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.     

Comparative efficacy of four commercially available heartworm preventive products against the MP3 laboratory strain of Dirofilaria immitis

A controlled laboratory study was conducted to evaluate the efficacy of four commercial products administered as a single treatment for the prevention of heartworm disease caused by Dirofilaria immitis in dogs. Forty-four commercially sourced Beagle dogs, 6-7 months of age, were received at the test site (Auburn University, Department of Pathobiology) on Study Day (SD) -72 to begin acclimation. On SD -30, each dog was inoculated subcutaneously with 100 infective, third-stage D. immitis larvae (MP3 strain, TRS Laboratories, Inc., Athens, GA). On SD -1, 40 dogs weighing 18.2-25.3 lbs were ranked by decreasing body weight and randomized to five groups of eight dogs each. On SD 0, the dogs assigned to Group 1 were treated orally with ivermectin/pyrantel pamoate chewable tablets, Group 2 dogs were treated orally with milbemycin oxime flavored tablets, Group 3 dogs were treated with selamectin topical solution, and Group 4 dogs were treated with imidacloprid/moxidectin topical solution. Group 5 dogs remained nontreated. Dosages for dogs in Groups 1-4 were based on the individual body weight of each dog and current labeled dose banding for each commercial product. All dogs were fasted overnight prior to treatment. Food was returned four hours after treatment. Animals were observed for abnormal clinical signs involving eyes, feces, respiration, behavioral attitude, locomotion/musculature, or skin conditions at prescribed intervals immediately after treatment and at twice daily intervals thereafter. On SD 90, whole blood was collected and tested for adult heartworm antigen. On SDs 119/120, the dogs were euthanized and subjected to necropsy examination for recovery of adult D. immitis and/or worm fragments. At necropsy, all 8 dogs in the nontreated group were infected with adult D. immitis (34-70 worms/dog, geometric mean (GM)=51.6 worms/dog). One or more adult D. immitis and/or worm fragments were recovered from 7 of 8 of the dogs each in Groups 1-3 (87.5% were heartworm positive). The respective GM worm burdens/dog for Groups 1-3 was 2.3, 2.4, and 2.3 which resulted in 95.6, 95.4 and 95.5% efficacy, respectively. No worms were recovered from any of the 8 dogs in Group 4 resulting in 100% efficacy.     

Evaluation of a covered-rod silicone implant containing ivermectin for long-term prevention of heartworm infection in dogs

OBJECTIVE: To evaluate use of covered-rod (CR) silicone implants containing ivermectin for long-term prevention of infection with Dirofilaria immitisin dogs. ANIMALS: 145 adult male and female dogs. PROCEDURES: Dogs received implants of different sizes, and ivermectin concentrations and serum ivermectin concentrations were monitored for 16, 57, and 56 weeks, respectively, in 3 preclinical dose selection studies. Ability of implants to prevent infection with D immitis was evaluated in 2 further studies; dogs were challenged with 50 infective third-stage larvae 52 weeks after implant administration and necropsied 145 days after challenge, and the total number of adult heartworms was counted. A field study was then undertaken in which client-owned dogs received an implant and plasma samples were collected at intervals until week 52 for ivermectin analysis and heartworm antigen determination. RESULTS: Use of the implants resulted in maintenance of an ivermectin concentration > or = 0.2 ng/mL for 12 months. In challenge studies, no treated dogs had adult heartworms, in contrast to untreated dogs, which all had adult heartworms at necropsy. In the field study, dogs treated with an implant had negative results of heartworm antigen testing for 12 months. CONCLUSIONS AND CLINICAL RELEVANCE: The CR silicone implant containing 7.3 mg of ivermectin was 100% effective in preventing experimental infection with D immitislarvae and resulted in negative results for heartworm antigen in a field trial. This product has the potential to alleviate poor owner compliance with monthly prevention regimens.     

