Fort Dodge Animal Health Research Articles

169 BEHAVIORAL ASPECTS OF ESTRUS IN THE COMMON ELAND ANTELOPE, TAUROTRAGUS ORYX

Knowledge of the estrous cycle and behavior is important in managing captive breeding programs. However, such information is negligible in spiral-horned antelopes, including the eland. In the present study, conducted between September 2007 and March 2008, we sought to characterize mounting activity and courtship behavior in a group of eight adult eland females. Estrus was induced in groups of four females by treatment with 25 mg PGF2 ∝ (IM, Lutalyse®, Pharmacia and Upjohn Company, Kalamazoo, MI, USA) administered after 7 days of daily oral progestin (5 mL of 2.2% altrenogest, DPT Laboratories, San Antonio, TX, USA) or 11 days after an initial treatment of PGF2 ∝ (25 mg). The eight females received each treatment in a crossover design. Females were induced and monitored during the induced and subsequent natural estrus for 34 to 38 days. Observations for estrus behavior were initially assisted by using Estrotect™ heat detector patches (Rockyway, Inc., www.estrotect.com). Since January 2008, the HeatWatch® electronic heat detection system (CowChips, Denver, CO, USA) and an androgenized eland female were used to assist with heat detection. For androgenization, 8 pellets of Synovex-H® (Fort Dodge Animal Health, Fort Dodge, IA) comprising a total dose of 1600 mg testosterone propionate and 160 mg estradiol benzoate were implanted (SC) on the convex side of the ear. To confirm mounting activity detected by Estrotect™ or HeatWatch®, eland behavior was recorded continuously using an 8-channel real time DVR. Chi-square analysis was used to test the association between time of day (day or night) and the frequency of standing to be mounted. The cycle length (n = 6 females) was the time interval (d) between the first mounts at the induced and natural estrus. The time of mounts was determined for a total of 52 mounts. More than half of the mounts (n = 32 or 61.5%) occurred between 6 pm and 6 am (night); however, there was no association between the number of mounts and time of the day (p = 0.886). Analysis of mounts by quarters of the day showed that mounts were evenly distributed between early afternoon (noon to 6 pm: 29%), late afternoon (6 pm to midnight: 33%) and early morning (midnight to 6 am: 29%) but were less frequent during late morning, between 6 am and noon (10%) possibly due to interference by human activities. The number of mounts observed per female ranged from 1 to 20. Mounts lasted for 2 seconds or less. The duration of estrus ranged from 2.1 to 29.0 hours. Typical courtship behaviors included prolonged head butting, flehmen response and following the female in estrus before mounting. The average length of the estrous cycle, based on mounting activities, was 19.3 d (range: 17–24). Although further studies are required in herds with eland males, the present results suggest that estrus detection for captive breeding or application of reproductive technologies in the eland should be spread around different times of the day and night. We have also demonstrated that an electronic mount detection system can be applied to assist with determination of estrus in the eland.

Endotracheal Stent Granulation Stenosis Resolution after Colchicine Therapy in a Dog

Endotracheal Stent Granulation Stenosis Resolution after Colchicine Therapy in a Dog

Effect of porcine circovirus type 2 (PCV2) vaccination on porcine reproductive and respiratory syndrome virus (PRRSV) and PCV2 coinfection

The objectives were to determine if PCV2 vaccination is effective in reducing disease and lesions associated with PRRSV and PCV2 coinfection and if there is a difference between intradermal (ID) and intramuscular (IM) route of PCV2 vaccination. Seventy-four, 21-day-old pigs were randomly allocated into one of six groups. On day 0, pigs were vaccinated with 2 ml Suvaxyn ® PCV2 One Dose (Fort Dodge Animal Health, Inc.) by intramuscular (VAC-M-COINF) or intradermal (VAC-D-COINF) routes. On day 28, pigs were either singularly (PRRSV-only, PCV2-only) or coinfected (COINF) with PRRSV and PCV2. All pigs in all groups were necropsied on day 42. All vaccinated pigs seroconverted (IgM, IgG, and neutralizing antibodies) to PCV2 between 14 and 28 days post-vaccination. After challenge, all groups inoculated with PRRSV had reduced average daily gain compared to CONTROLS and PCV2-only ( P < 0.001). COINF pigs had significantly ( P < 0.05) reduced anti-PCV2-IgG antibody levels and neutralizing antibody levels compared to both vaccinated groups. COINF pigs had more severe lung lesions compared to VAC-M-COINF ( P < 0.05). COINF pigs had higher amounts of PCV2 DNA in serum samples and feces ( P < 0.05) and increased amounts of PCV2 in lymphoid tissues ( P < 0.05) compared to both vaccinated groups. In summary, PCV2 vaccination was effective at inducing a neutralizing antibody response and significantly reducing PCV2-associated lesions and PCV2 viremia in pigs coinfected with PCV2 and PRRSV. Differences between intradermal and intramuscular routes of vaccine administration were not observed.

