MistyMeanor
December, 29th, 2003, 10:01 PM
(Dirofilariasis)
Dirofilaria immitis has a worldwide distribution and infects a wide variety of species (dog, cat, ferret, fox, wolf, sea lion, horse). The distribution is influenced by a reservoir population of animals (dogs usually) in which the life cycle is completed and microfilaremia occurs and by a mosquito vector in which the early larval stages develop. Different mosquito feeding patterns influence the areas and species of animal infected. For transmission to cats, the mosquito must first feed on a dog and then, after adequate warm environmental exposure, feed on a cat.
Life Cycle and Pathogenesis: Adult female (~27 cm long) and male (~17 cm long) heartworms normally reside in the pulmonary arteries and right ventricles without significantly interfering with blood supply. Microfilariae (~315 µm long and 6-7 µm wide) are discharged into the bloodstream and survive 1-3 yr. The number of circulating microfilariae in dogs is increased in warm ambient temperature, after eating, and late at night. The microfilariae are ingested by a mosquito during feeding. Within the mosquito, the larvae (L1) migrate to the stomach and then to the mouthparts (L3) during development. Adequate exposure to warm temperatures must occur during the relatively short life span (1 mo) of the mosquito, and the rate of development of the larvae, which varies depending on the temperature, can be as short as 8 days at 30°C or as long as 28 days at 1-8°C. When the mosquito feeds again, the infective L3 are deposited on the skin of the animal and enter through the bite wound. A single mosquito can transmit up to 10-12 L3.
Canine heart infected with Dirofilaria immitishttp://www.merckvetmanual.com/mvm/img/bgraph/cirhw02.jpg*courtesy of Merial
Dirofilaria immitis microfilaria, canine blood smearhttp://www.merckvetmanual.com/mvm/img/bgraph/cirhw01.jpg*courtesy of Merial
The L3 stages molt and migrate to the pulmonary arteries ~100 days after infection, during which time they develop to L5 (1-2 cm long). The L5 are found mainly in the caudal distal pulmonary arteries; over the next 2-3 mo, they develop to mature adult heartworms and migrate back toward the right ventricle. If both sexes of adults are present, microfilariae are produced 6-7 mo after the animal was infected with L3.
Adult heartworms can live 3-5 yr. Although an endarteritis develops, embolization and vascular occlusion is rare when the worms are alive. The severity of the pathology is influenced not only by the number of worms but also by the shear stress of high blood flow associated with exercise. Severe pathology can occur in athletic dogs with low worm burdens. The classically described cor pulmonale syndrome is seen only in dogs with an exercise pattern forcing right ventricular hypertrophy from increased cardiac outputs and increased pulmonary vascular resistance.
In endemic areas, the average worm burden is ~15 worms in dogs and 1-3 worms in cats. In cats and ferrets, respiratory failure can be associated with infection with a single worm. High worm burdens can be found in dogs with minimal cardiac changes if the dog is sedentary. High worm burdens (>75) also can be demonstrated in acute postcaval syndromes and chronic ascites from tricuspid valve dysfunction. Because many animals develop increased resistance from repeated exposure to L3 over time, high worm burdens are most likely to occur in dogs that have not been exposed previously to any mosquitoes with L3 and are then bitten by many mosquitoes over a 3-mo period.
Clinical Findings: The clinical signs of heartworm disease depend on the stage of the life cycle, the severity of infection, and the host response to infection. The initial arrival of L5 in the small vessels of the lungs is associated with an intense eosinophilic reaction and a diffuse radiographic pattern. The animal may begin to cough 2-3 mo before microfilariae are produced and antigen begins to circulate. Clinical diagnosis at this early stage of disease is difficult, especially in cats and ferrets. An active dog may develop exercise intolerance because of decreased cardiac output. Nonspecific signs of weight loss, fever, and dyspnea can occur in severe disease. Ascites may develop in right-sided heart failure from cor pulmonale or from mechanical dysfunction of the tricuspid valve as in postcaval syndromes. Many dogs and cats are asymptomatic, although subclinical disease may decrease their quality of life. In ~10% of dogs with heartworms, an intense immune reaction by the host clears the microfilariae; severe pulmonary reactions are seen, and coughing is the primary clinical sign. No pathology has been associated with circulating microfilariae.
Clinical signs in cats are primarily intermittent respiratory disease (coughing or dyspnea) or sporadic vomiting not associated with eating. The respiratory signs mimic those of bronchial asthma and initially respond to corticosteroid administration. Cats may present with acute dyspnea or collapse with no previous respiratory signs. In these cases, which are often confused with bronchial asthma, acute death is common. Other clinical signs associated with acute disease in cats include convulsions, vomiting and diarrhea, blindness, tachycardia, and syncope. Initial respiratory signs often occur 4-6 mo after the peak mosquito season. Nonspecific signs of weight loss and anorexia without respiratory or GI signs occur in some cats. Right-sided heart failure is rare in cats and is usually associated with a high worm burden (more than seven worms).