Efficacy and safety of selamectin against fleas and heartworms in dogs and cats presented as veterinary patients in North America

A series of randomized, controlled, masked field studies was conducted to assess the efficacy and safety of selamectin in the treatment of flea infestations on dogs and cats, and in the prevention of heartworm infection in dogs. In addition, observations were made on the beneficial effect of selamectin treatment on dogs and cats showing signs of flea allergy dermatitis (FAD). In all studies selamectin was applied topically, once per month, in unit doses providing a minimum dosage of 6mgkg(-1). Dogs and cats with naturally occurring flea infestations, some of which also had signs associated with FAD, were assigned randomly to receive three months of topical treatment with selamectin (220 dogs, 189 cats) or a positive-control product (dogs: fenthion, n=81; cats: pyrethrins, n=66). Selamectin was administered on days 0, 30, and 60. Day 0 was defined as the day that the animal first received treatment. Flea burdens were assessed by flea comb counts and clinical evaluations of FAD were performed before treatment, and on days 14, 30, 60, and 90. On days 30, 60, and 90, mean flea counts in selamectin-treated dogs were reduced by 92.1, 99.0, and 99.8%, and mean flea counts in fenthion-treated dogs were reduced by 81.5, 86.8, and 86.1%, respectively, compared with day 0 counts. Also, on days 30, 60, and 90, mean flea counts in selamectin-treated cats were reduced by 92.5, 98.3, and 99.3%, and mean flea counts in pyrethrin-treated cats were reduced by 66.4, 73.9, and 81.3%, respectively, compared with day 0 counts. Selamectin also was beneficial in alleviating signs in dogs and cats diagnosed clinically with FAD. A total of 397 dogs free of adult heartworm infection from four heartworm-endemic areas of the USA were allocated randomly to six months of treatment with selamectin (n=298) or ivermectin (n=99). Selamectin achieved a heartworm prevention rate of 100%, with all dogs testing negative for microfilariae and adult heartworm antigen on days 180 and 300. Selamectin was administered to a total of 673 dogs and 347 cats having an age range of 6 weeks to 19 years (3954 doses). The animals included 19 purebred or crossbred Collies (Bearded, Border, and unspecified). There were no serious adverse events. Results of these studies indicated that selamectin was highly effective in the control of flea infestations in dogs and cats without the need for simultaneous treatment of the environment or of in-contact animals and also was beneficial in alleviating signs associated with FAD. Selamectin also was 100% effective in preventing the development of canine heartworms and was safe for topical use in dogs and cats.     

Preliminary findings on the efficacy of selamectin in the treatment of dogs naturally infected with Dirofilaria repens

Subcutaneous dirofilariosis caused by Dirofilaria repens is common in dogs and it is an emerging helminthozoonosis in Europe, Asia, Africa and also in Hungary. Macrocyclic lactones are used for preventing the infection; however, their activity against the microfilariae and mature stages of this species is questionable. Selamectin is widely used for the prophylaxis of heartworm (D. immitis) infection. The objective of the present study was to test the microfilaricidal efficacy of the topical formulation of selamectin in dogs naturally infected with D. repens . A total of 78 Beagle dogs were examined for the presence of circulating microfilariae by Knott's test. Twenty-three of the microfilaraemic dogs were divided into four groups and included in the trial. The dogs received monthly or biweekly selamectin treatment and were subjected to monthly blood testing for a period of 252 or 336 days. At the end of the study, 65% of the dogs were not microfilaraemic and the rest had low number of microfilariae in their blood. These results indicate that chronic spot-on selamectin treatment may be a useful tool also in the control of canine subcutaneous dirofilariosis.     

Efficacy of selamectin against experimentally induced and naturally acquired ascarid (Toxocara canis and Toxascaris leonina) infections in dogs

The efficacy of selamectin against adult ascarids was evaluated in eight controlled and masked studies in dogs. Three laboratory studies evaluated selamectin against experimentally induced infections of Toxocara canis; three laboratory studies evaluated selamectin against naturally acquired infections of T. canis; one laboratory study evaluated selamectin against naturally acquired infections of both T. canis and Toxascaris leonina; one field study evaluated selamectin against naturally acquired infections of ascarids (T. canis and/or T. leonina) in dogs presented as veterinary patients. Selamectin was administered topically to the skin of dogs in unit doses designed to deliver a minimum of 6mgkg(-1) (range, 6-12mgkg(-1)). In all studies, dogs were allocated randomly to treatment assignments (selamectin or vehicle control in laboratory studies: selamectin or reference product in the field study) on the basis of pretreatment fecal egg counts. For induced infections, there were significant reductions in geometric mean numbers of adult T. canis after a single application of selamectin (93.9-98.1%, P=0.0001), after two monthly applications (> or =88.3%, P< or =0.0001), and after three monthly applications (100%, P< or =0.0002). In the natural infection laboratory studies, when selamectin was administered twice at an interval of 30 days, the percentage reductions in geometric mean numbers of adult T. canis at necropsy were 84.6, 91.3, and 97.9%, and when selamectin was administered on days 0, 14, and 30, the percentage reductions were 91.1 and 97.6%. Geometric mean fecal T. canis egg counts were reduced by > or =92.9% (P< or =0.0067) at the end of the studies. In the field study, geometric mean fecal ascarid egg counts were reduced by 89.5 and 95. 5% (P=0.0001) for 14 and 30 days, respectively, after a single treatment with selamectin, and by 94.0% (P=0.0001) 30 days after the second treatment with selamectin. These reductions compared favorably with the egg count reductions from dogs treated with a reference product containing praziquantel, pyrantel embonate, and febantel. There were no adverse drug experiences or treatment-related mortalities during any of the studies. Selamectin, when administered topically in a unit dose providing a minimum dosage of 6mgkg(-1), was safe and effective against adult T. canis and T. leonina and in reducing the fecal excretion of T. canis eggs in dogs.     

