Controlled efficacy study of the bioequivalence of Strongid C and generic pyrantel tartrate in horses.

The bioequivalence of Strongid C and generic pyrantel tartrate was determined in a controlled study using 30 horses with naturally acquired endoparasitic infections. Three horses were randomly allocated to each of ten replicates based on quantitative nematode and ascarid egg counts and fecal larvae culture results. Horses within each replicate were randomly assigned to one of three treatment groups. Horses in Treatment Group 1 received only oats; horses in Treatment Group 2 received generic pyrantel tartrate pellets (2.65 mg pyrantel tartrate kg-1) mixed with oats; horses in Treatment Group 3 were fed Strongid C pellets (2.65 mg pyrantel tartrate kg-1) mixed with oats. Horses were treated daily for a 30 day continuous treatment period. At the termination of the study the horses were necropsied and endoparasites recovered, identified, and enumerated. In all instances, no significant difference (P > 0.05) in mean numbers of parasites recovered existed between horses treated with generic pyrantel tartrate and Strongid C. Numbers of gastrointestinal parasites recovered from horses treated with generic pyrantel tartrate or Strongid C were shown to be significantly different (P < 0.05) from numbers of gastrointestinal parasites recovered from non-treated controls for the large strongyles (Strongylus vulgaris, S. edentatus, and Triodontophorus spp.), small strongyles (Cyathostomum spp., Cylicocyclus spp., and Cylicostephanus spp.) and fourth-stage Parascaris equorum. Numbers of adult P. equorum recovered from horses treated with Strongid C were also significantly different (P < 0.05) from those from non-treated controls. Numbers of adult P. equorum recovered from horses treated with generic pyrantel tartrate were not significantly different (P = 0.0761) from those from non-treated controls. The determination of bioequivalence was based upon the 95% confidence interval of the difference between the mean number of parasites recovered from horses treated with generic pyrantel tartrate and the mean number of parasites recovered from horses treated with Strongid C. For all instances in which the numbers of parasites recovered from horses treated with either Strongid C or generic pyrantel tartrate were significantly different from the numbers of parasites recovered from non-treated controls, bioequivalence was demonstrated.

Clinical trial of moxidectin oral gel in horses.

A clinical trial carried out over 98 days was done to evaluate treatment of horses with moxidectin gel for efficacy as measured by (1) reduction in the production of parasite ova post treatment, (2) a comparison of the posttreatment parasite egg count suppression of moxidectin to ivermectin, and (3) assessment of the field safety, animal acceptance of the moxidectin formulation, and the utility of the moxidectin delivery device. One hundred and fifty Standardbred horses with naturally acquired parasite infections were used in the study. Moxidectin had more prolonged and greater suppressive influence than did ivermectin on reappearance and magnitude of strongyle egg counts post treatment. Differences were not observed between the capability of ivermectin or moxidectin to reduce and suppress low Parascaris equorum egg counts. Adverse reactions to treatments were not observed, and the utility of the moxidectin delivery syringe and animal acceptance of moxidectin treatment were satisfactory.

A comparison of the bioequivalence of 0.5% fenbendazole top dress pellets or 10% fenbendazole oral suspension against a spectrum of equine parasites.

A controlled test was conducted to assess the efficacy bioequivalence of a single dose of 0.5% fenbendazole (FBZ) top dress pellets to a 10% FBZ suspension formulation (Panacur suspension 10%, Hoechst Roussel Vet). Thirty horses with naturally-acquired parasite infections, in replicates of three, were used. Strongyle egg per gram counts were not significantly different (P>0.1) between groups pretreatment, but FBZ treated groups were significantly different from the control group post-treatment. At necropsy, which occurred seven to nine days post-treatment, two methods of nematode recovery were compared to assess whether a small aliquot can be used in a control test to determine efficacy against large as well as small strongyles. Both post mortem worm recovery techniques revealed similar efficacies of both formulations (>95%) against small and large strongyles, but large differences in the number of worms recovered. Six species of small strongyles comprised 96% of all the small strongyles recovered: Coronocyclus coronatus, Cylicocyclus insigne, Cylicostephanus longibursatus, Cylicocyclus brevicapsulatus, Cylicocyclus nassatus, and Cyathostomum catinatum. The results of this study demonstrated therapeutic bioequivalence between FBZ formulations and also the need to sample at least a 10% aliquot to accurately estimate number of large strongyles. No adverse reactions to treatment were detected.