Effect of viral respiratory vaccine treatment on performance, health and carcass traits of auction-origin feeder steers.

A total of 3,147 auction-origin steers were used to compare the effects of three different virus vaccines on performance, health, carcass traits and economic return in a commercial feedlot. Vaccine products compared were Pyramid® 5 (Fort Dodge Animal Health, Overland Park, KS), Bovi-Shield Gold® 5 (Pfizer Animal Health, New York, NY) and Bovi-Shield Gold® IBR-BVD. Steers vaccinated with Pyramid 5 (PYR5) vaccine had 3.8% ( P =0.09) better feed conversion than those vaccinated with Bovi-Shield Gold IBR-BVD (BOV3) vaccine when calculated on a live-weight basis, but similar to steers in the Bovi-Shield Gold® 5 (BOV5) group. On a carcass-weight basis, feed conversion was 3.6% better ( P =0.09) in the PYR5 treatment group compared to steers in the other treatment groups. No differences ( P &gt;;0.10) in carcass traits were noted among the three treatment groups. The morbidity rate due to bovine respiratory disease was 11% lower ( P =0.09) in steers vaccinated with PYR5 compared to those vaccinated with BOV5, and the relapse rate was 22% lower ( P =0.04). Combined treatment and railer (culling) costs were $8.81/head and $7.56/head lower in the PYR5 group than in the BOV5 and BOV3 steers, respectively. Mortality costs did not differ among treatments ( P =0.52).

Discovery of metaflumizone, a novel semicarbazone insecticide

Metaflumizone, ( EZ)-2′-[2-(4-cyanophenyl)-1-(α,α,α-trifluoro- m-tolyl)ethylidene]-4-(trifluoromethoxy) carbanilohydrazide, was discovered by Nihon Nohyaku in the early 1990s and belongs to the new class of semicarbazone insecticides. It is now being globally co-developed as the animal health product, ProMeris ®, in cooperation with Fort Dodge Animal Health and as an agricultural and consumer insecticide in cooperation with BASF. Metaflumizone was developed in a synthesis program initiated from a pyrazoline insecticide lead. In this paper, we describe the development, discovery and structure activity relationships for metaflumizone and related compounds.

Efficacy of a novel formulation of metaflumizone for the control of fleas ( Ctenocephalides felis) on cats

A novel spot-on formulation containing metaflumizone (ProMeris ® for Cats, Fort Dodge Animal Health, Overland Park, KS) was evaluated in five laboratory studies to determine the duration of residual efficacy in cats against fleas after a single spot treatment. In each study, eight domestic shorthair cats were randomly allocated to each treatment group and individually housed. One group in each study remained non-treated. In one study, an additional group of eight cats was treated with a placebo formulation. Cats were treated topically with metaflumizone formulation to provide a dose of at least 40 mg metaflumizone/kg. Cats were infested with 100 cat fleas ( Ctenocephalides felis felis) once per week for approximately 8 weeks. Cats were comb counted 48 h after treatment and each infestation to determine the number of viable fleas present. There were no significant differences in flea counts between the non-treated control and the placebo-treated control ( P > 0.05) other than a 26% reduction at week 1, demonstrating that the formulation excipients had no activity. Metaflumizone treatment resulted in significantly lower flea numbers relative to non-treated controls on all post-treatment count days ( P < 0.05). Metaflumizone provided >90% control of flea infestations up to 7 weeks following a single treatment.

