Christelle Navarro

Induction of fertile oestrus in the bitch using Deslorelin, a GnRH agonist.

Oestrus induction in various canine breeds was attempted in 32 bitches. A group of 8 bitches were treated 80-160 d following their previous oestrus (G1) whereas a second group of 24 bitches (G2) were implanted 200-590 d following their previous oestrus. The treatment for each bitch consisted in one Deslorelin implant (Suprelorin® 4,7 mg, Virbac, France), inserted subcutaneously in the post-umbilical region. Ovulation, pregnancy rate and litter size were recorded. All bitches came in heat 4.3 ± 1.4 d after implantation (2-7 d). Ovulation was reported in 62.5% in G1 and 87.5% in G2. One bitch refused mating and since no AI was performed, she was not considered for further analysis. Pregnancy was obtained in 25% in G1 versus 78.3% in G2. Mean litter size was 6.7 ± 3.5 puppies (1-14). Luteal failure was suspected in 3 bitches, two that remained non-pregnant and one which aborted 58 d post-ovulation since the owner refused progesterone supplementation. Deslorelin implants can therefore be considered as a valuable alternative to induce fertile oestrus in bitches in anoestrus. Follow-up of the luteal phase is recommended, since some bitches might encounter luteal failure.

Treatment of queens in estrus and after estrus with a GnRH-agonist implant containing 4.7 mg deslorelin; hormonal response, duration of efficacy, and reversibility

Although slow release GnRH-agonist implants have been shown to effectively suppress the estrous cycle in queens, there are still several remaining questions about their use: if the probability and frequency of estrus induction because of initial stimulation is dependent on the stage of cycle when animals are treated, if all effects are reversible, and to what extent fertility is regained after the end of efficacy. The latter is of major interest to cat breeders who want temporary suppression of estrus in breeding animals. Twenty queens (14 with known fertility) were treated with a 4.7 mg deslorelin implant; hormonal changes (progesterone [P4], and estradiol [E2]) and behavioral changes with special respect to estrus signs and subsequent fertility were assessed. Group A cats (N = 10) were treated 3.2 ± 0.8 days after the beginning of estrus and estrus stopped 4.1 ± 2.5 days after treatment. Estrus induction was observed in one queen 6 days after treatment, and one queen showed estrous signs 138 and 155 days after treatment. Progesterone increased significantly after treatment in all animals until day 14, then slowly decreased reaching basal levels on day 56 without any further increase. Group B cats (N = 10) were treated 7 days after the end of estrus; nine cats had P4 > 1.5 ng/mL and basal E2, one cat (B10) had basal E2 and P4. In cat B10 estrus induction occurred after treatment, but in none of the others; however, E2 increased in all group B cats 1 day after treatment but reached pretreatment concentrations on Day 7 again and remained basal. The implant was still effective in one animal of the estrus group with a duration of efficacy >1102 days, in the others duration of efficacy varied between 483 and 1025 days. Eight queens were mated afterwards and gave birth to a healthy litter with 3.3 ± 1.5 kittens. This study proves that (1) the incidence of estrus induction-although very low-is highest after treatment in estrus or postestrus, (2) the duration of efficacy varies between 16 and 37 months, and (3) estrus suppression is reversible and animals remain fertile after the treatment effect has expired.

Efficacy of a new combination of fipronil and permethrin (Effitix®) against Phlebotomus perniciosus in dogs.

