Introduction
Heartworm disease (dirofilariasis) is a disease of the pulmonary blood vessels caused by the parasitic worm Dirofilaria immitis. It affects both wild and companion canines and felines with dogs being the most predominantly affected. The disease in cats is about 5 - 20% that in dogs. It is an emerging zoonotic disease, producing pulmonary dirofilariasis in humans. Heartworm disease is potentially fatal but preventable.
It is a vector-borne disease, transmitted by a variety of mosquitoes (over 70 species). However, four species are the most common, i.e. Aedes, Anopheles, Culex and Mansonia mosquitos, with Aedes mosquitos (Aedes vexans) being the best vector of transmitting the heartworm.
This mosquito species is also referred to as the salt marsh mosquito and is an aggressive biter and a strong flier, living in mangrove forests along coastlines with the potential to travel between 30 km and 90 km under ideal conditions.
This mosquito species bites during both day and night and is an important vector of canine heartworm (Dirofilaria immitis)
Geographic Distribution
Cardiopulmonary dirofilariasis is mainly located along the coastlines of countries with temperate and tropical climates which are warmer. The development and activity of mosquitoes are regulated by climate, primarily temperature and humidity and the right vegetation, the mangroves.
The transmission of heartworm disease depends on the presence of competent mosquito species, which is directly related to favourable climate conditions for its development and survival.
Life Cycle
The role of the endosymbiotic bacteria Wolbachia pipiens
Wolbachia pipiens is a symbiotic bacteria that lives intracellularly within the filarial parasite, Dirofilaria immitis, and are involved in the development of heartworm disease, possibly through endotoxin production. This bacterium is necessary for normal maturation, reproduction, and infectivity of the heartworm. The eradication of Wolbachia causes the heartworm to gradually die, after first becoming sterile. This is accomplished with doxycycline therapy, which has become an important part of the treatment regime against heartworms.
What are the Risk Factors?
Location is a significant risk factor for canine heartworm infection as it determines the distribution of the multiple vector species of the Aedes, Culex, Anopheles and Mansonia genera of mosquitos. The preferred locations are warmer conditions (27 °C with 80% humidity) which are mostly along the tropical coastal lines.
Lack of the administration of preventive medication to dogs and cats in endemic areas, with up to 45% of pets that do not receive preventive medication expected to have heartworm disease.
What are the clinical signs of heartworm disease?
In dogs, at the earliest, heartworm detection is possible between 5 and 6.5 months after infection if dogs do not receive preventive medication and the infection and disease progress undetected. Clinical signs of heartworm infection include:
unthriftiness
lethargy
cyanosis (blue gums)
lack of breath
spitting blood
collapse
ascites (accumulation of fluid in abdomen due to right-side Congestive Heart Failure - CHF)
blood in urine
sudden death
Comparison - Cats' vs Dogs' Heartworm Infection
Cats Dogs
1%–10% infective stage survive 75% of third-stage infective L3 survive
Low maturation rate High maturation rate
Microfilariae uncommon Microfilariae common
Worms survive 2–4 years Worms survive 5 years
1–5 worms present Many worms present
Smaller adult worms Larger adult worms
Stages of Heartworm Infection in Dogs
Stage Signs
I Minimal, if any, signs and none evident to the owner
II Mild to moderate signs of heartworm disease, most often including cough
III Severe signs of heartworm disease, including respiratory signs, weight loss,
exercise intolerance, and even heart failure
IV Caval syndrome
What is Caval syndrome?
Caval syndrome (CS) refers to the life-threatening illness caused by a mass of heartworms located aberrantly in the right atrium, the ventricle, and often the vena cava. The worm mass interferes with the closure of the tricuspid valve and impedes the normal flow of blood through the right heart, leading to cardiovascular collapse. This leads to Azotemia (An elevation of levels of urea (Blood urea nitrogen - BUN) and other nitrogen compounds (serum creatinine) in the blood, Hemoglobinemia (or haemoglobinaemia) - an excess of haemoglobin in the blood plasma and Hemoglobinuria - a condition in which the oxygen transport protein haemoglobin is found in abnormally high concentrations in the urine.
How is Heartworm infection Diagnosed?
Diagnosis of heartworm infection is by:-
Laboratory tests:-
Serum chemistry shows that most parameters are within the reference ranges, and in severe cases, there is increased liver enzyme activity due to liver congestion from right-sided heart failure. Complete blood count may show increased eosinophils.
Radiography (x-rays):-
The process of obtaining images (radiographs) of internal structures of the body using X-rays. Radiography shows an enlarged right side of the heart on ventral view with a prominent main pulmonary artery bulge. The dorsal view is best for the evaluation of pulmonary vessels.
Echocardiography:-
A procedure that uses high-energy sound waves (ultrasound) to look at tissues and organs inside the chest. Echoes from the sound waves form a picture of the size, shape, and position of the heart on a computer screen (echocardiogram). In general, abnormal findings will not be noted with uncomplicated heartworm disease. In severe cases, the echocardiogram shows that the right lower chamber (ventricle) of the heart is dilated and the tricuspid or pulmonic valves may not be closing properly. Worms may be visualized in the pulmonary arteries. Echocardiography results may provide good confirmation for caval syndrome, worms visualized in the right atrium/right ventricle.