Pharmacokinetics of metaflumizone in the plasma and hair of cats following topical application

Controlled laboratory studies have shown that a novel spot-on formulation containing 20% (w/v) metaflumizone (ProMeris ® for Cats, Fort Dodge Animal Health, Overland Park, KS) is effective for the treatment and control of fleas on cats. Two studies were conducted to determine the distribution of metaflumizone in the plasma and hair of cats following treatment at the minimum recommended dose of 40 mg/kg. Six purpose-bred cats, three males and three females, were used in each study. Plasma or hair samples were collected from each cat just prior to dosing and periodically through 56 days after treatment. Samples were analyzed by HPLC methods validated for the determination of metaflumizone. Metaflumizone concentrations in plasma were below the method limit of quantification (<50 ng/ml) in all samples but one, and were frequently not detectable (<1.1 ng/ml). Plasma collected 3 days post-treatment from one cat had a metaflumizone concentration of 57.8 ng/ml. The frequency of measurable levels of metaflumizone in the plasma was too low to allow the calculation of pharmacokinetic parameters. Analysis of hair samples indicated that metaflumizone was widely distributed in the hair coat of the cat within 1 day after administration, reaching maximum concentrations within 1 or 2 days post-treatment. Low but quantifiable levels were still present at the end of the 56-day study. Data from the present studies indicate that the ectoparasitic activity is due to exposure of the parasites to metaflumizone on the surface of the host (skin and hair), not to exposure via the circulatory system of the host.

Safety of a topically applied spot-on formulation of metaflumizone plus amitraz for flea and tick control in dogs

Four laboratory studies were conducted in Beagle dogs to evaluate the safety of a novel ectoparasiticide combination of metaflumizone plus amitraz (ProMeris ®/ProMeris Duo ® for Dogs, Fort Dodge Animal Health, Overland Park, KS) when applied according to the recommended dosage of ≥20 mg metaflumizone kg −1 plus ≥20 mg amitraz kg −1, at exaggerated and repeated dosages, and if accidentally orally ingested. Parameters evaluated included body weight, food consumption, clinical, physical and neurological examinations, clinical pathology and gross and microscopic pathology. Exaggerated and repeated topical treatment with metaflumizone plus amitraz administered at 1×, 3× and 5× the recommended dose had no effect on clinical findings, heart rates, body weight, food consumption, physical/neurological examinations, macroscopic and microscopic pathology. Very slight, transient, clinically insignificant increases in serum urea nitrogen were noted in some dogs treated at all dose rates tested. This effect was not persistent, was not dose-responsive, nor aggravated by repeated applications and was not associated with a corresponding increase in creatinine or renal pathology. Therefore, these increases in urea nitrogen were suspected to be of non-renal origin and were not considered toxicologically significant. Exaggerated doses (3× and 5×) caused very mild, transient hyperglycemia, most notably in some adult females. Transient and inconsistently noted mild increases in leukocytes, neutrophils and monocytes were observed in some 3× and 5× treated dogs at some intervals. None of the effects noted were aggravated by repeated administration. When 10% of the recommended topical dose was orally administered to mimic exposure due to licking the application, avoidance behaviors including spitting, head shaking, and salivation were noted immediately in all animals. Consequently, voluntary oral ingestion is considered unlikely. Transient decreased activity, slightly reduced body temperature and pale oral mucous membranes were noted in some animals beginning 1–2 h posttreatment. Ataxia, resolving within 4 h posttreatment, was noted in one female. Oral administration had no effect on clinical pathology. Results from these four studies indicate repeated use of metaflumizone plus amitraz causes no adverse health effects when used as recommended in dogs as young as 8 weeks of age.

Pharmacokinetics of metaflumizone and amitraz in the plasma and hair of dogs following topical application