Two controlled clinical trials were carried out to assess the anti-feeding and adulticidal effects of a spot-on combining fipronil and permethrin (Effitix(®), Virbac, Carros, France) against Phlebotomus perniciosus in dogs. The first study (Exp. A) was a dose-determination study in which 3 doses of permethrin (30 mg/kg, 60 mg/kg and 120 mg/kg) were compared. The second study (Exp. B) was an efficacy study using commercial dose of permethrin contained in Effitix(®) (the minimum dose of permethrin applied to dogs was 60 mg/kg). Twenty four and twelve Beagle dogs with equal sensitivity to sandflies were included in Exp. A and in Exp. B, respectively. Dogs were challenged with female sandflies (50 per dogs in Exp. A and 80 in Exp. B) for 60±5 min on Days - 7, 1, 7, 14, 21 and 28 (Day 0 being treatment day). Counts and engorgement determination of dead and alive sandflies were performed after each exposure to treated and untreated dogs. Dead sandflies were also counted 24 h after exposure. In Exp. A, the repellency induced by an administration of 30 mg/kg of permethrin to dogs was above 91% for the first two weeks and then dropped to 82.2, 83.1 and 81.1% on Days 14, 21 and 28, respectively. For dogs receiving 60 mg/kg of permethrin, the repellency was a bit higher with 95.8, 97.6, 92.1, 91.4, and 86.8%, for Days 1, 7, 14, 21 and 28, respectively. The repellency induced by 120 mg/kg of permethrin was significantly higher than that induced by 60 mg/kg of permethrin on Day 14 only. In Exp. B the anti-feeding effect of the spot-on formulation was 94.1, 97.8, 96.3, 90.8 and 87% on Days 1, 7, 14, 21 and 28, respectively. The mortality effect was 98.9, 99.1, 99.8, 97.0 and 89.7% on Days 1, 7, 14, 21 and 28, respectively. At each challenge point, the mortality and anti-feeding effects on sandflies were significantly different between control and treatment group (p<0.05). The results indicate that a monthly administration of this new combination of permethrin and fipronil could be used as an effective sandfly control strategy in dogs and therefore recommended for use in an integrated leishmaniosis prevention program.

The sustained speed of kill of ticks (Rhipicephalus sanguineus) and fleas (Ctenocephalides felis felis) on dogs by a spot-on combination of fipronil and permethrin (Effitix®) compared with oral afoxolaner (NexGard®)

The rapid speed of kill of a spot-on, combination of fipronil-permethrin (Effitix®, Virbac) was shown against infestations of Rhipicephalus sanguineus and Ctenocephalides felis on dogs. Efficacy was determined against new infestations at weekly intervals for one month after treatment. Dogs were allocated randomly to either an untreated control or to a single administration, given on Day 0, of either topical fipronil-permethrin (6.7-13.4mg/kg and 60-120mg/kg, respectively) or oral afoxolaner (2.72-6.8mg/kg), based on pre-treatment, host-suitability flea counts. Dogs were infested with 50, unfed, adult R. sanguineus on Days 7, 14, 21 and 28, and with 100C. felis on Days 8, 15, 22 and 29. Tick counts were performed 0.5, 2, 6, 12 and 24h, and flea counts were performed 0.5 and 24h after each infestation. No treatment-related adverse reactions occurred. Dogs in the untreated group maintained viable infestations throughout the study. Following infestation, live tick and flea counts for dogs treated with fipronil-permethrin compared with untreated dogs were rapidly and significantly reduced with efficacy apparent at 0.5h after infestation. Flea efficacies (arithmetic mean counts) at 0.5h after infestation on Day 7 (Day 28) were significantly greater for fipronil-permethrin, 70% (34%) compared with 8% (18%) for afoxolaner (P≤0.05). Tick efficacies at 2h on Day 7 (Day 28) were 74% (63%) for fipronil-permethrin compared with 10% (0%) for afoxolaner (P≤0.05). Efficacies for tick repellency as indicated by counts of ticks off the dogs at 2h on Day 7 (Day 28) were greater for fipronil-permethrin, 32% (22%) compared with afoxolaner, 0% (0%) (P≤0.05). Anti-attachment efficacies at 12h were greater for fipronil-permethrin compared with afoxolaner. Tick efficacies at 24h, based on arithmetic (geometric) means, were significantly greater on Day 28 for fipronil-permethrin compared with afoxolaner (P≤0.05), 74% (87%) and 45% (60%), respectively, and were similar (P >0.05) on Days 7, 14 and 21. Flea efficacies, 24h after infestation were >98% and similar for both treated groups on all infestation days (P >0.05). The topically applied fipronil-permethrin containing ectoparasiticide Effitix® offers rapid efficacy against R. sanguineus and C. felis which persists for one month after a single administration in dogs. Afoxolaner is also effective although speed of kill is slower. The rapid and sustained speed of kill of both parasites by fipronil-permethrin should contribute to effective management not only of these parasites and their direct adverse effects including irritancy and allergy, but also to reducing the risk of transmitting infections.