Other tests:-
Antibody testing (not often done)
Antigen testing (preferred - 100% confirmatory)
Microfilariae testing (confirmatory)
Treatment
Pre-treatment evaluation is usually done to determine the following:-
the clinical status of the dog,
the likelihood of coexisting diseases that may affect the outcome of treatment,
the owner's ability to restrict the dog's exercise, and cost considerations.
Clinical laboratory data is also collected selectively to complement information obtained from a thorough history, physical examination, antigen and microfilaria tests, and often, thoracic radiography.
Pre-treatment Stabilization is done in high-risk dogs before melarsomine administration as it often precipitates worsening of pulmonary and/or cardiac signs as worms die. Stabilizing treatment includes cage confinement, oxygen, corticosteroids, and doxycycline for 1–2 months before initiation of the split-dose melarsomine treatment protocol. The use of doxycycline and the split-dose protocol lessens the adverse reaction to dying worms.
Treatment involves the administration of a single injection of Melarsomine dihydrochloride at 2.5mg/kg intramuscularly, then this is repeated after 30 days by giving two injections 24 hours apart.
Adjunct Therapy involves the administration of Doxycycline to eliminate Wolbachia pipientis, a symbiotic bacterium harboured by the microfilariae, Dirofilaria immitis. Where Doxycycline is difficult to obtain, minocycline is a common replacement. This therapy weakens adult worms and makes them less fertile and improves pulmonary pathology, as Wolbachia spp have been shown to contribute to pulmonary inflammation. Corticosteroids (prednisolone at 1-2mg/kg every 12 hours) are recommended for dogs that show clinical signs (eg, coughing). Diphenhydramine at 2.2mg/kg can be administered before melarsomine administration to prevent an allergic reaction from the dying adult worms.
Post-treatment Client Education includes restriction of exercise for 4–6 weeks to minimize respiratory complications by observing strict cage rest throughout the duration of treatment to prevent life-threatening pulmonary embolism caused by dead worms. Gradual return to activity can take place 6–8 weeks after the final administration of melarsomine.
Prognosis is good to excellent with treatment. If untreated, the prognosis is variable.
Prevention
Heartworm infection is completely preventable, so year-round prevention in dogs is advised, beginning at 6–8 weeks of age and continuing for life. The following medications are normally used and they also have efficacy against some internal and external parasites.:-
Monthly oral
Ivermectin
Milbemycin oxime
Monthly topical
Selamectin
Moxidectin
6-Month injectable
Moxidectin
References
American Heartworm Society. (2014, March). Current feline guidelines for the prevention, diagnosis, and management of heartworm (Dirofilaria immitis) infection in cats. Retrieved from American Heartworm Society: www.heartwormsociety.org
Bemrick, W. J., & Sandholm, H. A. (1966). Aedes vexans and other potential mosquito vectors of Dirofilaria immitis in Minnesota. The Journal of parasitology, 762-767.
Bidgood, A., & Collins, G. H. (1996). The prevalence of Dirofilaria immitis in dogs in Sydney. Australian veterinary journal, 73(3), 103-104.
Ettinger SJ, F. E. (Ed.). (2010). Textbook of Veterinary Internal Medicine (7th ed.). St. Louis: Saunders Elsevier.
Grandi, G., Quintavalla, C., Mavropoulou, A., Genchi, M., Gnudi, G., Bertoni, G., & Kramer, L. (2010). A combination of doxycycline and ivermectin is adulticidal in dogs with naturally acquired heartworm disease (Dirofilaria immitis). Veterinary parasitology, 169(3-4), 347-351.
Kramer, L., Grandi, G., .Leoni, M., Passeri, B., McCall, J., Genchi, C., . . . Bazzocchi, C. (2008). Wolbachia and its influence on the pathology and immunology of Dirofilaria immitis infection. Veterinary parasitology(158), 191-195.
Lee, A. C., & Atkins, C. E. (2010). Understanding feline heartworm infection: Disease, diagnosis, and treatment. . Top Companion Animal Medicine, 25, 224-230.
Mandese, W., & Estrada, A. (2014, June). Canine Heartworm Infection. Retrieved from Clinician's Brief: https://www.cliniciansbrief.com/
McCall, J. W., Genchi, C., Kramer, L., Guerrero, J., Dzimianski, M. T., Supakorndej, P., . . . Carson, B. (2008). Heartworm and Wolbachia: therapeutic implications. Veterinary parasitology, 158(3), 204-214.
McHaffie, J. (2012). Dirofilaria immitis and Wolbachia pipientis: a thorough investigation of the symbiosis responsible for canine heartworm disease. Parasitology research, 110(2), 499-502.
Merck Sharp & Dohme Corp. (2021). Heartworm disease in dogs, cats, and ferrets. Retrieved October 21, 2021, from Merck Sharp & Dohme Corp.: https://www.merckvetmanual.com
Morchón, R., Carretón, E., González Miguel, J., & Mellado Hernández, I. (2012). Heartworm disease (Dirofilaria immitis) and their vectors in Europe–new distribution trends. Frontiers in physiology, 3, 196.
Snyder, P. S., Levy, J. K., Salute, M. E., Gorman, S. P., Kubilis, P. S., Smail, P. W., & George, L. L. (2000). Performance of serologic tests used to detect heartworm infection in cats. Journal of the American Veterinary Medical Association, 216(5), 693-700.
Textbook of Veterinary Internal Medicine. (2010). In F. J. Ettinger S (Ed.). Toronto: WB Saunders.