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Basics ⬇

Basics

Definition

Disease caused by infestation with Dirofilaria immitis

Pathophysiology

  • Disease severity is directly related to the number of worms, duration of infestation, host response, and host activity level.
  • Endothelial damage leads to myointimal proliferation and inflammation predisposing to periarterial edema.
  • Lobar arterial enlargement, tortuosity, and obstruction cause impaired compliance, loss of collateral recruitment, pulmonary hypertension, and thrombosis.
  • Pulmonary damage is exacerbated after the death of adult worms and with exercise.

Systems Affected

  • Respiratory-pulmonary hypertension (when severe), thromboembolism, allergic pneumonitis (some occult infections), eosinophilic granulomatosis (uncommon).
  • Cardiovascular-severe pulmonary hypertension causes right ventricular hypertrophy and, in some dogs, right-sided congestive heart failure (R-CHF=ascites).
  • Hemic/Lymphatic/Immune-venous inflow to the heart can become obstructed by worms causing traumatic hemolytic anemia and cardiogenic shock (caval syndrome).
  • Renal/Urologic-immune-complex glomerulonephritis.

Incidence/Prevalence

Virtually 100% in unprotected dogs living in highly endemic regions.

Geographic Distribution

  • Most common in tropical and subtropical zones
  • Common along the Atlantic/Gulf coasts and Ohio/Mississippi river basins
  • Diagnosed in all 50 states
  • Ubiquitous-mosquito vector

Signalment

Breed Predilections

  • Medium- to large-breed dogs > small dogs
  • Outdoor dogs > indoor dogs

Mean Age and Range

Infestation can occur at any age; most affected dogs are 3–8 years old

Predominant Sex

Males affected more often than females

Signs

Historical Findings

  • Dogs often asymptomatic or exhibit minimal signs such as occasional coughing (Class I).
  • Coughing and exercise intolerance associated with moderate pulmonary damage (Class II).
  • Cachexia, anemia, exercise intolerance, syncope, and/or ascites (R-CHF) in severely affected dogs (Class III).

Physical Examination Findings

  • No abnormalities-dogs with mild (Class I) and some with moderate infestation (Class II).
  • Labored breathing and/or crackles-dogs with severe pulmonary hypertension (Class III) or pulmonary thromboembolism.
  • Tachycardia, weight loss, exercise intolerance, syncope, coughing, anemia, and dyspnea (Class III).
  • Ascites, jugular vein distention/pulsation, and hepatomegaly indicate R-CHF (Class III).
  • Hemoptysis-occasionally.
  • Pale mucous membranes, dyspnea, weak pulses, hemoglobinemia, and hemoglobinuria (caval syndrome).

Risk Factors

  • Residence in endemic regions
  • Outside habitat
  • Lack of prophylaxis
  • Greater than 64°F all day, every day for at least 1 month
  • Greater than 80°F every day for 10–14 days.

Diagnosis ⬆ ⬇

Diagnosis

Differential Diagnosis

  • Other causes of pulmonary hypertension and thrombosis (e.g., hyperadrenocorticism, protein-losing nephropathy or enteropathy)
  • Chronic obstructive lung disease
  • Pneumonia
  • Allergic lung disease
  • Other causes of ascites (e.g., dilated cardiomyopathy)
  • Other causes of hemolytic anemia (e.g., immune-mediated).

CBC/Biochemistry/Urinalysis

  • Anemia-absent, mild, or moderate depending on chronicity, severity of disease, and thromboembolic complications. Anemia associated with Class III.
  • Eosinophilia and basophilia-vary.
  • Inflammatory leukogram and thrombocytopenia associated with thromboembolism.
  • Hyperglobulinemia-inconsistent finding.
  • Hemoglobinemia-evident with caval syndrome and less often with thromboembolism.
  • Proteinuria-common in dogs with severe and chronic infestation; caused by immune-complex glomerulonephritis or amyloidosis.
  • Hemoglobinuria-caval syndrome or severe lysis with thromboembolism (Class III).

