Dirofilaria immitis

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 immitus - Courtesy of the Laboratory of Parasitology, University of Pennsylvania School of Veterinary Medicine

• May cause muscle ischaemia in dogs due to arteritis and thrombosis of external iliac arteries and their branches
• Dirofilaria immitis live in heart and pulmonary arteries of dogs and cats

Nematodes of Dogs - CANINE HEARTWORM

• Dirofilaria immitis is one of the most important causes of morbidity and mortality in dogs in many regions of the world that have a warm, humid climate, including parts of southern Europe, USA and Australia.
• The presenting signs are usually those of heart failure, but sudden collapse may occur in heavily infected dogs.
• The endemic zone for canine heartworm disease is spreading as people increasingly travel with their pets.
• Strains of D. immitis are adapting to cooler climates.
• It is not endemic in the UK, but more infected dogs are likely to be imported now that the quarantine regulations have been relaxed.
• It has a very long prepatent period, so clinical signs may not appear for many months after importation.
• Although primarily a canine parasite, cats and ferrets can become infected.
• Owners taking their pets into endemic regions require advice on how the disease can be prevented.

Dirofilaria immitis:

• a filarial worm
• females: up to 30cm long; males: up to 15cm long
• life-span 5-7years
• up to 250 worms may establish in the heart and pulmonary arteries
• 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.

In dog:

• larvae migrate through connective tissues and moult twice
• immature adults (L5) are 1-5cm long → caudal distal pulmonary arteries in 4months → diffuse eosinophilic reaction in lung parenchyma, then migrate back towards right ventricle
• start producing microfilariae 6-7months post-infection.

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.

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.

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)

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.

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.

Cat

• 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).

Feline Heartworm Disease

• 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.

==Heart Worm== (Cardiology)

Description

• Life cycle of dirofilaria immitis

• Dogs, cats, and ferrets can be affected

• Cats are more resistant to infection compared to dogs, but it only takes one or two worms to cause serious disease in cats.

• Caval Syndrome is the result of extremely heavy worm burdens and is rarely seen.

Infection with heart worm can affect the following structures:

1. Pulmonary arteries

e.g. pulmonary thromboembolism of dead worms

2. Pulmonary parenchyma

e.g. allergic pneumonitis

3. Heart

e.g. pulmonary thromboembolism-->pulmonary hypertension-->increased right ventricular afterload-->right ventricular hypertrophy-->myocardial failure-->right heart failure

4. Liver

e.g. hepatic congestion from heart failure

5. Kidneys

e.g. antigen-antibody complexes lead to glomerulonephropathies

Distribution

• Endemic in the United States (especially southeast); South America, Southeast Asia, Middle East, Australia, Japan, Southern Europe

• Warm weather conditions that support the mosquito population contribute to heart worm disease

Transmission

• Several types of mosquitoes are the intermediate host to the nematode worm D. imitis

• Mosquitoes are infected with D. imitis when they bite an infected animal with circulating microfilaria (L1 stage)

Signalment

Genetics & Breed Predisposition: Large Breeds; Male>Female; 4-8 years old on average; Untreated with prophylactics

Cats: Outdoor cats; Male>Female; 3-6 years old on average; Untreated with prophylactics

Diagnosis

History & Clinical Signs

-Asymptomatic +/- (Acute Infections)

-Symptomatic +/- (Chronic Infection)

-Exercise Intolerance

-Haemoptysis

-Coughing

-Tachypnea

-Syncope

-Right Heart Failure +/-

-Vomiting (cats)

-CNS signs (cats)

-Collapse (cats)

-Sudden Death (cats)

Physical Exam

-Signs of right sided heart failure

-Crackles heard on auscultation

-Splitting of the S2 heart sound signifies pulmonary hypertension

Staging Heartworm Disease

Class	Description
Class 1	No physical or clinical signs
Class 2	Mild cough, Slight radiographic changes
Class 3	Cough, Exercise intolerance, Dyspnoea, Abnormal lung sounds, Enlarged pulmonary artery, Signs of right heart failure
Class 4	Caval Syndrome; Signs of right heart failure, Abnormal lung sounds, Abnormal heart sounds, Death

Laboratory Findings

Lab Tests

Heartworm Antigen Testing (dogs, cats)

-ELISA test kits test antigens associated with female D. immitis infections

-False negatives with male only infections (common in cats)

Direct Blood Smear (dogs)

-Detects microfilaria from a blood sample

-Only works if the infection is very severe

-Not used on cats because after 6-8 weeks of a heart worm infection the microfilaria disappear.

Modified Knott's Test or Filter Tests (dogs)

-These centrifugal concentration techniques detect small amounts of microfilaria from a direct blood smear

- (+) test indicates microfilaria production by adults

-(-) test indicates either no infection or an occult infection (immune system destroys L1)

-If negative test results, follow up with antigen test to rule out occult infections

-Not used on cats because after 6-8 weeks of a heart worm infection the microfilaria disappear.

Antibody Testing (dogs, cats)

-(+) test only indicates exposure to D. immitis

-(-) test rules out D. immitis infection (useful in cats)

Laboratory findings

Biochemistry: increased liver enzymes, azotemia, proteinuria, hypoalbuminemia

Haematology: eosinophilia, basophilia, thrombocytopenia, neutrophilia with left shift if the animal has a pulmonary thromboembolism, non-regenerative anaemia

Radiography

-Enlarged right heart

-Dilation of main pulmonary artery

-Enlarged peripheral branches of pulmonary arteries (especially diaphragmatic lobes)

Electrocardiography (ECG)

-Usually normal

-Right Ventricular Enlargement +/- (deep S waves)

-Right Atrial Enlargement +/- (tall P waves)

-Atrial arrhythmias +/-

Echocardiography

-Right heart enlargement

-Dilation of the main pulmonary artery

-Visualization of D. immitis if the infection is severe

Treatment

• Currently there are few treatment options for cats infected with heart worm except surgical removal in severe cases or the controversal use of thiacetarsamide.

• In dogs with allergic pneumonitis, give oral corticosteroids before starting heart worm treatment.

1. Adulticidal (kills worms slowly)

e.g. melarsomine dihydrochloride, Thiacetarsamide

-Give two doses 24 hours apart or perform a graded-kill protocol (1 dose into epaxial muscles; repeat 1-3 months later; repeat 24 later)

-Rest animal for up to six weeks after treatment to avoid a thromboemolism (major treatment risk)

(If thromboembolism develops treat with: prednisolone, heparin, and oxygen)

-Perform an antigen test 3-6 months after treatment to ensure adult worms have been killed

2. Microfilaricidal (kills microfilaria)

-Given about 4 weeks after adulticidal treatment

e.g. milbemycin, ivermectin

-Modified Knott's test should be performed 3 weeks after microfilaricide treatment. If it is positive repeat microfilaricidal protocol. If negative proceed to preventative treatment.

3. Prophylaxis

-Test animals for heart worm before administering preventative treatment

-Give dogs a supply of monthly macrocyclic lactones

e.g. ivermectin, milbemycin, selamectin, moxidectin

-All year coverage is usually the best way to ensure owner compliance

Prognosis

-Dependent on the stage at which heart worm has been diagnosed.

-Caval Syndrome has a 50% survival with surgical removal of the heart worms