Introduction

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

Heartworm disease is transmitted by mosquito bites and there are more than 70 species of mosquito

that are able to transmit infection; Aedes, Anopheles and Culex are the most common vector species.

Heartworm disease has been reported in many countries with temperate climate and is particularly

prevalent in the USA, Canada, and southern Europe. The introduction of the PETS travel scheme has

increased the concern over Dirofilariasis in the UK.

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.

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.

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.

Cats differ from dogs in that they are more resistant to infection with Dirofilaria immitis. A lower

percentage of exposed cats develop adult infections, and when this does occur the burden is usually

low1. L5 in the pulmonary arteries also have a relatively short (2 year) survival time in cats.

Pathogenesis

Heartworm disease primarily affects the cardiopulmonary system and the severity and extent of

lesions depends on several factors. These include the number and location of adult worms1, 2, the

duration of infection, and the level of activity of the host1. Parasites in the pulmonary arteries cause

mechanical irritation, leading to endothelial damage, proliferation of the intima and perivascular cuffing

with inflammatory cells. This results in narrowing and occlusion of the vessels which in turn causes

pulmonary hypertension. A combination of pulmonary hypertension and inflammatory mediators can

lead to an increase in the permeability of pulmonary vessels, giving periarterial oedema and intersitial

and alveolar infiltrates. Eventually, irreversible interstitial fibrosis arises.

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.

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-represented1, 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.

Diagnosis

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 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.

Class Clinical Signs

Class

I

Asymptomatic or mild disease

Weight loss, reduced exercise tolerance or an occasional cough may be seen.

No radiographic signs or laboratory abnormalities.

Class Moderate disease

II

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

Lung sounds may be increased

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

Anaemia and proteinuria may be present.

Class

III

Severe disease

Signs are variable but may include weight loss, exercise intolerance, tachypnoea,

dyspnoea, severe/persistent coughing, haemoptysis, syncope, or ascites.

Radiographs appear abnormal: right ventricular hypertrophy, enlargement of the main

pulmonary artery, and diffuse pulmonary densities. ECG often shows right ventricular

hypertrophy.

Anaemia, thrombocytopenia, and proteinuria are seen.

Class

IV

Caval syndrome

Sudden onset of collapse, haemoglobinuria, and respiratory distress.

Usually fatal without immediate surgery.

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 failure, 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 artery1, 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

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 enlarged1, 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 tortuous3, 5. Patchy parenchymal infiltrates may be seen in the region of vessels in animals

showing respiratory signs1, 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 silhouette1, 5. Right-

sided cardiomegaly is not considered a typical finding in the cat5.

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.

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 artery1, 3, 5.

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.

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

frequently as in the dog5.

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 common1, 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 finding1, 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 proteiunuria1, 3. Haemoglobinaemia and

haemoglobinuria are associated with caval syndrome3.

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 microfilariae2, 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 microscopic examination is of little use in this

species.

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 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.

Pathology

On post-mortem examination, Dirofilaria immitis worms are apparent in the pulmonary artery and

possibly the right side of the heart. The right side of the heart is found to be enlarged and there is

proliferation of the pulmonary arterial myointima. Pulmonary thromboembolism and haemorrhage may

be seen. If right-sided congestive heart failure was present in life, hepatomegaly and hepatic

congestion will be apparent.

Treatment

Animals with right-sided congestive heart failure require stablisation with diuretics, ACE inhibitors and

cage rest before treatment for heartworm disease is implemented. Animals with severe respiratory

signs also require stabilisation with oxygen supplementation, anti-inflammatory doses of corticosteroid

and anti-thrombotic drugs.

The specific adulticidal treatment for Dirofilaria immitis is melarsomine dihydrochoride, a new

generation arsenical compound. Melarsomine is administered intramuscularly into the epaxial

muscles, and pressure should be applied during and after needle withdrawal3. A "graded-kill" protocol

is recommended: an initial injection is followed one month later with two injections at an interval of 24

hours, given on opposite sides1-4. This spreads the killing effects over two treatments, with an aim to

reducing the occurrence of thromboembolism after parasite death. Cage rest and anti-inflammatory

doses of corticosteroids in the week following melarsomine treatment can also reduce the likelihood of

pulmonary thromboembolism. Antigen testing four months after adulticidal treatment will determine

whether it is necessary to repeat the therapy3.

Adulticidal treatment may be declined by the owner, owing to the risk of thromboembolism.

Alternatively, it may not be possible to implement adulticidal treatment if the patient is suffering renal

or hepatic failure3. In these cases, monthly administration of prophylactic doses of ivermectin is a

reasonable treatment option, as it prevents further infection and may kill some adult nematodes2.

