Chapter 237. Heartworm Disease

Question 1

What is heartworm disease caused by?

Answer 1

Caused by Dirofilaria immitis (parasitic roundworm)

Question 2

How is heartworm transmitted?

Answer 2

Transmitted by female mosquitos

Question 3

How do environmental factor affect the distribution of mosquitos and HW?

Answer 3

Mosquitos thrive in warm, humid climates which slow moving or stagnant waters. Habits can be influenced by natural disasters.

Question 4

Describe the life cycle of dirofilaria immitis in dogs.

Answer 4

• Mosquito bite and infected animal ingesting microfilariae (L1) and begin to develop within the mouth of the mosquito
• The larvae molt in the mosquito from L1-L2 and L2-L3 over a 2-week period at which point they become infective
• The transition from L1-L3 requires adequate temperature and humidity and benefits from the presence of the endosymbiotic bacteria, Wolbachia.
• A feeding mosquito infects a host by penetrating the host skin or mucous membranes and transmitting the L3 larval stage.
• The L3 larvae begin to molt and migrate to the fourth larval stage (L4) in the host tissues within 12 days of entry.
• The final molt to the fifth larval stage (L5, immature adult) occurs 2-3 months (50-70 days) after host infection, at which time immature adults enter into the vascular system and are carried through the right heart and to the pulmonary arteries, where they fully mature.
• Microfilariae (L1) are released from the mature female worms into the host’s circulatory system 6-9 months after the canine host becomes infected
• The presence of circulating microfilariae (L1) in a host provides a source of infection for biting mosquitoes to continue the D. immitis life cycle.
• Damage to the host begins early in the infection process with the molt to the immature adult (L4-L5) 2-3 months after host infection and importantly, before an antigen test for D. immitis would detect infection. This is the typical life cycle for D. immitis in a domestic dog.

Question 5

Describe the pathophysiology of heartworm in dogs.

Answer 5

• Pulmonary fibrosis & vascular damage develop secondary to worm-induced damage to the vascular endothelium and activation of the host’s immune response
  Increased pulmonary resistance
• Pulmonary hypertension Damage to the pulmonary arteries, reduced pulmonary arterial blood flow, and pulmonary thromboembolism contribute to the development of pulmonary arterial hypertension.
• Right-sided hypertrophy & dilation due to an increase in pulmonary vascular resistance and development of pulmonary hypertension
• Right atrial enlargement occurs secondary to both increased right heart pressure and volumetrically important tricuspid valve regurgitation, if present.
• Right-sided congestive heart failure
• Changes in the lungs: Immune complexes from microfilariae, adult worms, and Wolbachia drive systemic inflammation, with lung damage that may be diffuse or localised—often in the caudal, especially right, lung field. Pathologic changes include interstitial inflammation, hemorrhage, hemosiderosis, and fibrosis (± pleural involvement).
• Glomerulonephritis: due to immune complexes formed in response to microfilariae, adult worms, and Wolbachia promote systemic
• Caval syndrome: Occurs when there is a high worm burden and flow is obstructed through tricuspid valve results in - right-sided congestive heart failure, intravascular haemolytic anaemia (due to RBC fragmentation), hepatic & renal dysfunction (due to congestion, diminished perfusion and circulating pigments), immune-mediated glomerulonephritis and DIC & SIRS, treated by right jugular vein venotomy
• Can also cause aberrant migration (brain, spinal cord, muscle & eye)

Question 6

How is heartworm diagnosed in dogs?

Answer 6

1. Heartworm antigen test. Enzyme-linked immunosorbent assay (ELISA), immunochromatographic, and immunofluorescent antibody test systems are available for detecting circulating heartworm antigen, a glycoprotein generated by the reproductive tracts of adult worms, predominantly female worms which is nearly 100% specific when positive.
2. Microfilaria test to assess for microfilariaemia. The test of choice is the modified Knott test, sometimes can be view in the PCV tube in the buffy coat in larger numbers.

Ancillary test include:
- Thoracic radiographs
- Echocardiogram
- ECG
- CBC and biochemistry
- Urinaylsis

Question 7

What does a positive test on a heartworm antigen test mean in dogs and cats?

