Dirofilaria immitis

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Description

Dirofilaria immitus - Courtesy of the Laboratory of Parasitology, University of Pennsylvania School of Veterinary Medicine
Dirofilariasis. Courtesy of T. Scase
Dirofilariasis. Courtesy of T. Scase

Dirofilaria is a filarial worm. Female worms measure up to 30cm in length and males up to 15cm. The worms have a life-span of 5-7 years. Up to 250 worms may establish in the heart and pulmonary arteries of dogs and cats. Dirofilaria worms produce microfilariae, not eggs.

Microfilariae:

  • in peripheral circualtion
  • periodicity - maximum numbers in blood evening/night
  • greater than 300µm long
  • life-span 2years
  • present in approximately 60% of infected dogs
  • microfilariae are absent from the circulating blood if:
    • only immature worms present
    • only one worm present
    • only one sex
    • microfilariae killed by immune response (in 15% of dogs)
    • females sterilised by chemotherapy (e.g. ivermectin).

Intermediate hosts:

  • many, but not all, species of mosquito.

Local Epidemiology:

  • determined by feeding preferences of local species, and population density.
  • up to 45% of non-protected dogs infected in some parts of USA.

In mosquito:

  • microfilariae → L1 → L2 → infective L3
  • this takes 1week at 30°C, or 4weeks at 18°C - there is no development below 14°C.
  • when mosquito next feeds:
    • L3 moves to mouthparts
    • up to 12 L3 deposited on skin
    • enter body via puncture wound.

Zoonotic hazard:

  • human infection can occur, but few cases are diagnosed
  • this usually happens when a radio-opaque plaque is detected in the lung, and further investigation shows it to be caused by a trapped D. immitis larva.


Feline Heartworm Disease

  • A canine parasite - see under Dog Nematodes for life-cycle etc.
  • Cats are abnormal hosts, and so D. immitis is not very infective for cats.
  • Nevertheless, feline infection is common (up to 25%) in some heavily endemic areas.
  • But only small numbers of adult worms (1-3) establish.
  • The prepatent period is longer (approximately 8months) than in the dog.
  • Few, if any, microfilariae are produced (<20% of cases positive).
  • The life-span of the worm is shorter (2-3years).
  • However: one dead adult → acute pulmonary crisis (thromboembolism).
  • Lung pathology similar to dog, but little heart pathology.
  • Coughing starts 4-6months post-infection.
  • Antibody-detection ELISA used for diagnosis, but false positives occur (antigen ELISA cannot be used as antigen rarely expressed in cats).
  • There is no licensed adulticidal therapy, and treatment may be fatal for the cat as well as the worm.
  • Ivermectin or selamectin can be used for prevention.

Signalment

Diagnosis

Diagnosis:

  • Physical examination:
    • signs of heart disease
    • lung involvement
  • Radiography:
    • enlargement of right heart, main pulmonary arteries; arteries in lung lobes with thickening and tortuosity; inflammation in surrounding tissues
  • ECG:
    • right axis deviation → deep S waves
  • Echocardiography:
    • if post caval syndrome suspected - right ventricular enlargement with worms in ventricle appearing as parallel lines.

Clinical pathology:

  • needed alongside physical examination and other tests to determine treatment strategy and prognosis.

Parasite detection:

  • methods for demonstrating microfilariae in blood:
    • wet blood smear (okay for quick look, but insensitive) = D. immitis not progressively motile
    • Knott's test = red blood cells lysed; stained sediment examined
    • micropore filter = blood forced through; microfilariae held on filter; stained and examined
    • antibody detection ELISA = not reliable in dogs, but it is the best for cats (although some false positives)
    • antigen detection ELISA (using specific antigen from adult female worm) = reliable positives from 5-7months post-infection in dogs; although occasional false negatives occur → not useful for cats
  • the immunochromatographic test (ICT) uses coloured gold colloidal particles tagged to monoclonal antibodies to visualise the presence of adult worm antigen - performance similar to antigen detection ELISA, but quicker and easier to do (but not as quantitative as some ELISAs are)
  • operator error can give false positives, therefore best to confirm result with another test.