Controlled laboratory studies have shown that a metaflumizone plus amitraz combination (ProMeris ®/ProMeris Duo ® for Dogs, Fort Dodge Animal Health, Overland Park, KS) applied topically is effective for the treatment and control of fleas and ticks on dogs. Two studies were conducted to determine the distribution of both metaflumizone and amitraz in the plasma and hair of dogs following treatment at the minimum recommended dose of approximately 20 mg/kg of each active ingredient. Six purpose-bred, adult Beagle dogs were used in each study. Plasma or hair samples were collected from each dog just prior to dosing and periodically through 56 days after treatment. Samples were analyzed by HPLC methods validated for the simultaneous determination of metaflumizone and amitraz. Amitraz was detectable (>3.2 ng/ml) but not quantifiable (<50 ng/ml) in only two plasma samples, collected 1 and 2 days post-treatment from different dogs. Metaflumizone concentrations in plasma were generally detectable (>1.0 ng/ml) but not quantifiable (<50 ng/ml). Measurable levels were found in one dog 7 days post-treatment, increasing to a maximum of four dogs at 42 days after dosing, with a metaflumizone range of 59–138 ng/ml. Analysis of hair samples indicated that both metaflumizone and amitraz were widely distributed at basically similar levels in the hair within 1-day after administration, reaching maximum concentrations between 2 and 7 days post-treatment. Low but quantifiable levels of both compounds were still present on hair at the end of the 56-day study. These studies indicate that the ectoparasitic activity is due to exposure of the parasites to metaflumizone and amitraz on the surface of the host (hair and/or skin), not to exposure via the circulatory system of the host.

Confirmation of the efficacy of a novel formulation of metaflumizone plus amitraz for the treatment and control of fleas and ticks on dogs

A novel spot-on formulation containing metaflumizone plus amitraz (ProMeris ®/ProMeris Duo ® for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated in four laboratory studies to confirm efficacy against fleas and ticks on dogs for 1 month. Three different strains of cat flea ( Ctenocephalides felis felis) and four tick species were used. Rhipicephalus sanguineus and Dermacentor variabilis were evaluated concurrently in two studies and Ixodes scapularis and Amblyomma americanum in one study each. In all studies, dogs were randomly allocated to treatment groups and compared with nontreated dogs. One study also included a placebo treatment and a commercial product containing fipronil plus S-methoprene. All treatments were applied to the skin at a single spot between the scapulae on Day 0. Dogs were infested with fleas and/or ticks prior to treatment and then reinfested at weekly intervals for 6 weeks after treatment and evaluated for efficacy at 1 or 2 days after treatment and each reinfestation. These studies confirmed that treatment with ProMeris for Dogs at the proposed commercial dose rate rapidly controlled existing infestations of fleas and ticks on dogs. Treatment provided control of reinfesting fleas for up to 6 weeks and at least 4 weeks control of ticks. Efficacy was confirmed in a variety of dog breeds against three different flea strains and four common species of ticks found on dogs in the United States.

Efficacy of a novel formulation of metaflumizone plus amitraz for the treatment of demodectic mange in dogs

A novel spot-on formulation containing metaflumizone plus amitraz (ProMeris ®/ProMeris Duo ® for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated for efficacy against demodectic mange mites in naturally infested dogs. Sixteen dogs were allocated to two equal groups and individually housed. Eight of the dogs were treated topically with metaflumizone plus amitraz at the proposed minimum dose rate (20 mg /kg of each of metaflumizone and amitraz, 0.133 ml /kg) on Days 0, 28, and 56. The other eight were treated with metaflumizone plus amitraz at the proposed minimum dose rate on Days 0, 14, 28, 42, 56, and 70. Mite numbers were estimated from skin scrapings taken on Days −3 to −1, 28, 56, and 84. Clinical signs of mange and the extent of demodectic lesions on each dog were evaluated when skin scrapings were conducted. Efficacy of the treatment was based on a reduction in mite numbers and an assessment of the clinical signs associated with canine demodectic mange. Treatment at monthly or two-weekly intervals for 3 months resulted in a rapid reduction in mite numbers (>94 and >99% for the monthly and two-weekly treatments, respectively) and an improvement in clinical signs. Success rates, based on zero mite counts in skin scrapings at Day 84 were 42.9 and 62.5% of dogs for the monthly and two-weekly regimens, respectively.