Diagnosis: Diagnostic testing for dirofilariasis includes a complete blood count, Knott's test, thoracic radiographs, fecal examination, ECG, immunofluorescent antibody (microfilariae), ELISA-adult antibody (cats only), ELISA-adult antigen, tracheal wash, and arteriogram.
Concentration techniques (modified Knott's and filter tests) successfully demonstrate microfilariae in a blood sample in ~60% of dogs and <10% of cats with heartworms. Because microfilariae survive after adult worms have died, a small percentage of dogs can have microfilaremia but no adults in the heart. In addition, puppies born to *****es with a high microfilariae count can have a transient microfilaremia that cannot become an adult infection. Microfilariae of D immitis should be differentiated from those of the nonpathogenic filarids D repens and Dipetalonema reconditum on the basis of morphology and staining characteristics with acid phosphatase.
Occult infections, in which the animal is amicrofilaremic, can be seen when the infection is due to immature (<6 mo old) worms, a single worm, or worms of all the same sex. Occult infections can also result from host immunologic reactions to microfilariae or from iatrogenic infection. Monthly preventive medications will induce embryo stasis in the female heartworm, and occult infections have been demonstrated in most heartworm-positive dogs after many months of medication. Therefore, antigen testing is necessary to determine the heartworm status of a dog that has been on monthly preventive medication.
Circulating adult antigen can be detected before or after the initial microfilaremia. The detection of circulating antigen is based on a laboratory-derived antibody binding to an adequate amount of circulating heartworm antigen. Although the glycoprotein detected by most assays is found throughout the parasite, the major source of circulating antigen is the reproductive tract of the mature female heartworm. The maturity and number of females influences the amount of antigen. Animals with immature worms and low worm burdens (especially cats) will be antigen negative—even when worms are present in the pulmonary arteries and clinical signs are present.
Thoracic radiographs can be a screening tool for dogs and cats with clinical signs suggestive of heartworm disease. In dogs, the pulmonary arteries can be tortuous and enlarged, with an enlarged pulmonary arterial segment at the 1 o'clock position on a ventrodorsal view. Right ventricular enlargement may not be noted if the hypertrophy has not been induced by physical activity or severe vascular lesions. The pulmonary parenchymal changes can be diffuse in early L5 infection but also can become granulomatous in chronic severe infections. In cats, cardiac changes are rare, and even an enlarged pulmonary arterial segment on the ventrodorsal view is not visible beyond the cardiac shadow. Enlarged caudal pulmonary arteries are the most consistent lesion in cats with heartworms. Severe lung parenchymal changes may obscure the vascular pattern. A fluid density lung lobe is associated with acute signs in cats and may be confused with a consolidating pneumonia.
Feline heartworm disease, ventrodorsal projection.http://www.merckvetmanual.com/mvm/img/bgraph/cirhw06.jpg*Courtesy of Merial
Feline heartworm disease, lateral projectionhttp://www.merckvetmanual.com/mvm/img/bgraph/cirhw05.jpg*Courtesy of Merial
Severe radiographic lesions of canine heartworm disease in a 6-yr-old female Boxer, ventrodorsal projection. Note the moderate to severe right-sided cardiomegaly producing a reverse D appearance and the bulge in the region of the main pulmonary artery.http://www.merckvetmanual.com/mvm/img/bgraph/cirhw08.jpg*Courtesy of the University Of Florida
Severe radiographic lesions of canine heartworm disease in a 6-yr-old female Boxer, lateral projection. Note dorsal displacement of the apex of the heart, severely enlarged and tortuous pulmonary arteries and moderately increased bronchointerstitial pulmohttp://www.merckvetmanual.com/mvm/img/bgraph/cirhw07.jpg*Courtesy of the University Of Florida
Mild canine heartworm disease in a 5-yr-old male German Shepherd Dog, ventrodorsal projection. Note enlargement of the right caudal lobar pulmonary artery (greater than the width of the 9th rib) and the small bulge in the region of the main pulmonary artehttp://www.merckvetmanual.com/mvm/img/bgraph/cirhw04.jpg*Courtesy Of University Of Florida
Mild radiographic lesions of canine heartworm disease in a 5-yr-old male German Shepherd Dog, lateral projection.http://www.merckvetmanual.com/mvm/img/bgraph/cirhw03.jpg*Courtesy Of the University of Florida
Echocardiograms are diagnostic, with typical “double parallel” white lines noted in the pulmonary arteries or right ventricles of dogs or cats. Echocardiograms are especially useful in diagnosis of postcaval syndromes and ascitic conditions associated with heartworm disease. The typical right axis deviation and deep S waves are seen on an ECG only if right ventricular hypertrophy is significant.
