Coughing cats: Asthma or heartworm? (Proceedings)

The cat is considered a resistant, yet susceptible host for Dirofilaria immitis. Worm burdens are much lower in cats than in dogs (average 15 worms in dogs and 1-3 in cats in endemic areas) and about 1/3 of feline infections involve worms of the same sex. Feline heartworm (HW) was first described in the 1920s; awareness has increased greatly since the introduction of Heartgard for cats in 1997 and the associated marketing campaign. Feline HW remains a difficult to diagnose, yet fully preventable disease.

Cats are infected with HW in the same way as dogs, but far fewer larvae mature to adulthood. It is difficult to estimate prevalence of feline HW for several reasons – there is no ideal test, inapparent infections go unnoticed, and some cats die acutely without a diagnosis. The prevalence of immature infections is higher than the adult infection rate. Based on necropsy surveys of shelter cats, feline HW is thought to be present at about 5-15% of the canine rate in endemic areas.1 Certainly wherever canine heartworm is found, feline HW is present as well.

Our understanding of feline heartworm infection has progressed rapidly in recent years, especially with regard to the pathophysiology of the respiratory tract signs associated with various stages of infection.1-3 Many cats will have no clinical signs of HW disease and they will spontaneously eliminate the infection without incident. Other cats may have clinical signs associated with infection at two possible time points:

     1) Upon arrival of immature worms (L5s) in the pulmonary arteries and arterioles in the 3 to 6 month post-infection period. The high mortality of immature worms stimulates a severe vascular and parenchymal inflammatory response. Pulmonary lesions may be long-lasting. The clinical response in the cat is termed HARD because respiratory signs predominate (dyspnea, tachypnea, and cough). The clinical signs may be transient or intermittent. Clinical signs subside as the worms mature. Many cats with HARD are misdiagnosed as having asthma or bronchitis.

     2) Upon death of adult worms, with release of antigens and toxins leading to pulmonary inflammation and thromboembolism. Clinical signs include rapid onset of respiratory compromise or sudden death (occurs in 10% or more of HW infected cats). Even the death of 1 adult worm can be lethal by causing circulatory collapse and respiratory failure. Adult worms are able to suppress pulmonary intravascular macrophage activity and so actually induce little inflammation until they die in 1 to 2 years.

Nonspecific clinical signs associated with feline HW include chronic vomiting (present in 25-33% of cases), lethargy, anorexia, and weight loss.4 Less common signs due to aberrant migration include ascites, pneumothorax, chylothorax, neurological signs (ataxia, seizures, syncope, collapse, blindness, vestibular signs), and hemoptysis. Signs of cardiac disease or failure are very uncommon in cats with HW. Sudden death occurred in 10% of infected cats in one study.4

Our understanding of the role of Wolbachia, an endosymbiont Rickettsial bacterium found in D. immitis in feline HW disease is evolving. HW infected cats may be exposed to Wolbachia when larvae or adult worms die, and probably at other times in the worm's life cycle. A strong antibody response against Wolbachia surface protein has been demonstrated in HW infected cats.5 Wolbachia may play a role in the inflammatory response seen in HARD; raising the possibility that treatment with antibiotics such as doxycycline may help reduce clinical signs in cats with HARD. Research is currently underway to define the exact relationship between Wolbachia and pulmonary inflammation in cats.6

Diagnosis of feline HW may be difficult. Cats are rarely microfilaremic so filtration or IFA testing for microfilaria is not recommended. No single diagnostic test can detect feline HW at all life stages of the worm. Combining antigen and antibody testing achieves higher sensitivity than either test alone7-8, but may generate more false positives.

A positive HW antibody test documents exposure to early stage infection but not necessarily current infection, and a negative test does not rule out infection. The different tests available also vary widely in sensitivity and specificity, as each brand may detect a different stage of larval development. Interestingly, up to 30% of cats on HW prevention may become antibody positive although they are not at risk for HARD.

HW antigen testing detects proteins associated with the reproductive tract in mature female worms, so that a positive test confirms the presence of at least one adult female HW. A negative antigen test does not rule out infection with adult worms as antigen levels may be below the detection threshold of the test. Antigen tests miss the early stages of HW infection and don't detect the immature worms that cause HARD. While sensitivities and specificities of the various tests vary, false positives should be uncommon.

The American Heartworm Society (www.heartwormsociety.org) guidelines for testing cats:

     • Screen healthy cats with both antigen (for adult worms) and antibody (for immature worms) tests

     • For cats with clinical signs compatible with HARD, use both an antigen and antibody test, and thoracic radiography

     • Testing may be used to monitor the progress of cats previously diagnosed with HW

     • Testing cats before administering preventative medication helps increase awareness about local risk potential and will establish a baseline reference in case the cat must be retested

     • A positive test does not preclude administration of chemoprophylaxis in order to prevent additional infections

Thoracic radiography can also provide evidence for HW disease independent of serology. Radiography is also valuable for assessing severity of disease and monitoring progression or resolution. The most characteristic radiographic features of feline HW disease are a subtle enlargement of the pulmonary arteries (especially the caudal lobar), loss of taper and sometimes tortuosity in the caudal lobar branches. These characteristics are best seen with a ventrodorsal view and may only be visible in the right hemithorax. They may be found in about 50% of HW positive cats. A common secondary feature is a bronchointerstitial lung pattern that is not unique to feline HW disease. In fact, feline asthma and feline HW disease may have a very similar radiographic appearance.