Long-term delivery of ivermectin by use of poly(D,L-lactic-co-glycolic)acid microparticles in dogs

OBJECTIVE: To evaluate the potential utility of poly(D,L-lactic-co-glycolic)acid (PLGA) as a long-acting biodegradable drug delivery matrix for ivermectin used in the prevention of heartworm disease in dogs. ANIMALS: 30 adult female dogs. PROCEDURE: Microparticle formulations containing 25 weight percent (wt%), 35 wt%, and 50 wt% ivermectin were prepared by an oil-in-water emulsion technique with solvent extraction into excess water. A fourth formulation, consisting of a mixture of 15 wt% and 50 wt% ivermectin microparticles, was blended in a 1:1 ratio to result in a 32.5 wt% ivermectin formulation. Formulations were administered once on Day 0 to groups of 6 dogs at a dose of 0.5 mg of ivermectin/kg, s.c. Half of the dogs in each treatment group and 3 untreated control dogs were infected with Dirofilaria immitis larvae 121 and 170 days after treatment. Six months after infection, dogs were euthanatized and necropsies were performed. Pharmacokinetics and efficacy were investigated. RESULTS: Analysis of pharmacokinetic data revealed sustained release of ivermectin during at least 287 days in 3 distinct phases: a small initial peak, followed by release of drug through diffusion, and polymer degradation. Untreated control dogs were all infected with heartworms. Heartworms were not found in any of the dogs in the ivermectin-PLGA treated groups. Adverse clinical signs were not observed. CONCLUSIONS AND CLINICAL RELEVANCE: All formulations were 100% effective in preventing development of adult heartworms. Results indicate that PLGA microparticles are a promising drug delivery matrix for use with ivermectin for the prevention of heartworm disease for at least 6 months after treatment.     

Comparison of serologic tests for detection of antigen in canine heartworm infections

In 30 random-source dogs, we determined sensitivity and specificity of 5 serologic tests for detection of canine heartworm antigens. Seventeen of the dogs were infected naturally with adult Dirofilaria immitis, and 4 of the infected dogs were amicrofilaremic. The ability of the serologic tests to predict whether a dog was infected or uninfected (overall test accuracy) ranged from 73 to 97%. Sensitivity was not affected by circulating D immitis microfilariae, but was markedly influenced by the number of adult D immitis present. False-positive reactions were rare and were not associated with intestinal parasites or Dipetalonema reconditum microfilariae. Modifications of some of the test procedures were necessary to maximize test accuracy and reproducibility. These modifications and other technical details might limit the usefulness of some of the tests in a veterinary practice.     

Efficacy of selamectin against experimentally induced tick (Rhipicephalus sanguineus and Dermacentor variabilis) infestations on dogs