Answer 7

A positive heartworm antigen test indicates the presence of specific heartworm antigen.

Question 8

What does a negative test on a heartworm antigen test mean in dogs and cats?

Answer 8

A negative antigen test result does not confirm that an animal is free of heartworm infection; it simply indicates that no antigen can be detected.

Question 9

What are the causes of false negative on a heartworm antigen test in dogs?

Answer 9

• Ab-Ag complex formation (can be managed by heat treatment of serum),
• Light infections, immature infections
• Unisex male infection
• Improper testing.

Question 10

What are the causes of false positives on a heartworm antigen test in dogs?

Answer 10

• Cross-reactivity (eg. Spirocera)
• Improper washing technique
• Circulating antigen post-adulticide therapy

Question 11

What are the causes of false negative on a microfilariae HW test in dogs?

Answer 11

This is called an occult infection. Causes of false negative include:
- Testing early in the prepatent period
- All-male infections
Host immune system destruction of microfilariae
- Use of medications that kill microfilariae including macrocyclic lactone-based preventatives.

Question 12

What changes can be seen on thoracic radiograph in cases of heart worm in dogs?

Answer 12

1. Can be normal - particular early in the disease couse.
2. Enlarged pulmonary trunk
3. Enlarged right ventricle due to pulmonary hypertension
4. Enlarged right branch pulmonary artery, also becomes tortuous, in some cases it becomes blunt, tapered, or prune.
5. Enlarged branch pulmonary arteries can be assessed by comparing the artery diameter to the diameter of the 4th rib on a lateral view or 9th rib on a dorsoventral view.
6. Abnormalities in the caudal or cranial lobar arteries
7. Pulmonary patterns associated with heartworm disease range from bronchial, to interstitial secondary to inflammation and fibrosis to alveolar usually due to pulmonary thromboembolism, hemorrhage, or edema.
8. Signs of RSCHF e.g. Caudal vena cava enlargement and ascites

Question 13

What are the benefits of echocardiography in HW cases in dogs?

Answer 13

• Identifies presence and location of intracardiac heartworms
• Estimates probability of pulmonary hypertension
• Evaluates secondary cardiac changes (e.g., chamber enlargement, functional changes)
• Assess for caval syndrome

Question 14

What are the limitations of echocardiography in HW cases in dogs?

Answer 14

• Not required or feasible for all infected animals
• Cannot image distal pulmonary arteries due to interference from air in the lungs
• Estimation of worm number is unreliable due to entanglement of worms
• Intracardiac worm burden categories are approximate, not precise
• Limited sensitivity

Question 15

What are the expected ultrasonographic findings of HW in dogs?

Answer 15

• Visualisation of adult heartworms appear as hyperechoic parallel lines (worm cuticle) with a central hypoechoic area (~1.3 mm)
• Typical worm locations seen include pulmonary arteries (proximal only), right atrium and right ventricle, caval veins and rarely in aberrant sites: left atrium or left ventricle
• Categorization of worm burden based on how the worm fill the right atrium.
• Can assess for pulmonary hypertension

Question 16

What are the CBC and biochemical changes that can be seen in heartworm in dogs?

Answer 16

CBC:
- Mild non-regenerative anemia (tends to be more severe in caval syndrome),
- Mild mature neutrophilia
Thrombocytopenia.
Eosinophilia and basophilia are indicators of parasitic disease.
- Microfilariae can be identified on a blood smear

Biochemistry:
- Hyperproteinemia (albumin and globulin)
- Less often azotemia as indicators of dehydration (pre-renal)
- Increased liver enzyme activities can also develop with caval syndrome

Question 17

What are the ECG findings in HW disease in dogs?

Answer 17

1. Can be normal
2. In advanced disease where there is right heart enlargement or myocardial damage:
   - Prominent S waves in the QRS complex
   - Right axis deviation (electrical axis shift indicating right ventricular enlargement)

Question 18

What changes on urinalysis can be seen in cases of heartworm in dogs?

