Heartworms in cats: new insights (Proceedings)

August 1, 2011

Article

A new study performed at Auburn University's College of Veterinary Medicine is radically changing our understanding of how heartworms affect the cat. In this study three groups of cats were studied for 8 and 16 months with antibody and antigen tests, radiographs of the heart and lungs, and necropsy examinations of the heart and lungs.

"If you're not seeing heartworm-positive cats in your clinic, rest assured that heartworm-positive cats are seeing you."

Ray Dillon, DVM, DACVIM

A new study by Dillon and Blagburn

Life cycle

1. Mosquitoes bite cats about as frequently as they bite dogs. Some cats are allergic to the bite and show a characteristic dermatitis on the nose and pinnae. The majority do not have this reaction, as the majority of dogs bitten by fleas do not have flea bite dermatitis.

2. When a mosquito bites a cat, third-stage larvae (L3) are deposited on the cat's skin. Within minutes they enter the subcutaneous tissue through the bite wound.

3. The L3 molt within a couple of days to fourth-stage larvae (L4). L4 migrate subcutaneously in fat and muscle for 2 months then molt to become a juvenile worm. (Juvenile worms have been incorrectly called L5.)

4. Juvenile worms enter circulation via a peripheral vein. This occurs about 60 days after infection.

5. An antibody response begins about this time; some cats test antibody positive.

6. Within the next 15 to 30 days (75 to 90 days post infection) the juvenile worms arrive in the caudal pulmonary arteries.

7. By about 100 days post infection there are 2 inch long juvenile heartworms in the caudal pulmonary arteries.

8. The vast majority of the juvenile worms die causing an intense inflammatory response affecting the pulmonary arterioles, bronchi, and alveoli.

9. Antibodies begin to wane as the juvenile worms die.

10. If the juvenile worms mature to adults, the adult worms suppress the immune system causing antibodies to wane. Most antibody tests turn negative about 4 months later as long as new infections do not occur. In locales with long mosquito seasons, antibody tests will remain positive due to formation of new juvenile worms.

Hard

1. Heartworm Associated Respiratory Disease (HARD) is unique to the cat.

2. It is defined as vascular, airway, and interstitial lung lesions caused by the death of juvenile worms. The inflammation may last up to 8 months.

3. If we administer 100 infective larvae to a dog, 75 will mature to adults.

4. If we administer 100 infective larvae to a cat, many will become juvenile heartworms, but only 3-4 will mature to adults.

5. A very large number of juvenile worms develop but never make it to adulthood due to the effects of the cat's immune system. They are the cause of HARD.

6. Juvenile worms are, according to Ray Dillon, "hit and run drivers." "They get into the cat, cause significant lung damage, and leave no evidence they were there." Severe lung lesions are present, but:

a. There will be no adult worms on necropsy.

b. The juvenile worms disintegrate within the lung tissue.

c. Antibody disappears very quickly.

d. Antigen tests will be negative because there have been no adults.

7. Radiographically these cats look similar to cats with allergic bronchitis. Interstitial or bronchial patterns may be present. In addition, the caudal pulmonary arteries may be enlarged and blunted. In some cats, apparent enlargement may be due to periarterial inflammation.

8. Clinically these cats look like a cat with allergic bronchitis. Coughing is common and is usually relieved with corticosteroids.

9. The lung damage caused by the juvenile worms may not show up until later in life as chronic interstitial lung disease, chronic bronchitis, or COPD.

10. Many of these cats are antibody positive and antigen negative. However, many of these cats test negative on both antigen and antibody tests making differentiation from cats with allergic bronchitis virtually impossible.

11. In colder states, HARD occurs 4 to 6 months after the mosquito season. In warmer states, HARD is a year round problem but may have higher incidence in winter and spring. Allergic bronchitis is also most common in winter and spring.

12. HARD occurs even if an adult heartworm never develops because it is not caused by adult heartworms.

Incidence

1. A large necropsy study in Gainesville, Florida found 5% of cats to have adult heartworms, virtually the same incidence as FeLV and FIV infections.11

a. In the same group of cats 15% were antibody positive.

b. In the same group of cats many that did not have adult worms present had signs of severe lung disease. At the time HARD was not understood.

