Chapter 152 Heartworm Disease
Heartworm disease is a common problem in many areas of the world, particularly in tropical and subtropical regions. The disease has been endemic along the southeastern Atlantic and Gulf coasts of the United States as far west as Texas for more than 50 years. Heartworm infection has spread north and west to most areas of the United States, but the prevalence is still low at high elevations and in most northern states. Endemic foci frequently occur in regions with otherwise low prevalence. It is difficult to eliminate heartworms from a region once they have been established; therefore, all dogs should be tested regularly, and veterinarians should be alert for dogs that emigrate from endemic regions.
ETIOLOGY and pathogenesis
Life Cycle in Dogs
• Female mosquitoes are the intermediate hosts and acquire the first-stage larvae (microfilaria) during feeding on infected dogs. Two molts then occur to produce the infective L3 stage.
• Larvae development within the mosquito to the third stage usually requires 1 to 2.5 weeks, depending on the ambient temperatures.
• Larvae development within the mosquito requires an average daily temperature of at least 57°F.
• The cooler the temperature, the longer the time required for L3 to develop. The warmer the temperature, the shorter the time required for L3 development.
• Third-stage larvae (L3) infect the dog via the bite wound created during the feeding of the mosquito. The next molt to the (L4) stage occurs within 2 weeks.
• Larvae migrate through the subcutaneous tissues and vascular adventitial tissues for approximately 100 days. During this time, two molts occur.
• Young adults (fifth-stage, or L5, larvae) enter the vascular system at 3 to 3.5 months post-infection.
• Young adult Dirofilaria immitis worms are in the small pulmonary arteries at 5 to 6 months post-infection.
• Microfilaria, when present, increase in concentration for the next 6 months, plateau for several months, and then decrease if further infection does not occur.
• Microfilaremia does not occur in 10% to 67% of all heartworm infections and many of these are the result of an immune-mediated host reaction. Microfilaria-specific antibody-mediated, occult infections occur in the presence of persistent host antibody excess. Antibody-dependent leukocyte adhesion entraps microfilaria in the pulmonary microcirculation.
• In most endemic regions, the incidence of occult infections, other than drug induced, is approximately 20% to 25% of all heartworm infections.
• Microfilaria-leukocyte (neutrophils and eosinophils) complexes are engulfed by phagocyte cells of the mononuclear phagocyte system, resulting in granulomatous inflammation.
• Predominately eosinophilic inflammation, with minimal granulomatous inflammation, produces allergic pneumonitis.
• Other causes of occult mature infections include single sex infections and one high-dose (>200 mcg/kg) ivermectin administration.
Life Cycle in Cats
• The cat is relatively resistant to infection, requiring a greater L3 inoculum. Some cats appear to be immune. Consequently, the infection rate in unprotected cats is likely to range from one-fifth to one-tenth that of unprotected dogs in an endemic area. Some mosquito species, as intermediate hosts, do not like to feed on cats. The numbers of infective larvae that mature are less than in dogs, and the pre-patent period is usually one to two months longer.
Epizootiology
Prevalence
• Infection rates in unprotected dogs approach 50% along the Atlantic and Gulf coasts as far inland as 150 miles.
Pathogenesis
Worm Location
• Until the adult worm burden exceeds 50 in a 25-kg dog, nearly all worms are located in the pulmonary arteries.
Response to Live Worms in Dogs
• Even if infection is identified 7 months post-infection with L3, the L5 have already been in the pulmonary arteries for a few months and some pathology has occurred.
• Pulmonary arterial endothelial damage and subsequent myointimal proliferation most often affects the caudal and intermediate lung lobes, that is, those receiving the highest blood flow.
• Pulmonary lobar arterial enlargement, tortuosity, and obstruction of smaller branches begin within a few weeks of worm arrival.
• Intrapulmonary blood flow is obstructed as the disease progresses, and blood is diverted to less severely affected lobes.
• Small downstream arterioles become damaged and leak plasma and inflammatory cells into the surrounding lung parenchyma. This causes interstitial and alveolar lung infiltrates and granulomatous inflammation.
• Pulmonary arterial obstruction and lung inflammation cause fever, coughing, dyspnea, hemoptysis, leukocytosis, and thrombocytopenia.
• Pathology is more severe and accelerated in active dogs, relative to inactive dogs, for any given worm burden.
Response to Live Worms in Cats
The response of cats and ferrets is similar to that of dogs. However, there is more arterial muscular hypertrophy. In cats, parenchymal pathology differs from that of dogs in that there is more alveolar Type II hyperplasia. This creates a barrier to oxygen diffusion that is more severe than in the dog. Mortality in cats and ferrets is higher than in dogs.
Response to Dead Worms
• The most severe disease is seen in response to dead worm fragments that are swept into small arterioles.
• Worm death may be spontaneous or from melarsamine dihydrochloride (Immiticide, Merial) administration.