Evaluation of the in vitro effect of Boldo and Meadowsweet plant extracts on the expression of antimicrobial peptides and inflammatory markers in canine keratinocytes

Dogs with allergies are prone to skin infections and treatments/preventatives to boost innate immune-defenses are beneficial. The aim of this study was to evaluate the effects of Boldo and Meadowsweet extracts on the expression of β-defensins (cBD), cathelicidin (cCath), and pro-inflammatory cytokines in canine keratinocyte. This study had two phases. Phase I evaluated mRNA expression of cBD103 and cCath, and secretion of cCath, IL-8 and TNF-α by keratinocytes harvested from healthy (n=5) and atopic (n=5) age-matched beagles exposed to Boldo (2% to 0.2%) and Meadowsweet (1% to 0.2%) extracts. Phase II focused on atopic keratinocytes (n=14) exposed to 0.2% Boldo, 0.2% Meadowsweet, and a mixture of 0.1% of both extracts. Phase I: cBD103 mRNA (all concentrations) and TNF-α secretion (2% Boldo) were increased in atopic compared with healthy keratinocytes. In atopic keratinocytes, cBD103 was increased after exposure to 1.5% and 0.2% Boldo. In healthy keratinocytes, 1% and 0.2% Meadowsweet, and 2% Boldo increased and decreased IL-8 secretion, respectively. In atopic keratinocytes, IL-8 increased after exposure to 1% and 0.4% Meadowsweet extract. Phase II: cBD103 mRNA increased after exposure to 0.2% Meadowsweet and to 0.1% mixture. cCath was increased after 0.2% Boldo, but decreased after 0.2% Meadowsweet or the 0.1% mixture. TNF-α secretion was decreased after 0.2% Boldo. It is concluded that low concentrations of both extracts and their combination may have some effects on cCath and cBD103 without stimulating an inflammatory response. However, more studies are needed to clarify the effects of these extracts on the local immunity.

Evaluation on the effects of 0.1% Peumus boldus leaf and Spiraea ulmaria plant extract combination on bacterial colonization in canine atopic dermatitis: A preliminary randomized, placebo controlled, double-blinded study

Defective skin barrier characterize canine atopic dermatitis (AD). Pyoderma is the most common complication. Herbal compounds have been suggested as alternatives to control bacterial colonization for their effect on natural antimicrobial peptides (AMPs). This study evaluated the effects of 0.1% Peumus boldus leaf and Spiraea ulmaria plant extract combination on clinical signs, bacterial colonization and AMPs secretion in atopic dogs compared to placebo. Twenty privately-owned atopic dogs were randomly divided in 2 groups (treatment: n = 10; placebo: n = 10) and their abdomen was sprayed every 24 h for 4 weeks. Total and inguinal clinical scores (CADESI-03), manual bacterial count, and skin washes for AMPs (cBD3-like and cCath) were performed on days 0, 14 and 28. AMPs were detected using in-house, previously-validated, canine-specific ELISAs. Data were statistically analyzed and a p < 0.05 was considered significant. Clinical scores and AMPs secretion did not differ significantly between the two groups at any time point. A significant reduction of the clinical scores was seen in the placebo group at 14 and 28 days (p < 0.04). On days 14 and 28, a reduction in the bacterial count was seen in the treated group compared with placebo (p < 0.009 and p = 0.04, respectively). Compared to baseline, a reduction in Staphylococcus spp. was seen in the treated group after 14 days of treatment (p < 0.03). These results show the efficacy of this plant extract combination against bacterial colonization, suggesting its potential usefulness in preventing bacterial infection in atopic dogs. The influence of this compound on AMPs secretion or other mechanisms should be further evaluated.

Treatment of Neotrombicula species infestation in cats using a 10% (w/v) fipronil topical spot-on formulation: a pilot study:

