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. Even as immature adults, the worms mate and the females release their offspring (microfilariae), pronounced: (micro fil ar ee), into the blood stream. The time elapsed from when the larvae enter the dog until the minute offspring can be detected in the blood (pre-patent period) is about six to seven months. 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 be at least 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 is usually high, as the number of worms in dogs can range from one to approximately 250. 

Microfilaremia, the presence of heartworm offspring in the blood of the host, is relatively common in dogs. 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 will 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). In an occasional dog with a large number of heartworms, the worms may not only be in the heart but also the caudal vena cava (large primary vein of the lower body) between the liver and the heart. This syndrome (Vena Cava or Liver Failure Syndrome) is characterized by sudden collapse and even death within two to three days if they are not removed surgically. 

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, and dog population factors that allow a higher incidence of heartworm infection. Regions where heartworm disease is common have infections diagnosed 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 such regions should be considered at risk, placed on prevention programs and frequently examined by a veterinarian. 

Clinical Signs 

Heartworm disease may cause combinations of medical problems within the same dog including dysfunction of the lungs, heart, liver and kidneys. The disease may have an acute onset but usually begins with slow barely detectable signs resulting from a chronic infection with a combination of physiologic changes. Dogs with a low number of adult worms in the body that are not exercised strenuously may never have overt signs of heartworm disease. The heart and lungs are the major organs affected by heartworms in dogs with varying degrees of clinical signs. 

Clinical Signs Associated with Canine Heartworm Disease

Diagnosis 

The diagnosis of canine heartworm disease depends upon the following: an accurate patient history, the recognition of varied clinical signs, and the use of several diagnostic procedures that may include X-ray (radiology), angiography and ultrasound (echocardiography), blood (serological) testing, microfilarial detection and differentiation, clinical laboratory tests and, in the worst case scenario, examination after death (necropsy). 

Serology 

Diagnostic tests for the study of antibodies and antigens in blood serum. 

Antigen Tests 

Antigen tests detect specific antigens from 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 they generally do not detect infections of less than five months duration. 

Antibody Tests 

Since the late 1970's and early 1980's, several canine heartworm antibody tests were developed and introduced, but such tests for dogs have been largely replaced by the more useful antigen tests. Necropsy (Autopsy: 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. 

Physical Examination 

A physical examination may appear to be perfectly normal in heartworm-infected dogs with mild disease. Severely affected dogs, however, may demonstrate right-sided heart failure. Labored breathing or crackles may be heard in the lungs due to vascular clots and elevated pressure. A history of chronic cough and exercise intolerance 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 thromboembolic (clots) 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 atypical 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. 

Radiology (X-ray) 

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 and worms may be visualized as filing defects on the angiogram. 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. 

Microfilarial Detection and Differentiation T

he identification of the offspring (microfilaria) of heartworms (Dirofilaria immitis) from a blood sample indicates infection with adult heartworms. Identifying such 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 their absence in a sample. If they are present, it is a definitive diagnosis for the presence of adult heartworms. 

One other parasite infection of dogs is capable of producing circulating microfilariae, detected on examination of the blood. Acanthocheilonema (dipetalonema) reconditum (a genus of filarial nematodes) is a non-disease causing parasite that localizes 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 ability to move spontaneously. 

Treatments 

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 are 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 anything previously available. It is administered by deep intramuscular injection into the lumbar muscles. With this drug, veterinarians have the advantage over its predecessor of minimizing post-adulticide complications in dogs with high heartworm numbers. In addition the drug itself is less toxic to dogs than the drug that was its predecessor. For complete information on the classification and treatment for heartworm infected dogs using this product, consult your veterinarian. 

Post-Adulticide Complications 

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). These patients require both the administration of anti-inflammatory doses of corticosteroids and a strict reduction in exercise. 

Elimination of Microfilariae 

The most effective drugs for this purpose are the macrocyclic lactone (ML) anthelmintics, i.e.,milbemycin oxime, selamectin, moxidectin and high doses of ivermectin. These drugs are the active ingredients in the commonly used heartworm preventives. Although their usage as microfilaricides has not been approved by the FDA, they are widely used as such because there are no approved microfilaricidal drugs currently available. It is recommended that microfilariae positive dogs being treated with these drugs be hospitalized for at least eight hours following treatment for observation of possible adverse reactions 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 by four 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. 

Preventives 

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 daily and monthly tablets and chewables, and monthly topicals. All of these methods are extremely effective and when the drugs are administered properly on a timely schedule, heartworm infection can be completely prevented. 

Due to the temperature dependent nature of the heartworm life cycle, use of heartworm preventives may be considered seasonal in some of the northernmost parts of the United States. The heartworm preventive season which veterinarians will employ depends upon their knowledge of the heartworm life cycle, the transmission pattern in their region, and the individual client’s activity profile. Before starting a preventive program, all dogs that could possibly be infected with mature heartworms should be tested. 

Diethylcarbamazine 

Diethylcarbamazine requires daily oral administration throughout the heartworm season and two months after in order to be effective in preventing heartworm infection. The drug is available in several formulations and has a history of being reliable, safe, and efficacious. The primary drawback to the usage of this drug is the necessity to make sure the dog is microfilariae free and the strict client compliance to its daily administration in order for it to be effective. 

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 being either monthly doses or a six month injection administered by a veterinarian. Each of the macrocyclic lactones can have additional intestinal parasite or external parasite activity, or an additive incorporated to do such, which could be the determining factor that a veterinarian uses to recommend a particular product for a certain region or an individual situation. 

Ivermectin 

Ivermectin (Heartgard®, Heartgard Plus®, Merial, IverhartTM Plus, Virbac) was the first in this family of drugs to be approved for use in preventing heartworm infection. Infection with larvae as long as two months prior to initiation of ivermectin treatment will be blocked from development. Milbemycin Milbemycin oxime (Interceptor®, Sentinel, Novartis) has benefits, which are similar to ivermectin. Selamectin Selamectin (Revolution®, Pfizer) is applied topically to prevent heartworm disease.