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Also known as: heartworm disease.

Also known as: '''heartworm disease

Do not confuse with: ''Angiostrongylus vasorum'', angiostrongylosis.

Do not confuse with: ''[[Angiostrongylus vasorum]]'', [[angiostrongylosis]].

==Description==

==Introduction==

[[Image:Dirofilaria immitus.jpg|thumb|right|200px|''Dirofilaria immitus'' - Courtesy of the Laboratory of Parasitology, University of Pennsylvania School of Veterinary Medicine]]

[[Image:Dirofilaria immitus.jpg|thumb|right|200px|''Dirofilaria immitus'' - Courtesy of the Laboratory of Parasitology, University of Pennsylvania School of Veterinary Medicine]]

''Dirofilaria immitis'' is a nematode parasite that causes heartworm disease in dogs, cats and ferrets. Heartworm

''Dirofilaria'' does have zoonotic potential: infected mosquitos can transmit ''D. immitis'' to humans, but the infection does not become patent. The infective larvae instead reach the lungs, become encapsulated, and die causing granulomatous reactions called "coin lesions" in the process. These are only important because they may be confused with neoplastic metastasis to the lungs on radiography¹.

 

Dirofilarias does have zoonotic potential: infected mosquitos can transmit ''Dirofilaria immitis'' to humans, but the infection does not become patent. The infective larvae instead reach the lungs, become encapsulated, and die causing granulomatous reactions called "coin lesions" in the process. These are only imporant because they may be confused with neoplastic metastasis to the lungs on radiography¹.

==Life Cycle==

==Life Cycle==

 

''Dirofilaria immitis'' adults reach maturity and sexually reproduce in the pulmonary arteries and right ventricle. Adult males are around 15cm in length, and females are around 25cm¹. After mating, female worms release larvae known as microfilariae (or L1) into the circulation. When a mosquito takes a blood meal from the infected dog or cat, microfilariae are ingested. Mosquitoes are true intermediate hosts for ''Dirofilaria immitis'', since microfilariae require a period of maturation to L2 then L3 in the vector. The duration of this development depends upon environmental conditions. For example, maturation at 30°C takes around 8 days, but when temperatures are down to 18°C, this takes around one month². Below 14°C, development is halted and resumes when temperatures rise. In cooler climates, this means that transmission of heartworm disease to new canine or feline hosts can only occur in warmer months.  

''Dirofilaria immitis'' adults reach maturity and sexually reproduce in the pulmonary arteries and right ventricle. Adult males are around 15cm in length, and females are around 25cm¹. After mating, female worms release larvae known as microfilariae (or L1) into the circulation. When a mosquito takes a blood meal from the infected dog or cat, microfilariae are ingested. Mosquitos are true intermediate hosts for ''Dirofilaria immitis'', since microfilariae require a period of maturation to L2 then L3 in the vector. The duration of this development depends upon environmental conditions. For example, maturation at 30°C takes around 8 days, but when temperatures are down to 18°C, this takes around one month². Below 14°C, development is halted and resumes when temperatures rise. In cooler climates, this means that transmission of heartworm disease to new canine or feline hosts can only occur in warmer months.  

Once matured, L3 in the mosquito migrate to the labium, from which they erupt onto the host's skin as the mosquito feeds. Larvae then migrate into the bite wound and, as most dogs are highly susceptible to heartworm disease, most L3 then establish infection. It takes 2-3 days for L3 to moult to L4, which remain in the subcutaneous tissues for up to two months before becoming young adults (L5) and migrating to the pulmonary arteries.  

Once matured, L3 in the mosquito migrate to the labium, from which they erupt onto the host's skin as the mosquito feeds. Larvae then migrate into the bite wound and, as most dogs are highly susceptible to heartworm disease, most L3 then establish infection. It takes 2-3 days for L3 to moult to L4, which remain in the subcutaneous tissues for up to two months before becoming young adults (L5) and migrating to the pulmonary arteries.  