Other Laboratory Tests

  • Highly specific, sensitive serologic tests that identify adult female D. immitis antigen; test 7 months after the end of the previous transmission season.
  • Antigenemia absent in absence of adult female worms.
  • Weak positive test verified by repeat testing using different test.
  • Strong reaction indicates relative high worm burden or recent death of worms and is highly predictive of thromboembolic complications following adulticide therapy.
  • Microfilaria identification tests are not recommended for routine heartworm screening; mainly used to confirm weak positive antigen tests, determine microfilarial status prior to patients receiving milbemycin as heartworm preventative, and to identify microfilaria which may contribute to the development of resistance when treated chronically with macrolide preventative.

Imaging

Radiographic Findings

  • Use DV projection.
  • Main pulmonary artery segment enlargement, lobar arterial enlargement, and tortuosity/pruning vary from absent (Class I) to severe (Class III). Right caudal artery > left caudal artery > cranial arteries.
  • Parenchymal lung infiltrates of variable severity-surround lobar arteries; may extend into most or all of one or multiple lung lobes when thromboembolism occurs.
  • Diffuse, symmetrical, alveolar, and interstitial infiltrates occasionally occur secondary to allergic reaction to microfilaria (allergic pneumonitis) in about 10% of occult infestations.

Echocardiographic Findings

  • Often unremarkable; may reflect right ventricular dilation and wall hypertrophy, tricuspid regurgitation, pulmonary hypertension, small left heart due to under-loading (pulmonary obstruction/hypertension).
  • Parallel, linear echodensities produced by heartworms may be detected in the right ventricle, right atrium, and pulmonary arteries.

Diagnostic Procedures

Electrocardiographic Findings

  • Usually normal.
  • May reflect right ventricular hypertrophy in dogs with severe infestation.
  • Heart rhythm disturbances-occasionally seen (atrial premature contractions and atrial fibrillation most common) in severe infestation.

Pathologic Findings

  • Large right heart
  • Pulmonary arterial myointimal proliferation
  • Pulmonary thromboembolism
  • Pulmonary hemorrhage
  • Hepatomegaly and congestion in dogs with R-CHF

Treatment ⬆ ⬇

Treatment

Appropriate Health Care

  • Most dogs hospitalized during adulticide administration.
  • Eliminate microfilaria with monthly prophylaxis and doxycycline/minocycline; milbemycin may cause rapid decrease in microfilaria numbers and should be used with caution in that scenario; dogs should be rendered microfilaria free 3 months post diagnosis.
  • Hospitalization recommended for dogs experiencing thromboembolic complications.

Activity

Severely restrict activity for 4–6 weeks after adulticide administration.

Client Education

  • Good prognosis for animals with mild-to-moderate disease.
  • Post-adulticide pulmonary complications likely in patients with moderate-to-severe pulmonary artery pathology and those with high worm burden.
  • Reinfestation can occur unless appropriate prophylaxis administered.

Surgical Considerations

  • Treatment of choice for caval syndrome.
  • Worm removal from right heart and pulmonary artery via jugular vein, by use of fluoroscopy and a long, flexible, alligator forceps or horsehair brush, is highly effective for treating high worm burden when employed by an experienced operator.

Medications ⬆ ⬇

Medications

Drug(s) Of Choice

  • Stabilize animals with R-CHF with diuretics, ACE inhibitor, pimobendan, sildenafil, cage rest, and moderate sodium restriction before adulticide treatment.
  • Stabilize pulmonary failure with oxygen supplementation, antithrombotic agents (e.g., aspirin or heparin), or anti-inflammatory dosages of corticosteroid depending on the clinical and radiographic findings.
  • Adulticide drug: melarsomine dihydrochloride (Immiticide, 2.5 mg/kg IM/dose)-injections are given into the epaxial muscles using 22-gauge needles; apply pressure over the injection site during and after needle withdrawal.
  • Graded-kill protocol recommended in most cases; administer one injection followed in 1 month by two injections (first injection on left or right epaxial muscles, followed by injection on the opposite side 24h later).
  • For Class III in small dogs or severe Class III with high worm burden administer one injection every 4–6 weeks for a total of three injections. Maintain the strictest patient confinement practical for 4–6 weeks. Perform antigen test 6 months after third injection.
  • Allergic pneumonitis: administer prednisone or prednisolone (2 mg/kg PO q12–24h for several days) and then immediately administer Immiticide.
  • Rapid microfilariacidal therapy (e.g., milbemycin or high-dose ivermectin) not recommended by authors; eliminate the microfilaria with monthly prophylaxis and doxycycline/minocycline; confirm elimination of microfilaria by testing 3 months after initiating therapy.

