Prevention of experimentally induced heartworm (Dirofilaria immitis) infections in dogs and cats with a single topical application of selamectin

In a series of six controlled studies (four in dogs, two in cats), heartworm-free dogs and cats were inoculated with Dirofilaria immitis larvae (L(3)) prior to topical treatment with the novel avermectin selamectin or a negative control containing inert formulation ingredients (vehicle). Selamectin and negative-control treatments were administered topically to the skin at the base of the neck in front of the scapulae. In dogs, selamectin was applied topically at dosages of 3 or 6mgkg(-1) at 30 days post-inoculation (PI), or of 3 or 6mgkg(-1) at 45 days PI, or of 6mgkg(-1) at 60 days PI. Cats were treated topically with unit doses providing a minimum dosage of 6mgkg(-1) selamectin at 30 days PI. Of the animals that were treated 30 days PI, some dogs were bathed with water or shampoo between 2 and 96h after treatment, and some cats were bathed with shampoo at 24h after treatment. Between 140 and 199 days PI, the animals were euthanized and examined for adult D. immitis. Adult heartworms developed in all control dogs (geometric mean count, 18.7 worms) and in 88% of control cats (geometric mean count, 2.1 worms). Selamectin was 100% effective in preventing heartworm development in dogs when administered as a single topical dose of 3 or 6mgkg(-1) at 30 days after infection, 3 or 6mgkg(-1) at 45 days after infection, or 6mgkg(-1) at 60 days after infection. Selamectin was 100% effective against heartworm infections in cats when administered as a single topical unit dose of 6mgkg(-1). Bathing with water or shampoo between 2 and 96h after treatment did not reduce the efficacy of selamectin as a heartworm prophylactic in dogs. Likewise, bathing with shampoo at 24h after treatment did not reduce the efficacy of selamectin in cats. These studies demonstrated that, at the recommended dosage and treatment interval, a single topical administration of selamectin was 100% effective in preventing the development of D. immitis in dogs and cats.     

Safety of selamectin in dogs

Selamectin is a broad-spectrum avermectin endectocide for treatment and control of canine parasites. The objective of these studies was to evaluate the clinical safety of selamectin for topical use in dogs 6 weeks of age and older, including breeding animals, avermectin-sensitive Collies, and heartworm-positive animals. The margin of safety was evaluated in Beagles, which were 6 weeks old at study initiation. Reproductive, heartworm-positive, and oral safety studies were conducted in mature Beagles. Safety in Collies was evaluated in avermectin-sensitive, adult rough-coated Collies. Studies were designed to measure the safety of selamectin at the recommended dosage range of 6-12mgkg(-1) of body weight. Endpoints included clinical examinations, clinical pathology, gross and microscopic pathology, and reproductive indices. Selected variables in the margin of safety and reproductive safety studies were subjected to statistical analyses. Pups received large doses of selamectin at the beginning of the margin of safety study when they were 6 weeks of age and at their lowest body weight, yet displayed no clinical or pathologic evidence of toxicosis. Similarly, selamectin had no adverse effects on reproduction in adult male and female dogs. There were no adverse effects in avermectin-sensitive Collies or in heartworm-positive dogs. Oral administration of the topical formulation caused no adverse effects. Selamectin is safe for topical use on dogs at the recommended minimum dosage of 6mgkg(-1) (6-12mgkg(-1)) monthly starting at 6 weeks of age, and including dogs of reproducing age, avermectin-sensitive Collies, and heartworm-positive dogs.     

