Dirofilariasis in the Dog: An Overview

Charles Lobeck, DVM and Kenneth S. Latimer, DVM, PhD, Diplomate ACVP

Class of 2008 (Lobeck) and Department of Pathology (Latimer) College of Veterinary Medicine, University of Georgia, Athens, Georgia 30602-7388.

Introduction

            Dirofilariasis (Heartworm Disease) is caused by the filarial organism, Dirofilaria immitis (Fig. 1).  While D. immitis can infect over 30 species of animals, the dog is considered its definitive host.  D. immitis is a vector borne disease that is transmitted via the mosquito.  Aedes, Anopheles, and Culex spp. are the most prominent mosquitos responsible for transmitting this disease (Fig. 2).  In dogs, heartworm disease has been diagnosed in all 50 states and is considered endemic in 49 states.  Transmission of D. immitis has not been proven to occur in Alaska.  

Fig. 1. Adult heartworms (with an appearance similar to spaghetti) are present in the right ventricle and extend into the pulmonary artery (image courtesy of Noah’s Arkive, The University of Georgia).

Fig. 2. Female Anopheles sp. mosquito in flight after obtaining a blood meal (image from National Geographic malaria photogallery http://science.nationalgeographic.com/science/photos/malaria.html).

Life Cycle

            The mosquito obtains microfilariae from feeding on an infected host (Fig. 3).  Depending on environmental conditions, the first stage larvae (L1 microfilariae) will progressively mature to second stage larvae (L2) and then to third stage larvae (L3).  Studies suggest that development of the infective L3 stage is directly related to temperature.  Maturation requires 24 hours of temperatures above 64˚F for at least one month.  If temperatures are consistently greater than 80˚F, larvae will mature to L3 within 10-14 days.  If at any point the temperature drops to 57˚F, larval development will be retarded.  When mature, the L3 larvae migrate to the labium of the mosquito.  During the mosquito’s next meal, the larvae are deposited onto the host and molt to L4 larvae within 3 days.  After two months the L4 larvae will molt into L5 larvae and relocate from the subcutaneous tissue to the pulmonary arteries.  These larvae will become sexually mature adults over the next 2-3 months.  If both sexes of D. immitis are present, they will mate and microfilariae will be released into the bloodstream.  Microfilariae can be seen in the blood approximately 6-7 months after exposure to the infective L3 larvae.           

Fig. 3.  Life cycle of Dirofilaria immitis (image courtesy of Merial, Inc., heartgard.au.merial.com/disease/dogs/index.asp).

Clinical Signs

            Clinical signs related to heartworm disease are based on the severity of infection (number of filarids), the age of the infection (stage of life cycle), and the host’s immune response to this disease.  During the early disease stages, the host may appear asymptomatic.  With mild to moderate disease, clinical signs may include chronic cough, dyspnea, and exercise intolerance.  As the disease process progresses, syncope and hemoptysis may be noted.  With severely advanced disease, ascites, hepatomegaly and congestive heart failure may occur (Fig. 4).            

Fig. 4.  Globose or rounded heart from dilation of the right atrium in a dog with advanced heartworm disease (image courtesy of Noah’s Arkive, The University of Georgia).

Pathogenesis

            Death of the host may occur during cardiac hypertrophy due to microfilarial thrombi, or may not occur until severe dilatation and cardiac failure are prominent.  Expected necropsy and histopathology related changes may include the following: 1) cardiac hypertrophy due to obstruction of the right ventricle and pulmonary arteries with adult heartworms, 2) chronic multifocal granulomatous pneumonitis caused by adult worm and microfilarial thrombi, 3) bronchiectasis with mucous hyperplasia of the bronchial epithelium, and 4) centrolobular hepatopathy (Fig. 5).

Fig. 5.  Pulmonary hemorrhage (left, arrows) and roughened, fibrotic liver from a dog with advanced heartworm disease.

Diagnosis

            Laboratory test findings depend on the stage, severity, and chronicity of the disease.  Possible findings on a CBC, chemistry profile, and urinalysis include anemia, eosinophilia, basophilia, inflammatory leukogram, thrombocytopenia, and proteinuria.  Antigen testing is the preferred diagnostic method to detect D. immitis infections.  These tests detect parasitic antigens that are found on mature female heartworms.  Therefore, it is imperative that the test be used at least 7 months post-infection.  Antigen tests have both high specificity and high sensitivity.  As with all tests, false positives and false negatives may occur.  It is very important to follow the manufacture’s guidelines when using their antigen test.  A negative result can have three interpretations:  1) heartworm infection is not present, 2) infection with immature filarids (subadults) may be present, or 3) the dog has a unisex heartworm infection consisting of male adult worms (remember that the test detects female heartworm antigens), and 4) the test kit has been refrigerated and not warmed to room temperature before use.  A positive result can mean the dog is infected with heartworms or an infection has recently been cleared but antigens are still present.  False positive test results may occur due to technical error, such as delayed reading of the test. 