Safety of a topically applied metaflumizone spot-on formulation for flea control in cats and kittens

Four laboratory studies were conducted in cats of various ages to evaluate the safety of a novel low-volume topical spot-on containing 20% metaflumizone (ProMeris ® for Cats, Fort Dodge Animal Health, Overland Park, KS) when used in cats according to the recommended minimum dosage of 40 mg metaflumizone kg −1 delivered via fixed volume doses of 0.8 ml for cats ≤4.0 kg and 1.6 ml for cats >4.0 kg. Study parameters included body weight, food consumption, clinical, physical and neurological examinations, and clinical pathology including complete hematology, coagulation, clinical chemistry and urinalysis. Exaggerated and repeated topical applications of metaflumizone at 1×, 3× and 5× the proposed recommended dose in adult cats and kittens 8 weeks of age had no effect on mortality, body weight, food consumption, clinical, physical or neurological examinations, or clinical pathology parameters. Transient salivation was sporadically noted following some, but not all treatment applications. It occurred and resolved within minutes of treatment application in all groups, including cats treated with placebo. Consequently, it was not considered a direct result of treatment with the active ingredient, metaflumizone. Cats orally administered 10% of the recommended topical dose exhibited considerable avoidance behaviors including spitting, head shaking, and salivation. Therefore, voluntary oral exposure is unlikely. No other adverse signs were observed. Repeated use of metaflumizone caused no adverse health effects when administered at 5× the recommended dose and is safe when used as directed, even on kittens as young as 8 weeks of age.

Evaluation of the efficacy and safety of a novel formulation of metaflumizone in cats naturally infested with fleas in Europe

The efficacy and safety of a novel spot-on formulation of metaflumizone (ProMeris ® for Cats, Fort Dodge Animal Health, Overland Park, KS) was assessed in cats naturally infested with fleas in a multiregional, clinical field study. Sixteen veterinary clinics in Germany and eight clinics in France enrolled patients to the study. A total of 173 cats with flea infestation qualified as primary patients and were randomly allocated to one of the two treatments in a ratio of approximately 2:1 for metaflumizone (minimum dosage of 40 mg/kg) or fipronil (at the recommended label rate). Clinical examinations and baseline parasite counts were performed on Day 0 prior to treatment. Flea counts and safety evaluations were repeated at approximately 2-week intervals for 8 weeks. Both treatments resulted in consistent reductions (>84%) in flea numbers throughout the study, but metaflumizone resulted in numerically higher reductions on most count days. Within groups the flea reduction was highly significant ( p < 0.0001) compared to baseline at all observation periods. The efficacy of metaflumizone against fleas compared to baseline was 91.0%, 89.4%, 90.8% and 90.7% at Day 14, 28, 42 and 56, respectively. The corresponding efficacies for fipronil were 91.7%, 86.9%, 84.6% and 87.7%. Metaflumizone was highly effective in controlling existing infestations of fleas on cats and was effective against reinfestation for at least 56 days. Metaflumizone showed a good tolerance profile in cats.

Dose determination of a novel formulation of metaflumizone plus amitraz for control of cat fleas ( Ctenocephalides felis felis) and brown dog ticks ( Rhipicephalus sanguineus) on dogs

A novel spot-on formulation containing metaflumizone and amitraz (ProMeris ®/ProMeris Duo ® for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated in a laboratory study to determine the appropriate dose for efficacy against fleas and ticks on dogs for 1 month. Thirty-six Beagles were randomly allocated to six equal groups and individually housed. One group remained nontreated. Another was treated with a placebo formulation (solvents with no active ingredients). Three groups of dogs were treated topically with the metaflumizone plus amitraz formulation (150 mg of each of metaflumizone and amitraz/ml), at volumes providing doses of 10, 20 and 40 mg each active/kg. The final group was treated with a commercial spot-on providing 6.7 mg fipronil/kg. All treatments were applied to the skin at a single spot between the scapulae on Day 0. Dogs were infested with 50 adult brown dog ticks ( Rhipicephalus sanguineus) on each of Days −2, 5, 12, 19, 26, 33 and 40, and with 100 cat fleas ( Ctenocephalides felis felis) on Days −1, 6, 13, 20, 27, 34 and 41. Dogs were examined and parasites “finger counted” on Day 1 to estimate knock down efficacy, and all animals were comb counted to determine the numbers of viable fleas and ticks on Days 7, 14, 21, 28, 35 and 42. There were no significant differences in parasite counts between the nontreated control and the placebo-treated control groups for either fleas or ticks ( P > 0.05) except for very slight reductions on Day 7 for fleas and Day 14 for ticks, demonstrating that the formulation excipients had no activity. The qualitative finger counts on Day 1 indicated that all of the insecticidal treatments resulted in a noticeable reduction in flea and tick numbers within 1 day of treatment. All of the metaflumizone and amitraz treatments and fipronil resulted in significantly lower flea and tick numbers relative to nontreated controls on all posttreatment count days ( P < 0.05). For the metaflumizone plus amitraz treatments, mean flea and tick counts for the 10 mg/kg dose were significantly higher than those for the 20 mg/kg dose ( P < 0.05) from Day 21 on. There was no significant advantage provided by the 40 mg/kg dose over the 20 mg dose throughout the entire study ( P > 0.05). The two higher metaflumizone plus amitraz doses provided >95% control of fleas and >90% control of ticks for at least 35 days after treatment, and this level of control was similar to that of the commercial fipronil product. The 20 mg/kg dose was selected as the minimum commercial dose rate to provide effective flea and tick control for at least 1 month following a single treatment.

