Heartworm Disease

Chapter 10 Heartworm Disease



Clay A. Calvert, Justin David Thomason



INTRODUCTION


Heartworm disease is a common problem in tropical and subtropical regions. Heartworm infection has spread throughout most areas of the United States, but the prevalence is still low at high elevations and in most northern states. Endemic foci frequently occur in regions with otherwise low prevalence and it is difficult to eliminate heartworms from a region once they have been established. Wild animal reservoirs include wolves, coyotes, foxes, California gray seals, sea lions, raccoons, and ferrets.



HEARTWORM DISEASE



Etiology and Life Cycle


Heartworm infection is produced by the parasite Dirofilaria immitis and is transmitted to dogs mostly by 10 to 15 species of mosquitoes. Mosquitoes can transmit infective larvae (L3) 2 to 3 weeks after ingesting a blood meal. Infection rates vary among cats in endemic regions but are usually 10% to 20% of that of dogs within the same enzootic region. Being male, a large breed, and outdoors increases the risk of infection in dogs.



Canine Infection Life Cycle



• Female mosquitoes are the intermediate hosts and acquire the first-stage larvae (microfilaria) by feeding on infected dogs. Two molts then occur to produce the infective L3 stage.

• Larvae development to the third stage usually requires 1 to 2.5 weeks, depending on the ambient temperatures. Mosquitoes can survive the development of only low numbers (<10) of larvae. Larvae development within the mosquito requires an average daily temperature of at least 57° Fahrenheit. The cooler the temperature, the longer the time required for L3 to develop and vice versa. Transmission is unlikely to occur during the cold months of the year, even in most southern regions of the United States. This is because when the temperatures are moderately low, the time required for development from L1 to L3 may exceed the life-span (30 days) of the mosquito. Third-stage larvae (L3) infect the dog via the bite wound created during feeding.

• Larvae migrate through the subcutaneous tissues and vascular adventitial tissues for about 100 days. During this time, two molts occur. Young adults (L5 larvae) enter the vascular system at 3 to 3.5 months post-infection and are in the small pulmonary arteries after 5 to 6 months.

• In the dog, adult worms and microfilaria are thought to have a natural life-span of 3 to 5 years and 1 to 2 years, respectively.

Key Point


Adult worms are present in the pulmonary arteries approximately 6 months after transmission from the mosquito.


• See Figure 10-1.

• Microfilaria can appear after 6 months, increase in concentration for 6 months, plateau for several months, and then decrease in concentration as long as super-infection does not occur.

• Microfilaria-specific antibody-mediated, occult infections occur in the presence of persistent host antibody excess. Antibody-dependent leukocyte adhesions entrap microfilaria in the pulmonary microcirculation. Between 10% and 67% of all heartworm infections are occult, and some of these are due to immune-mediated host reaction. In most endemic regions, the incidence of occult infections is approximately 20% to 25% of all infections. Dogs administered macrolide prophylaxis that are, or become, infected will not have microfilaremia.

• Microfilaria-leukocyte (neutrophils and eosinophils) complexes are engulfed by phagocytic cells of the mononuclear phagocyte system, resulting in granulomatous inflammation.

• Predominately eosinophilic inflammation, with minimal granulomatous inflammation, produces allergic pneumonitis.

• Progressive granulomatous inflammation occasionally occurs and leads to lethal pulmonary eosinophilic granulomatosis.

image

Figure 10-1 Life cycle of Dirofilaria immitis.


(Courtesy Idexx Corp., Westbrook, Maine.)



Feline Infection Life Cycle



• Some mosquito species do not like to feed on cats and cats are relatively resistant to infection, requiring a greater L3 inoculation. Therefore, the infection rate in unprotected cats is at least 80% lower than that of unprotected dogs. The numbers of infective larvae that mature are fewer than in dogs, and the pre-patent period is usually 1 to 2 months longer. The natural survival time of adult worms in the cat is thought to be no more than 2 years.


Prevalence


Heartworm infection is most common in tropical and subtropical climates. Infection is inevitable in chronically unprotected dogs along the southern Atlantic and Gulf coasts and other highly endemic regions. The prevalence in cats varies by geographic region. It is much lower than dogs in some areas, similar to dogs in some areas, and the incidence is probably underestimated. Dogs housed outdoors have a four- to five-fold increased risk compared to those housed indoors. Infection is most common in dogs 4 to 7 years of age, but in highly endemic regions infection is common in younger dogs.



Pathogenesis


Disease onset and severity largely reflect the number of adult heartworms. In infected cats, the average number of adult worms is 3 to 6, depending on the concentration of infected mosquitoes and the ambient temperature in any given region.



Worm Location



• Until the adult worm burden exceeds 50 in a 25 kg dog, nearly all worms are located in the pulmonary arteries. Worm burdens of approximately 75 are associated with worms located in the right atrium. Caval syndrome typically is associated with worm burdens of 100 or greater.


