and no health abnormality was observed in any treated cat.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel against adult and immature stages of the cat flea (Ctenocephalides felis) on cats.

The efficacy of a novel topical combination of fipronil 8.3% (w/v), (S)-methoprene 10% (w/v), eprinomectin 0.4% (w/v) and praziquantel 8.3% (w/v) (BROADLINE(®)) was tested against adult and immature stages of Ctenocephalides felis fleas in six studies. For that purpose, fleas from different colonies from North America, Germany and South Africa were used to induce infestations in cats under laboratory conditions. In each study, between 12 and 16 cats were allocated randomly to 2 groups. Cats in Group 1 were not treated and served as controls. Cats in Group 2 were treated once on Day 0 with BROADLINE(®) at the minimum recommended dosage of 0.12 mg/kg body weight. In 4 studies, all animals were infested experimentally with unfed C. felis (100 ± 5) on Days 2 (or 1), 7, 14, 21, 28 and 35. Live fleas were counted 24h post-treatment or infestation. In 2 additional studies, animals were infested at the same frequency with gravid C. felis fleas (100 ± 5) that were fed previously on an untreated host. Forty-eight hours post-infestation, flea eggs were collected, counted and incubated for the evaluation of the reduction of emergence of adults. The combined curative efficacy against adult fleas at 24h after treatment was 94.3% and the combined preventive efficacy values remained greater than 95.9% at 24h after 5 subsequent weekly infestations. In addition, the product reduced dramatically the emergence of new adult fleas for at least 5 weeks (>98.1% for one month and 93.2% at 5 weeks after infestation), demonstrating its efficiency in preventing environmental contamination by immature stages.

Efficacy of a novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel against larval and adult stages of the cat lungworm, Aelurostrongylus abstrusus.

The efficacy of a novel topical combination of fipronil 8.3% w/v, (S)-methoprene 10% w/v, eprinomectin 0.4% w/v, and praziquantel 8.3% w/v (BROADLINE(®),(1) Merial) against larval and adult Aelurostrongylus abstrusus lungworms in cats was assessed in a controlled laboratory study. The study included 48 purpose-bred, short-haired cats which were each inoculated with 225 infective A. abstrusus larvae. The cats were formed into eight blocks based on pre-treatment bodyweight and were then, within each block, randomly allocated to one of six treatment groups: untreated control; treated once when A. abstrusus were expected to be third-stage larvae (4 days post inoculation [dpi]), fourth-stage larvae (7 dpi), immature adults (14 dpi) or adult nematodes (32 dpi), or treated twice, once when A. abstrusus were expected to be third-stage larval and once again when A. abstrusus were expected to be adult nematodes (4 dpi+32 dpi). Cats weighing ≥ 0.8-2.5 kg received one 0.3 mL applicator and cats weighing >2.5-7.5 kg received one 0.9 mL applicator. For determination of the efficacy of treatments, lungworm larval counts were established on faecal samples collected from all cats 32, 39, 46, 53 and 60 dpi. At each occasion from 46 dpi on, cats treated with fipronil, (S)-methoprene, eprinomectin and praziquantel had significantly lower A. abstrusus larval counts than the untreated controls with percentage reductions of 91.6% (cats treated 14dpi; P=0.012), ≥ 98.9% (cats treated either 4 dpi, 7 dpi or 32 dpi; P<0.001) or >99.9% (cats treated 4 dpi+32 dpi; P<0.001) at 60 dpi. Thus, the novel topical combination of fipronil, (S)-methoprene, eprinomectin and praziquantel was highly effective in the prevention and treatment of A. abstrusus lungworm infection in cats.

The combined mode of action of fipronil and amitraz on the motility of Rhipicephalus sanguineus.