==Pathogenesis==

==Pathogenesis==

Sequelae to heartworm infection include pulmonary thromboembolism, which can either occur due to the death and metastasis of adult worms, or due to platelet aggregation induced by the parasite. In severe cases, live nematodes can migrate to the right ventricle, right atrium and caudal vena cava. The resulting incompetence of the tricuspid valve, augmented by concurrent pulmonary hypertension, leads to signs of right-sided heart failure. Flow of erythrocytes through the mass of parasites formed can also cause haemolysis and thus haemoglobinaemia. This combination of acute right-sided heart failure and intravascular haemolysis is referred to as "caval syndrome", which in severe cases can also be characterised by thromboembolic events and [[Disseminated Intravascula Coagulation|disseminated intravascular coagulation]]. Due to the smaller numbers of adult worms, caval syndrome is less common in cats².

 

Sequelae to heartworm infection include pulmonary thromboembolism, which can either occur due to the death and metastasis of adult worms, or due to platelet aggregation induced by the parasite. In severe cases, live nematodes can migrate to the right ventricle, right atrium and caudal vena cava. The resulting incompetence of the tricuspid valve, augmented by concurrent pulmonary hypertension, leads to signs of right-sided heart failure. Flow of erythrocytes through the mass of parasites formed can also cause haemolysis and thus haemoglobinaemia. This combination of acute right-sided heart failure and intravascular haemolysis is referred to as "caval syndrome", which in severe cases can also be characterised by thromboembolic events and disseminated intravascular coagulation. Due to the smaller numbers of adult worms, caval syndrome is less common in cats².

In cats, heartworm disease generally causes a diffuse pulmonary infiltrate and an eosinophilic pneumonia². Adult worms may die and embolise to the lungs, resulting in severe haemorrhage and oedema of the affected lobe. Immature nematodes have also been known to migrate to sites other than the pulmonary arteries and heart such as the CNS, eye and subcutaneous tissues. These ectopic infections are far more common in cats than in dogs, suggesting that ''D. immitis'' is not well adapted to feline hosts.

In cats, heartworm disease generally causes a diffuse pulmonary infiltrate and an eosinophilic pneumonia². Adult worms may die and embolise to the lungs, resulting in severe haemorrhage and oedema of the affected lobe. Immature nematodes have also been known to migrate to sites other than the pulmonary arteries and heart such as the CNS, eye and subcutaneous tissues. These ectopic infections are far more common in cats than in dogs, suggesting that ''D. immitis'' is not well adapted to feline hosts.

==Signalment==

==Signalment==

''Dirofilaria immitis'' infection affects dogs more commonly than cats, and risk is greatest in outdoor animals. Dogs of any age may be affected, but infections are most common in 3 to 8 year old dogs, and medium and large breeds are over-represented^{1, 3}. In cats, there are no breed or age predispositions, but males are more frequently affected³. Ferrets may also contract dirofilariasis; there are no age or sex predilections¹.

''Dirofilaria immitis'' infection affects dogs more commonly than cats, and risk is greatest in outdoor animals. Dogs of any age may be affected, but infections are most common in 3 to 8 year old dogs, and medium and large breeds are over-represented^{1, 3}. In cats, there are no breed or age predispositions, but males are more frequently affected³. Ferrets may also contract dirofilariasis; there are no age or sex predilections¹.