Objectives Few data are available concerning therapeutic aspects of feline trombiculiasis. This study evaluated the efficacy of a 10% w/v fipronil-based spot-on solution in 15 cats with natural Neotrombicula species infestation. Methods Ten cats received 1 drop per affected site on day (D)0 and D14, with the rest of the 0.5 ml pipette applied on the skin between the shoulders. Five cats served as non-treated controls. Parasite score (0 = absent; 3 = severe, >10 parasites/zone) was assessed on D0, D14 and D28 on all animals. Skin lesions (SCORing Feline Allergic Dermatitis lesion severity scale [SCORFAD]) and investigator pruritus scale (IPS; 0 = cat comfortable, grooming like any normal cat; 4 = cat uncomfortable, pruritic all the time) were assessed on treated cats on the same days. Global assessment of efficacy, tolerance and ease of use (GAS; 1 = very poor; 5 = excellent) was assessed on D28. Results All the cats completed the study. Parasite scores of the control cats were maintained throughout the trial (mean ± SD: D0 4 ± 0.7, D14 3.2 ± 1.1 and D28 3.2 ± 0.4). In treated cats, SCORFAD (D0 3.2 ± 5.4, D14 1.1 ± 2.1 [P <0.002] and D28 0.5 ± 1.3 [P <0.002]), parasite (D0 3.9 ± 1.3, D14 1.2 ± 0.8 [P <0.005] and D28 0.4 ± 0.5 [P <0.005]) and IPS (D0 1 ± 1.2, D14 0.5 ± 1.1 [P <0.05] and D28 0.3 ± 0.7 [P <0.05]) scores significantly decreased throughout the trial. On D28, the GAS was 4.2 ± 0.9. There were no adverse effects from treatment. Conclusions and relevance The 10% w/v fipronil preparation appeared to be effective, safe and practical in the treatment of localised Neotrombicula species infestation in these cats.

Control of lice infestation in horses using a 10 mg/mL deltamethrin topical application

BackgroundTwo open-controlled studies evaluated the tolerance and the efficacy of a 10 mg/mL deltamethrin-based pour-on solution (Deltanil®; Virbac, France) in treating (study 1) and preventing (study 2) natural Damalinia equi infestations in horses. In study 1, seven adult horses received 10 mL of the solution from mane to tail head on day 0 (D0). Four adult horses, living separately, served as non-treated controls. All were naturally infected. Lice burden was recorded by counting the number of live parasites, bilaterally, over seven anatomic regions. Lesional score was based on alopecia, crusts, papules/pustules, nodules/plaques, scales and wounds, each assessed on a 0–3 scale. Evaluation was performed on D0 and subsequently weekly until D56 in treated horses and on D0 and D56 in control horses. In study 2, six adult horses free of parasites were similarly treated on D-2 and D30. Two adult horses, naturally infested with D. equi and left untreated, were mixed with the treated horses from D0 to D60. Evaluation was performed similarly to study 1 on all horses, fortnightly until D60.ResultsNo adverse event was recorded in either study. In study 1, parasite and lesional scores of control horses were maintained on D56. Parasite scores of the treated horses were reduced by 98% on D7 and 100% from D15 to D56 (mean [SD]: D0 44 [58.4]). Lesional score in treated horses was reduced by 24, 82, 47, 91, 96, 93, 93 and 100% on D7, 15, 21, 28, 35, 42, 50 and 56, respectively (mean [SD]: D0 3.1 [1.8]).In study 2, the lice populations remained high in the two control horses throughout the study (max mean [SD]: D0 159 [151.3], min D45 34 [39.6]). On treated animals, all parasite counts were negative except on D15 (one louse found). The protection rate was 99.7% on D15 and 100% from D30 to D60.ConclusionsA single application of the 10 mg/mL deltamethrin preparation was effective and safe in the treatment and in the prevention of lice infestation in these horses. It was also effective in preventing new infestations for one month.

Efficacy and Safety of a Permethrin-Fipronil Spot-On Solution (Effitix®) in Dogs Naturally Infested by Ticks in Europe.

Effitix is a new broad spectrum product based on the combination of fipronil 6.1% and permethrin 54.5% in a solution for spot-on application. It has been shown to be safe and efficacious in dogs in controlling tick, flea, sandfly, and mosquito infestations in laboratory conditions. The aim of this controlled, randomised study was to assess its safety and efficacy against natural tick infestations in field conditions. One hundred eighty-two privately owned dogs were included in France and Germany: 123 dogs were treated on day 0 with the permethrin-fipronil combination (Effitix) and 59 with a permethrin-imidacloprid combination (Advantix®). Tick counts were conducted on days 0 (before treatment), 7, 14, 21, and 28. The percentages of efficacy on days 7, 14, 21, and 28 were, respectively, 91.2%, 97%, 98.3%, and 96.7% with Effitix and were 94.8%, 96.9%, 95.7%, and 94.6% with Advantix. Very few adverse events were reported. Most were not serious and/or not related to the treatment with pruritus being the most common. One administration of Effitix was highly effective and safe to treat and control tick infestations for four weeks in field conditions and had a similar efficacy as the permethrin-imidacloprid combination for all visits.