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Canine Heartworm Disease
Dogs are considered the definitive host for heartworms (Dirofilaria immitis). However, heartworms may infect more than 30 species of animals (e.g., coyotes, foxes, wolves and other wild canids, domestic cats and wild felids, ferrets, sea lions, etc.) and humans as well. When a mosquito carrying infective heartworm larvae bites a dog and transmits the infection, the larvae grow, develop and migrate in the body over a period of several months to become sexually mature male and female worms. These reside in the heart, lungs and associated blood vessels. As mature adults, the worms mate and the females release their offspring (microfilariae), pronounced: (micro fil ar ee), into the blood stream.
Offspring can be detected in the blood (pre-patent period) about six to seven months after the infective larvae from the mosquito enter the dog. The male heartworms (four to six inches in length) and the females (10-12 inches) become fully grown about one year after infection, and their life span in dogs appears to average up to five to seven years.
In experimentally induced infections of heartworms in dogs, the percentage of infective larvae developing to adults is high (40% to 90%). However, the percentage of experimentally infected dogs from which adult worms are recovered is virtually 100%. The number of worms infecting a dog can be very high, with the number of worms in dogs ranging from one to approximately 250.
Microfilaremia, the presence of heartworm offspring in the blood of infected dogs, is relatively common. However, not all heartworm infections result in such offspring circulating in the blood. These are known as occult heartworm infections and may be the result of a number of factors such as single sex heartworm infections, host immune responses affecting the presence of circulating offspring (microfilariae) and most significantly, the administration of heartworm preventives.
The onset and severity of disease in the dog is mainly a reflection of the number of adult heartworms present, the age of the infection and the level of activity of the dog. Dogs with higher numbers of worms are generally found to have more severe heart and lung disease changes. Until the number of mature heartworms exceeds 50 in a 25-kg dog (approximately 55 pounds), nearly all of the heartworms reside in the lower caudal pulmonary arteries (the arteries of the lower lung lobes). Higher numbers of heartworms result in their presence in the right chambers of the heart. In such infections, the most common early pathological changes caused by heartworms are due to inflammatory processes that occur in and around the arteries of the lower portion of the lungs in response to the presence of heartworms. Later, the heart may enlarge and become weakened due to an increased workload and congestive heart failure may occur. A very active dog (e.g., working dog) is more likely to develop severe disease with a relatively small number of heartworms than an inactive one (e.g., a lap dog or couch potato). Occasionally, a dog with a large number of heartworms may not only have worms in the heart, but also in the caudal vena cava (large primary vein of the lower body) between the liver and the heart. If the heartworms are not removed surgically, this syndrome causes sudden collapse and death within two to three days.
Canine heartworm infection is widely distributed throughout the United States. Heartworm infection has been found in dogs native to all 50 states. All dogs, regardless of their age, sex, or habitat, are susceptible to heartworm infection. The highest infection rates (up to 45%) in dogs (not maintained on heartworm preventive) are observed within 150 miles of the Atlantic and Gulf coasts from the Gulf of Mexico to New Jersey and along the Mississippi River and its major tributaries. Other areas of the United States may have lower incidence rates (5% or less) of canine heartworm disease, while some regions have environmental, mosquito population and dog population factors that allow a higher local incidence of heartworm infection. Regions where heartworm disease is common have diagnosed infections in dogs as young as one year of age, with most areas diagnosing infections primarily between the ages of three and eight years. Although there are differences in frequency of infection for various groups of dogs, all dogs in all regions should be considered at risk, placed on prevention programs and frequently examined by a veterinarian.
Heartworm disease may cause a combination of medical problems in the same dog including dysfunction of the lungs, heart, liver and kidneys. The disease may have an acute onset but usually begins with barely detectable signs resulting from a chronic infection and a combination of physiologic changes. Dogs with a low number of adult worms in the body that are not exercised strenuously may never have apparent signs of heartworm disease. However, in most dogs, the heart and lungs are the major organs affected by heartworms with varying degrees of clinical signs.
The diagnosis of canine heartworm disease depends upon the following:
Antigen tests detect specific antigens primarily found in adult female heartworms and are used with much success to detect canine heartworm infection. Currently, tests are available as in-clinic tests as well as at many veterinary reference laboratories. Most commercial tests will accurately detect infections with one or more mature female heartworms that are at least seven or eight months old, but the tests generally do not detect infections of less than five months duration.