===Clinical Signs===

===Clinical Signs===

In dogs, historical findings at the time of presentation can vary. Some animals are asymptomatic, or cough only occasionally. In countries where heartworm is endemic, animals may be routinely tested for dirofilariasis six months after the end of the high-risk season³. Therefore, positive laboratory testing may be the first indication of disease¹. More obvious signs may be seen depending on the severity of disease. Generally, the onset of heartworm disease is insidious, and clinical signs are related either to a high parasite burden, or to an allergic response to the parasite². Affected dogs most often show coughing, and dyspnoea/tachypnoea, exercise intolerance, loss of condition and syncope may also be seen. In severe cases the pulmonary vessels may rupture, leading to haemoptysis or epistaxis. There is a tendency for signs to only manifest during exercise, and so patients with a sedentary lifestyle may never show overt disease. Right-sided congestive heart failure may ensue when worm burden is high, and signs can include jugular disension, ascites, marked exercise intolerance and hepatomegaly. A systolic murmur is sometimes audible on cardiac auscultation.

In dogs, historical findings at the time of presentation can vary. Some animals are asymptomatic, or cough only occasionally. In countries where heartworm is endemic, animals may be routinely tested for dirofilariasis six months after the end of the high-risk season³. Therefore, positive laboratory testing may be the first indication of disease¹. More obvious signs may be seen depending on the severity of disease. Generally, the onset of heartworm disease is insidious, and clinical signs are related either to a high parasite burden, or to an allergic response to the parasite². Affected dogs most often show coughing, and dyspnoea/tachypnoea, exercise intolerance, loss of condition and syncope may also be seen. In severe cases the pulmonary vessels may rupture, leading to haemoptysis or epistaxis. There is a tendency for signs to only manifest during exercise, and so patients with a sedentary lifestyle may never show overt disease. Right-sided congestive heart failure may ensue when worm burden is high, and signs can include jugular distension, ascites, marked exercise intolerance and hepatomegaly. A systolic murmur is sometimes audible on cardiac auscultation.

A classification system for the presentation of heartworm disease exists¹, outlined in the table below.

A classification system for the presentation of heartworm disease exists¹, outlined in the table below.

  |'''Moderate disease'''

  |'''Moderate disease'''

*Animal coughs occasionally and shows mild-to-moderate exercise intolerance.  

*Animal coughs occasionally and shows mild-to-moderate exercise intolerance.  

*Lung sounds may be increasd

*Lung sounds may be increased

*Radiography may show mild-to-moderate changes, e.g. right ventricular enlargement.  

*Radiography may show mild-to-moderate changes, e.g. right ventricular enlargement.  

*Anaemia and proteinuria may be present.  

*Anaemia and proteinuria may be present.  

  |}

  |}

Caval syndrome is a very severe form of heartworm disease that can occur in dogs and cats. It is characterised by respiratory distress, signs of right-sided heart failuer, intravascular haemolysis and haemoglobinuria. Disseminated intravascular coagulation frequently occurs, and the syndrome is often fatal.

'''Caval syndrome''' is a very severe form of heartworm disease that can occur in dogs and cats. It is characterised by respiratory distress, signs of right-sided heart failuer, intravascular haemolysis and haemoglobinuria. Disseminated intravascular coagulation frequently occurs, and the syndrome is often fatal.

In cats, most infections are asymptomatic. However, sudden death can occasionally occur. This may be preceded by an acute respiratory crisis, thought to be due to parasitic thromboembolism and obstruction of a major pulmonary artery^{1, 2}. When clinical signs are less acute, they are vague and may include anorexia, weight loss and lethargy. Intermittent coughing and dyspnoea can appear similar to feline asthma. Syncope may also occur, and cats may vomit. The cause of this vomiting is undetermined³.

In cats, most infections are asymptomatic. However, sudden death can occasionally occur. This may be preceded by an acute respiratory crisis, thought to be due to parasitic thromboembolism and obstruction of a major pulmonary artery^{1, 2}. When clinical signs are less acute, they are vague and may include anorexia, weight loss and lethargy. Intermittent coughing and dyspnoea can appear similar to feline asthma. Syncope may also occur, and cats may vomit. The cause of this vomiting is undetermined³.