Physiological responses in foals weaned by abrupt or gradual methods

Physiological responses to weaning procedures were studied in 21 foals assigned to one of five treatments: (1) abrupt, total separation of mare and foal, no preweaning creep feed (TSNC); abrupt, total separation with preweaning creep feed (TSC); partial separation of mare and foal allowing fenceline contact, no preweaning creep feed (PSNC); (4) partial separation with creep feed (PSC); and (5) control (CON) no separation of mare and foal, foals creep fed. Changes in adrenal response to exogenous ACTH, basal and peak plasma cortisol concentrations, plasma triiodothyronine (T3) and thyroxine (T4) concentrations, weight gains and feed consumption were measured. Foals on the total separation treatments had higher adrenal responses (P<.05) and pre-ACTH basal (P<.05) and post-ACTH peak plasma cortisol concentrations (P<.05) than foals on other treatments indicating they were stressed at weaning. The PSNC, PSC and CON treatments did not differ (P>.05) in any cortisol response. No treatment differences were found in thyroid hormone concentrations in this study. On partial separation treatments, creep-fed and non-creep-fed foals consumed similar amounts of feed during the first week postweaning. On total separation treatments, non-creep-fed foals consumed more feed (P<.05) than creep-fed foals. All foals without creep feed gained more weight immediately after weaning (0–2 weeks) than creep-fed foals (P<.05), reflecting higher feed intakes and possible compensatory gains. Total postweaning weight gains (0–8 weeks) of foals were not significantly affected by treatment.     

Efficacy of ivermectin against Dirofilaria immitis larvae in dogs 30 and 45 days after induced infection

Forty-two Beagles, 14 to 15 weeks of age, were injected subcutaneously with 50 infective larvae of Dirofilaria immitis and were allotted by weight, within sex, to 6 treatment groups. Group 1 served as nonmedicated vehicle-treated controls; groups 2 through 5 were given an oral tablet form of ivermectin at dosages of 0.3 micrograms/kg, 1.0 micrograms/kg, 2.0 micrograms/kg, and 3.3 micrograms/kg at 30 days after inoculation; group 6 was given the 2.0 micrograms/kg dosage at 45 days after inoculation. Dogs were euthanatized and necropsied 154 days after treatment (day 139 for dogs in group 6) and examined for heartworms. On the numerical bases of helminths recovered in the groups, the efficacies for preventing heartworm maturation were 0% (group 2), 53.2% (group 3), 97.2% (group 4), 98.1% (group 5), and 63.8% (group 6). Drug-related adverse reactions were not detected.     

An aspirin-prednisolone combination to modify postadulticide lung disease in heartworm-infected dogs

A combination of aspirin and prednisolone was used in an attempt to modify the pulmonary disease produced by thiacetarsamide treatment of heartworm-infected dogs. Results of 6 heartworm-infected dogs treated with prednisolone (1 mg/kg, daily for 4 weeks) and aspirin (10 mg/kg, daily for 4 weeks) after thiacetarsamide treatment were compared with previously published results of 3 groups of dogs (6 dogs/group). One of these 3 groups was a nontreated control group, another was treated with prednisolone, and the 3rd was treated with aspirin. All dogs, each with 9 adult heartworms transplanted, were treated with a 2-day, twice-a-day treatment of thiacetarsamide (1 mg/kg) 4 weeks after the transplant. Thoracic radiographs were taken before and at 1, 2, and 3 weeks after thiacetarsamide treatment to evaluate lung disease. Pulmonary arteriography was performed before and 3.5 weeks after thiacetarsamide treatment to evaluate pulmonary blood flow. After treatment, radiographs of the aspirin-prednisolone group were similar to radiographs of the prednisolone group, both with a marked attenuation of the parenchymal disease, as compared with the non-treated group. Addition of aspirin to prednisolone prevented the blood flow obstruction and intraluminal filling defects that were present in the groups not receiving aspirin. Sixteen of 54 transplanted heartworms survived thiacetarsamide treatment in both prednisolone-treated groups, in contrast to complete elimination of heartworms in the nontreated group. Aspirin may be considered for treatment of any heartworm-infected dog that does not have hemotypsis, but postthiacetarsamide use of prednisolone should be restricted to the dog that develops severe lung disease after the heartworms have been killed.