Since the late 1970's and early 1980's, several canine heartworm antibody tests have been developed and introduced, but such tests for dogs have been largely replaced by the more useful antigen tests. This lack of utility of the antibody tests is due to the fact that these tests detect the antibody response to exposure to infection, but not necessarily actual disease. This is important because not all infections fully mature.
Microfilarial Detection and Differentiation
The identification of the offspring (microfilaria) of heartworms (Dirofilaria immitis) from a blood sample indicates infection with adult heartworms. Identifying offspring can also be accomplished through either one of two concentration tests: the modified Knott's test (a technique requiring spinning the blood sample in a mechanical device called a centrifuge) or a filter test. Practitioners will often do a quick examination of a blood smear to look for the presence of the offspring (microfilaria), but this procedure is not sensitive enough to rule out heartworms and only verifies the presence of an infection.
Another parasitic infection of dogs that is capable of producing circulating microfilariae, detectable upon examination of the blood, is called Acanthocheilonema (Dipetalonema) reconditum. A reconditum is a non-disease-causing parasite that matures in the tissues beneath the skin of dogs. Its offspring can be differentiated from those produced by heartworms through microscopic examination evaluating size, shape and their movement.
A heartworm infected dog with mild disease may appear to be perfectly normal upon physical examination. Severely affected dogs, however, may show signs of right-sided heart failure. Labored breathing or crackles may be heard in the lungs due to vascular clots and elevated pressure. A history of coughing and inability to exercise are among the earliest detectable abnormalities. Tachycardia (rapid heartbeat), ascites (fluid in the abdomen) and hepatomegaly (enlarged liver) indicate right-sided congestive heart failure. Hemoptysis (blood in the sputum) occasionally occurs and indicates severe clots and complications within the lungs. Anorexia (loss of appetite), cachexia (severe weight loss), syncope (fainting) jaundice or yellow bile pigmentation present in the skin and mucus membranes may appear in severely affected dogs. Occasionally, heartworms are reported in abnormal locations such as the eyes, abdominal cavity, cerebral artery and spinal cord. Clinical signs and disease experienced in such infections depend largely on the location of the worms. The primary response to the presence of heartworms in dogs, however, occurs in the heart and lungs.
Radiographic abnormalities develop early in the course of the disease. X-rays of the heart and lungs are the best tools available to evaluate the severity of the disease and to develop a prognosis. Typical changes observed are enlargement of the following structures: pulmonary arteries in the lobes (particularly the lower lobes) of the lung, main pulmonary artery, and right side of the heart. Blunting and thickening, usually along with tortuosity (abnormal twists or turns), of pulmonary arteries, is often noted. Inflammation is often found in the lung tissue, particularly the tissue that surrounds the pulmonary arteries.
Angiography and Ultrasonography
These forms of imaging are rarely used in the diagnosis of canine heartworm infection outside of referral practices and teaching institutions. Angiography is a technique that permits visualization of blood vessels in the body by taking radiographs within seconds after injecting a contrast material (dye) into those blood vessels. In canine heartworm infection, angiography is used to study changes to the pulmonary arteries. Worms may be visualized on the angiogram as filing defects. Ultrasonography (echocardiography) has been used to evaluate enlargement of the heart chamber and to look for the presence of heartworms in the right ventricle or main pulmonary artery.
Necropsy (examination after death)
Although necropsy is probably the most definitive diagnostic test, it is hoped that it never reaches that stage. Heartworms are usually found in the right ventricle of the heart or in the major pulmonary arteries, at times in its farthest branches. Occasionally heartworms may be found in organs other than the heart and lungs but such infections are rare.
Most dogs infected with heartworm can be successfully treated. The goal of treatment is to kill all adult worms with an adulticide and all microfilariae with a microfilaricide. It is important to try to accomplish this goal with a minimum of harmful effects from drugs and a tolerable degree of complications created by the dying heartworms. Heartworm infected dogs showing no signs or mild signs have a high success rate with treatment. Patients with evidence of more severe heartworm disease can be successfully treated, but the possibility of complications and mortality is greater. The presence of severe heartworm disease within a patient in addition to the presence of other life-threatening diseases may prevent treatment for heartworm infection.
Adult Heartworm Therapy (Adulticide Therapy)
There is currently one drug approved by the FDA for use in dogs for the elimination of adult heartworms. This drug is an organic arsenical compound. Dogs receiving this drug therapy will typically have had a thorough pretreatment evaluation of its condition and will then be hospitalized during the administration of the drug.