Answer 18

• Proteinuria, which is associated with glomerular deposition of immune complexes
• Bilirubinuria as an indicator of red blood cell lysis attributed to traumatic destruction from passing through intracardiac worms

Question 19

How is heartworm treated in dogs?

Answer 19

Adulticidal therapy, combination of
1. Melarsomine dihydrochloride
2. Doxycycline: Utilised to eliminate Wolbachia (obligate intracellular G- bacteria)
3. Prednisone
4. Macrocyclic lactones:
Performed two months prior to first melarsomine injection. Utilised to reduce new infection, eliminate susceptible larvae and allow juvenile worms to mature and become susceptible to melarsomine

Macrocyclic lactones are utilised on a monthly basis (with doxycycline) where arsenical therapy (melarsomine) not possible

Surgical extraction is utilised for cases of caval syndrome

Question 20

How is heartworm controlled in dogs?

Answer 20

1. Macrocyclic lactones (MLs) are effective at clearing microfilariae, L3 & L4 larvae (+/- juvenile & adult heartworms)
   - Recommended in puppies from 8 weeks of age
   - Mechanism of action include: Glutamate chloride channel binding ,Chloride influx,
   flaccid paralysis
   - Examples include:
   Ivermectin, selamectin, moxidectin or milbemycin oxime

Question 21

What is the lifecycle of heartworm in cats?

Answer 21

The D. immitis life cycle in cats is shorter, which is attributed to differences in host-species immune response.

• Mosquito bite and infected animal ingesting microfilariae (L1) entering via the proboscis and begin to develop within the mouth of the mosquito
• The larvae molt in the mosquito from L1-L2 and L2-L3 over a 2-week period at which point they become infective
• The transition from L1-L3 requires adequate temperature and humidity and benefits from the presence of the endosymbiotic bacteria, Wolbachia.
• A feeding mosquito infects a host by penetrating the host skin or mucous membranes and transmitting the L3 larval stage.
• The L3 larvae begin to molt and migrate to the fourth larval stage (L4) in the host tissues within 12 days of entry.
• The final molt to the fifth larval stage (L5, immature adult) occurs 2 months after host infection, then to the mature adult in approximately 4-6 months.
• If mature adult female worms are present, they are able to produce microfilariae 7-8 months after the initial host infection.
• The presence of circulating microfilariae (L1) in a host provides a source of infection for biting mosquitoes to continue the D. immitis life cycle.

Question 22

What are the main differences in cats compared to dogs with heartworm disease?

Answer 22

1. Less common in cats (as they are more resistant to adult heartworm infections)
2. Low adult burden (with usually only 1 or 2 worms or unisex worms present)
3. Low microfilaria burden (with prevalence of <20% and less persistent due to immune reponse)
4. More frequent aberrant migration
5. Often asymptomatic (with 80% of cats self-curing)

Question 23

Describe the pathophysiology of the HW in cats.

Answer 23

1. Feline heartworm infection is the presence of migrating heartworm larvae in tissues or adult worms within the pulmonary vasculature.
2. Feline heartworm disease (FHWD), also known as heartworm-associated respiratory disease (HARD), is pathology caused by a current or past infection.
3. Although live adult worms in the pulmonary arteries cause local arteritis, some cats never manifest clinical signs. When signs are evident, they usually develop during one or more of the three stages of the disease.

• Stage 1: occurs with the arrival of sexually immature adult worms in the pulmonary arteries and arterioles approximately 75 to 90 days post infection, there is an intense inflammatory response due to the presence ofpulmonary intravascular macrophages (PIMs).
• Stage 2: mature worms begin to die and the suppression of the immune system ends; the degenerating parasites result in pulmonary inflammation and thromboembolism, which often leads to fatal acute lung injury.
• Stage 3: Occurs if the cat survives the death of an adult worm. Hyperplasia of Type 2 alveolar cells replaces normal Type 1 alveolar cells, potentially leading to permanent lung injury.

4. Caval syndrome occurs rarely in cats because infections are usually light; however, even one or two worms may cause tricuspid regurgitation and resultant heart murmur.