The motility of adult Rhipicephalus sanguineus was evaluated subsequent to treatments of amitraz, fipronil and the combination of fipronil plus amitraz against a vehicle control in a Petri dish assay using the LemnaTec Scanalyzer Imaging System. The assay was run using a fixed dilution of amitraz (0.32µg/cm(2)); serial dilutions of fipronil (1.3, 0.33, 0.08, 0.02, or 0.005µg/cm(2)); and the same serial dilutions of fipronil in combination with the fixed dilution of amitraz. Measurement of motility was made of unstimulated ticks and then after stimulation at 1, 4, 18-22, and 24h post exposure (hpe) of the Petri dishes. For the unstimulated ticks, there was no difference in motility between the amitraz treatment group and the fipronil plus amitraz treatment group at the early time points. However, these two treatment groups had significantly higher motility than the solvent control and fipronil treatment groups. The unstimulated ticks in the amitraz treatment group had significantly higher motility than the fipronil plus amitraz treatment group at the later time points. Measurements after stimulation demonstrated there was no difference in motility between the amitraz treatment group and the fipronil plus amitraz treatment group at the early time points. By 18 hpe, the fipronil plus amitraz treatment group had significantly lower motility than all other treatment groups and at 21-22 and 24 hpe the other treatment groups did not differ from the control group. The action could be divided in two phases in the combination experiment: phase 1: an early increase in motility due to amitraz is identified in both amitraz alone or fipronil plus amitraz groups; phase 2: the combination of fipronil plus amitraz caused a significantly greater reduction in motility, suggesting mortality of the ticks, compared to fipronil or amitraz alone. These results demonstrate a synergism resulting from the combination of fipronil plus amitraz.

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.

The prevention of transmission of Babesia canis canis by Dermacentor reticulatus ticks to dogs using a novel combination of fipronil, amitraz and (S)-methoprene.

Four groups of seven dogs were treated topically with a novel combination of fipronil, amitraz and (S)-methoprene in a spot-on formulation (CERTIFECT™, Merial Limited, GA, USA) on 28, 21, 14 and 7 days prior to tick infestation, respectively and acaricidal efficacy and transmission blocking compared with an untreated control group (seven dogs). All dogs were infested with adult Dermacentor reticulatus ticks harbouring Babesia canis canis. Babesia canis canis was transmitted by D. reticulatus to all seven untreated control dogs, confirmed following demonstration of clinical signs, by the detection of B. canis parasites in thin blood smears and B. canis canis PCR-RLB DNA assay on blood and the development of B. canis canis antibody titres by 14-21 days after tick infestation. The majority of treated dogs remained sero-negative for 42 days after infestation. Therefore, the treatment of dogs with CERTIFECT applied up to 28 days prior to infestation with D. reticulatus harbouring B. canis canis, successfully prevented the development of clinical signs of canine babesiosis.

Three-year duration of immunity in cats following vaccination against feline rhinotracheitis virus, feline calicivirus, and feline panleukopenia virus.

Forty-two seronegative cats received an initial vaccination at 8 weeks of age and a booster vaccination at 12 weeks. All cats were kept in strict isolation for 3 years after the second vaccination and then were challenged with feline calicivirus (FCV) or sequentially challenged with feline rhinotracheitis virus (FRV) followed by feline panleukopenia virus (FPV). For each viral challenge, a separate group of 10 age-matched, nonvaccinated control cats was also challenged. Vaccinated cats showed a statistically significant reduction in virulent FRV-associated clinical signs (P = .015), 100% protection against oral ulcerations associated with FCV infection (P < .001), and 100% protection against disease associated with virulent FPV challenge (P < .005). These results demonstrated that the vaccine provided protection against virulent FRV, FCV, and FPV challenge in cats 8 weeks of age or older for a minimum of 3 years following second vaccination.

Efficacy of ceftiofur hydrochloride sterile suspension administered parenterally for the treatment of acute postpartum metritis in dairy cows.

OBJECTIVE: To evaluate the efficacy of ceftiofur hydrochloride sterile suspension administered parenterally for treatment of acute postpartum metritis (APM) in dairy cows. DESIGN: Multilocation, randomized block, field trial. ANIMALS: 406 cows in the first 14 days postpartum. PROCEDURE: Cows with rectal temperatures > or = 39.5 degrees C (103.1 degrees F) without clinical signs of respiratory or gastrointestinal tract disease and with a fetid vaginal discharge were allocated randomly in blocks of 3 to 3 treatment groups: sterile saline (0.9% NaCl) solution administered at a dosage of 2 mL/45.4 kg (2 mL/100 lb), SC or IM, once daily for 5 days (control); or ceftiofur hydrochloride administered at a dosage of 1.1 or 2.2 mg of ceftiofur equivalents (CE)/kg (0.5 or 1 mg/lb, respectively), SC or IM, once daily for 5 days. Cows were evaluated on days 6, 10, and 14, and clinical cure or failure to cure was determined. Clinical cure was defined as no additional antimicrobial treatment administered, rectal temperature < 39.5 degrees C, and absence of a fetid vaginal discharge. RESULTS: On day 14, clinical cure rates were 77%, 65%, and 62% for the 2.2 mg of CE/kg, 1.1 mg of CE/kg, and control groups, respectively. No significant differences were detected in clinical cure rates between control and treatment groups on day 10 or 6. CONCLUSIONS AND CLINICAL RELEVANCE: Ceftiofur hydrochloride administered at a dosage of 2.2 mg of CE/kg, SC or IM, once daily for 5 days was efficacious for treatment of APM in dairy cows.