===Radiography===

===Radiography===

In dogs, thoracic radiography provides good information on disease severity and is useful for screening dogs showing clinical signs compatible with ''D. immitis'' infection¹. However, thoracic radiograph do not neccessarily reflect the current worm burden: radiographic signs of advanced disease can persist long after an infection has run its course⁴. Conversely, dogs with high burdens may be inactive and thus show few clinical signs or radiographic changes. Radiographic signs are mild-to-moderate in class II disease, but become more obvious in class III infections. The main pulmonary artery is enlarged^{1, 4}, and the caudal lobar vessels appear tortuous¹. Ill-defined, fluffy infiltrates are apparent, and often surround the caudal lobar vessels. Right-sided cardiomegaly may be appreciated, and pleural and peritoneal effusions can be noted in right-sided congestive heart failure⁴.

In dogs, thoracic radiography provides good information on disease severity and is useful for screening dogs showing clinical signs compatible with ''D. immitis'' infection¹. However, thoracic radiograph do not necessarily reflect the current worm burden: radiographic signs of advanced disease can persist long after an infection has run its course⁴. Conversely, dogs with high burdens may be inactive and thus show few clinical signs or radiographic changes. Radiographic signs are mild-to-moderate in class II disease, but become more obvious in class III infections. The main pulmonary artery is enlarged^{1, 4}, and the caudal lobar vessels appear tortuous¹. Ill-defined, fluffy infiltrates are apparent, and often surround the caudal lobar vessels. Right-sided cardiomegaly may be appreciated, and pleural and peritoneal effusions can be noted in right-sided congestive heart failure⁴.

Cardiac changes on thoracic radiography are less common in cats than dogs. The caudal lobar veins are enlarged (greater than 1.5 times the width of the ninth rib), and the pulmonary arteries are blunted and tortuous^{3, 5}. Patchy parenchymal infiltrates may be seen in the region of vessels in animals showing respiratory signs^{1, 3}. Enlargement of the main pulmonary artery cannot normally be seen in cats, as it is has a relatively midline position and is thus obscured by the cardiac silhouette^{1, 5}. Right-sided cardiomegaly is not considered a typical finding in the cat⁵.

Cardiac changes on thoracic radiography are less common in cats than dogs. The caudal lobar veins are enlarged (greater than 1.5 times the width of the ninth rib), and the pulmonary arteries are blunted and tortuous^{3, 5}. Patchy parenchymal infiltrates may be seen in the region of vessels in animals showing respiratory signs^{1, 3}. Enlargement of the main pulmonary artery cannot normally be seen in cats, as it has a relatively midline position and is thus obscured by the cardiac silhouette^{1, 5}. Right-sided cardiomegaly is not considered a typical finding in the cat⁵.

===Echocardiography===

===Echocardiography===

In dogs, echocardiography is not particularly useful as a diagnostic tool for heartworm disease. In severe, chronic pulmonary hypertension, right ventricular hypertrophy, septal flattening, underloading of the left heart, and high-velocity tricuspid and pulmonic regurgitation may be seen¹. With caval syndrome or high-burden infections, worms may be visualised in the right heart and vena cava.

In dogs, echocardiography is not particularly useful as a diagnostic tool for heartworm disease. In severe, chronic pulmonary hypertension, right ventricular hypertrophy, septal flattening, underloading of the left heart, and high-velocity tricuspid and pulmonic regurgitation may be seen¹. With caval syndrome or high-burden infections, worms may be visualised in the right heart and vena cava.

Echocardiography is more important in cats than dogs because of the increased difficulty of diagnosis and the fact that this test can have a high sensitivity depending on operater experience¹. Specificity is 100%⁵, and the test can help exclude or confirm other primary cardiac diseases such as hypertrophic cardiomyopathy³. Worms can be visualised as parallel hyperechoic lines¹, and are seen in the right atrium and ventricle and main pulmonary artery^{1, 3, 5}.