Seven controlled studies were conducted to investigate the efficacy of selamectin against weekly infestations of dogs with Rhipicephalus sanguineus and Dermacentor variabilis. Treatments (selamectin or vehicle alone) were applied topically at weekly, 2-week, or monthly intervals or in a "Monthly Plus" regimen (monthly treatment with an additional treatment at 14 days after the first treatment). Selamectin was supplied in unit dose tubes designed to deliver a minimum dosage of 6mgkg(-1). The studies ranged in duration from 37 to 90 days. Fifty adult ticks (+/-2) were applied approximately weekly, and tick counts were performed 3, 4, and 5 days after each infestation. The efficacy of selamectin was expressed as the percentage reduction in geometric mean tick counts on selamectin-treated dogs compared with those for dogs treated with the vehicle alone (negative-control). In one study, the engorgement of Dermacentor variabilis was assessed by weighing ticks after removal on the fifth day after each infestation. Weekly and 2-week interval treatments with selamectin provided efficacies against R. sanguineus of >89% across the entire study periods, with 100% efficacy being achieved from 21 days after the first dose and thereafter (study duration, 37 days for the weekly regimen and 44 days for the 2-week interval regimen). D. variabilis also was well controlled by the 2-week interval treatment regimen, with >96% efficacy being achieved from 21 days after the first treatment and thereafter until the end of the study (study duration: 90 days). In five of six studies incorporating three treatments at monthly intervals, the percentage reduction in R. sanguineus and D. variabilis counts 5 days after infestation ranged from 90 to 100% in the second and third months after treatment began. In the sixth study, reductions of > or =95% in D. variabilis counts 5 days after infestation were achieved for 2 weeks after each treatment in the second and third months. For the Monthly Plus regimen, from the second treatment (day 14) onwards, selamectin achieved 83-100% reductions in R. sanguineus and D. variabilis counts 3 days after infestation, and 94-100% reductions 5 days after infestation in three of the four studies. In the fourth study, selamectin demonstrated good efficacy against D. variabilis for 2 weeks after each treatment. In all seven studies, the counts from the selamectin-treated dogs were significantly (P< or =0.018) lower than those from the vehicle-treated dogs on 77 of the 80 assessments made 5 days after infestation. Selamectin also significantly (P< or =0.0105) reduced engorgement of female D. variabilis. These studies demonstrated that selamectin, administered topically to the skin in a single spot at a minimum dosage of 6mgkg(-1) at monthly intervals, was effective in the control of experimentally induced R. sanguineus and D. variabilis infestations on dogs.     

Evaluation of a single injection of a sustained-release formulation of moxidectin for prevention of experimental heartworm infection after 12 months in dogs

OBJECTIVE: To evaluate the efficacy of a single injection of a sustained-release formulation of moxidectin in preventing heartworm (Dirofilaria immitis) infection for 12 months in dogs. ANIMALS: 14 healthy dogs. PROCEDURE: Group A (nontreated control dogs; n = 6) received sterile vehicle administered SC, and group B (treated dogs; n = 6) received a sustained-release formulation of moxidectin administered SC. All dogs were housed in a heartworm-endemic area for 11.5 months, and heartworm antigen and modified Knott tests were performed monthly. All dogs (including 2 additional control dogs [group C]) were then inoculated with infective-stage larvae (L3) of D. immitis, and 4.5 months later, all dogs were euthanatized and post-mortem examinations were performed. Adult D. immitis were counted and measured, and their age was estimated. RESULTS: All dogs in groups A and C were infected with young (4- to 4.5-month old) adult male and female D. immitis. No dogs in group B were infected with heartworms. CONCLUSIONS AND. CLINICAL RELEVANCE: The age of heartworms recovered suggests that infection was the result of experimental inoculation and not natural exposure to mosquitoes during the 11.5-month period the dogs resided in a heartworm-endemic area. A single SC injection of a sustained-release formulation of moxidectin was effective in providing protection against heartworm infection after 12 months in dogs. This formulation is a convenient method of heartworm prophylaxis that could eliminate the problem of poor owner compliance.     

Prevalence and epidemiological aspects of Dirofilaria immitis in dogs from Kayseri Province, Turkey

This study was conducted to determine the prevalence of Dirofilaria immitis infection and to investigate the risk factors related to heartworm disease in dogs from Kayseri, Turkey. Blood samples were collected from 280 dogs from May 2005 to March 2006 and were examined by membrane filtration-acid phosphatase histochemical staining and antigen Elisa techniques to detect circulating microfilariae and antigens of D. immitis, respectively. Of the total of 280 dogs, 27 were positive for D. immitis with a prevalence value of 9.6%. In addition 29.6% of positive dogs determined to have occult D. immitis infections. D. immitis was the only canine filarial parasite present in the study area. The mean number of microfilariae in infected dogs was 4730+/-5479 per ml of blood. The highest heartworm prevalence were observed in 7-10 age group (28.6%) followed by 4-6 (17.1%) and 0.5-3 (4.8%) age groups. The differences between 0.5-3 and other age groups were found significant, whereas no statistically significant difference was observed between 4-6 and 7-10 age groups. The infection was more prevalent in males, larger breeds and the dogs not on prophylaxis. No statistically significant difference was observed between stray and owned dogs. Our results suggest that heartworm treatment and prophylaxis should be considered in Kayseri Province.     

