- 1 Life cycle of Dirofilaria immitis
- 2 Pathophysiology of heartworm disease
- 3 Clinical signs
- 4 Electro cartography
- 5 Radiographic findings
- 6 Clinicopathological findings
- 7 Diagnosis of Dirofilariasis
- 8 Dirofilariasis: Treatment
- 9 Prevention of heartworm disease
Canine heart worm disease caused by Dirofilaria immitis is endemic in most temperate and tropical coastal zones of the world (United States. Japan and Australia especially). Heartworm disease is occasionally diagnosed in imported dogs in the United Kingdom. Affected animals are often between 4 and 7 years of age although the condition has been diagnosed in animals less than one year of age.
Life cycle of Dirofilaria immitis
When a mosquito bites an infected dog circulating microfilaria (first stage larvae) are ingested and develop into third stage (L3) larvae which migrate to the mouth parts of the mosquito. The third larval stage of the heartworm (Dirofilaria immitis) stage enters the subcutaneous tissues of the host via a bite from an infected mosquito. Young adult worms (L5 stage) reach the right side of the heart by 90-100 days postinfection. There is a prepatent time of approximately 6 months before microfilaria appear in the circulation. Occult infections occur where there is an absence of circulating microfilaria.
Pathophysiology of heartworm disease
Adult worms live most commonly in the right ventricle, main pulmonary artery and parenchymal pulmonary arteries. As the number of heart-worms increases they enter the right atrium and eventually migrate into the caudal vena cava. Large numbers of worms may obstruct the caudal vena cava and flow of blood to the right atrium (vena caval syndrome).
Adult worms initiate a parasite-host reaction which damages the pulmonary artery endothelium. Histologically this reaction is characterized by the proliferation of smooth muscle cells on the endothelial surface of the vessels. Circulating antibodies trap the microfilaria within the pulmonary arteries which results in pulmonary infarction and areas of consolidation around the affected vessels. Alveolar hypoxia increases pulmonary vascular resistance and leads to pulmonary hypertension. Pulmonary hypertension results in increased right ventricular afterload, right ventricular hypertrophy and eventually signs of right-sided heart failure (cor pulmonale).
The clinical signs of heartworm disease, once apparent, are usually severe and progress rapidly. Damage to the pulmonary arteries results in coughing, haemoptysis, dyspnoea and decreased exercise tolerance. There is a rapid loss of body condition and pulmonary hypertension leads to right-sided heart failure. Tricuspid valve murmurs may be heard due to mechanical interference with valvular function by the adult worms.
Some infected dogs show few if any clinical signs. Those with occult heartworm disease develop an allergic pneumonitis characterized by severe coughing and dyspnoea. Two conditions which may have an immune-mediated pathogenesis, eosinophilic granulomatosis and pulmonary infiltrates with eosinophilia (eosinophilic pneumonia), may also occur in association with heart-worm disease. Severe pulmonary artery disease may result in thromboembolic complications and thrombocytopenia especially after adulticide therapy.
Haemolysis and haemoglobinuria may occur when a large number of worms obstruct the caudal vena cava and result in fragmentation of red cells. Dogs with the caval syndrome become severely dyspnoeic and show signs of acute hypotension (tachycardia, pale mucous membranes and prolonged capillary refill time).
Electrocardiographs signs of right ventricular enlargement may be evident especially in dogs showing signs of right-sided heart failure.
Radiographic changes develop early during the course of heartworm infection. Typical abnormalities include right ventricular enlargement and a bulging pulmonary artery segement with enlarged lobar pulmonary arteries. As the disease progresses the peripheral pulmonary arteries become truncated and tortuous especially in the caudal lung lobes. Patchy alveolar densities may be apparent especially after adulticide therapy.
Eosinophilia often accompanied by basophilia are the most consistent haematological abnormalities, occurring once die young adult worms enter the circulation. A mild regenerative anaemia may be present and neutrophilia may occur following aduhicide treatment. Platelet numbers are often reduced as a result of increased consumption in response to endothelial damage. Liver enzymes may be increased especially if signs of right-sided cardiac failure are present; total plasma proteins may also be increased due to an increase in the globulin fraction. Proteinuria occurs in 20-30% of cases; some animals develop a glomerulonephropathy and nephrotic syndrome, and become hypoalbuminaemic.