Precautions

  • Adulticide treatment-not indicated in patients with renal failure, hepatic failure (icterus), or nephrotic syndrome.
  • Caval syndrome-remove worms surgically and stabilize patient with conservative management for at least 1 month prior to adulticide therapy.

Alternative Drug(s)

  • Sodium heparin (75–100 units/kg SC q8h), aspirin (5–7 mg/kg PO q24h), or low molecular weight heparin (dalteparin: 100 units/kg SC q12–24h) for 1–3 weeks before, during, and for 3 weeks after adulticide administration are controversial recommendations for the most severe cases of Class III disease; therapy is combined with strict, extended cage confinement.
  • Sodium heparin (200–500 units/kg SC q8h) is recommended for dogs with pulmonary thromboembolism or hemoglobinuria with goal of prolonging APTT 1.5–2 times baseline.
  • Soft or slow kill: ivermectin (6 µg/kg weekly) and doxycycline (10 mg/kg/day) combination may result in worm eradication with 9 months of therapy (generally not recommended due to possible promotion of resistance to the macrolides).
  • Doxycycline/minocycline (5–10 mg/kg PO q12h) is used prior to adulticide therapy to kill Wolbachia, a gram-negative, intrafilarial bacterium that is associated with post-adulticide inflammation of the lungs and kidneys.

Follow-Up ⬆ ⬇

Follow-Up

Patient Monitoring

Perform an antigen test 6 months after adulticide treatment. Some dogs with persistent, low-grade antigenemia may not require retreatment. Weak antigenemia indicates most worms killed, pulmonary pathology will improve, and ivermectin prophylaxis will eventually kill remaining worms.

Prevention/Avoidance

  • Heartworm prophylaxis should be provided for all dogs at risk. Authors recommend year-round prophylaxis. Otherwise begin with mosquito season and continue for 1 month following first frost.
  • Antigen test prior to starting preventive treatment.
  • Antigen test 7 months after end of previous season.
  • Ivermectin (Heartgard, Iverhart, Triheart)-a highly effective, monthly preventive that can be given safely to microfilaremic dogs.
  • Milbemycin oxime (Interceptor, Sentinel, Trifexis)-a highly effective, monthly prophylaxis in which acute reactions may occur when given to microfilaremic dogs.
  • Moxidectin (Advantage Multi)-a topical solution administered monthly..
  • Selamectin (Revolution)-a highly effective monthly topical preparation.
  • Administer to puppies soon after 8 weeks of age as dictated by seasonal risk.
  • All of the prophylactic drugs can be administered safely to collies at the appropriate dosages.
  • For dogs infected with adult worms and not already taking prophylactic drug, any of the above drugs can be started immediately and should be started within one month of diagnosis. The authors recommend against using milbemycin in microfilaremic dogs.
  • The authors do not practice initiating prophylaxis and then delaying adulticide treatment for 1 or more months.
  • All macrocyclic lactones with combination doxycycline/minocycline should eliminate microfilaria in 1–3 months.
  • Due to the recent increase in the number of lack of efficacy (LOE) reports and the concern of possible heartworm resistance to the current heartworm preventives, dogs should be rendered microfilaria free 3 months post diagnosis.

Possible Complications

  • Post-adulticide pulmonary thromboembolic complications-may occur up to 4–6 weeks after treatment; usually more severe in dogs with Class III disease and those not properly confined.
  • Thrombocytopenia and intravascular coagulation.
  • Melarsomine adverse effects-pulmonary thromboembolism (usually 7–30 days after therapy); anorexia; injection site reaction-myositis; lethargy or depression; elevation of hepatic enzymes; paresis/paralysis/altered mentation; lack of efficacy.

Expected Course and Prognosis

  • Class I-usually uneventful with excellent prognosis
  • Class III-guarded prognosis with higher risk of complications

Miscellaneous ⬆

Miscellaneous

Associated Conditions

Wolbachia

Anesthesia

When anesthesia/surgery required, delay heartworm treatment until after procedure.

Pregnancy/Fertility/Breeding

  • Delay adulticide treatment.
  • Transplacental infestation by microfilaria can occur.

See Also

Authors Justin D. Thomason and Clay A. Calvert

Consulting Editors Larry P. Tilley and Francis W.K. Smith, Jr.

Client Education Handout Available Online