Dose selection of selamectin for efficacy against adult fleas (Ctenocephalides felis felis) on dogs and cats

Selamectin, a novel avermectin, was evaluated in two controlled studies (one in Beagles, one in domestic shorthaired cats) to determine an appropriate topical dose for efficacy against adult Ctenocephalides felis felis (C. felis) fleas on dogs and cats for 1 month. For each study, animals were allocated randomly to four treatments. One treatment consisted of the inert formulation ingredients (vehicle) administered as a negative control, and the other three treatments consisted of a single topical dosage of 3, 6, or 9mgkg(-1) of selamectin. In each study, selamectin was administered as a topical dose applied to the skin in a single spot at the base of the neck in front of the scapulae. Dogs and cats were infested with 100 viable unfed C. felis (50 males and 50 females) on days 4, 11, 18, and 27. Seventy-two hours (+/-2h) after each infestation, on days 7, 14, 21, and 30, a comb count to determine the number of viable fleas present on each animal was performed. Efficacy of selamectin on day 30 was used to select an appropriate dose. For dogs and cats, percentage reductions in geometric mean flea comb counts for the three selamectin treatments ranged from 94. 6 to 100% on days 7, 14, and 21, compared with the negative-control treatment. On day 30, reductions in flea comb counts were 81.5, 94.7, and 90.8% for dogs, and 79.8, 98.0, and 96.2% for cats treated with selamectin at 3, 6, or 9mgkg(-1), respectively. For day 30 flea comb counts for dogs and cats, analysis of variance showed that the three selamectin treatments resulted in significantly (P< or =0.05) lower counts than did the negative-control treatment. For dogs and cats, geometric mean flea counts for selamectin administered at a dosage of 3mgkg(-1) were significantly (P< or =0.05) higher than those for the 6 and 9mgkg(-1) treatment dosages combined. There were no significant differences in flea counts between the 6 and 9mgkg(-1) treatments. This analysis was confirmed by linear-plateau modeling. Thus, the optimal dose of selamectin for efficacy against adult fleas for both dogs and cats, as estimated by the turning point (plateau) in the dose response curve, was 6mgkg(-1).     

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.     

The safety-net story about macrocyclic lactone heartworm preventives: a review, an update, and recommendations

A number of safe, effective, and convenient heartworm preventatives are currently available for virtually all canine and feline pets. Yet, a 2001 survey of over 18,000 veterinary clinics in the United States identified more than 240,000 dogs and 3000 cats infected with Dirofilaria immitis. This high level of owner compliance failure is alarming. Prolonged administration of some of the macrocyclic lactone (ML) preventatives kills young larvae, older larvae, "immatures," young adults, and/or old adults. Efficacy of 95% or more requires dosing for 9-30 months, with older worms being more difficult to kill. Of the various MLs, ivermectin (IVM) has the most potent safety-net and adulticidal activity, milbemycin oxime has the least, and selamectin and moxidectin injectable lie somewhere in between. The unique effects of IVM are related to the age of the heartworms at initiation of treatment. The earlier treatment is started, the more stunted and smaller the worms and the shorter their survival time. Conversely, the later treatment is started, the longer the worms live, and the more likely the dog will be antigen- and microfilariae-positive. Drug effects do not appear to be enhanced by increasing the dosage or administering at shorter intervals, and it appears that continuous monthly treatment is needed to produce the full effects of the drug. The American Heartworm Society (AHS) recognizes the safety-net (or reach-back effect) and adulticidal properties of some MLs, particularly IVM. The AHS 2003 (American Heartworm Society, 2004. 2003 Updated guidelines for the diagnosis, prevention, and management of heartworm (Dirofilaria immitis) infection in dogs. In: McCall, et al., (Eds.), Proceedings of the Symposium Session on Recent Advances in Heartworm Disease, The 19th International Conference of the World Association for the Advancement of Veterinary Parasitology, New Orleans, LA, 10-14 August, 2003. Vet. Parasitol. 125, 105-130) canine guidelines state that it is beneficial to administer prophylactic doses of IVM before treatment with melarsomine. Results of laboratory studies suggest that less active dogs are at low risk of severe thromboembolism and death. However, heartworm-positive working dogs might be more at risk. Worsened radiographic and echocardiographic images in a client-owned dog given IVM monthly for 2 years with greatly restricted exercise suggests that such treatment of dogs with clinical, radiographic, and/or echocardiographic evidence of heartworm disease as well as for asymptomatic working dogs is contraindicated. Furthermore, until further data are available, such treatment of even the less active asymptomatic dog should be administered only with much caution and with examination by a veterinarian at least once every 4-6 months. IVM clearly provides potent "safety-net" activity against older larvae, immatures, and young adults in cases of owner compliance failure, even when the owner and veterinarian are not aware that the animal is infected, and offers much promise as a unique "soft-kill" treatment for young, and possibly older adult heartworms, with reduced risks.     