Transplacental transmission and abortion in cows administered Neospora caninum oocysts.

Neospora caninum infection is a common cause of bovine abortion. One method by which cattle can acquire infection is through ingestion of oocysts; however, this has not yet been proved to cause transplacental infection or abortion. In this study, 19 cows, pregnant between 70 and 176 days, were administered 1500 to 115,000 oocysts through an esophageal tube. Seventeen of the cows became seropositive, indicating acquisition of infection, whereas 8 negative control cows remained seronegative (P < 0.001). Offspring were examined using serology, histology, immunohistochemistry, parasite isolation, and polymerase chain reaction (PCR). Six offspring were infected and 1 of them was aborted. The aborted fetus had typical lesions and positive immunohistochemistry and PCR for N. caninum. All 6 cows with infected offspring had continuously rising antibody titers, whereas 10 of 11 infected cows with uninfected offspring had falling titers after an early apex. The risk of transplacental transmission was increased by later exposure times during gestation and by the dose of oocysts (P < 0.01 for the 2 combined variables). The lowest dose of oocysts, when administered after the 160th day of gestation, caused transplacental infection in 1 of 2 animals. This study demonstrates that infection with N. caninum oocysts can cause transplacental transmission and abortion in cattle.

Lysozyme, alkaline phosphatase and neutrophils in uterine secretions of mares with differing resistance to endometritis.

A study was conducted to 1) determine differences in the inflammatory response following bacterial challenge between normal mares and mares with chronic endometritis and 2) to determine if enzyme activity in uterine fluid can be used to evaluate degree of inflammation in the equine uterus. Six normal mares (Group 1) and four mares with chronic endometritis (Group 2) received an intrauterine infusion of beta-hemolytic streptococci on the second day of estrus. Neutrophil concentration as well as lysozyme and alkaline phosphatase activity were determined in uterine secretions obtained by placing tampons in the uterus of mares. All mares had a similar inflammatory response following bacterial challenge of the uterus, as indicated by a neutrophil response of the same magnitude. Neutrophil numbers, lysozyme and alkaline phosphatase concentrations were all increased 12 h postinoculation and declined rapidly to normal preinoculation values by 48 h after inoculation. In spite of the similarity of the clinical signs, neutrophil concentrations and enzyme activity, mares in group 1 demonstrated a markedly higher ability to eliminate the infection than mares in group 2. It is concluded that factors other than neutrophil numbers, lysozyme and alkaline phosphatase activity account for the inability of the mare to eliminate uterine infections.

Spontaneous and oxytocin-induced uterine motility in cyclic and postpartum mares.

Intrauterine pressure was measured in three cyclic and two postpartum mares. Pressure was recorded using a catheter tip pressure transducer. The transducer was passed transcervically into the uterus.. In cyclic mares recordings were started on Day 1 of estrus and continued daily until ovulation as well as on Days 1 and 8 of diestrus. In postpartum mares recordings were started within 48 h after foaling and continued until the mares ovulated. The intrauterine pressure changes in postpartum mares was also recorded on Days 1 and 8 of diestrus. Spontaneous uterine contractions were recorded in cyclic mares for 30 min and in postpartum mares for 10 min. Induced uterine motilities were recorded for 30 min in both groups after the administration of oxytocin (40 USP, i.v.). Total area under the contraction curve in a 10-min period was used as a uterine motility quantitating unit. All mares demonstrated uterine contractions during estrus and diestrus. All mares demonstrated significant responses to oxytocin during estrus and diestrus. It appears that estrogen priming is not necessary for a significant uterine response to oxytocin.