2. In the 1997 Heska Heartworm Survey4, 15.9% of tested cats were heartworm antibody positive.

3. In the 1998 Miller, et al study5, 12% of tested cats, many from non-endemic areas, tested antibody positive.

4. Because many cats with HARD test antibody negative, the 12 to 16% incidence is probably much lower than reality.

5. There is strong evidence that heartworm disease is at least three times more prevalent than renal disease, diabetes, FeLV infection, and FIV infection. It should be taken much more seriously than it has been in the past. The only reason we have not done so in the past is our lack of understanding of the disease and the testing problems.

6. For every 10 heartworm infected dogs in a given locale, there is one cat that has adult heartworms. However, it is likely that only about 10% of heartworm infected cats have an adult worm. That makes the exposure and infection rates of dogs and cats about the same.

7. If you practice in an area in which heartworms affect dogs, they also affect your feline patients at about the same rate but in different ways.

Testing

1. A positive antibody test means there is (one or more):

a. A current infection with late L4.

b. A current infection with juvenile heartworms.

c. A current infection with adult heartworms.

d. A previous heartworm infection. Antibody persists about 4 months.

2. The different antibody tests turn positive at different times in the life cycle. This was clearly demonstrated when several were run simultaneously at different times in the life cycle.8 The ideal, but not practical, way to test for antibody is to simultaneously perform tests made by several manufacturers or offered by several laboratories.

3. A positive antigen test means there is (one or more):

a. One or more adult female heartworms.

b. One or more dying adult female heartworms.

c. > 5 dying male adult heartworms.

4. About 75% of cats carrying adult heartworms will test antigen positive.

5. All-male infections and infections with only juvenile heartworms test antigen negative.

6. Antigen or antibody testing is not necessary to begin heartworm prevention. However, if testing is performed and produces a positive result it is meaningful.

a. Positive antibody: This cat is or has been infected with heartworms. It is clearly at risk of future infections.

b. Positive antigen: This cat is infected with adult heartworms. It is clearly at risk of future infections.

Diagnosis of adult heartworm infections

1. A positive antigen test is diagnostic for the presence of adult heartworms.

2. An antibody test may or may not be positive when adult heartworms are present, depending on the specific test and the number of heartworms present.

3. Heartworm disease should be suspected when:

a. Chronic coughing occurs.

b. Chronic vomiting occurs.

c. Gradual weight loss occurs in a cat with normal CBC, chemistry panel, electrolytes, FeLV test, FIV test, and TT4.

4. If adult heartworm disease is suspected:

a. Antigen and antibody testing is recommended.

b. Chest radiographs should be made looking for interstitial lung or bronchial disease, enlarged caudal pulmonary arteries that may also be tortuous and/or blunted.

c. Ultrasound can be employed looking for "two parallel lines" in the right ventricle or pulmonary outflow tract. However, worms usually only exist in the caudal pulmonary arteries, which are usually not visualized with ultrasound.

d. Corticosteroids may be given to see if clinical improvement occurs. However, this is not specific for heartworm disease and should be considered a "test" of last resort.

Treatment of hard

1. Most of these cats have mild clinical signs (coughing), but a severe respiratory crisis can occur when an a large number of juvenile heartworms die at once.

2. Corticosteroids at shock doses (dexamethasone sodium phosphate; 1-2 mg/kg IM or IV or prednisolone sodium succinate; 50-100 mg/kg IV) and a bronchodilator should be used in a crisis.

3. Oral prednisolone (1-2 mg/kg) can be used prophylactically for inflammation.

Treatment of adult infections

1. Melarsomine is not recommended in cats due to potential toxicity. The recommended dose and the toxic dose (for cats) is very close. In addition, the consequences of rapid worm die-off can be very serious.

2. Adult heartworms in small numbers usually cause relatively mild clinical signs that include coughing and chronic vomiting. Rarely, sudden death occurs due to pulmonary thrombosis.

3. A severe respiratory crisis can occur when an adult heartworm dies.

4. Corticosteroids at shock doses (dexamethasone sodium phosphate; 1-2 mg/kg IM or IV or prednisolone sodium succinate; 50-100 mg/kg IV) and a bronchodilator should be used in a crisis.