The occurrence of Dirofilaria immitis in dogs in South Australia

Heart, lung and samples of blood from 230 dogs were examined for infections of filarial parasites. Dirofilaria immitis worms and microfilariae were detected in one dog. Blood samples from a further 1428 dogs were examined for microfilariae and 22 were found to be infected. Eighteen dogs were infected with D immitis microfilariae and four with Dipetolonema reconditum microfilariae. The histories were available for 18 of the dogs infected with heartworm and only seven dogs had not travelled outside South Australia. It was concluded that heartworm infection was endemic in South Australia but the apparent prevalence was only about 1%.     

Efficacy and safety of selamectin against Sarcoptes scabiei on dogs and Otodectes cynotis on dogs and cats presented as veterinary patients

A series of randomized, controlled and masked field studies was conducted in veterinary patients to evaluate the efficacy of selamectin, a novel avermectin, in the treatment of naturally occurring Sarcoptes scabiei infestations on dogs and Otodectes cynotis infestations on dogs and cats. A total of 342 dogs and 237 cats participated in these studies, which were conducted at 40 veterinary practices in the USA and Europe. Animals were randomly assigned to treatment with selamectin or a positive-control product (existing approved products). Selamectin was administered as a unit dose providing a minimum of 6mgkg(-1) (range: 6-12mgkg(-1)) in a topical preparation applied to the skin in a single spot on day 0 (O. cynotis in cats, n=144), or on days 0 and 30 (O. cynotis and S. scabiei in dogs, n=83 and n=122, respectively). The presence of parasites was assessed before treatment and at 30 days (for all studies) and 60 days (for O. cynotis and S. scabiei dog studies) after first treatment. The animals were also evaluated clinically at each assessment period. Based on skin scrapings, the efficacy of selamectin against S. scabiei infestations on dogs was >95% by day 30, and 100% by day 60. Against O. cynotis, selamectin eliminated mites in 94-100% of cats by day 30, and in 90% of dogs by day 60. The positive-control products achieved similar results. Thus, selamectin was safe and effective against ear mites in dogs and cats and sarcoptic mange in dogs when used in field (veterinary patient) studies in dogs and cats of a wide variety of ages and breeds.     

The efficacy of selamectin in the treatment of naturally acquired aural infestations of otodectes cynotis on dogs and cats

The efficacy of a novel avermectin, selamectin, was evaluated against naturally acquired aural infestations of Otodectes cynotis on dogs and cats. In four controlled and masked studies conducted in the USA and Europe, animals were allocated randomly to treatment with either selamectin at a minimum dosage of 6mgkg(-1) (range, 6-12. 5mgkg(-1)) or the vehicle only from the commercial formulation of selamectin (negative control). Treatments were administered topically in a single spot to the skin of each animal's back at the base of the neck in front of the scapulae. Cats were treated on day 0 only, and dogs were treated either on day 0 only or on days 0 and 30. The ears of dogs were examined otoscopically on day 14 for the presence of viable mites. Mite counts were conducted on day 30 for animals that had received one dose and on day 60 for animals that had received two doses. Percentage reductions in geometric mean mite counts for selamectin treatment compared with the vehicle were 100% for all animals on all count days. Analysis of variance, confirmed by Savage Scores, showed that ln(mite count+1) values were significantly (P< or =0.0015) lower for selamectin than for the vehicle for all animals on all count days. Thus, selamectin administered topically at a minimum dosage of 6mgkg(-1) was safe and 100% effective against naturally acquired aural infestations of O. cynotis in dogs and cats after a single dose or after two doses administered 1 month apart.     