The effect of method of GnRH administration and short-term calf removal on ovarian function and reproductive performance in postpartum suckled beef cows administered PGF(2)alpha for estrous synchronization.

The first experiment was a 2 x 2 factorial experiment with calf removal (none or short-term) and method of GnRH administration (intramuscularly in saline or subcutaneously in gelatin capsules) as main effects. The durations of the GnRH-induced LH surges were similar among groups but the LH surges were delayed in the cows that received GnRH subcutaneously in gelatin capsules. Calf removal enhanced the GnRH-induced LH release for cows administered GnRH subcutaneously in a gelatin capsule but not for cows administered GnRH intramuscularly in saline. In the second experiment, 191 postpartum suckled beef cows were administered two injections of prostaglandin F(2)alpha(PGF(2)alpha) 11 days apart. After the second PGF(2)alpha injection, the cows were assigned to a 2 x 2 factorial experiment as in Experiment 1 plus one control group. Short-term calf removal (47 h) began 28 h after the second PGF(2)alpha injection. GnRH was administered 30 h after the time of calf removal. The number of cows that ovulated following the time of the GnRH treatment, the number that had abnormal luteal phases and the first-service pregnancy rates among treatment groups within the anestrous and cyclic cows classifications were not significantly different. However, several effects were detected and are reported.

The effect of short term calf removal in combination with GnRH treatment and the effect of limited nursing on reproductive performance of postpartum suckled beef cows administered PGF2alpha for ovulation control.

Over a two year period, postpartum suckled Hereford and Angus Cows (n=213) were administered two injections of PGF2alpha (25 mg/injection) and divided into three groups. No additional treatments were administered to cows in Group I and calves were allowed to nurse their dams ad libitum. In Group II, calves were removed for 48 hours beginning on the third day following the initial PGF2alpha injection. These cows were given a subcutaneous injection of 250 microg GnRH dissolved in 2% carboxymethylcellulose midway through the 48 hour period. In Group III, calves were allowed to nurse their dams for only one hour per day for the first 7 days after the initial PGF2alpha injection. In year 1, PGF2alpha was administered 14 days apart whereas in year 2, PGF2alpha was administered 11 days apart. Cows were artificially inseminated at 72 and 96 hours after the second injection of PGF2alpha. In year 1, the numbers of cows that conceived to the timed inseminations were similar (P>.10) for the three groups. In year 2, a higher percentage of cows in groups II (P<.10) and III (P<.05) conceived to the timed inseminations than in group I. Other reproductive performance parameters were similar (P>.10) between groups for both years 1 and 2. In summary, limited nursing and short term calf removal in conjunction with GnRH treatment may improve the pregnancy rate in cows administered PGF2alpha for ovulation control.

An evaluation of the haemostatic suture in hysterotomy closure in the mare.

This study was designed to evaluate the haemostatic suture as a means of preventing haemorrhage from the hysterotomy in mares after caesarean section. At 2 university hospitals 1982-1994, 48 mares had caesarean section for dystocia, 10 as an elective, and 8 mares concurrently with colic surgery. The haemostatic suture was used in 31 of 66 mares (47%) and surgery period was significantly (P<0.05) shorter when it was not applied. Anaemia (PCV<30%) was recorded in 13 (22%) of 58 mares, excluding the colic group, and the haemostatic suture did not after this proportion of mares that had anaemia. Anaemia was 5 times more probable following caesarean section than vaginal delivery, evidence that bleeding from the hysterotomy is a serious and common complication of caesarean section in mares. Severe uterine haemorrhage was recorded in 3 mares that had an haemostatic suture (10%) and in 2 mares that did not (6%). The latter two mares died of haemorrhage. The suture, therefore did not eliminate post operative anaemia and severe uterine haemorrhage. If omitted, the hysterotomy should be closed with a full thickness pattern that is sufficiently tight to compress vessels in the uterine wall.