5. Montelukast (Singulair®), a antileukotriene, may help to prevent an acute pulmonary crisis when an adult heartworm dies. It is used prophylactic ally at 2 mg/day/cat.

6. Doxycycline has been used for treating Wolbachia in dogs; it is controversial in cats. There are no studies showing benefit to cats, but it is a very well tolerated drug. Dose: 10/mg/kg/day for one month. Some recommend 20 mg/kg/day.

7. In the past, it was believed that adult heartworms live about 18-24 months; however, a recent Italian study shows that they can live up to 4 years.

8. If we had a drug to kill adult heartworms, it would not be advisable to use because dead worms cause more pathology than live worms, especially if several worms are killed simultaneously.

9. Adult heartworm extraction via the jugular vein has been used to rapidly reduce the adult worm burden.

What should we do?

1. Heartworm disease is much more common than we have thought in the past; heartworms are difficult to diagnose; there is no good way to treat infected cats.

2. It is estimated that currently less than 5% of cats are on heartworm prevention.

3. All cats should be on heartworm prevention using the same schedule as for dogs in that locale.

a. About 25% of diagnosed cats are indoors only.

4. We should be proactive about promoting the use of heartworm prevention.

Recommended References

Compendium, July 2008.

Supplement to the Compendium, August 2008.

Client Handout to Promote Use of Heartworm Prevention

New Findings Regarding Heartworms in Cats

Heartworms have traditionally been considered a parasite of dogs; however, they have been occasionally found in cats for many years. Our concept of heartworms in cats has been that they were very uncommon and an "accidental" infection. As such, heartworm prevention has been recommended as a good "insurance policy" against a very unlikely happening.

How cats get heartworms

Mosquitoes are carriers of heartworm larvae (Stages L1 and L2). Although not all mosquitoes carry heartworm larvae, a large percentage do so in most geographic areas of the United States. Dogs are the main source of the larvae that are ingested by the mosquitoes and injected into the next victim, either canine or feline. Cats living in a house with a heartworm infected dog have about an 80% chance of being infected.

When the mosquitoes bite cats, they deposit larvae under the cats' skin; these are known as Stage 3 larvae (L3). L3 larvae mature to L4 then become juvenile or immature adults, which migrate to the major blood vessels near the heart. They are present about 3-4 months after the cat has been bitten by the mosquito. Further maturation shortly thereafter results in adult heartworms. The adults grow to be 4-6 inches in length, living primarily in the pulmonary arteries, the arteries carrying blood from the heart to the lungs. They cause tremendous inflammation to these arteries and to the lung tissue surrounding the arteries. If the number of adult exceeds the capacity of these blood vessels, they "spill over" into the right side of the heart, where they occasionally can be seen with an ultrasound study.

The cat's immune system is constantly trying to kill the larvae and the adults. It is largely successful so we do not see a large number of cats with adult heartworms. However, as the juvenile adults and the adult heartworms die, they cause a great deal of inflammation in the lungs before they are finally removed. Because over 90% of the juvenile heartworms are killed and thrown in to the lungs, inflammatory lung disease is very significant.

A new study

A new study performed at Auburn University's College of Veterinary Medicine is radically changing our understanding of how heartworms affect the cat. In this study three groups of cats were studied with blood tests, x-rays of the heart and lungs, and post-mortem (autopsy) examinations of the heart and lungs for 8 months. The first group looked at the effects when heartworm larvae were deposited under the skin and allowed to mature without interference. The second group also received heartworm larvae under the skin; however, three months later a drug was given to kill the larvae before they became adults. The third group was put on a heartworm prevention product (Revolution® ) about one month after being infected with the larvae. This study allowed us to understand the disease caused by adult heartworms and the disease caused by larvae, as well as to validate the effectiveness of the heartworm prevention product, Revolution® .

The findings are significantly different from our prior concepts regarding what heartworms do to the cat. They also further exposed the weaknesses we have in our ability to diagnose heartworms and their effects. There are several important findings.