Response to Live Worms in Dogs



• Pulmonary pathology is produced beginning with the young adults. Even if infection is identified 7 months post-infection, the L5 have already been in the pulmonary arteries for a few months and some pathology has occurred. Pulmonary arterial endothelial damage and subsequent myointimal proliferation most severely affects the caudal and intermediate lung lobes, which are those receiving the highest blood flow.

• Pulmonary lobar arterial enlargement, tortuosity, and obstruction of smaller branches begin within a few weeks of worm arrival. Intrapulmonary blood flow is obstructed as the disease progresses, and blood is diverted to less severely affected lobes. Small downstream arterioles become damaged and leak plasma and inflammatory cells into the surrounding lung parenchyma. This causes interstitial and alveolar lung infiltrates and granulomatous inflammation.

• Pulmonary arterial obstruction and lung inflammation cause fever, coughing, dyspnea, hemoptysis, leukocytosis, and thrombocytopenia. Pathology is more severe and accelerated in active dogs, relative to inactive dogs, for any given worm burden. Small dogs do not tolerate heartworm infection as well as large dogs.


Response to Live Worms in Cats



• The response in cats and ferrets is similar to that of dogs but there is more pulmonary arterial muscular hypertrophy and the barrier to oxygen diffusion is more severe than in the dog. Mortality in cats and ferrets is higher than in dogs.


Response to Dead Worms



• The most severe disease is seen in response to dead worm fragments that are swept into small arterioles. Pulmonary vascular compliance and blood flow become impaired to varying degrees and severe arterial disease results in pulmonary hypertension, increased right ventricular afterload, and eventually right-sided congestive heart failure (CHF). Parenchymal lung disease (infarction and consolidation) develops secondary to pulmonary arterial thromboembolism and increased vascular permeability.


History



Dogs


• The history in dogs with heartworm infection varies considerably. Many infections are discovered in asymptomatic dogs by immunodiagnostic screening. Some dogs are totally without signs; others have unexplained tachypnea, exercise intolerance, or cough. Signs consistent with pulmonary hypertension, with or without overt right-sided CHF, are associated with severe heartworm disease.


Cats


• The history in cats also varies considerably. Lethargy and decreased appetite may be reported by the owners. Coughing, emesis, and sudden or episodic dyspnea are typical signs in cats. However, sudden death may be the first sign of infection. CHF is uncommon.


Clinical Signs


The clinical signs associated with heartworm infection reflect the adult worm burden, duration of infection, and host-parasite interaction. Respiratory signs are most prominent.



Dogs



• Exercise intolerance, coughing, dyspnea, and respiratory crackles occur in dogs with moderate and advanced heartworm disease. Hemoptysis occurs with severe disease and is caused by pulmonary thromboembolism. It can be seen before, but occurs more often after adulticide treatment. Acute dyspnea and increased pulmonary radiographic infiltrates may develop secondary to spontaneous worm death. Syncope is associated with severe pulmonary arterial disease and pulmonary hypertension. Signs of elevated central venous pressure indicate severe pulmonary hypertension with incipient or overt right-sided CHF. Physical findings include prominent jugular pulse, distended jugular veins, hepatomegaly, and ascites.

• Hemoglobinuria commonly occurs in association with caval syndrome (i.e., acute hemolytic crisis caused by obstruction of the vena cava with adult worms) and occasionally when severe pulmonary arterial disease results in hemolysis due to fibrin-thrombus related RBC trauma. Thrombocytopenia is usually a consequence of these complications.

• Nephrotic syndrome occasionally occurs as the result of severe glomerular disease (amyloidosis or immune complex glomerulonephritis). Manifestations include proteinuria, hypoalbuminemia, hypercholesterolemia, ascites and occasionally peripheral edema and azotemia.


Cats



• Clinical signs in cats are different than in dogs. The common signs are vomiting, collapse or syncope, asthma-like syndrome, coughing, sudden death, and occasionally central nervous system signs. Signs occur most often early in the infection and again when young adult worms arrive in the pulmonary arteries. Severe pulmonary complications and death are most likely to occur whenever one or more adult worm dies, either spontaneously or as a result of Immiticide administration.

• Asthmatic signs are a common manifestation and often occur about 3 to 4 months post-infection. A strong antibody response at this time may destroy the developing larvae. If not, then a period of quiescence occurs only to have asthma-like signs recur in some cats 7 to 8 months post-infection.

• Vomiting is a common, sporadic sign. It often is not associated with eating, may include food, but mucus and bile are often the major components. Vomiting and coughing in a cat should increase the index of suspicion.

• Sudden death related to spontaneous worm death and thromboembolism is more common in cats than in dogs.

• Neurologic signs, usually seizures, occur occasionally when aberrant worm migration to the brain occurs.

• See Box 10-1.