            Identification of microfilariae on a wet blood smear or in a concentrated specimen of blood following erythrocyte lysis (modified Knott’s test) are other diagnostic techniques that predate antigen testing (Fig. 6).  Relying on identification of the microfilaremia to diagnosis disease may be misleading.  Many heartworm infected dogs do not have detectable microfilaremia, such as with an occult infection.  In addition, the presence of microfilariae doesn’t always indicate active heartworm disease.  For example, puppies that are born to mothers with a high load of microfilaria can have transient microfilaremia.  In both direct smear examination and the modified Knott’s test, the nonpathogenic infection with Acanthocheilonema (Dipetalonema) reconditum must be distinguished from that of Dirofilaria immitis.  D. immitis and A. reconditum look very similar under a microscope, but there are some subtle differences that allow for differentiation (Table 1).  Most notably, D. immitis exhibits stationary, writhing movement in the wet blood smear and the anterior end of the parasite tapers in the modified Knott’s preparation.  In contrast, A. reconditum exhibits rapid, directional movement in the wet blood smear and the anterior end of the parasite is blunt (like a broomstick handle) in the modified Knott’s test.
 

Table 1. Morphologic differentiation of D. immitis and A. reconditum filariae.

Fig. 6. Microfilaria of Dirofilaria immitis in a fine-needle aspirate of a lymph node from a dog with heartworm disease (Dog, prescapular lymph node, Diff-Quik stain).

            Radiographs also may show evidence of heartworm disease.  Common changes in survey films include enlargement of the main pulmonary artery, enlargement of the right ventricle, and diffuse pulmonary densities.  Echocardiography can be useful in cases of high worm load.  Parallel, linear, echo densities may be seen in the right atrium, right ventricle, and pulmonary arteries. 

Treatment

Note: Treatment of animals should only be performed by a licensed veterinarian. Veterinarians should consult the current literature and current pharmacological formularies before initiating any treatment protocol.

            Current recommendations by the American Heartworm Society suggest that all dogs with a positive antigen test result be fully evaluated before beginning heartworm treatment.  This evaluation should include a thorough medical history, physical examination, survey radiographs, CBC, biochemical profile, and a urinalysis.  These procedures and tests will help stage the severity of the heartworm disease as well as identify any concurrent disease(s). 

            There are two options for treatment of heartworm disease.  The first is via a series of deep intramuscular injections of melarsomine dihydrochloride into the epaxial lumbar muscles.  This currently is the only adulticide agent available. The American Heartworm Society currently recommends a gradual two stage elimination of the heartworms.  One injection is given initially.  In four weeks, two more injections are given within 24 hours of each other.  This protocol will kill the adult worms slowly, decreasing the chance of post-adulticide thromboembolic complications.  Treatment of the microfilariae should begin immediately after the dog is diagnosed with the disease.  Administering the monthly prophylactic dose of Ivermectin will eliminate microfilariae within a couple of weeks. 

The second option for treatment of adult heartworms is continuous prophylactic doses of Ivermectin.  This process can take up to 2 years for complete elimination of adult worms.  It is important to keep in mind that with this method, the adult worms (and any microfilariae) are killed slowly and lung pathology continues. 

Despite the method chosen to treat the adult heartworms, it is very important to limit the dog’s activity for 4-6 weeks.  Exercise restriction decreases the chance of pulmonary thromboembolic complications as potions of dead heartworms are carried from the heart and pulmonary arteries to the lungs.  Six months after treatment is complete, a heartworm antigen test and a microfilariae test should be used to confirm efficacy of the treatment. 

Prevention

            Heartworm disease can be easily prevented by periodic medication.  All dogs in endemic areas should be on macrolide prophylaxis throughout the year and especially during the region’s vector season when mosquitos are prevalent and active.  Puppies should begin monthly treatments for heartworm prophylaxis before 8 weeks of age.  Heartworm antigen tests also should be evaluated annually. 

References

1.  American Heartworm Society: 2005 Guidelines for the Diagnosis, Prevention and Management of   Heartworm (Dirofilaria immitis) Infection in Dogs, 2005, pp. 2-24.

2.  American Heartworm Society: Canine Heartworm Disease. www.heartwormsociety.org/article.asp?id=11, accessed June 26, 2007.

3.  Cheville NF: Introduction to Veterinary Pathology, 3rd ed. Blackwell Publishing, Ames, 2006, pp. 143.

4.  Dillon R: Dirofilariasis in Dogs and Cats. www.vetmed.auburn.edu/distance/cardio/aiello.htm, accessed June 26, 2007.

5. Heska Corporation: “Solo Step CH, Canine Heartworm Test Cassettes” Canine Heartworm Antigen Test Kit Insert, 2005.

6.  Kemp RL, Sloss MW, Zajc AM: Veterinary Clinical Parasitology, 6th ed. Iowa State University Press, Ames, 1994, pp. 105-108.

7.  Latimer KS, Mahaffey EA, Prasse KW: Veterinary Laboratory Medicine: Clinical Pathology, 4th ed. Iowa State Press, Ames, 2003, pp. 113-114, 418.

8.  McCall JW: “Canine Heartworm Disease” Veterinary Parasitology (IDIS 5200) Notes, 2005, pp. 1-9.

9.  The Merck Veterinary Manual, 9th ed. Merck & Company, Inc., New Jersey, 2005, pp. 100 - 107.

10.  Smith F, Tilley LP: The 5-Minute Veterinary Consult – Canine and Feline, 3rd ed. Lippincott Williams and Wilkins, 2004, pp. 538-539.

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