Tracheal cytology is usually nonspecific and is rarely positive for bacteria in either dogs or cats. An eosinophilic cytology is usually a stage-specific reaction.
Complete necropsy with thorough examination of the distal pulmonary arteries may be required to demonstrate heartworms in cats.
Treatment in Dogs: Steps to manage treatment of dogs infected with heartworms consist of the following: 1) diagnostic evaluations (before therapy) to determine subclinical disease, especially of the liver and kidneys; 2) adulticidal therapy to eliminate mature worms; 3) a rest period of 4-6 wk to allow the dog to recover from the lung injury associated with worm death; 4) microfilaricidal therapy if required; 5) a test for microfilariae to determine success of microfilaricidal therapy; 6) an antigen test to determine success of adulticidal therapy; and 7) preventive medication.
Use of aspirin, aspirin and dipyridamole, serotonin antagonist, short-acting heparin, and high-dose corticosteroids to decrease the clinical significance of heartworm lesions has been unsuccessful. Abnormal pressor vessel dynamics and pulmonary parenchymal damage may contribute to the failure of these agents. Because of the pressure overload of heartworm disease, treatment with digitoxin is usually not recommended. An angiotensin-converting enzyme inhibitor may be used in severe right ventricle hypertrophy. The interstitial edema associated with acute signs of worm death is not aided by diuretic therapy.
Adulticidal therapy eliminates the adult heartworms and allows repair of damage where fibrosis has not occurred. Death of the worms (either spontaneous or induced) in both dogs and cats is associated with severe parenchymal lung damage, and limitation of exercise is critical after adulticidal therapy. Platelet consumption and coagulopathies develop in most dogs 2-3 wk after adulticide treatment. Thiacetarsamide (2.2 mg/kg, four IV doses over 2 days) will kill most male and some female worms but has poor efficacy against immature and young female worms. Arsenical toxicity cannot be predicted in clinically normal dogs based on laboratory tests. Melarsomine (2.5 mg/kg, two IM doses over 24 hr) has improved efficacy (>95% kill). However, increased worm death can cause serious complications in dogs with high worm burdens. One IM dose followed 1 mo later by two IM doses is a safer alternative in dogs with severe heartworm disease or high antigen loads, which suggest large worm burdens. No agent has been successful as a pretreatment in decreasing the complication rate. Dogs should be rested for 4-6 wk.
Complications of worm death often include impaired pulmonary function and vessel damage, which may initiate disseminated intravascular coagulation (DIC). A platelet count <100,000/µL is not uncommon, but an activated clotting time should be performed to determine if DIC is present (if so, the prognosis is poor). Dyspnea after adulticidal therapy is an emergency. Nasal oxygen and an immediate-acting glucocorticoid at doses used in shock are needed to provide adequate oxygenation and decrease the acute lung injury. Many dogs will respond within 24 hr. Because of the fragile nature of the capillary beds of the lungs, no exercise or stress should be allowed during this time.
Currently, there are no FDA-approved drugs for microfilaricidal therapy. However, ivermectin at 50 µg/kg or milbemycin at the preventive dose is effective within 2-3 wk. Most microfilariae are killed quickly, and reactions, which usually occur within 1 hr of administration, are associated with high microfilariae counts in small dogs. Concentration techniques should be used to assess microfilarial status.
Antigen assays 12-16 wk after successful adulticidal therapy should be negative. However, low worm burdens and immature worms can still be present with a negative antigen test. Positive antigen tests should be rechecked in 1 mo before initiating a second adulticidal regimen.
Treatment in Cats: After the diagnosis has been confirmed, the therapeutic options must be carefully considered. Because feline heartworm disease can result in no signs or signs such as chronic vomiting or intermittent respiratory signs, owners often think the disease is less severe than it is. Without treatment, acute complications and death occur in a small percentage of cats. However, in asymptomatic cats, this risk appears to be small compared with the potential complications of adulticidal therapy. In addition, the life span of the adult heartworm is shorter in cats than in dogs, and spontaneous recovery is possible. However, adulticidal therapy has been used safely in cats and should be considered for cats with recurrent dyspnea that is life-threatening or with clinical signs that are unacceptable to the owner.