Question 24

What are the clinical signs and physical exam finding of heartworm disease in cats?

Answer 24

1. Can be vague malaise or can consist of respiratory, gastrointestinal (e.g., emesis), or occasionally neurologic manifestations, either chronically or acutely.
2. Signs of chronic respiratory disease such as persistent tachypnea, intermittent coughing, and increased respiratory effort are most common.
3. A right sternal border systolic heart murmur may be present in cats when worms reside in the right atrioventricular junction interfering with tricuspid valve function.
4. Anorexia and weight loss occur in some cats.
5. Intermittent vomiting
6. A peracute syndrome consisting of some combination of signs including respiratory distress, ataxia, collapse, seizures, hemoptysis, or sometimes sudden death may arise without warning.

Question 25

How is heartworm disease in cats diagnosed?

Answer 25

Combination of testing include 1. Heartworm antibody test which detects antibodies produced by the cat in response to presence of heartworm larvae, it can detect infection by both male and female worms, as larvae of either sex can stimulate a detectable immune response as early 2 months. 2. Heartworm antigen test. Detects antigen produced by the adult female heartworm or from the dying male (>5) or female heartworms. It is usually utilised as a comfirmatory test. 3. Thoracic radiography which may provide strong evidence of feline heartworm 4. Echocardiogram, - aids diagnosis in cats with clinical or radiographic signs suggestive of heartworm disease

Question 26

What does a positive HW antibody test indicate in cats?

Answer 26

Positive test indicates prior infection (detected from any worm stage) or; Confirms a current infection particularly when combined with a positive antigen test or identification of adult worms

Question 27

What does a negative HW antibody test indicate in cats?

Answer 27

Lower index of suspicion

Question 28

What does a positive HW antigen test indicate in cats?

Answer 28

Confirms presence of heartworms

Question 29

What does a negative HW antigen test indicate in cats?

Answer 29

Lower index of suspicion

Question 30

What are the causes of a false negative on a HW antigen test in cats?

Answer 30

False negative not uncommon due to immune-mediated destruction of juvenile worms and low burden consisting of an all-male infection

Question 31

What are the limitations of the HW antibody test in cats?

Answer 31

The sensitivity of different tests varies, results are often transient during the course of the infection, and false negative results occur as the immune response wanes.

Question 32

What are the radiographic findings of HWD in cats?

Answer 32

1. Subtle enlargement of the main lobar and peripheral pulmonary arteries, characterized by loss of taper, and sometimes tortuosity and truncation in the caudal lobar branches. - Quantitatively, a ratio of greater than 1.6 when comparing either caudal lobar pulmonary artery to the size of the 9th rib at the 9th intercostal space is indicative of pulmonary arterial enlargement 2. Enlargement of the main pulmonary artery segment may occur in heavily infected cats (not reliable as most cats do not develop pulmonary hypertension 3. A bronchial and/ or unstructured interstitial lung pattern 4. Other less common findings include an alveolar pattern, hyperinflation of the lungs with flattening of the diaphragm, focal parenchymal radiodensities, focal hyperlucency, consolidated lung lobes, pleural effusion, and pneumothorax

Question 33

What are the echocardiographic findings of HWD in cats?

Answer 33

- Visualisation of adult heartworms appear as hyperechoic parallel lines (worm cuticle) with a central hypoechoic area (~1.3 mm) - Most often in the main and right lobar branch of the pulmonary artery - Pulmonary hypertension is uncommon

Question 34

How is HWD treated in cats?

Answer 34

1. Macrocyclic lactones: utilised for asymptomatic cases where no radiographic changes 2. Prednisolone: utilised for symptomatic cases or where radiographic changes are present. 4. +/- Doxycycline (as role of Wolbachia in feline infection is unknown) 5. Surgical extraction NB: Melarsomine is toxic in cats

Question 35

How is HWD disease in cats prevented

Answer 35

1. HW preventatives: Heartworm chemoprophylaxis can be achieved in cats with monthly doses of milbemycin oxime orally, or topical eprinomectin, moxidectin or selamectin 2. Vector control e.g. mosquito repellent and environmental control.