• Pulmonary vascular compliance and blood flow become impaired to varying degrees and severe arterial disease results in pulmonary hypertension, increased right ventricular afterload, and eventually right-sided CHF.
CLINICAL SIGNS
Clinical Signs in Dogs
• Exercise intolerance, coughing, dyspnea, and respiratory crackles occur in dogs with moderate and advanced heartworm disease.
• Hemoptysis occurs in severe disease and is caused by pulmonary thromboembolism. It can be seen before, but occurs more often after adulticide treatment.
• Acute dyspnea and increased pulmonary alveolar densities may develop secondary to spontaneous worm death.
Nephrotic Syndrome
This syndrome occasionally occurs as the result of severe glomerular disease manifested as amyloidosis or immune complex glomerulonephritis (see Chapter 77). Manifestations can include proteinuria, hypoalbuminemia, hypercholesterolemia, azotemia, ascites and occasionally peripheral edema.
Clinical Signs in Cats
• Respiratory signs
• Coughing in cats usually is associated with allergic or parasitic lung diseases; heartworm disease represents one cause.
• Asthmatic signs are a common manifestation and often occur about 3 to 4 months post-infection. A strong antibody response at this time may destroy the developing larvae. If not, then a period of quiescence occurs only to have asthma-like signs reoccur in some cats 7 to 8 months post-infection.
• Vomiting (intermittent) is a common sign (approximately 20%) and occurs sporadically. It often is not associated with eating, but vomitus may include food. Mucus and bile are often the major components of the vomitus. Vomiting and coughing in the same cat should increase the index of suspicion.
• Sudden death related to spontaneous worm death and thromboembolism is more common in cats than in dogs.
DIAGNOSIS
The diagnosis of heartworm infection is usually based on a positive immunodiagnostic test result. Microfilaria in the peripheral blood can be detected in some dogs by a direct smear or a concentration test (modified Knott test or milipore filter [Difil, Evsco]) in dogs with or without clinical or radiographic findings consistent with the disease. Testing puppies younger than 6 months of age is not indicated.
History in Dogs
• The history in dogs with heartworm infection varies considerably. Many infections are discovered in asymptomatic dogs by immunodiagnostic screening.
• Some dogs are totally without signs; others have unexplained tachypnea, exercise intolerance, or cough.
History in Cats
• The history in cats varies considerably. Most infected cats have not been receiving prophylaxis. Lethargy and decreased appetite may be reported by the owners.
Laboratory Studies
• Standard laboratory studies vary, depending on the patient’s age, clinical signs, and preference of individual clinicians.
• The minimum pretreatment database for all dogs suspected of having heartworm infection includes packed cell volume (PCV), blood urea nitrogen (BUN), urine specific gravity, urine protein determination, and heartworm antigen test.
• We recommend thoracic radiographs because they reveal more about disease severity than any other single test.
• Cardiac ultrasound and fecal studies for lungworms are useful for the differential diagnosis of heartworm infection, feline asthma, cardiomyopathy, bronchitis, pulmonary fibrosis, and lung parasites.
• A tracheal or bronchial wash may be useful for detecting lung parasitic lesions such as those produced by Filaroides spp.
Immunodiagnostic Tests
• These tests must be performed in strict compliance with the manufacturer’s instructions. False-positive test results are usually the result of poor technique.
• The absence of circulating microfilaria in infected dogs is common (10-50%), and microfilaremia is rarely detected in infected cats.
• In some highly endemic regions, such as Hawaii, as many as 50% of infected dogs lack circulating microfilaria.
Heartworm Antigen Tests
• Positive antigen test results are the result of the presence of adult female worms. The antigen is associated with the worms’ reproductive tracts.
• The particular test employed is influenced by the number of tests performed daily, the amount of whole blood or serum required, and the speed of results.
• Some tests, such as Dirochek (Synbiotics), are very efficient for testing multiple samples simultaneously. Either serum or plasma is required.
• Most immunodiagnostic tests (ELISA based) are semiquantitative because rapid and strong positive test results are thought to be related to higher antigen concentrations.
• Low antigenemia indicates a low adult heartworm burden and reduced risk of post-adulticide thromboembolic complications.
• Large quantities of antigen released from dead worms results in a quick, strong test reaction but does not necessarily mean that the worm burden is high.
• In cats, antigen tests are specific but are less sensitive, and false-negative results are common. False-negative test results are explained by low worm burden, male-only infections, and infection with young (<7 month old) female worms that have immature reproductive tracts. When adult worm infection is present in cats, the antigen test is usually positive if there are 3 or more mature female worms.
Heartworm Antibody Tests
• Asthma-like signs due to developing larvae often occur months before the antigen test can become positive.
• A strongly positive test result indicates preadult infection, live adult infection, or persistent (at least 6 months) antibodies after adult heartworm death. An antigen test and perhaps cardiac ultrasound are needed to confirm the diagnosis.
