New trends and technologies in heartworm prevention

Veterinarians continue to diagnose heartworm infections regularly in dogs in many regions of the country, despite the availability of effective and convenient preventative medications, and despite a market that has seen sales of heartworm prevention products increase to more than $329 million dollars per year. When I speak to veterinarians, I often ask how many still diagnose canine heartworm infections on a regular basis. I am continually surprised at the number of positive responses that I receive. It is generally accepted that the numbers of infected dogs has decreased continually since the introduction of ivermectin in the mid-1980s, but all continue to see infected dogs. Most veterinarians agree that they are also diagnosing fewer cases of clinical heartworm disease compared to 10 or 15 years ago. I attribute the success that we have achieved in reducing the numbers of infected dogs and clinical cases of heartworm disease to increased pet owner awareness of heartworm and how it is transmitted, the advocacy of heartworm prevention by veterinarians, and the efficacy and convenience of heartworm preventative products. Not only do newer product combinations and formulations provide veterinarians and pet owners with added convenience, some also control additional internal and external parasites (Table 1, p 17). In the discussions that follow, I will emphasize newer formulations for heartworm prevention and briefly review current trends in diagnosis and prevention of heartworm infections in dogs and cats.

New trends in heartworm prevention

Recent trends in heartworm prevention have seen the introduction of some new active agents, combinations of existing agents to increase spectrum of activity, and the development of chewable, topical and injectable formulations to provide more product choices for veterinarians and pet owners (Table 1). We also have seen the introduction of several products for prevention of heartworm infection in cats (Table 1). Because of the differences in heartworm infections in dogs and cats, it is sometimes necessary to use different diagnostic and treatment strategies when dealing with feline heartworm infections (Table 2, p. 21).

After years of research, veterinarians now have a variety of options to choose from when selecting heartworm preventives. New product combinations and formulations have paved the way for these advancements which also help control other parasites.

With new trends also come new technologies necessary to support their efficacy and convenience. The introduction of chewable or flavored tablets in both single entity and combination medications has made daily and monthly prevention of heartworms, gastrointestinal parasites, and even fleas more convenient for pet owners. Combinations of parasiticides are the basis for broad spectrum parasite control claimed by Heartgard Plus (ivermectin/pyrantel pamoate) and Sentinel (milbemycin oxime/lufenuron). Heartgard Plus combines the efficacy of ivermectin at 6 ������������������g/kg against L3 and L4 stages of heartworm with the activities of pyrantel pamoate at 5 mg/kg against common roundworms (Toxocara canis, Toxascaris leonina) and hookworms (Ancylostoma caninum, Ancylostoma braziliense, and Uncinaria stenocephala) in dogs. Heartgard Plus is the only canine monthly broad-spectrum heartworm preventative product that also carries a label claim for U. stenocephala and A. braziliense. In addition Heartgard Plus chewables is packaged in boxes of six or 12 chewables to provide veterinarians and pet owners with options for prevention periods that may be more suited for their needs. Interceptor (milbemycin oxime) is an example of a single entity product which exploits the potential broad spectrum capabilities of macrocyclic lactone (i.e. ivermectin, milbemycin oxime, moxidectin, selamectin) compounds. At its label dosage of 0.5 mg/kg of bodyweight. Interceptor is effective in preventing heartworm infections and also in the removal and control of roundworms (T. canis, Toxascaris leonina) and whipworms (Trichuris vulpis), and in the control of hookworms (A. caninum). Interceptor was recently approved for use in cats at the target dose of 2.0 mg/kg. At that dosage, Interceptor not only prevents heartworm infections but also removes roundworms (T. cati) and hookworms (A. tubaeforme). Novartis has elected to dual label the existing product for use in either dogs or cats. For example, the 5.75-mg tablet, now used in dogs weighing 11-25 pounds, can also be used for cats weighing 1.5-6 pounds. The 11.5-mg tablet will treat dogs weighing 26-50 pounds, and cats weighing 6.1-12 pounds. Likewise, the 23-mg table is intended for dogs in the 51-100 pound weight range and cats weighing 12.1-25 pounds. Dual labeling will help reduce the veterinarian's inventory below what would be maintained if the dog and cat products were packaged separately. Interceptor is approved for use in cats and kittens 6 weeks old and older and 1.5 pounds and greater. Sentinel is an additional example of the strategy of combining agents to increase spectrum of activity. Sentinel combines the internal parasiticidal properties of milbemycin oxime and the flea ovicidal and larvicidal effects of lufenuron in a single flavored tablet. Additional combination products for heartworm prevention and internal parasite control are nearing approval and launch as this article is in preparation.

The development of topically administered products such as selamectin (Revolution ) has added an additional dimension to the convenience of regular application of preventative medications. The active agent in Revolution is selamectin, a novel semi-synthetic avermectin compound. Revolution is an example of the use of chemical synthesis and bioengineering techniques to specifically target both internal and external parasites in dogs and cats. Combined activity against internal and external parasites has earned Revolution and similar products the name endecticides. Revolution contains selamectin specifically formulated in a butylhydroxytoluene, dipropylene glycol methyl ether, isopropyl alcohol base to promote absorption when applied to the pet's skin surface. Following absorption from the skin, Revolution enters the bloodstream, which is the basis of its activity against heartworms. It is also excreted into the intestinal tract, resulting in activity against some gastrointestinal parasites. Its redistribution from the bloodstream into the skin, including the sebaceous glands, provides persistent activity against fleas, ear mites and scabies mites. Revolution was welcomed by pet owners who either could not or preferred not to administer tablets to pets orally. Revolution is particularly convenient for those interested in internal and external parasite control in cats but do not wish to administer oral medications. Topical heartworm preventative medications also are more likely to be accepted by veterinarians and pet owners now that topical products have become the principal means of flea and tick control.