Caesarean section and other methods for assisted delivery: comparison of effects on mare mortality and complications.

Data from 116 mares that had caesarean section or vaginal delivery at 2 university hospitals were analysed in 5 groups, as follows: dystocia corrected by caesarean section, Group DCS (n = 48); elective caesarean section, Group ECS (n = 10); caesarean section concurrently with colic surgery, Group CCS (n = 8); assisted vaginal delivery, Group AVD (n = 22); and controlled vaginal delivery under general anaesthesia, Group CVD (n = 28). Survival rate in all mares that had caesarean section, excluding Group CCS, was 88% (51/58). All mares in Group ECS survived and Group CCS had the lowest survival rate (38%). In 98 mares with dystocia, Groups DCS (15%) and AVD (14%) had significantly lower (P<0.05) mortality rates than Group CVD (29%). There were no differences between groups for duration of dystocia. The placenta was retained in 75 (65%) of 116 mares, and for a longer period following elective caesarean section than following assisted vaginal delivery. Multiple complications (> or = 3) were recorded in 6 mares in Group CVD but not in the other groups. Of the 102 foals delivered from 98 mares with dystocia, 11 (11%) were alive at delivery and 5 (5%) survived to discharge. Survival rate for foals was 38% in Group CCS, and 90% in Group ECS. Under conditions similar to those in this study, it is calculated that caesarean section is preferable to CVD if dystocia is protracted and great difficulty and trauma is involved, even if CVD allows delivery of the foal.

Vaccination of pregnant ponies against equine rhinopneumonitis.

Bovine herpesvirus 1247 (one dose) was given subcutaneously to five pregnant pony mares between 227 and 319 days of their gestations. There were no adverse clinical reactions, and the virus was not recovered from nasal swabs collected during a 2-week period after vaccination. Four ponies foaled full-term, live, healthy foals. The foal of the fifth mare (No. 1) was found dead, but on the basis of the pathologic and virologic examinations, the virus was not considered to be the cause of the death. At 3 weeks after vaccination, the pregnant pony mares had a 13- to 250-fold increase in serum antibody titer to equine herpesvirus-1. A virulent-virus challenge exposure of all pony mares at 208 days after vaccination resulted in antibody titers greater than those just before this exposure. Virus was recovered from nasal swabs from vaccinated mares only on postexposure day 1, whereas the one control (nonvaccinated) pony shed virus for at least 3 days after challenge exposure. The immunogenic and the nonabortifacient characteristics of the herpesvirus 1247 in pregnant pony mares indicate that it may be useful to vaccinate horses against equine herpesvirus-1.

Evaluation of ivermectin for larvicidal effect in experimentally induced Parascaris equorum infections in pony foals.

A controlled test was carried out on 15 pony foals inoculated with 1,500 +/- 108.8 infective Parascaris equorum eggs. The foals were assigned to 3 treatment groups. Treatments given on postinoculation day 11 included 0.2 mg of ivermectin/kg of body weight, formulated as paste (n = 5), or liquid (n = 5), or no treatment (controls; n = 5). The foals were euthanatized on postinoculation day 25, and examined for larvae in the small intestine, lungs, and liver. Larvae were not found in foals treated with ivermectin liquid or paste, whereas significantly (P less than 0.05) higher mean numbers (960.9; range, 379 to 1,736) of 4th-stage larvae were found in the controls. Histologic and gross examination of lungs and liver revealed pathologic changes attributable to P equorum migration that were similar in all foals. Adverse reactions to treatment were not observed.

Anthelmintic efficacy of ivermectin given intramuscularly in horses.