Efficacy of a novel formulation of metaflumizone plus amitraz for the treatment of sarcoptic mange in dogs

A novel spot-on formulation containing metaflumizone plus amitraz (ProMeris ®/ProMeris Duo ® for Dogs, Fort Dodge Animal Health, Overland Park, KS) was evaluated for efficacy against sarcoptic mange mites in naturally infested dogs. Sixteen dogs were allocated to two equal groups and were housed individually. Eight of the dogs were treated topically with metaflumizone plus amitraz at the proposed minimum dose rate (20 mg/kg of each of metaflumizone and amitraz, at a dose volume of 0.133 ml/kg) on Days 0 and 28. The other eight were treated with metaflumizone plus amitraz at the proposed minimum dose rate on Days 0, 14, 28 and 42. To enumerate Sarcoptes scabiei mites, skin scrapings were taken on each of Days 2, 14, 28, 42 and 56. Clinical signs of mange and the extent of sarcoptic lesions were evaluated on each dog when scrapings were made. Evaluation of the efficacy of the treatment was based on the absence of mites supported by the absence of clinical signs associated with canine sarcoptic mange. Treatment with metaflumizone plus amitraz at the minimum proposed dose rate at monthly (two treatments) or two-weekly (four treatments) intervals resulted in a rapid reduction of mites and improved clinical signs. The overall cure rates at Day 56, based on zero mite counts and/or resolution of clinical signs were 75% and 83% of dogs for the monthly and two-weekly regimens, respectively.

Evaluation of the efficacy and safety of a novel formulation of metaflumizone plus amitraz in dogs naturally infested with fleas and ticks in Europe

The efficacy and safety of a novel spot-on formulation of metaflumizone plus amitraz (ProMeris ®/ProMeris Duo ® for Dogs, Fort Dodge Animal Health, Overland Park, KS) was assessed in dogs naturally infested with ticks and/or fleas in a multiregional, clinical field study. Nineteen veterinary clinics in Germany and 11 clinics in France enrolled patients to the study. One hundred eighty one dogs with tick infestation and 170 dogs with flea infestation (plus three dogs harboring both ticks and fleas) qualified as primary patients and were randomly allocated to one of two treatments in a ratio of approximately 2:1 for metaflumizone plus amitraz (minimum dosage of 20 plus 20 mg/kg) or fipronil (at the recommended label rate). Clinical examinations and baseline parasite counts were performed on Day 0 prior to treatment. Tick and/or flea counts and safety evaluations were repeated at intervals of about 2 weeks for 8 weeks. Both products resulted in consistent reductions in tick numbers (>81%) throughout the study, with metaflumizone plus amitraz giving consistently higher reductions in tick numbers. The efficacy against tick count compared with Day 0 was 97.6%, 93.5%, 89% and 94% at Day 14, 28, 42 and 56, respectively, for metaflumizone plus amitraz. The corresponding efficacies for fipronil were 86.3%, 81.1%, 84.8% and 86.1%. Within groups, the tick reduction was highly significant ( P < 0.0001) compared to baseline at all observation periods. Both treatments resulted in consistent (>89%) and highly significant ( P < 0.0001) reductions in flea numbers relative to the baseline counts throughout the study, although fipronil resulted in numerically higher reductions on each count day. The efficacy against fleas compared to baseline was 91.8%, 88.7%, 91.5% and 92.0% at Day 14, 28, 42 and 56, respectively, for metaflumizone plus amitraz. The corresponding efficacies for fipronil were 98.2%, 96.3%, 95.9% and 96.7%. Metaflumizone plus amitraz was highly effective in controlling existing infestations of fleas and ticks on dogs and was effective against reinfestation for at least 56 days. Metaflumizone plus amitraz showed a good tolerance profile in dogs.