Feedlot performance of steers treated concurrently with ceftiofur crystalline-free acid subcutaneously in the posterior aspect of the ear and a growth-promoting implant.

Ceftiofur crystalline-free acid sterile suspension (CCFA-SS), a long-acting formulation of ceftiofur formulated for subcutaneous injection in the middle third of the posterior aspect of the ear, is being developed for the control and treatment of bovine respiratory disease. A study was designed to evaluate average daily gain (ADG) and feed efficiency (FE) for cattle through 140 days in the feedlot after CCFA-SS was administered concurrently in the same ear with a growth-promoting implant. On Day 0, steers (n = 207) averaging 189 kg in weight were randomly assigned to the following treatments: Revalor -S implant (120 mg trenbolone acetate and 24 mg estradiol per implant; Hoechst-Roussel Agri-Vet Company) (n = 64); CCFA-SS at 6.6 mg ceftiofur equivalents/kg and a Revalor -S implant (n = 64); untreated control (no CCFA-SS or implant) (n = 63); or CCFA-SS only (n = 16). On Day 56, an Implus-S implant (200 mg progesterone USP plus 20 mg estradiol benzoate; Pharmacia and Upjohn Animal Health) was administered to all cattle. Tolerance of administration of all materials was observed visually and by palpation of the treated ears. Average daily gain and FE from Day 0 through Day 56 were significantly (P <.001) better for steers of both groups with an implanted growth-promotant than for untreated controls. From Day 0 through Day 140, ADG was significantly (P <.05) better for cattle given an implant or an implant plus CCFA-SS than for untreated controls and FE was significantly (P <.05) better for cattle given an implant plus CCFA-SS than for controls. Mild or moderate, transient swelling of the treated ear was observed in two cattle (CCFA-SS plus implant) on Day 52. On Day 56, 88 % of cattle treated with CCFA-SS, 84 % of the cattle treated with an implant plus CCFA-SS, and 100 % of cattle in other groups were normal. Administration of CCFA-SS in the middle third of the posterior aspect of the ear at the same time as growth-promoting implants did not affect performance of cattle in the feedlot and was well tolerated by the animals.

Dose determination and confirmation for ceftiofur crystalline-free acid administered in the posterior aspect of the ear for control and treatment of bovine respiratory disease.

Three studies were conducted to determine and confirm the effective dosage rate of ceftiofur crystalline-free acid sterile suspension (CCFA-SS, 200 mg ceftiofur equivalents [CE]/ml), a long-acting ceftiofur formulation, for control and treatment of bovine respiratory disease (BRD). In each study, CCFA-SS was administered once by subcutaneous (SC) injection in the middle third of the posterior aspect of the ear. Study 1 was conducted using an intratracheal challenge with Mannheimia (formerly Pasteurella) haemolytica and dosages ranging from 0 to 8.8 mg CE/kg to select a dosage for further field testing. In Study 2, a single dose of CCFA-SS at 0.0, 4.4, or 6.6 mg CE/kg was administered when uniform clinical signs of BRD were present in feedlot cattle. Study 3 was conducted in several feedlots to evaluate the efficacy, practicality, and safety of CCFA-SS at 4.4 or 6.6 mg CE/kg compared with a placebo control or tilmicosin for preemptive control of BRD. In Study 1, the effective dose was determined to be 5.35 mg CE/kg; therefore, 4.4 and 6.6 mg CE/kg were selected as the dosages for further field testing. Administration of CCFA-SS at 4.4 or 6.6 mg CE/kg improved treatment success compared with negative controls (P < or =.05 for both doses) in Study 2. In Study 3, a single administration of 4.4 or 6.6 mg CE/kg was comparable to tilmicosin (P <.001) and was significantly better than placebo (P <.001) for the control of BRD. Using the ear as an administration site was acceptable under field conditions and was well tolerated by all animals. These studies demonstrated that a single administration of CCFA-SS by SC injection in the middle third of the posterior aspect of the ear at 4.4 or 6.6 mg CE/kg is effective, safe, and practical for preemptive control and treatment of the bacterial component of BRD in feedlot cattle. Administration in an inedible tissue results in a short withdrawal time and no injection-site trimming at slaughter.