Treatment of feline heartworm disease with thiacetarsamide sodium (2.2 mg/kg, given slowly IV, b.i.d., for 2 days) is tolerated by cats without immediate complications of hepatotoxicity or renal toxicity. However, pulmonary edema has been seen, and oxygen therapy and corticosteroids should be considered if dyspnea or cyanosis occurs. The use of ketamine as a sedative to aid in careful administration of thiacetarsamide is recommended in active cats.
In symptomatic cats, clinical signs tend to improve after therapy. Chronically anorexic cats may require hyperalimentation. Although the presence of circulating microfilariae is uncommon, dithiazanine iodide and levamisole hydrochloride have both been used successfully as microfilaricides.
Complications after therapy are more severe in cats than in dogs and are usually related to embolization. Sudden death from embolization can occur, especially within the first 10 days after adulticidal therapy. Embolization can result in severe lung infarction, hemoptysis, and dyspnea. Severe thrombocytopenia has not been noted. Based on the assumption that heartworm mass is related to antigen load, a cat with a “strong positive” antigen test would be more likely to develop complications after adulticidal therapy than a cat that has a low worm burden and is antigen negative or “weakly positive.”
Embolization most often affects the caudal lung lobes, and thoracic radiographs may demonstrate a lung lobe with increased density. Oxygen therapy is indicated if hypoxemia or dyspnea occurs. High doses of corticosteroids (eg, prednisolone at 1-2 mg/lb, t.i.d.) with careful IV fluid therapy will often support the cat through the crisis. However, the routine use of corticosteroids before or after thiacetarsamide administration is not recommended in cats.
There is evidence that aspirin may inhibit prostaglandin formation and thus increase leukotriene production in the lungs; the result would be bronchospasm and pulmonary hypertension. Aspirin is not currently recommended for use in feline heartworm disease, and it may be contraindicated when acute embolization occurs.
The peracute nature of the postadulticidal reaction dictates that the cat be under constant surveillance, especially during the first 2 wk. The clinical and radiographic signs of acute embolization can resolve over 1-2 days. However, death can be so rapid that it occurs before therapy can be instituted. In asymptomatic cats, the risk and severity of the postadulticidal reaction and the resultant embolization is probably greater than that from the spontaneous death of heartworms.
Unfortunately, the efficacy of thiacetarsamide cannot often be evaluated in cats because of the occult nature of the disease. However, in some cats that have had microfilariae, repeated attempts to eliminate microfilariae have failed and repeated adulticidal therapy has been required. If a cat was antigen positive before therapy, the antigen test should be negative 12 wk after adulticide therapy; a positive test would indicate that adult heartworms are still present.
Melarsomine has not been evaluated in cats for routine clinical use.
When adulticidal therapy is not done, such as in cats with intermittent clinical signs, owners should be educated about the nature of the peracute signs of embolization. An emergency dose of prednisolone (5 mg/kg) should be dispensed to be administered PO if collapse or dyspnea are noted. The onset of acute respiratory signs in a cat with heartworm disease is an emergency, and immediate treatment is needed. The radiographic signs of severe lung pathology should not be interpreted as consolidation or pneumonia. Oxygen therapy, cage rest, small volumes of IV fluids, and injectable prednisolone have resulted in clinical improvement and resolution of radiographic signs within 24 hr in some cats with life-threatening dyspnea and collapse.
Prevention: In dogs, diethylcarbamazine (DEC), ivermectin, and milbemycin oxime are orally administered preventives. Dogs >6 mo old should test negative for microfilariae and antigen assay before preventive medications are administered. Dogs <6 mo old can be started on preventive medication but should be tested for microfilariae and antigen 6 mo to1 yr later. DEC is administered daily from 1 mo before to 2 mo after the mosquito season. Ivermectin and milbemycin oxime are administered once monthly from 1 mo after the onset to 1 mo after the end of the mosquito season. In temperate areas, preventive medications can be used year round. Dogs on monthly preventive should have antigen assays to determine their heartworm status. Preventive medications should not be administered to dogs that test positive for microfilariae.
In cats in areas highly endemic for heartworm disease in dogs, the incidence of heartworms (20%) would indicate that preventives are warranted. In nonendemic areas, the incidence is not sufficient to warrant preventive therapy in cats. In endemic areas, it is suggested that preventive medication (ivermectin at 25 µg/kg or milbemycin at 50 µg/kg, administered PO once a month) be administered at 4-6 wk of age and continued for the life of the cat. Although incidence of heartworm disease is low in many areas and heartworm disease can be self-limiting in many cats, the high rate of complications associated with feline heartworm disease and the potential to initiate inflammatory lung disease and predispose to bronchial asthma may prove to be adequate indications for preventive medications.