The latest of novel formulations for heartworm prevention is an injectable suspension comprised of sterile moxidectin-containing microspheres. Moxidectin is also related chemically to ivermectin, milbemycin oxime and selamectin. The injectable formulation (ProHeart 6) is marketed as separate vials containing microspheres and diluent. The microspheres and diluent are combined (constituted) just prior to injection. After mixing, the suspended microspheres are allowed to stand for five minutes, and can then be used for four weeks if stored in the refrigerator. The ProHeart 6 formulation of moxidectin is administered subcutaneously to dogs at the target dose of 0.17 mg of moxidectin per kg of body weight, or 1 cc of constituted product per 44 pounds of body weight. The product insert recommends subcutaneous injection of ProHeart 6 in the subcutaneous tissues of the neck cranial to the scapula. Subsequent injections are given at a corresponding location on the alternate side. Microsphere technology involves the unique incorporation of the moxidectin molecule into the microsphere matrix. As the microspheres disintegrate, the moxidectin molecule is released, resulting in an immediate (one to two week) achievement of peak measurable blood levels of moxidectin. The amounts of detectable moxidectin decline over the subsequent six-month period. Studies supporting efficacy of the injectable microsphere formulation of moxidectin indicate that sufficient amounts remain in dogs to prevent heartworm infections for six months. The ProHeart 6 formulation also carries a label claim for removal of larval and adult hookworm (Ancylostoma caninum) at the time of injection. The label does not support continued control of hookworm throughout the subsequent six-month period as for heartworm. ProHeart 6 is approved for use in dogs that are 6 months old and older.

Heartworm prevention also includes periodic monitoring. Improvements have been made to in-clinic antigen and antibody tests which encourage practitioners to incorporate these tests ino their monitoring strategies.

Testing

As with all heartworm prevention products, dogs that are not currently on a heartworm prevention product should be tested to determine their infection status. Veterinarians can then decide whether to remove adult worms with an approved adulticide. I favor treatment of all dogs, whenever possible, to remove adult heartworms prior to placement on any preventative medication.

ProHeart 6 provides veterinarians and pet owners with another convenient option for heartworm prevention. ProHeart 6 could be particularly useful in regions of the United States for which transmission of Dirofilaria immitis is six months or less. Also, for pet owners who visit heartworm endemic areas during times of the year when heartworm prevention is not normally practiced in their regions (for example, travel to the southern United States during the cooler fall and winter months), ProHeart 6 could be considered as a convenient prevention alternative.

Monitoring efficacy and pet owner compliance

Periodic monitoring of pets on heartworm prevention is also an important component of heartworm prevention strategies. Continual improvements in performance and ease of conduct of in-clinic antigen and antibody tests have encouraged more veterinarians to consider the use of one or more of these tests in their monitoring strategies. Periodic testing is not based on our distrust of active ingredients in available heartworm preventatives, but rather on the presumption that not all pet owners either can or will administer medications regularly and according to label recommendations. Often, when pets are not treated properly, pet owners are completely unaware that any failure has occurred. Table 3, p. 24 contains a summary of available heartworm tests for dogs and cats. Selection of a test by veterinarians is likely based on a number of criteria including type of blood specimen required, time required to conduct the test, numbers of test steps required, ease of visualizing test results, available test performance data such as sensitivity (capability of test to identify a true positive) and specificity (capability of test to identify a true negative), whether tests can be batched or must be conducted individually, and perhaps cost of the test. It is important to remember several points about either antigen or antibody tests before results can be interpreted accurately. Antigen tests are used to determine the presence of adult worms. These tests detect only female worms and in some cases only when a minimum number of female worms are present or have matured to approximately six months. Keep in mind that positive test results can persist after worms have died or after they have been removed with an adulticide. In the latter case, positive results can persist for up to four months after treatment. Because cats usually harbor fewer worms (thus oftentimes fewer female worms) than dogs, antigen tests are frequently less sensitive in cats than in dogs (Table 2, p. 21). Also keep in mind that although antibody test results can be very important and helpful in confirming or ruling out heartworm infections in cats, they cannot confirm the presence of adult worms. They do provide important data regarding exposure of cats to infected mosquitoes and can be convincing aids when heartworm prevention is recommended to pet owners with cats. Certainly the conduct of annual heartworm antigen tests in dogs seems a reasonable component of a conscientious heartworm prevention program. However, I cannot fault the veterinarian who does not recommend testing or prefers biennial testing because he/she knows and trusts the compliance capabilities of the client.

American Heartworm Society Guidelines

Veterinarians are reminded of the recommendations and resources available to them from the American Heartworm Society. For those who seek additional information, see the Suggested Reading list on page 22. Among those articles are summaries of recommendations assembled by the Executive Board of the American Heartworm Society and published either in veterinary journals or in the proceedings of the triennial Heartworm Symposium.

Suggested Reading:

• Dillon AR: Dirofilariasis in dogs and cats, in Textbook of Veterinary Internal Medicine, 2000, pp 937-963.

• Knight DH: Heartworm testing and prevention in dogs and cats, in Kirks Current Veterinary Therapy XIII, 2000, pp 777-790.

• Calvert CA, Rawlings CA, McCall J: Heartworm disease, in Saunders Manual of Small Animal Practice, 1999, pp 557-567.

• Knight DH et al: 1999 guidelines for the diagnosis, treatment, and prevention of heartworm (Dirofilaria immitis) infection in cats, 2001, Veterinary Therapeutics, pp 78-87.

• American Heartworm Society (Executive Board): 1999 Guidelines for the diagnosis, prevention and management of heartworm (Dirofilaria immitis) infection in dogs, in Proceeding of Heartworm Symposium 98, 1999, pp 257-264.