The anthelmintic activity of ivermectin was evaluated in 18 female horses with naturally acquired parasitic infections. Horses were treated once (IM) with vehicle only (n = 6), 200 microgram/kg of body weight (n = 6), and 300 microgram/kg (n = 6). Efficacy of both dosages of ivermectin was greater than 99% against Gasterophilus spp, 100% against Trichostrongylus axei, Habronema muscae, H majus, and Draschia megastoma, 98% to 99% against adult cyathostomes, 86% to 97% against 4th-stage cyathostomes, and 100% against adult large strongyles. Although ivermectin was incomplete in its activity against arterial stages of Strongylus vulgaris, it was effective against microfilariae of Onchocerca spp. Adverse local or systemic reactions were not observed due to treatment with ivermectin.

Distribution of chloramphenicol in the genital tract of postpartum cows.

Chloramphenicol was administered by constant IV infusion to 7 healthy postpartum cows at rates predicted to approach a steady-state plasma concentration of 5 micrograms/ml. After 8 hours of constant IV infusion, uterine tissues were removed surgically and were assayed for chloramphenicol concentrations. Mean plasma-to-tissue ratios of chloramphenicol concentrations were 3.05, 3.63 (6 cows only), and 3.22 for caruncles, endometrium, and uterine wall, respectively. Plasma-to-tissue ratios of the 3 tissues were not significantly different (P greater than 0.10). Intrauterine (IU) injections of chloramphenicol (20 mg/kg of body weight) were administered to 3 healthy post-partum cows. The mean value of the fraction of the drug absorbed from the uteri of these cows was 0.40. Mean concentrations of chloramphenicol were 43.8 micrograms/g in caruncles, 34.6 micrograms/g in endometrium, 2.8 micrograms/g in uterine wall, and 2.9 micrograms/ml in plasma 8 hours after IU injections. Chloramphenicol has now been banned for use in food-producing animals in the United States because of its potential for causing toxicosis in human beings. It is illegal to use chloramphenicol in food-producing animals in the United States and in some other countries as well. This includes use by the IU route of administration because chloramphenicol and most drugs are absorbed from the uterus into the bloodstream and are distributed to milk and tissues.

Distribution of oxytetracycline in the genital tract of cows.

Pharmacokinetic parameters of the disposition of oxytetracycline (OTC) were investigated in healthy cycling dairy cows after a single IV dose of 22 mg/kg of body weight. The biological half-life of OTC was 6.5 hours. These data were used to predict an IV priming dose and a rate of constant IV infusion of OTC sufficient to approach steady-state equilibrium of the drug between a plasma concentration of approximately 5 microgram/ml and a uterine tissue concentration. After 8 hours' constant IV infusion, the mean plasma concentration of OTC was 4.86 +/- 0.68 microgram/ml and the mean uterine tissue concentration of OTC was 4.50 +/- 0.45 microgram/ml. The mean ratio of plasma-to-uterine tissue OTC concentrations was 1.08. Computer-stimulated IV multiple doses of OTC at 11 mg/kg every 12 hours and 11 mg/kg every 24 hours suggested that the former dosage regimen could provide uterine tissue concentrations greater than 5 microgram/ml during the dosage interval, whereas the latter could provide such concentrations for only the first 12 hours of a 24-hour dosage interval.

Hyperglycemia and hypoinsulinemia during xylazine-ketamine anesthesia in Thoroughbred horses.

Plasma glucose and serum insulin concentrations in Thoroughbreds administered xylazine hydrochloride (1.1 mg/kg; IV) and ketamine hydrochloride (2.2 mg/kg; IV) at dosages sufficient to induce short periods of recumbency and anesthesia were measured. Samples of blood were collected from 6 adult horses before, during, and after the anesthetic period. Plasma glucose (mg/dl) was significantly increased above control (-30 minute concentration) from 15 to 150 minutes after xylazine administration with the peak value occurring at 30 minutes. Serum insulin (microU/ml) was significantly decreased from control from 5 to 90 minutes after xylazine administration, with the nadir occurring at 15 minutes. The alterations in plasma glucose and serum insulin concentrations in xylazine-ketamine-anesthetized horses were similar to the changes in xylazine-sedated horses.

Evaluation of febantel used concurrently with piperazine citrate in horses.