Pharmacokinetics assessment of moxidectin long-acting formulation in cattle

The plasma kinetics disposition of moxidectin following a subcutaneous administration with a long-acting formulation (Cydectin® 10%, Fort Dodge Animal Health, France) at the recommended dose of 1mgkg−1 body weight was evaluated in Charolais cattle breed (five females weighing 425–450kg) for 120 days. Furthermore, its concentration was measured in hair for the same period. After plasma extraction and derivatization, samples were analysed by HPLC with fluorescence detection. Moxidectin was first detected at 1h after treatment for plasma (2.00±1.52ngml−1) and at 2 days for hair (446.44±193.26ngg−1). The peak plasma concentration (Cmax) was 55.71±15.59ngml−1 and 444.44±190.45ngg−1 for plasma and hair, respectively. The mean calculated time of peak occurrence (Tmax) was 3.40±3.36 and 2 days for plasma and hair, respectively. The mean residence time (MRT) was 28.93±2.87 and 13.32±2.48 days for plasma and hair cattle. The area under concentration–time curve (AUC) was 1278.95±228.92ngdayml−1 and 2663.82±1096.62ngdayg−1 for plasma and hair, respectively. At the last sampling time (120 days), the concentration was 1.91±0.26ngml−1 and 0.69±0.52ngg−1 for plasma and hair, respectively. The bioavailability of this long-acting formulation of moxidectin is similar to that registered after subcutaneous administration of moxidectin in cattle at 0.2mgkg−1 body weight. For the first time the moxidectin pharmacokinetics parameters in hair after a subcutaneous administration was described. The moxidectin profile concentrations in hair reflected that registered in plasma. The previous studies of efficacy have to be correlated to the extended period of absorption and distribution by the LA formulation due to the fivefold higher dose rate in comparison with the 1% injectable formulation (0.2mgkg−1 body weight).

Intestinal Humoral Immune Response and Resistance to Salmonella Challenge of Progeny from Breeders Vaccinated with Killed Antigen

3 Abstract: Salmonella vaccination programs using killed bacterins in breeders and live auxotrophic-strain vaccines early in the life of their progeny have gained popularity in today's poultry industry. In this study we evaluated the intestinal humoral immune response to a live auxotrophic vaccine used on hatchlings with and without maternal antibody and related this response to challenge with a blend of two antibiotic-resistant Salmonella marker strains. Forty wk-old ISA Brown (Institute de Selection Animale, France) breeders from ® a Salmonella-free flock were vaccinated twice at a three wk interval with commercially-prepared autogenous trivalent bacterin, serogroups B, C and D1 (Lohmann Animal Health International, Gainesville, GA), or a serovar Enteritidis bacterin (Fort Dodge Animal Health Inc, Overland Park, KS). Half of the progeny from these treatments (hatched from eggs laid 3 wks after second bacterin dose) were given a live Salmonella serovar Typhimurium (LiveST) mutant vaccine (Fort Dodge Animal Health Inc, Overland Park, KS), by coarse spray on arrival in the brooding premises. On days 3, 13 and 34, intestinal immunoglobulins (Ig) A and G were sampled and measured on enzyme-linked immunosorbent assay plates coated with Salmonella serovars Enteritidis (SELPS) or Typhimurium (STLPS) Lipopolysaccharide. On the same days, a second group of birds was challenged with a blend of antibiotic-resistant serovars Enteritidis and Typhimurium strains. Cecal and composite liver-heart-spleen samples obtained 7 days post-challenge were cultured and colonies enumerated. Maternal IgG observed up to 13 days had no effect on subsequent LiveST-stimulated antibody production. No protective effect of maternal antibody was demonstrated, except when combined with LiveST given to the progeny. Killed vaccines delivered to the breeders combined with a live vaccine delivered to the progeny resulted in reduced invasiveness after challenge, as shown by a reduction in liver-heart-s pleen Salmonella counts. One dose of LiveST enhanced intestinal IgG (Optical Densities (OD) >0.576) up to 34 days when measured on STLPS, but only to 13 days when measured on SELPS, with titers decreasing with age. Increased IgA was observed only at 13 days. Three and 13 but not 34 days bacterial counts were decreased by the live ST vaccine treatment, for both cecal (1.05 and 1.09 log ) and liver-heart-spleen (0.32 10 and 0.06 log ) samples, indicating that a second dose might be necessary for prolonged protection. The 10 protective effect of the live vaccine, but not of maternal IgG, leads us to hypothesize that protection might be due to stimulation of cell-mediated intestinal immunity and/or a competitive exclusion effect of the LiveST vaccine. Reduction but not elimination of Salmonella colonization by vaccination highlights the importance of vaccines as complementary tools and not substitutes of integral biosecurity programs to contro l Salmonella in poultry.

