Heartworm disease

From Dog
Dirofilaria immitis microfilaria (L3) under light microscopy
Angiogram of a dog with heartworm disease, showing cardiomegaly and pulmonary arterial distension[1]

Heartworm disease (cardiopulmonary dirofilariosis) is a mosquito-borne zoonotic[2] parasitic disease caused by Dirofilaria immitis that affects canines worldwide.

Although dogs are considered the definitive hosts, this parasite also affects other carnivores such as wolves, coyotes, foxes, horses[3], cats[4], rabbits[5] and rarely, humans[6].

Heartworm disease should be considered a dual parasitism since the endosymbiont Wolbachia pipientis, which is essential to L3 growth to adulthood within the canine host[7], contributes significantly to the inflammatory pathology of heartworm disease[8]. More than 30% of dogs are infected by this proteobacteria[9] and D. immitis-infected animals can have circulating Wolbachia antibodies and pro-inflammatory Wolbachia antigens deposited in tissues[10].


Since its first detection in 1969[11], the disease has been reported in every continent, with a worldwide incidence of heartworm in dogs worldwide varies from 5 - 30% depending on geographical location, season (higher prevalence in warmer months due to mosquito-populations[12]), exposure rates (outdoor roaming versus indoor activity)[13] and use of preventative therapy in the general dog population[14]. The disease, although increasingly reported, even in geographically-isolated communities, is likely to have been extant within stray dog populations for millenia[15], and increasing due to interstate and intercontinental movements of dogs[16].

Genetic analysis has shown at least 4 different genetic clusters with the D. immitis species, allowing for the emerging spread of drug resistance alleles[17].

While avermectin-class drugs are widely used for prevention, the American Heartworm Society estimated that 27 million dogs remain untreated in the United States alone[18].

Adult Dirofilaria maintain homeostasis with the canine host immune system by proffering over 600 antigenic protein secretomes to the host's immune system[19] due to single nucleotide polymorphism[20], which activates over 14 immune-system pathways during the evasive process of modulating the host immune response[21].

Coinfections with Dirofilaria spp and other hemoparasites such as Leishmania spp[22], Anaplasma phagocytophilum, Babesia vogeli[23], Borrelia burgdorferi and Ehrlichia canis[24] is common in some countries and exacerbates both clinical signs and eventual therapy.

Prior to the widespread use of drugs such as selamectin, the incidence of heartworm in tropical and subtropical regions was high, approaching 80% of urban dogs. Over the last twenty years, these monthly topical and yearly injectable agents have markedly reduced the risk of endemic heartworm disease to the dog population.

The prepatent period of this parasite is approximately 6 months from time of infection to detection of circulating microfilariae, and by this time, pathological changes are already evident within the pulmonary parenchyma[25]. Clinical signs usually develop 1 - 5 years post-infection.

Clinical signs

D. immitis infection is primarily a cardiovascular disease and symptoms relate to right-sided congestive heart failure, endarteritis, pulmonary hypertension, pulmonary effusion, pneumonitis, bronchitis and alveolitis, and is directly related to worm burden. Although up to 100 or more adult worms have been found on necropsy in some dogs, commonly reported infestations show an average infestation with 10 - 20 worms associated with clinical disease[26].

Worms can be found in the portal vein, vena cava, right atrium and ventricle and pulmonary veins. Microfilariae circulate thorughout the cardiovascular system and can be found in the lungs, kidneys, liver, heart, brain, and spleen[27]. Chronic glomerulonephritis due to immune-complex deposition is a long-term complication of this disease in older dogs[28].

Aberrant migrations of adult worms can also result in translocation to organs such as the brain, eye, peritoneum and chest cavity, leading to meningitis, chorioretinitis, peritonitis and spontaneous pneumothorax respectively [29].

Affected dogs are usually over 5 years of age[30] and present with exercise intolerance, varying amounts of coughing, and in heavy infestations, dyspnea, epistaxis and ascites due to cor pulmonale. Early symptoms of intermittent coughing are commonly due to heartworm-associated respiratory disease.

Blood tests usually reveal microfilaremia, varying degrees of leucocytosis, eosinophilia, thrombocytopenia and elevated levels of myoglobin, D-dimer[31] and cardiac troponin I[32]. Significant reduction in circulating minerals and antioxidants, particularly zinc, copper, iron, glutathione peroxidase and glutathione-S-transferase, have also been noted in infected dogs[33].