Melarsomine dihydrochloride (Immiticide®, Merial) has demonstrated a higher level of effectiveness and safety than any other adult heartworm treatment previously available. It is administered by deep intramuscular injection into the lumbar muscles. For complete information on the classification and treatment for heartworm infected dogs using this product, consult your veterinarian.
The primary post-adulticide complication is the development of severe pulmonary thromboembolism. Pulmonary thromboembolism results from the obstruction of blood flow through pulmonary arteries due to the presence of dead heartworms and lesions in the arteries and capillaries of the lungs. If heartworm adulticide treatment is effective, some degree of pulmonary thromboembolism will occur.
When dead worms are numerous and arterial injury is severe, widespread obstruction of arteries can occur. Clinical signs most commonly observed include fever, cough, hemoptysis (blood in the sputum) and potentially sudden death. It is extremely important to not allow exercise in any dog being treated for heartworms. Often dogs with severe infections will also require the administration of anti-inflammatory doses of corticosteroids.
Elimination of Microfilariae
The most effective drugs for this purpose are the macrocyclic lactone (ML) anthelmintics, i.e.,milbemycin oxime, selamectin, moxidectin and ivermectin. These drugs are the active ingredients in commonly used heartworm preventives. Although their usage as microfilaricides has not been approved by the FDA, they are widely used by veterinarians as there are no approved microfilaricidal drugs currently available. It is recommended that microfilariae positive dogs being treated with these macrocyclic lactones be hospitalized for at least eight hours following treatment for observation of possible adverse reactions, including those resulting from rapid death of the microfilariae.
Circulating microfilariae usually can be eliminated within a few weeks by the administration of the ML-type drugs mentioned above. Today however, the most widely used microfilaricidal treatment is to simply administer ML preventives as usual, and the microfilariae will be cleared slowly over a period of about six to nine months.
Confirmation of Adulticide Efficacy
The goal of adulticide treatment is the elimination of all adult heartworms. However, clinical improvement in dogs treated for heartworm infection is possible without completely eliminating the adult heartworms. Heartworm antigen testing is the most reliable method of confirming the efficacy of adulticide therapy. If all the adult worms have been destroyed or very few survive, heartworm antigen should be undetectable after six months post-adulticide. Dogs that remain antigen positive at that time could be considered a potential candidate for repeat treatment with an adulticide only after a full review of each case. In some cases, an alternative is to not retreat with the arsenical but to continue with a preventive such as ivermectin which will gradually eliminate the remaining worms.
While treatment of canine heartworm disease is usually successful, prevention of the disease is much safer and more economical. There are a variety of options for preventing heartworm infection, including monthly tablets, chewables and topicals. These products are extremely effective and when administered properly on a timely schedule, heartworm infection can be prevented.
The American Heartworm Society is now recommending year-round prevention, even in seasonal areas. One reason for this is compliance - to make sure the medicine has been given properly by the pet owner. In addition, most monthly heartworm preventives have activity against intestinal parasites. Many of these same intestinal parasites that infect dogs can also infect people, with estimated infections occurring in three to six million people every year. So this added benefit of monthly deworming makes great sense.
Before starting a preventive program, all dogs that could possibly be infected with mature heartworms should be tested.
Macrocyclic Lactone (ML)
Macrocyclic lactones are highly effective parasiticides used in preventing heartworm infections. Their primary benefits lie in their safety and ease of administration of once- monthly doses. Each of the macrocyclic lactones can have additional intestinal parasite or external parasite activity, which could be the determining factor that a veterinarian uses to recommend a particular product for a certain region or an individual situation.
Ivermectin (Heartgard® & Heartgard® Plus by Merial, Iverhart® Plus & Iverhart MAX™ by Virbac and Tri-Heart® Plus by Schering-Plough) was the first in this family of drugs to be approved for preventing heartworm infection. An infection with larvae as long as two months prior to the initiation of ivermectin treatment will be blocked from development.
Milbemycin oxime (Interceptor® & Sentinel® by Novartis) has benefits, which are similar to ivermectin.
Selamectin (Revolution® by Pfizer) is applied topically to prevent heartworm disease.
Moxidectin (Advantage Multi™ by Bayer) is available in a topical formulation, in combination with a flea control product, imidacloprid.