Fifty horses from a herd known to have benzimidazole-resistant small strongyles were treated with febantel (6 mg/kg), combinations of febantel (6 mg/kg) and piperazine citrate (25 or 55 mg base/kg), thiabendazole (44 mg/kg), or placebo (0.6 ml of water/kg). Pretreatment and 7-day posttreatment fecal examinations were done. Fecal cultures, strongyle egg per gram (epg) counts, sugar flotation fecal examinations, and in vitro testing for benzimidazole resistance were performed. Results of fecal examinations before treatment were similar in all horses, and results of testing were positive for benzimidazole resistance. Horses treated with febantel and piperazine at all dosages had significantly lower mean strongyle epg counts and greater percentage reduction in mean strongyle epg counts (99.7% to 99.9%) 7 days after treatment, compared with those determined for horses treated with febantel, thiabendazole, or placebo. Adverse reactions to treatment were not observed.

Evaluation of fenbendazole for larvacidal effect in experimentally induced Parascaris equorum infections in pony foals.

Fifteen pony foals were inoculated with 1,500 +/- 298.7 infective Parascaris equorum eggs. The foals were assigned to 3 treatment groups. Treatments included 10 mg of fenbendazole/kg given once on postinoculation day (PID) 11, 10 mg of fenbendazole/kg given daily on PID 11 to 15, and no treatment (controls). The foals were euthanatized on PID 25 and examined for P equorum larvae in the small intestine, lungs, and liver. Significantly (P less than 0.05) lower mean numbers of P equorum larvae were found in the small intestine of foals treated on PID 11 to 15 (1.4 [range, 0 to 6]) than in the small intestine of foals treated on PID 11 (428.2 [range, 0 to 777]) and in controls (500 [range, 284 to 802]).

Evaluation of ivermectin paste in the treatment of ponies for Parascaris equorum infections.

Twenty ponies less than 18 months of age and infected with Parascaris equorum were treated with either 0.2 mg of ivermectin/kg of body weight (n = 10) or a placebo (n = 10; controls). Five control and 5 ivermectin-treated ponies were euthanatized 14 and 35 days after treatment, respectively. At necropsy, the small intestinal contents, lungs, and liver were examined for larvae and/or adult P equorum. Significantly (P less than 0.02) higher mean total numbers of P equorum were found in the small intestinal contents of the controls on day 14 (51) and on day 35 (21) than in the ivermectin-treated ponies on days 14 (0) and 35 (3). The efficacy of ivermectin in removing adult and intestinal larvae of P equorum at 14 days after treatment was 100%. The efficacies of ivermectin in removing adults and intestinal larvae of P equorum at 35 days after treatment were 100% and 76.9%, respectively. Gross examination of liver and lung tissues revealed damage as a result of P equorum infections in all ponies. The Baermann technique used on liver and lung tissues did not yield any P equorum larvae. Adverse reactions attributable to treatment were not observed.

Efficacy of ivermectin in the treatment of induced Parascaris equorum infection in pony foals.

Eighteen pony foals inoculated with 1,500 +/- 109 infective Parascaris equorum eggs were given 0.02 ml of ivermectin vehicle (liquid)/kg of body weight, PO, (control); 0.2 mg of ivermectin paste/kg, PO; or 0.2 mg ivermectin liquid/kg, PO, on postinoculation day (PID) 28. Foals were euthanatized on PID 42, and the small intestinal contents were examined for P equorum larvae. The mean number of fourth-stage P equorum larvae in foals treated with ivermectin paste and liquid were 3.5 and 6, respectively. Significantly (P less than 0.01) higher mean numbers of larvae (1,250) were detected in foals treated with ivermectin vehicle. Larvae recovered from foals treated with ivermectin vehicle were of significantly (P less than 0.002) longer mean length than those from foals treated with ivermectin paste or liquid. Gross examination of lungs and liver revealed similar pathologic changes from the migration of P equorum in all foals. Adverse reaction to treatment was not observed.