*Information from Merck Veterinary Manual
Dirofilaria immitis has a worldwide distribution and infects a wide variety of species (dog, cat, ferret, fox, wolf, sea lion, horse). The distribution is influenced by a reservoir population of animals (dogs usually) in which the life cycle is completed and microfilaremia occurs and by a mosquito vector in which the early larval stages develop. Different mosquito feeding patterns influence the areas and species of animal infected. For transmission to cats, the mosquito must first feed on a dog and then, after adequate warm environmental exposure, feed on a cat.
Life Cycle and Pathogenesis: Adult female (~27 cm long) and male (~17 cm long) heartworms normally reside in the pulmonary arteries and right ventricles without significantly interfering with blood supply. Microfilariae (~315 µm long and 6-7 µm wide) are discharged into the bloodstream and survive 1-3 yr. The number of circulating microfilariae in dogs is increased in warm ambient temperature, after eating, and late at night. The microfilariae are ingested by a mosquito during feeding. Within the mosquito, the larvae (L1) migrate to the stomach and then to the mouthparts (L3) during development. Adequate exposure to warm temperatures must occur during the relatively short life span (1 mo) of the mosquito, and the rate of development of the larvae, which varies depending on the temperature, can be as short as 8 days at 30°C or as long as 28 days at 1-8°C. When the mosquito feeds again, the infective L3 are deposited on the skin of the animal and enter through the bite wound. A single mosquito can transmit up to 10-12 L3.
Canine heart infected with Dirofilaria immitishttp://www.merckvetmanual.com/mvm/img/bgraph/cirhw02.jpg*courtesy of Merial
Dirofilaria immitis microfilaria, canine blood smearhttp://www.merckvetmanual.com/mvm/img/bgraph/cirhw01.jpg*courtesy of Merial
The L3 stages molt and migrate to the pulmonary arteries ~100 days after infection, during which time they develop to L5 (1-2 cm long). The L5 are found mainly in the caudal distal pulmonary arteries; over the next 2-3 mo, they develop to mature adult heartworms and migrate back toward the right ventricle. If both sexes of adults are present, microfilariae are produced 6-7 mo after the animal was infected with L3.
Adult heartworms can live 3-5 yr. Although an endarteritis develops, embolization and vascular occlusion is rare when the worms are alive. The severity of the pathology is influenced not only by the number of worms but also by the shear stress of high blood flow associated with exercise. Severe pathology can occur in athletic dogs with low worm burdens. The classically described cor pulmonale syndrome is seen only in dogs with an exercise pattern forcing right ventricular hypertrophy from increased cardiac outputs and increased pulmonary vascular resistance.
In endemic areas, the average worm burden is ~15 worms in dogs and 1-3 worms in cats. In cats and ferrets, respiratory failure can be associated with infection with a single worm. High worm burdens can be found in dogs with minimal cardiac changes if the dog is sedentary. High worm burdens (>75) also can be demonstrated in acute postcaval syndromes and chronic ascites from tricuspid valve dysfunction. Because many animals develop increased resistance from repeated exposure to L3 over time, high worm burdens are most likely to occur in dogs that have not been exposed previously to any mosquitoes with L3 and are then bitten by many mosquitoes over a 3-mo period.
Clinical Findings: The clinical signs of heartworm disease depend on the stage of the life cycle, the severity of infection, and the host response to infection. The initial arrival of L5 in the small vessels of the lungs is associated with an intense eosinophilic reaction and a diffuse radiographic pattern. The animal may begin to cough 2-3 mo before microfilariae are produced and antigen begins to circulate. Clinical diagnosis at this early stage of disease is difficult, especially in cats and ferrets. An active dog may develop exercise intolerance because of decreased cardiac output. Nonspecific signs of weight loss, fever, and dyspnea can occur in severe disease. Ascites may develop in right-sided heart failure from cor pulmonale or from mechanical dysfunction of the tricuspid valve as in postcaval syndromes. Many dogs and cats are asymptomatic, although subclinical disease may decrease their quality of life. In ~10% of dogs with heartworms, an intense immune reaction by the host clears the microfilariae; severe pulmonary reactions are seen, and coughing is the primary clinical sign. No pathology has been associated with circulating microfilariae.
Clinical signs in cats are primarily intermittent respiratory disease (coughing or dyspnea) or sporadic vomiting not associated with eating. The respiratory signs mimic those of bronchial asthma and initially respond to corticosteroid administration. Cats may present with acute dyspnea or collapse with no previous respiratory signs. In these cases, which are often confused with bronchial asthma, acute death is common. Other clinical signs associated with acute disease in cats include convulsions, vomiting and diarrhea, blindness, tachycardia, and syncope. Initial respiratory signs often occur 4-6 mo after the peak mosquito season. Nonspecific signs of weight loss and anorexia without respiratory or GI signs occur in some cats. Right-sided heart failure is rare in cats and is usually associated with a high worm burden (more than seven worms).