Canine Dirofilaria immitis infection in a hyperenzootic area: examination by parasitologic findings at necropsy and by two serodiagnostic methods

A total of 174 dogs from an area hyperenzootic for Dirofilaria immitis were grouped into 4 age categories and necropsied; information was obtained on adult D immitis infections and on the presence of microfilariae. Serum samples from these dogs were examined by an enzyme-linked immunosorbent assay (ELISA) for antibody to adult D immitis and by an indirect fluorescent antibody test (IFAT) for antibody to microfilarial surface antigens. In dogs less than or equal to 5 months of age, necropsy demonstrated no evidence of infection; however, positive serologic results indicated that some of these dogs had prepatent infections. The percentage of dogs with ELISA titers (positive) increased with age, as did the percentage of dogs with adult D immitis infections. The IFAT results were positive in some dogs in each age category. Sera from all 29 dogs with occult infections were positive by ELISA. Sera from 6 of 20 dogs with occult dual-sex heartworm infections and 1 of 9 dogs with occult single-sex heartworm infections were positive by IFAT. For diagnosing occult dirofilariasis, the ELISA had a positive predictive value which increased with age of the dog to a maximum of 65.0% in dogs greater than or equal to 12 months of age; ELISA had a negative predictive value of 100% in all age groups. In contrast, positive and negative predictive values for the IFAT decreased with age of the dog to 60% and 37.5%, respectively, in dogs greater than or equal to 12 months of age.     

Efficacy of long-term monthly administration of ivermectin on the progress of naturally acquired heartworm infections in dogs

This study was designed to evaluate the efficacy of prolonged monthly ivermectin treatment against Dirofilaria immitis in client-owned dogs with naturally acquired infections and to clinically monitor the animal's response to the slow killing of heartworms, with death of the worms distributed over a period of up to 2 years. A total of 17 male and female dogs of different breeds and ages were used. Prior to treatment, all of the dogs tested positive for heartworm antigen (Ag) and all but two had microfilariae (mf). The dogs were randomly allocated to one group of seven dogs which received a commercial formulation of ivermectin (minimum, 6 mcg IVM/kg) plus pyrantel (minimum, 5 mg PP/kg) (Heartgard Plus Chewables, Merial, Ltd.), another group of seven dogs which received a commercial formulation of IVM (min, 6 mcg/kg) (Heartgard Chewables, Merial Ltd.), and a group of three dogs which served as an untreated controls. All dogs were evaluated prior to initiation of treatment and thereafter at 3- to 5-month-intervals for mf, Ag, and radiographic and echocardiographic findings. All of the 17 dogs, with the exception of two dogs in the IVM group, had circulating mf of D. immitis prior to the 1st monthly dose, and a few also had mf of Dirofilaria repens. After 4 monthly doses, only one dog in the IVM/PP group and two dogs in the IVM group had a patent heartworm infection, and no heartworm mf were seen in the 14 treated dogs thereafter. After 10 monthly doses, the number of Ag-positive dogs in both of the treated groups decreased gradually. Efficacy, based on the reduction in number of Ag-positive dogs, was similar for the IVM/PP and IVM groups, with overall efficacy scores for the 14 dogs of 21, 21, 43, and 71% after 10, 14, 19, and 24 monthly doses, respectively. Two of the seven dogs treated with IVM/PP, one of the seven treated with IVM, and two of the three untreated controls showed echocardiographic evidence of a parasitic burden prior to treatment, and all of these scores had decreased by the end of the study. Only one dog (IVM/PP group) had a cardiovascular pattern of heartworm disease by echocardiography prior to treatment, but this dog's score increased to two and the scores of two additional dogs increased from zero to two (IVM group) or three (IVM/PP group) by the end of the study. Only 1 (IVM/PP group) of the 17 dogs showed a pulmonary pattern of heartworm disease by radiography prior to treatment, but this dog's score increased to three by the end of the study. The radiographic scores of two additional dogs in the treated groups increased from zero to three (IVM/PP) or two (IVM) by the end of the study. Thus, monthly administration of IVM to dogs with clinical, radiographic or echocardiographic evidence of heartworm disease is ill-advised and such treatment of even the asymptomatic dog should be done only with much caution and frequent monitoring by the veterinarian.     

Efficacy of avermectin B1a against microfilariae of Dirofilaria immitis

Avermectin B1a given at a dose level of 0.05 or 0.1 mg/kg of body weight caused rapid removal of Dirofilaria immitis microfilariae from the blood of dogs with heartworm infections. If the adult worms were also killed with an arsenical (melarsoprol), the removal of microfilariae was permanent.