Key Point


The combination of vomiting, eosinophilia, and hyperglobulinemia warrant a high index of suspicion of heartworm infection in cats.



Box 10-1 Clinical Signs Associated with Feline Heartworm Disease


Modified from Calvert C. Feline heartworm disease. In Fox PR, ed: Canine and feline cardiology, New York, 1988, Churchill Livingstone.

























































Acute Signs Chronic Signs
Sudden death* PIE† syndrome
Respiratory Coughing
Pulmonary embolism Dyspnea
Collapse; shock Cardiopulmonary
Hemoptysis Lethargy
Dyspnea; cough Weakness
Pneumonitis Right-sided CHF‡
Dyspnea; cough Anorexia
Neurologic Gastrointestinal
Blindness Vomiting
Seizures  
Ataxia  
Coma  
Circling  
Syncope  
Gastrointestinal  
Vomiting  

* From severe pulmonary thromboembolism or heartworm occlusion of main pulmonary artery.


† Pulmonary infiltrates of eosinophilia.


‡ Congestive heart failure.



Diagnosis


The diagnosis of heartworm infection in dogs is based on immunodiagnostic antigen testing. Microfilaria in the peripheral blood can be detected by a direct smear or a concentration test (modified Knott test or millipore filter test) in dogs with or without clinical or radiographic findings consistent with the disease. Testing puppies younger than 6 months of age is not indicated.


Affected cats usually lack circulating microfilaria, may have suggestive radiographic abnormalities, and echocardiography is very useful. A positive enzyme-linked immunosorbent assay (ELISA) test for heartworm antigen, antibody or both may be present.



Laboratory Studies


• The minimum data base varies depending on the patient’s age, clinical signs, and preference of individual clinicians. The minimum pretreatment database for all dogs suspected of having heartworm infection includes packed cell volume, blood urea nitrogen, urine specific gravity, urine protein determination, and heartworm antigen test. Thoracic radiographs should always be taken because they reveal more about disease severity than any other single test.

• The minimum data base for cats should include thoracic radiographs. Echocardiography and fecal studies for lungworms are useful for the differential diagnosis of heartworm infection, feline asthma, cardiomyopathy, bronchitis, pulmonary fibrosis, and lung parasites. A tracheal or bronchial wash may be useful for detecting lung parasitic lesions, such as those produced by Aelurostrongylus spp.


Clinical Pathology


No abnormal test results are pathognomonic for heartworm infection.



Complete Blood Count


• Eosinophilia and basophilia are the most common abnormalities in dogs. Eosinophilia is more common and the highest counts tend to occur with occult infections. Dipetalonema (Acanthocheilonema) reconditum infections produce eosinophil counts as high as those associated with D. immitis infection.

• Neutrophilic leukocytosis with a left shift is usually the result of pulmonary thromboembolism.

• Thrombocytopenia is usually present when there is severe pulmonary arterial disease and thromboembolism.

• Hemoglobinuria, usually accompanied by thrombocytopenia, is seen with caval syndrome and with severe pulmonary thromboembolic disease.


Serum Biochemistry and Urinalysis


• Azotemia may occur in dogs with complicated infections. Prerenal azotemia can be caused by dehydration or right-sided CHF. Primary azotemia can result from glomerulopathies. Increased hepatic enzyme activities may occur; however, increases up to 10-fold do not affect treatment, complications, or survival. Hepatic failure with icterus can occur in dogs with chronic right-sided CHF.

• Proteinuria is common and is most pronounced in patients with severe infections or renal amyloidosis. Mild proteinuria usually resolves after Immiticide treatment.

• Hypoalbuminemia occurs in some dogs with severe infections; hyperglobulinemia is common in dogs and cats with chronic heartworm disease.

• Loss of albumin into the third space occurs with right-sided CHF and is complicated by hepatic insufficiency, intestinal congestion, and free-water retention. Hyponatremia and/or mild hyperkalemia may result.


Screening in Dogs


• Screening in dogs is usually recommended for the late spring in cooler climates to maximize the likelihood of detecting infections acquired in the previous year. In hotter climates, infections may be acquired as late as November or early December and these infections are not detectable until May or June. Run an antigen test 7 months after the end of the previous transmission season (Figure 10-2).

image

Figure 10-2 An algorithm approach to the diagnosis of heartworm infection (HWI).


(Modified from Ettinger SE, Feldman EC: Textbook of veterinary internal medicine: diseases of the dog and cat, ed 6, St Louis, 2005, WB Saunders.)



Screening in Cats


• Infections in cats can usually be identified by echocardiography. Combined antibody and antigen testing is recommended for cats. A negative antibody test weighs against the diagnosis. Although a positive antigen test confirms infection in cats, many infected cats are antigen test negative (Figures 10-3 and 10-4).

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Aug 15, 2016 | Posted by in SMALL ANIMAL | Comments Off on Heartworm Disease

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