Diagnosis: Diagnostic testing for dirofilariasis includes a complete blood count, Knott's test, thoracic radiographs, fecal examination, ECG, immunofluorescent antibody (microfilariae), ELISA-adult antibody (cats only), ELISA-adult antigen, tracheal wash, and arteriogram.
Concentration techniques (modified Knott's and filter tests) successfully demonstrate microfilariae in a blood sample in ~60% of dogs and <10% of cats with heartworms. Because microfilariae survive after adult worms have died, a small percentage of dogs can have microfilaremia but no adults in the heart. In addition, puppies born to *****es with a high microfilariae count can have a transient microfilaremia that cannot become an adult infection. Microfilariae of D immitis should be differentiated from those of the nonpathogenic filarids D repens and Dipetalonema reconditum on the basis of morphology and staining characteristics with acid phosphatase.
Occult infections, in which the animal is amicrofilaremic, can be seen when the infection is due to immature (<6 mo old) worms, a single worm, or worms of all the same sex. Occult infections can also result from host immunologic reactions to microfilariae or from iatrogenic infection. Monthly preventive medications will induce embryo stasis in the female heartworm, and occult infections have been demonstrated in most heartworm-positive dogs after many months of medication. Therefore, antigen testing is necessary to determine the heartworm status of a dog that has been on monthly preventive medication.
Circulating adult antigen can be detected before or after the initial microfilaremia. The detection of circulating antigen is based on a laboratory-derived antibody binding to an adequate amount of circulating heartworm antigen. Although the glycoprotein detected by most assays is found throughout the parasite, the major source of circulating antigen is the reproductive tract of the mature female heartworm. The maturity and number of females influences the amount of antigen. Animals with immature worms and low worm burdens (especially cats) will be antigen negative—even when worms are present in the pulmonary arteries and clinical signs are present.
Thoracic radiographs can be a screening tool for dogs and cats with clinical signs suggestive of heartworm disease. In dogs, the pulmonary arteries can be tortuous and enlarged, with an enlarged pulmonary arterial segment at the 1 o'clock position on a ventrodorsal view. Right ventricular enlargement may not be noted if the hypertrophy has not been induced by physical activity or severe vascular lesions. The pulmonary parenchymal changes can be diffuse in early L5 infection but also can become granulomatous in chronic severe infections. In cats, cardiac changes are rare, and even an enlarged pulmonary arterial segment on the ventrodorsal view is not visible beyond the cardiac shadow. Enlarged caudal pulmonary arteries are the most consistent lesion in cats with heartworms. Severe lung parenchymal changes may obscure the vascular pattern. A fluid density lung lobe is associated with acute signs in cats and may be confused with a consolidating pneumonia.
Feline heartworm disease, ventrodorsal projection.http://www.merckvetmanual.com/mvm/img/bgraph/cirhw06.jpg*Courtesy of Merial
Feline heartworm disease, lateral projectionhttp://www.merckvetmanual.com/mvm/img/bgraph/cirhw05.jpg*Courtesy of Merial
Severe radiographic lesions of canine heartworm disease in a 6-yr-old female Boxer, ventrodorsal projection. Note the moderate to severe right-sided cardiomegaly producing a reverse D appearance and the bulge in the region of the main pulmonary artery.http://www.merckvetmanual.com/mvm/img/bgraph/cirhw08.jpg*Courtesy of the University Of Florida
Severe radiographic lesions of canine heartworm disease in a 6-yr-old female Boxer, lateral projection. Note dorsal displacement of the apex of the heart, severely enlarged and tortuous pulmonary arteries and moderately increased bronchointerstitial pulmohttp://www.merckvetmanual.com/mvm/img/bgraph/cirhw07.jpg*Courtesy of the University Of Florida
Mild canine heartworm disease in a 5-yr-old male German Shepherd Dog, ventrodorsal projection. Note enlargement of the right caudal lobar pulmonary artery (greater than the width of the 9th rib) and the small bulge in the region of the main pulmonary artehttp://www.merckvetmanual.com/mvm/img/bgraph/cirhw04.jpg*Courtesy Of University Of Florida
Mild radiographic lesions of canine heartworm disease in a 5-yr-old male German Shepherd Dog, lateral projection.http://www.merckvetmanual.com/mvm/img/bgraph/cirhw03.jpg*Courtesy Of the University of Florida
Echocardiograms are diagnostic, with typical “double parallel” white lines noted in the pulmonary arteries or right ventricles of dogs or cats. Echocardiograms are especially useful in diagnosis of postcaval syndromes and ascitic conditions associated with heartworm disease. The typical right axis deviation and deep S waves are seen on an ECG only if right ventricular hypertrophy is significant.