In younger dogs or dogs recently acquiring infection, migration of adult worms to the vena cava can trigger a thrombotic embolic episode within the anterior vena cava known as caval syndrome, which has high mortality.


A presumptive diagnosis is based on exposure to mosquitoes in heartworm endemic regions and presenting clinical signs, which may be absent in low worm-burden dogs.

Determining parasitism by D. immitis requires use of available Knott's filtration, in-house ELISA assays or laboratory IFAT, ELISA and when required PCR assays[34], and exclusion of less pathogenic filariids such as Acanthocheilonema dracunculoides and A. reconditum[35].

The use of the Knott's test should be interpreted with caution to exclude unisex infections ('occult' infections)[36] and confusion with other dermal filariids such as Dirofilaria repens, Acanthocheilonema spp, Onchocerca spp, Brugia pahangi[37], and Cercopithifilaria spp[38].

Supportive diagnostic and prognostic tests include thoracic radiographs and ultrasonography to determine the severity of lung and heart disease due to adult worms.

Fecal copromicroscopical flotations and Baermann technique should be employed to help exclusion of lungworm[39].

A differential diagnosis would include respiratory diseases such as kennel cough and lungworms (e.g. Angiostrongylus spp, Capillaria aerophila[40] and Filaroides osleri)[41].

Infections with other dirofilariids such as Dirofilaria repens are usually less pathogenic, resulting in self-limiting cutaneous nodular panniculitis[42] but should be excluded in areas where this parasite is endemic, usually by using PCR assays[43].


Treatment is usually dictated by the age of patient (old dogs and heavy-burden dogs are usually treated more conservatively) and severity of symptoms.

Conservative microfilaricidal, antimicrobial and anti-inflammatory therapy is usually appropriate in older dogs or dogs with severe filariid loads and secondary congestive heart failure, pneumonia and circulatory disorders.

Instigation of preventative therapy in prepatent infections may result in persistent microfilaremia for months or years>, and diagnosis of infections should therefore be conducted prior to dogs starting heartworm prevention[44].

Surgical intervention involves percutaneous removal of adult worms from the heart via the vena cava and has been routinely used in severe heartworm loads[45].

Adulticidal drugs are effective but come with elevated risks of mortality associated with dead and dying adult worms being washed into the pulmonary tree as a result of pulmonary thromboembolism[46]. Doxycycline treatment alone or combined with ivermectin-based drugs have less pathological reactions than patients receiving melarsomine-based adulticidals[47].

Patients with clinical signs associated with pneumonitis benefit from short-term therapy with anti-inflammatory doses of corticosteroids before and after adulticide treatment.

Strict cage rest is recommended for 4 - 6 weeks after adulticide administration[48] to minimize the potentially fatal risk of secondary pneumonia and thromboembolism[49] as adult worms die and are pumped into the pulmonary tree.

Medications indicated in the treatment of D. immitis infection include:

The use of daily diethycarbamazine medication has become less commonly used due to reactions associated with microfilaremic dogs[50] and the ease of monthly macrycylic lactone administration.

Use of antihistamines such as diphenhydramine have shown to be ineffective at minimizing post-adulticidal complications[51].

Failure of owner compliance to maintain regular monthly preventative therapy[52] is estimated at 10 - 20%[53]. Adding further to this problem is the growing resistance of fourth- and fifth-stage larvae to milbemycin[54][55] are two common causes of recrudescence of canine heartworm disease.


Prevention of heartworm disease remains the mainstay of effective control of the disease in dog populations, and despite extensive genomic sequencing of this parasite[56], vaccine development have as yet remained elusive.

A large number of oral medications, primarily avermectin-based have shown 100% efficacy at halting L3 development and migration in dogs.

As well, the use of preventative doxycycline, given at 10mg/kg orally twice daily has efficacy against migrating L3 - L5 and will delay or restrict microfilarial production[57], growth and development within the new canine host[58].

However, despite aggressive veterinary and pharmaceutical marketing to clients about the serious and prevalence of this disease, satellite sentinel populations of urban, free-roaming dogs, wolves and foxes remain at risk and are responsible for maintaining the parasite's prevalence, particularly in indigenous and impoverished communities[59][60].


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