Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania
Philadelphia, PA, USA
Heartworm infections in dogs and cats caused by Dirofilaria immitis are curable and completely preventable. The veterinary practitioner has now a full armamentarium of very efficient chemoprophylactics that are easy and convenient to use and one efficient and safe compound useful for treatment. Yet in spite of all this tools on hand a survey conducted in 2001 among 18,000 veterinary clinics in the USA indicated that the practitioners that responded had detected more than 240,000 dogs and 3,000 cats that needed adulticide treatments just in that year. This alarming information calls attention to potential misuse of the prophylactics available or lack of compliance by the pet owners.
Chemoprophylaxis in dogs. All the several formulations available as prophylactic drugs for heartworm infections fall into two basic classes, the macrocyclic lactones or macrolides (avermectins and milbemycins) and diethylcarbamazine.
Diethylcarbamazine citrate. The first drug to be employed for prevention of canine heartworm disease was diethylcarbamazine citrate (DEC). At present, the use of daily DEC is fairly limited to the United States and it is rapidly being replaced by the macrocyclic lactones.
Macrocyclic lactones or macrolides. Since the discovery of ivermectin and the initial description of activity against developmental stages of D. immitis, a large number of publications have appeared reporting on their attributes and were reviewed by Campbell (1989) and Guerrero et al (2002).
Presently, monthly oral administration of ivermectin at 6 to 12 mcg/kg, milbemycin oxime at 500 to 999 mcg/kg, moxidectin at 3 mcg/kg, or topical selamectin at 6 mg/kg provide effective protection against heartworm infections in dogs.
An ivermectin/pyrantel pamoate chewable formulation has been available for veterinary use since 1993. This product expands the indications to include treatment and control of certain gastrointestinal parasites as: Toxocara canis, Toxascaris leonina, Ancylostoma caninum, Ancylostoma braziliense and Uncinaria stenocephala.
Milbemycin oxime, is highly efficacious against developmental stages of D. immitis in dogs when administered in monthly oral doses as low as 0.05 mg/kg. At the recommended dose for heartworm prophylaxis milbemycin oxime is also effective against T. canis, T. leonina, A. caninum, and Trichuris vulpis.
Moxidectin is effective in preventing the development of third-stage larvae when administered orally at a dose of 3 mcg/kg one month after infection.. Six month protection is also afforded by a sustained released injectable formulation at doses of 170 mcg/kg. Recently (September 2004) the producers of PROHEART 6 in the USA have voluntarily recalled the product off the market and suspended its commercialization. This same commercial injectable formulation is sold in Canada, Europe and Australia. The Australian formulation has a higher concentration of Moxidectin and claims of prevention for a full year.
Selamectin the most recently developed avermectin monosaccharide is formulated to be used as a topical formulation at a dose of 6mg/kg. Selamectin is a true endectocide since its activity encompasses internal and external parasites.
At present the topical combination formulations like Imidacloprid-Ivermectin and Imidacloprid-Moxidectin represent the new trend to expand the label claims of heartworm preventives to also serve as monthly flea control products. The pioneer product in this class was a combination of Milbemycin oxime/Lufenuron tablet which is available in the USA for the combined control of D. immitis infections and Ctenocephalides felis infestations in dogs.
Chemoprophylaxis in cats. Heartworm preventive treatment in cats follows the same regimen established for dogs. Ivermectin is marketed in the US for use as a prophylactic agent in cats given monthly at the dose of 24 mcg/kg. At this dose ivermectin is also effective in the treatment and prevention of A. tubaeforme and A. braziliense.
Milbemycin oxime is also commercially available for this purpose in the same flavor tablet formulation used in dogs. The recommended dosage for cats is 2000 mcg/kg. At that dose milbemycin oxime is effective in the prevention of D. immitis and the removal of adult A. tubaeforme and T. cati.
The topically applied single dose of selamectin at 6 mg/kg completely prevents the development of D. immitis in experimentally infected cats. Selamectin has also been found to be effective against the roundworm T. cati and the hookworm A. tubaeforme in cats.
Heartworm clinical prophylaxis in dogs and cats. All macrocyclic lactones are completely efficacious against D. immitis larvae when administered every 30 to 60 days. This characteristic provides a safety-net in the case of omission or delay of a monthly treatment, or when the chemoprophylactic history of the dog cannot be verified. Ivermectin and Milbemycin oxime have both been found to provide a high degree of protection when administered on a regular basis, beginning three months after infection. In fact prolonged administration of Ivermectin kills not only young larvae but older larvae, "immature" young adults, and/or old adults as well. Ivermectin has the most potent safety-net and adulticidal activities, while milbemycin oxime has the least activity, and the effectiveness of selamectin and moxidectin injectable lies in between.
Melarsomine Dihydrochloride. The organoarsenical adulticide, Melarsomine, is the only adulticide available for use in dogs, its efficacy in cats is questionable. Melarsomine is administered via deep intramuscular injection into the epaxial lumbar muscles. If adulticide treatment is elected for clinically ill dogs, an attempt should be made to stabilize the patient's clinical signs with medical support before proceeding with treatment. Exercise restriction during the recovery period is mandatory. The administration protocol of two injections separated by a 24-hour interval (=standard protocol) is recommended by the manufacturer for dogs at low risk of thromboembolic complications. For dogs at greater risk, a gradual, two-stage elimination of worms is possible using a three-injection treatment protocol of one dose initially, followed in four to six weeks with a two-dose treatment (= alternative protocol). This three-injection protocol is the treatment of choice of the American Heartworm Society regardless of stage of disease. It is also beneficial to administer a prophylactic doses of Ivermectin for one to six months prior to the administration of Melarsomine, when the clinical presentation does not demand immediate intervention.
Ivermectin. Continuous monthly administration of prophylactic doses of Ivermectin, alone or in combination with Pyrantel pamoate, is highly effective against late precardiac larvae and young (< 7 month post-infection) adult heartworms. The adulticide effect of Ivermectin generally requires more than a year of continuous monthly administrations and may take more than two years before heartworms are eliminated completely. The older the worms when first exposed to Ivermectin, the slower they are to die. In the meantime, the infection persists and continues to cause disease. Therefore, long-term continuous administration of Ivermectin generally is not a substitute for conventional arsenical adulticide treatment. Recently published clinical observations suggests that 2 heartworm-positive active dogs in prolonged Ivermectin treatment showed worsened radiographic and echocardiographic images where client-owned dogs were given Ivermectin monthly for 2 years (Venco et al 2004).
1. Campbell, W.C. (1989) Use of ivermectin in dogs and cats. In: Campbell, W.C. (ed.) Ivermectin and Abamectin, Springer-Verlag, New York, pp. 245-259.
2. Guerrero, J.., McCall, J.W. and Genchi, C.(2002). Macrocyclic lactones in the control and prevention of heartworm and other parasites in dogs and cats. In: Macrocyclic Lactones in Antiparasitic Therapy. Rew, R. and Vercruysse,J. Eds. CABI Publishing, New York, NY, 353-369.
3. McCall , J., Guerrero, J., Genchi, C. and Kramer, L.(2004) Recent advances in heartworm disease Vet Parasitology, 125 ( 1-2): 105-130
4. Venco, L., McCall, J.W., Guerrero, J. and Genchi, C. (2004) Efficacy of long-term monthly administration of ivermectin on the progress of naturally acquired heartworm infections in dogs. Vet. Parasitology, 124 (3-4): 259-268