Diagnosis of Dirofilariasis
The presence of microfilaria on a peripheral blood film implies the presence of adult worms. Dirofilaria immitis microfilaria should be differentiated from those of Dipetalonema reconditum and other Dipetalonema species which cause asymptomatic infections in dogs. This can be done by examining the acid phosphatase staining pattern of filter-treated micro-filariae. The blood of young dogs from endemic areas should be screened annually for the presence of microfilaria using a Knott’s test. With occult infections, no circulating microfilaria are present and diagnosis is dependent on the detection of appropriate radiographic abnormalities and the results of other serodiagnostic tests.
An indirect fluorescent antibodv test detecting antibodies to microfilarial antigens is useful in the diagnosis of occult heartworm disease. An ELISA test for detecting antibodies against adult worms has proved to be less satisfactory because of the high incidence of false positive results, although a negative ELISA result can be regarded as reliable evidence that occult heart-worm disease is not present. More recently, ELISA tests using monoclonal antibodies against circulating adult antigens have been developed which appear to be more sensitive and specific than tests which detect adult antibodies.
Thiacetarsamide (22 mg kg-1 body weight intravenously twice daily for two days) eliminates a high percentage of the adult heart worms (young female heart worms are often resistant). The second dose should be given not more than 10 hours after the first. Treatment with thiacetarsamide should be delayed in dogs with radiographic signs of severe pulmonary artery disease since such animals are at risk from developing thromboembolic complications and thrombocytopenia post-treatment. Toxic reactions to thiacetarsamide occasionally occur; these include anorexia, vomiting, depression, fever, diarrhoea and the presence of tubular casts in the urine. Adulticide treatment is usually followed 4-6 weeks later by the administration of a microfilaricide. The benefits of giving a microfilaricide three weeks before treatment with thiacetarsamide are questionable.
Levamisole has been used as an alternative adulticide drug but is less effective than thiacetarsamide. It is more effective as a microfilaricidal drug but toxic side effects (vomiting and CNS signs) are common.
The prophylactic use of aspirin to combat the potential thromboembolic complications has been questioned. Recent studies have shown that even doses of aspirin greater than 50 mg kg-1 in some dogs will not prevent thromboembolism or imimal hyperplasia associated with heart worm emboli.
Corticosteroids are indicated if there is evidence of an eosinophilic pulmonary infiltrate. Heparin has been recommended for dogs showing signs of chronic or low-grade disseminated intravascular coagulation (DIC).
Levamisole, milbemycin and ivermectin are available for use as microfilaricides (the last two can also be used prophylactically). The American Heartworm Society currently recommends that cither ivermectin (50 μg kg-1) or milbemycin (500 μg kg-1) be given 3-4 weeks after treatment with adulticide. Treatment of dogs with large numbers of microfilaria may lead to circulatory collapse due to rapid death of the microfilaria. Dogs should therefore be observed for 6-8 h after treatment. The use of ivermectin and milbemycin in collies and collie cross breeds has been associated with anaphylactic reactions and, in some cases, death; although both the microfilaricidal and the preventative doses of these drugs are reportedly safe in susceptible collies other drugs, for example levamisole (10 mg kg-1 day-1 for 7 days) have been recommended for this breed.
Prevention of heartworm disease
Chemoprophylaxis should be initiated 2-3 weeks after administration of a microfilaricide providing no microfilariae are detected in the blood; if microfilariae are still present microfilaricidal treatment should be repeated). In endemic areas, either ivermectin (6-12 μg kg-1) or milbemycin (500-999 μg kg-1) can be administered once a month. Young pups can be treated prophylactically from 6-8 weeks of age onwards. Although both drugs can be safely given to dogs which may already have circulating microfilariae, they only kill D. immitis larvae during the first six weeks of their development. Both drugs are also known to induce sterility in adult worms there-fore dogs greater than 6 months of age on monthly preventative treatment should be tested for antigen to detect occult infections which may develop within 6 months of starting monthly macrolide administration.