Humoral and Mucosal-Humoral Immune Response to a Salmonella vaccination Program in Broiler Breeders

3 Abstract: Although vaccination against Salmonella has been used more frequently in broiler breeders in recent years, there is limited information in the literature demonstrating the immunological response of combinations of live and killed whole cell vaccines. The present research assesses the immunological response generated by three different vaccination protocols. Treatment vaccines consisted of a live Aro-A mutant commercial Salmonella Typhimurium (ST) vaccine (Fort Dodge Animal Health) and a commercially prepared killed vaccine consisting of a pool of Salmonella serovars Berta (D ), Heidelberg (B) and Kentucky 1 (C ). Three vaccination treatments using live, killed or a live-killed combination plus a non-vaccinated control 2 were evaluated. Serum (SER), Crop Lavage (CL), Gut Lavage (GL), hatchling serum and egg yolk were tested for specific IgA and IgG anti-Salmonella Enteritidis (SE) or Salmonella Typhimurium lipopolysaccharide (SELPS or STLPS, respectively) antigen by indirect ELISA. Immunological response was stronger on STLPS than SELPS. IgA of SER and CL were short-lived peaks after the first killed vaccine, with Optical Densities (OD) greater than 1.000. A short-lived peak of IgG of CL on STLPS (OD>1.500) was also observed. Strong GL IgG after first live and both killed vaccine events were observed (OD>1.000), with the response to the killed preparation enduring longer. SER IgG responses observed after killed vaccination lasted throughout 40 wks of age with no demonstrable differences between treatments. Hatchling serum and egg yolk IgA were negligible and IgG was comparable among all treatments throughout time. Results confirm that killed antigen is vital in eliciting adequate IgG in serum and gut. Live vaccination with Aro-A mutant ST vaccine enhances gut IgG and possibly aids in conferring adequate immunity during the breeder's first wks of life.

Keratoconjunctivitis sicca associated with administration of etodolac in dogs: 211 cases (1992–2002)

To characterize features and response to treatment of keratoconjunctivitis sicca (KCS) associated with oral administration of etodolac in dogs. Retrospective case series. 65 cases obtained from a survey of veterinary ophthalmologists (group A) and 146 cases reported to Fort Dodge Animal Health (group B). Data analyzed included breed, sex, age, weight, dose and duration of etodolac administration, results of Schirmer tear test at the time of diagnosis and last follow-up, treatments, and response to treatments. Groups A and B were analyzed separately by use of forward stepwise logistic regression models developed to predict probability of complete remission or clinical improvement as a function of several variables. Most dogs developed severe KCS (84 eyes of 50 dogs [group A]; 111 eyes of 62 dogs [group B]). Resolution of KCS occurred in 7 of 65 (A) and 23 of 146 (B) dogs. No response to treatment was observed in 26 of 65 (A) and 27 of 146 (B) dogs. Fifty-one (A) and 52 (B) dogs had records that were sufficiently complete to use in models. In group B, dogs with etodolac treatment intervals < 6 months prior to the onset of KCS were 4.2 times as likely to have remission as were dogs with treatment intervals > or = 6 months. Shorter duration of etodolac administration (< 6 months) was associated with improved outcome in 1 population of dogs. Monitoring of tear production should be considered prior to and during administration of etodolac in dogs.