Interpretation of HW tests in cats (after Nelson, 2007)

Echocardiography is useful for antigen positive cats. Heartworms are most often found in the main and right lobar branch of the pulmonary artery. The body wall of an adult HW is strongly echogenic, producing a signature sign with echocardiography. With an experienced sonographer and good quality equipment, there may be a greater chance of finding adult HW in infected cats than in infected dogs. Quantification of the worm burden is difficult, however.

Only 4% of cat owners give HW preventatives, compared to 59% of dog owners. Even indoor cats in endemic areas should be on HW prevention. In one North Carolina study, 27% of HW positive cats were considered indoor only.4 Four drugs are currently licensed for prevention of feline HW by preventing development of L3 and L4 in subcutaneous tissues. Two products are oral: ivermectin (Heartgard; Merial), milbemycin (Milbemax, Interceptor; Novartis); and two are topical: selamectin (Revolution; Pfizer), moxidectin (Advocate; Bayer),

Treatment of Asthma or HW Patients with Acute Clinical Signs

Patients in acute respiratory distress may be unstable and should be examined and treated with great care. Some drugs may cause a temporary increase in heart and respiratory rate. When using combination drug therapy, be aware of the risk of arrhythmia in stressed, hypoxic cats. Some very anxious and stressed dyspneic cats may benefit from mild sedation with a low dose of acepromazine (0.05 mg/kg, IM, SQ).

     First line therapy

     Supplemental oxygen: Preferably using an oxygen cage

     Bronchodilators: Best via nebulizer or metered dose inhaler as the effects are seen within 5 minutes (versus 15-30 minutes by injection); give 2-4 puffs of inhaled drugs such as albuterol every 20 minutes; repeat injectable drugs in 15 minutes if required

     Short-acting corticosteroid: Intravenous dexamethasone or prednisolone sodium succinate; may take 3-6 hours for maximum effect; useful in cats on chronic oral bronchodilator therapy to reverse down-regulation of airway β-adrenergic receptors causing drug tolerance

     Second line therapy

Anticholinergics: Atropine, glycopyrrolate; block vagal input causing bronchoconstriction and decrease bronchial secretions; not useful for long term therapy as these drugs will cause increased viscosity of airway mucus

     Third line therapy

Epinephrine: α- and β-agonist, can reverse bronchoconstriction; may cause arrhythmia

Treatment of HW Positive Cats

Heartworm positive cats with no clinical signs of disease, but with radiographic evidence of pulmonary vascular/interstitial disease, should be monitored every 6 to 12 months with repeat antigen and antibody testing, and radiography. Recovery is indicated by improvement in radiographic signs and seroconversion of a positive antigen test to negative. It may be prudent to administer prednisone to cats with radiographic signs of disease whether or not they have clinical signs of illness, although this is controversial. Whenever antibody or antigen positive cats have clinical signs, prednisone should be administered on a decreasing dose schedule (2 mg/kg/day, decreasing to 0.5 mg/kg/day every other day by 2 weeks, discontinuing after an additional 2 weeks). The effect of treatment should be assessed by clinical response and radiographs. Cats with recurrent signs can be retreated. Anecdotally, treatment with a leukotriene receptor antagonist such as montelukast (Singulair, Merck®) at 0.5 mg/kg/day PO may also be beneficial.

Adulticide therapy is rarely indicated in cats. No safe and efficacious adulticides are available for cats. Removal of adult worms via right jugular venotomy or left thoracotomy has been described when worms can be identified ultrasonographically, but extraction procedures can result in acute shock and death if the worm cuticle is damaged.

References

1. Litster AL, Atwell RB. Feline heartworm disease: a clinical review. J Feline Med Surg 2008;10:137-144.

2. Atkins CE. Reassessing the definition of heartworm infection in cats. J Am Vet Med Assoc 2007;231:1338.

3. Browne LE, Carter TD, Levy JK, et al. Pulmonary arterial disease in cats seropositive for Dirofilaria immitis but lacking adult heartworms in the heart and lungs. Am J Vet Res 2005;66:1544-1549.

4. Atkins C, DeFrancesco T, Coats J, et al. Heartworm infection in cats: 50 cases (1985-1997). J Amer Vet Med Assoc 2000;217:355-358.

5. Morchon R, Ferreira AC, Martin-Pacho JR, et al. Specific IgG antibody response against antigens of Dirofilaria immitis and its Wolbachia endosymbiont bacterium in cats with natural and experimental infections. Vet Parasitol 2004;125:313-321.

6. Dingman P, Levy JK, Kramer LH, et al. Association of Wolbachia with heartworm disease in cats and dogs. Vet Parasitol 2010;170:50-60.

7. Snyder P, Levy J, Salute M, et al. Performance of serologic tests used to detect heartworm infection in cats. J Amer Vet Med Assoc 2000;216:693.

8. Berdoulay P, Levy JK, Snyder PS, et al. Comparison of serological tests for the detection of natural heartworm infection in cats. J Am Anim Hosp Assoc 2004;40:376-384.