Tracheal cytology is usually nonspecific and is rarely positive for bacteria in either dogs or cats. An eosinophilic cytology is usually a stage-specific reaction.
Complete necropsy with thorough examination of the distal pulmonary arteries may be required to demonstrate heartworms in cats.
Treatment in Dogs: Steps to manage treatment of dogs infected with heartworms consist of the following: 1) diagnostic evaluations (before therapy) to determine subclinical disease, especially of the liver and kidneys; 2) adulticidal therapy to eliminate mature worms; 3) a rest period of 4-6 wk to allow the dog to recover from the lung injury associated with worm death; 4) microfilaricidal therapy if required; 5) a test for microfilariae to determine success of microfilaricidal therapy; 6) an antigen test to determine success of adulticidal therapy; and 7) preventive medication.
Use of aspirin, aspirin and dipyridamole, serotonin antagonist, short-acting heparin, and high-dose corticosteroids to decrease the clinical significance of heartworm lesions has been unsuccessful. Abnormal pressor vessel dynamics and pulmonary parenchymal damage may contribute to the failure of these agents. Because of the pressure overload of heartworm disease, treatment with digitoxin is usually not recommended. An angiotensin-converting enzyme inhibitor may be used in severe right ventricle hypertrophy. The interstitial edema associated with acute signs of worm death is not aided by diuretic therapy.
Adulticidal therapy eliminates the adult heartworms and allows repair of damage where fibrosis has not occurred. Death of the worms (either spontaneous or induced) in both dogs and cats is associated with severe parenchymal lung damage, and limitation of exercise is critical after adulticidal therapy. Platelet consumption and coagulopathies develop in most dogs 2-3 wk after adulticide treatment. Thiacetarsamide (2.2 mg/kg, four IV doses over 2 days) will kill most male and some female worms but has poor efficacy against immature and young female worms. Arsenical toxicity cannot be predicted in clinically normal dogs based on laboratory tests. Melarsomine (2.5 mg/kg, two IM doses over 24 hr) has improved efficacy (>95% kill). However, increased worm death can cause serious complications in dogs with high worm burdens. One IM dose followed 1 mo later by two IM doses is a safer alternative in dogs with severe heartworm disease or high antigen loads, which suggest large worm burdens. No agent has been successful as a pretreatment in decreasing the complication rate. Dogs should be rested for 4-6 wk.
Complications of worm death often include impaired pulmonary function and vessel damage, which may initiate disseminated intravascular coagulation (DIC). A platelet count <100,000/µL is not uncommon, but an activated clotting time should be performed to determine if DIC is present (if so, the prognosis is poor). Dyspnea after adulticidal therapy is an emergency. Nasal oxygen and an immediate-acting glucocorticoid at doses used in shock are needed to provide adequate oxygenation and decrease the acute lung injury. Many dogs will respond within 24 hr. Because of the fragile nature of the capillary beds of the lungs, no exercise or stress should be allowed during this time.
Currently, there are no FDA-approved drugs for microfilaricidal therapy. However, ivermectin at 50 µg/kg or milbemycin at the preventive dose is effective within 2-3 wk. Most microfilariae are killed quickly, and reactions, which usually occur within 1 hr of administration, are associated with high microfilariae counts in small dogs. Concentration techniques should be used to assess microfilarial status.
Antigen assays 12-16 wk after successful adulticidal therapy should be negative. However, low worm burdens and immature worms can still be present with a negative antigen test. Positive antigen tests should be rechecked in 1 mo before initiating a second adulticidal regimen.
Treatment in Cats: After the diagnosis has been confirmed, the therapeutic options must be carefully considered. Because feline heartworm disease can result in no signs or signs such as chronic vomiting or intermittent respiratory signs, owners often think the disease is less severe than it is. Without treatment, acute complications and death occur in a small percentage of cats. However, in asymptomatic cats, this risk appears to be small compared with the potential complications of adulticidal therapy. In addition, the life span of the adult heartworm is shorter in cats than in dogs, and spontaneous recovery is possible. However, adulticidal therapy has been used safely in cats and should be considered for cats with recurrent dyspnea that is life-threatening or with clinical signs that are unacceptable to the owner.