Echocardiography is more important in cats than dogs because of the increased difficulty of diagnosis and the fact that this test can have a high sensitivity depending on operator experience¹. Specificity is 100%⁵, and the test can help exclude or confirm other primary cardiac diseases such as hypertrophic cardiomyopathy³. Worms can be visualised as parallel hyperechoic lines¹, and are seen in the right atrium and ventricle and main pulmonary artery^{1, 3, 5}.

===Electrocardiography===

===Electrocardiography===

 

The ECG of infected dogs is usually normal. Right ventricular hypertrophy patterns may be seen in chronic ,severe pulmonary hypertension and are associated with impending or apparent right-sided congestive heart failure⁴. Arrhythmias do not normally occur, buy atrial fibrillation is is occasionally seen in Class III disease.

The ECG of infected dogs is usually normal. Right ventricular hypertrophy patterns may be seen in chronic ,severe pulmonary hypertension and are associated with impending or apparent right-sided congestive heart failure⁴. Arrhythmias do not normally occur, buy atrial fibrillation is is occasionall seen in Class III disease.

Electrocardiography is less useful in the cat, as involvement of the heart chambers does not occur as frequently as in the dog⁵.

Electrocardiography is less useful in the cat, as involvement of the heart chambers does not occur as frequently as in the dog⁵.

===Laboratory Tests===

===Laboratory Tests===

In both dogs and cats, routine haematology, biochemistry and urinalysis should be performed. Most parameters are usually within normal limits, but an anaemia can often be seen. Eosinophilia and basophilia are also common^{1, 3}. Eosinophilia peaks as L5 enter the pulmonary arteries and subsequently varies. An inflammatory leukogram is possible³. Hyperglobulinaemia due to antigenic stimulation is an inconsistent finding^{1, 3}. Right-sided heart failure or immune-complex glomerulonephritis can lead to hypoalbuminaemia and, very occasionally, nephrotic syndrome¹. Because of this, it is possible for urinalysis to reveal proteiunuria^{1, 3}. Haemoglobinaemia and haemoglobinuria are associated with caval syndrome³.  

In both dogs and cats, routine haematology, biochemistry and urinalysis should be performed. Most parameters are usually within normal limits, but an anaemia can often be seen. Eosinophilia and basophilia are also common^{1, 3}. Eosinophilia peaks as L5 enter the pulmonary arteries and subsequently varies. An inflammatory leukogram is possible³. Hyperglobulinaemia due to antigenic stimulation is an inconsistent finding^{1, 3}. Right-sided heart failure or immune-complex glomerulonephritis can lead to hypoalbuminaemia and, very occasionally, nephrotic syndrome¹. Because of this, it is possible for urinalysis to reveal proteiunuria^{1, 3}. Haemoglobinaemia and haemoglobinuria are associated with caval syndrome³.  

[[Image:dirofilariasis.jpg|right|thumb|200px|Dirofilariasis. Courtesy of T. Scase]]

[[Image:dirofilariasis.jpg|right|thumb|200px|Dirofilariasis. Courtesy of T. Scase]]

There are several methods for the specific demonstration of ''Dirofilaria immitis'' in the animal. Firstly, direct microscopic examination allows rapid identification of microfilariae in a drop of fresh blood, as their movements can vigorously displace the surrounding red blood cells². Despite being quick, simple and inexpensive, this test is not sufficiently sensitive to provide a definitive diagnosis, particularly when there is a low concentration of microfilariae in the bloodstream. Filtration methods therefore exist to facilitate the microscopic demonstration of microfilariae^{2, 3}. These include the modified Knott's test, which involves haemolysis, centrifugation and staining with methylene blue before direct examination. Tests such as this are more sensitive than merely examining a drop of blood, and the morphology of microfilariae can be clearly seen. However, sensitivity in comparison to other methos is still low and so microfilarial identification tests are often reserved for confirmation of weak positive antigen tests and determination of microfilarial status prior to treatment with a microfilaricide³. Cats frequently lack circulating microfilariae, and so direct micrscopic examination is of little use in this species.