Clinical Signs

Clinical signs:

  • often sudden onset severe lethargy and weakness, but:
  • signs variable, reflecting multiple system dysfunction - pulmonary circulation, heart, liver and kidneys:
    • lung damage (severe pulmonary hypertension; thromboembolism)
    • heart failure (right-sided congestive)
  • therefore, not pathognomonic
  • acute prepatent = coughing
  • chronic = exercise intolerance, sometimes with ascites
  • acute post caval syndrome = collapse (dyspnoea, pale mucous membranes or jaundice, haemoglobinuria)

Diagnostic Imaging

Laboratory Tests

Pathology

Worms produce:

  • substances that are:
    • antigenic
    • immunomodulatory
    • pharmacologically active.

Lesions are:

  • not confined to the location of the worms
  • also caused by shear stress of high blood flow.

Severity:

  • not associated with the number of worms
  • exacerbated by exercise (i.e. by high blood flow rate)
  • sedentary dogs often asymptomatic - symptoms most commonly associated with racing greyhounds.

Acute prepatent disease:

  • immature adult worms in caudal distal pulmonary arteries
  • leads to intense diffuse eosinophilic reaction, which in turn leads to coughing.

Chronic disease:

  • mature worms in right heart and pulmonary arteries
  • endothelial swelling and sloughing
  • increased permeability → inflammation → periarteritis
  • platelets/white blood cells activated → thrombosis
  • proliferation of smooth muscle, thickening of media:

→ impairment of blood flow

→ pulmonary hypertension

→ right ventricular strain

→ right ventricular hypertrophy and right-sided heart failure

  • insufficient blood pumped through pulmonary capillary bed → insufficient preload for left ventricle.

Post Caval Syndrome (Dirofilarial haemoglobinuria):

  • can be acute or chronic
  • heavy heartworm infestation:
    • entangled clumps of worms → impaired closure of tricuspid valve → post-caval stagnation → hepatic congestion and hepatic failure
  • this is accompanied by increased red blood cell fragility, haemolytic anaemia and haemolobinuria.

Treatment

Chemotherapy:

  • three treatment objectives needing different approaches:

1) Adulticidal

  • risk that dead worms → thromboembolism → respiratory failure
  • therefore, hospitalise and strict exercise restriction for at least 3weeks post-treatment
  • organic arsenicals for adulticidal therapy:
    • Thiacetarsamide (2.2mg/kg IV bid for 2days) - hepatotoxic; skin sloughing
    • Melarsomine (2.5mg/kg IM sid for 2days) - generally safer, but greater risk of thromboembolism

NB - Ivermectin preventative doses over 16months reduces adult worm numbers

2) Microfilaricidal

  • start 3-6weeks after adulticidal therapy:
    • Ivermectin (50µg/kg)
    • Milbemycin oxime (0.5mg/kg)

NB - risk of reaction to dead microfilariae in sensitised animals (lethargy, retching, tachycardia, circulatory collapse) - observe for 8hours post-treatment

3) Preventative (prophylactic)

  • objective = kill migrating L4 before they reach the heart
  • monthly treatments are 100% effective and safe if used properly, but often fail because of inadequate owner compliance
  • test for adult infection/microfilarie before start and annually thereafter:
    • Ivermectin (6µg/kg monthly) - blocks maturation of larvae; these die only after several months
    • Selamectin (6mg/kg monthly)
    • Moxidectin (injectable formulation - 0.17mg/kg gives 6months protection)
    • Milbemycin oxime (0.5mg/kg monthly) - care → kills microfilarie, therefore risk of reaction
    • DEC (diethylcarbamazine) daily - care → kills microfilarie, therefore severe risk of reaction

Treatment of Post Caval Syndrome:

  • surgical removal with forceps via jugular vein
  • usually very successful, but:
  • do not crush or fragment worms

→ massive release of antigen

→ cardiac failure and acute respiratory distress

→ rapid death

A typical therapy protocol:

1) Pre-treatment evaluation

2) Adulticide: 4-6weeks restricted exercise

3) Microfilaricide: 3weeks after adulticide

4) Initiation of monthly preventative treatments

5) Check for microfilariae after 2weeks

6) Check for adults (ELISA) 4-6months after adulticide, and before start of each subsequent mosquito season.

Prognosis

Links

References