Even low grade infections in cats may result in pulmonary thromboembolism with adulticidal

treatment. Because of this, symptomatic treatment of sick cats may be followed by surgical or

catheter-based extraction of nematodes once the patient is stable3. Stablisation is similar to that for

feline asthma, and can include cage rest, oxygen supplementation, bronchodilators (e.g.

theophylline), tapering doses of prednisolone, and balanced fluid therapy if indicated3. Heartworms

have a much shorter life-span in cats, and spontaneous remission is seen in some cases. Regular

monitoring may therefore be the best course of action in clinically well cats.

In caval syndrome, surgery is the treatment of choice. Worms are removed from the right side of the

heart and the main pulmonary artery using flexible crocodile or basket-type retrieval forceps2. This

procedure is complex and requires general anaesthesia and fluoroscopic imaging, but reduces the

risk of thromboembolism following subsequent adulticidal treatment. Symptomatic and supportive

therapy to stabilise the patient should be continued for around one month after surgery before

adulticidal treatment is administered3.

No drugs are specifically approved for microfilaricidal treatment of Dirofilaria immitis, and

successful elimination of adult worms should result in the demise of circulating microfilariae four to six

weeks later2. Single doses of ivermectin, milbemycin oxime, moxidection or selamectin are,

however, effective at removing microfilariae from the circulation. The sudden death of large numbers

of microfilariae may invoke an anaphylactic response, and oral prednisolone may be administered

with microfilaricides to help prevent this.

Heartworm prophylaxis should be implemented in all cats and dogs living in or visiting areas in

which Dirofilaria immitis is endemic. Ivermectin or milbemycin oxime can be given per os on a monthly

basis, and selemectin spot-on is effective when applied each month. If animals have already been

exposed to Dirofilaria immitis it may be wise to perform an antigen test before starting treatment. In

endemic countries, routine antigen testing six months after the end of the previous heartworm season

will detect infections that have slipped through the net, and enable treatment during the mild, early

stages of disease3.

Prognosis

In mildly symptomatic or asymptomatic animals, the course of dirofilariasis is usually uneventful

following treatment and the prognosis is excellent3. Animals with severe infection carry a guarded

prognosis with a higher risk of complications.

Dirofilaria immitis Learning Resources

Literature Search 

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A review of American heartworm society guidelines for the management of heartworm infections in cats. Guerrero, J.; The North American Veterinary

Conference, Gainesville, USA, Small animal and exotics. Proceedings of the North American Veterinary Conference, Orlando, Florida, USA, 16-20 January 2010,

2010, pp 1173-1176, 1 ref.

Epidemiology and prevention of Dirofilaria infections in dogs and cats. Genchi, C.; Guerrero, J.; McCall, J. W.; Venco, L.; Veterinary Parasitology and Parasitic

Diseases, Naples, Italy, Mappe Parassitologiche, 2007, 8, pp 145-161, many ref.

Heartworm of dog - its aetiopathogenesis, diagnosis, treatment and prevention. Kundu, P.; Intas Pharmaceuticals Ltd, Ahmedabad, India, Intas Polivet, 2006, 7,

1, pp 106-110, 16 ref.

The utility of echocardiography in the diagnosis of feline heartworm disease: a review of published reports. Defrancesco, T. C.; Atkins, C. E.; Seward, R. L.;

Knight, D. H.; American Heartworm Society, Batavia, USA, Recent advances in heartworm disease: Symposium '98, Tampa, Florida, USA, 1-3 May, 1998, 1998, pp

103-106, 20 ref.

Sample Book ChaptersPublisher Free chapter Book Authors

Cardiopulmonary

Dirofilariasis

Arthropod-borne

Infectious

Diseases of the

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Susan E. Shaw,

Michael J. Day

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Links

The Merck Veterinary Manual - Heartworm Disease

dogheartworm.org

DEFRA - Dog and Cat Travel and Risk Information

References

1. Merck & Co (2008) The Merck Veterinary Manual (Eighth Edition), Merial.

2. Ferasin, L (2004) Disease risks for the travelling pet: Heartworm disease, In Practice, 26(6),

350-357.

3. Tilley, L P and Smith, F W K (2004) The 5-minute Veterinary Consult (Fourth

Edition),Blackwell.

4. Venco, L (2007) Heartworm (Dirofilaria immitis) disease in dogs. Dirofilaria immitis and D.

repens in dog and cat and human infections, 117-125.

5. Venco, L (2007) Heartworm (Dirofilaria immitis) disease in cats. Dirofilaria immitis and D.

repens in dog and cat and human infections, 126-132.

6. Ridyard, A (2005) Heartworm and lungworm in dogs and cats in the UK, In Practice, 27(3),

147-153.