There are several methods for the specific demonstration of ''Dirofilaria immitis'' in the animal. Firstly, direct microscopic examination allows rapid identification of microfilariae in a drop of fresh blood, as their movements can vigorously displace the surrounding red blood cells². Despite being quick, simple and inexpensive, this test is not sufficiently sensitive to provide a definitive diagnosis, particularly when there is a low concentration of microfilariae in the bloodstream. Filtration methods therefore exist to facilitate the microscopic demonstration of microfilariae^{2, 3}. These include the modified Knott's test, which involves haemolysis, centrifugation and staining with methylene blue before direct examination. Tests such as this are more sensitive than merely examining a drop of blood, and the morphology of microfilariae can be clearly seen. However, sensitivity in comparison to other methods is still low and so microfilarial identification tests are often reserved for confirmation of weak positive antigen tests and determination of microfilarial status prior to treatment with a microfilaricide³. Cats frequently lack circulating microfilariae, and so direct micrscopic examination is of little use in this species.

[[Image:dirofilariasis 2.jpg|right|thumb|200px|'''Dirofilariasis'''. Courtesy of T. Scase]]

[[Image:dirofilariasis 2.jpg|right|thumb|200px|'''Dirofilariasis'''. Courtesy of T. Scase]]

Tests exist to detect ''D. immitis'' antigens. ELISAs specific for proteins released from the reproductive tract of adult female worms are available for in-house use². Sensitivity and specificity are excellent, but small worm burdens and the

Tests exist to detect ''D. immitis'' antigens. ELISAs specific for proteins released from the reproductive tract of adult female worms are available for in-house use². Sensitivity and specificity are excellent, but small worm burdens and the presence of immature female- or male-only infections can give low antigen titres hence false negatives. This is especially common in cats. Specific agglutination and immunochromatography techniques are also available for use in dogs. Any antigen test performed in the first six months of infection may give false negative results as levels of circulating antigen are initially low while female worms mature. In-house tests are also available to detect antibody against ''Dirofilaria immitis''. The presence of antibodies confirms exposure, but does not necessarily provide information about current infection. These tests are therefore most useful for ruling out infection. ''D. immitis'' antibody tests have a low specificity² and so have largely been superceded by tests for antigen.

presence of immature female- or male-only infections can give low antigen titres hence false negatives. This is especially common in cats. Specific agglutination and immunochromatography techniques are also available for use in dogs. Any antigen test performed in the first six months of infection may give false negative results as levels of circulating antigen are initially low while female worms mature. In-house tests are also available to detect antibody against ''Dirofilaria immitis''. The presence of antibodies confirms exposure, but does not necessarily provide information about current infection. These tests are therefore most useful for ruling out infection. ''D. immitis'' antibody tests have a low specificity² and so have largely been superceded by tests for antigen.

PCR-based tests are highly sensitive and specific for the diagnosis of immature and adult heartworms, and are especially useful in unconventional (e.g. wildlife) hosts². At present, these tests are not widely available for the diagnosis of ''Dirofilaria immitis''.

PCR-based tests are highly sensitive and specific for the diagnosis of immature and adult heartworms, and are especially useful in unconventional (e.g. wildlife) hosts². At present, these tests are not widely available for the diagnosis of ''Dirofilaria immitis''.

[[Category:Dog_Nematodes]]

[[Category:Dog_Nematodes]]

[[Category:Cat_Nematodes]]

[[Category:Cat_Nematodes]]

[[Category:To_Do_-_Parasites]]

[[Category:Zoonoses]]

 

[[Category:Respiratory Parasitic Infections]]

[[Category:Respiratory Parasitic Infections]]

[[Category:To_Do_-_Lizzie]]

[[Category:To_Do_-_Lizzie]]

[[Category:To_Do_-_Review]]

[[Category:To_Do_-_Review]]