Treatment of feline heartworm disease with thiacetarsamide sodium (2.2 mg/kg, given slowly IV, b.i.d., for 2 days) is tolerated by cats without immediate complications of hepatotoxicity or renal toxicity. However, pulmonary edema has been seen, and oxygen therapy and corticosteroids should be considered if dyspnea or cyanosis occurs. The use of ketamine as a sedative to aid in careful administration of thiacetarsamide is recommended in active cats.
In symptomatic cats, clinical signs tend to improve after therapy. Chronically anorexic cats may require hyperalimentation. Although the presence of circulating microfilariae is uncommon, dithiazanine iodide and levamisole hydrochloride have both been used successfully as microfilaricides.
Complications after therapy are more severe in cats than in dogs and are usually related to embolization. Sudden death from embolization can occur, especially within the first 10 days after adulticidal therapy. Embolization can result in severe lung infarction, hemoptysis, and dyspnea. Severe thrombocytopenia has not been noted. Based on the assumption that heartworm mass is related to antigen load, a cat with a “strong positive” antigen test would be more likely to develop complications after adulticidal therapy than a cat that has a low worm burden and is antigen negative or “weakly positive.”
Embolization most often affects the caudal lung lobes, and thoracic radiographs may demonstrate a lung lobe with increased density. Oxygen therapy is indicated if hypoxemia or dyspnea occurs. High doses of corticosteroids (eg, prednisolone at 1-2 mg/lb, t.i.d.) with careful IV fluid therapy will often support the cat through the crisis. However, the routine use of corticosteroids before or after thiacetarsamide administration is not recommended in cats.
There is evidence that aspirin may inhibit prostaglandin formation and thus increase leukotriene production in the lungs; the result would be bronchospasm and pulmonary hypertension. Aspirin is not currently recommended for use in feline heartworm disease, and it may be contraindicated when acute embolization occurs.
The peracute nature of the postadulticidal reaction dictates that the cat be under constant surveillance, especially during the first 2 wk. The clinical and radiographic signs of acute embolization can resolve over 1-2 days. However, death can be so rapid that it occurs before therapy can be instituted. In asymptomatic cats, the risk and severity of the postadulticidal reaction and the resultant embolization is probably greater than that from the spontaneous death of heartworms.
Unfortunately, the efficacy of thiacetarsamide cannot often be evaluated in cats because of the occult nature of the disease. However, in some cats that have had microfilariae, repeated attempts to eliminate microfilariae have failed and repeated adulticidal therapy has been required. If a cat was antigen positive before therapy, the antigen test should be negative 12 wk after adulticide therapy; a positive test would indicate that adult heartworms are still present.
Melarsomine has not been evaluated in cats for routine clinical use.
When adulticidal therapy is not done, such as in cats with intermittent clinical signs, owners should be educated about the nature of the peracute signs of embolization. An emergency dose of prednisolone (5 mg/kg) should be dispensed to be administered PO if collapse or dyspnea are noted. The onset of acute respiratory signs in a cat with heartworm disease is an emergency, and immediate treatment is needed. The radiographic signs of severe lung pathology should not be interpreted as consolidation or pneumonia. Oxygen therapy, cage rest, small volumes of IV fluids, and injectable prednisolone have resulted in clinical improvement and resolution of radiographic signs within 24 hr in some cats with life-threatening dyspnea and collapse.
Prevention: In dogs, diethylcarbamazine (DEC), ivermectin, and milbemycin oxime are orally administered preventives. Dogs >6 mo old should test negative for microfilariae and antigen assay before preventive medications are administered. Dogs <6 mo old can be started on preventive medication but should be tested for microfilariae and antigen 6 mo to1 yr later. DEC is administered daily from 1 mo before to 2 mo after the mosquito season. Ivermectin and milbemycin oxime are administered once monthly from 1 mo after the onset to 1 mo after the end of the mosquito season. In temperate areas, preventive medications can be used year round. Dogs on monthly preventive should have antigen assays to determine their heartworm status. Preventive medications should not be administered to dogs that test positive for microfilariae.
In cats in areas highly endemic for heartworm disease in dogs, the incidence of heartworms (20%) would indicate that preventives are warranted. In nonendemic areas, the incidence is not sufficient to warrant preventive therapy in cats. In endemic areas, it is suggested that preventive medication (ivermectin at 25 µg/kg or milbemycin at 50 µg/kg, administered PO once a month) be administered at 4-6 wk of age and continued for the life of the cat. Although incidence of heartworm disease is low in many areas and heartworm disease can be self-limiting in many cats, the high rate of complications associated with feline heartworm disease and the potential to initiate inflammatory lung disease and predispose to bronchial asthma may prove to be adequate indications for preventive medications.
*Information from Merck Veterinary Manual