Major Findings in the New Study

1. The majority of disease caused by heartworms occurs in the blood vessels within the lungs and within the lung tissue itself because this is the primary location of the larvae and adults. This finding resulted in a new term: HARD, Heartworm-Associated Respiratory Disease.

2. Most of the lung disease occurs when the juvenile adults and the adult heartworms die. This means that the body's successful termination of the infection may cause more respiratory disease and even life-threatening situations than the presence of the adult heartworms.

3. The blood tests that we have relied upon for diagnosis are less useful than we thought. We knew many cats would test negative even though they had heartworms, but now we know that the various tests made by different companies have short windows of time in which they are positive and that these windows occur at different times between the tests. This means that repeated testing is more accurate than one test, and even then, we may consistently get negative results when heartworms are present.

4. The findings on x-rays are often different than what we have thought because the amount of lung disease is often more severe than the changes in the heart and blood vessels. In addition, the lung changes are usually identical to other recognized feline lung diseases.

5. We have no drug that will safely kill adult heartworms. The drug used in dogs is not safe in the cat. In addition, as stated, killing many worms at once may create severe lung disease that may be fatal to the cat. Although some cats recover from a heartworm infection, many do not.

What does this mean?

1. Heartworm disease is more common than we thought because in the past we have considered it a heart disease, not a lung disease. The lung changes are identical to other lung diseases we see in cats. Consequently, many cats formerly diagnosed with primary lung disease likely have had HARD.

2. Our ability to diagnose heartworms in cats is actually less than we thought.

3. Killing heartworms in cats would probably not be advisable even if we had a safe drug to do so.

4. We need to give a heartworm prevention product to all cats, whether they go outdoors or not, for three reasons: 1) mosquito exposure is almost inevitable, 2) heartworms are very difficult to diagnose, 3) heartworms probably cause much of the lung disease that we have attributed to infections and allergies, and 4) successful treatment is difficult to impossible.

What are Our Choices for Heartworm Prevention?

1. Revolution® or AdvantageMulti™: These are liquids that are applied to the back of the cat's head once monthly. We have used these products in the past primarily because of their effects on fleas, ear mites, and intestinal worms. Now, they are even more important because of the heartworm protection they offer.

2. Interceptor® or Heartgard®: These are chewable tablets that are given once per month. They do not offer the broad spectrum of parasite control found in the topicals, but they are very effective in preventing heartworm infection.

Client Handout for Cats Infected with Heartworms or Having HARD

Heartworm Infections in Cats

Heartworms have traditionally been considered a parasite of dogs; however, they have been occasionally found in cats for many years. Our concept of heartworms in cats has been that they were very uncommon and an "accidental" infection. However, newer data has changed this concept showing that heartworms are probably as common in cats as in dogs.

How cats get heartworms

A new study

A new study performed at Auburn University's College of Veterinary Medicine is radically changing our understanding of how heartworms affect the cat. In this study three groups of cats were studied with blood tests, x-rays of the heart and lungs, and post-mortem (autopsy) examinations of the heart and lungs for 8 months. The first group looked at the effects when heartworm larvae were deposited under the skin and allowed to mature without interference. The second group also received heartworm larvae under the skin; however, three months later a drug was given to kill the larvae before they became adults. The third group was put on a heartworm prevention product (Revolution® ) about one month after being infected with the larvae. This study allowed us to understand the disease caused by adult heartworms and the disease caused by larvae, as well as to validate the effectiveness of the heartworm prevention product, Revolution® .

2. Most of the lung disease occurs when the juvenile adults and the adult heartworms die. This means that, in some cases, the body's successful termination of the infection may cause more respiratory disease and even life-threatening situations than the presence of the adult heartworms.

Diagnosis of Heartworm Disease

1. There are two types of blood tests: antibody and antigen. Both are included in a "heartworm test." However, these tests are limited in their usefulness.

• Antibodies are made by the cat in response to heartworm larvae or adults. If it is positive, there has been an infection of at least the later larval stages. However, not all larvae mature past the early stages. In addition, the presence of a few later stage larvae may not be significant even if they cause a positive antibody test result. We know that the various tests made by different companies have short windows of time in which they are positive and that these windows occur at different times between the tests. This means that repeated testing is more accurate than one test, and even then, we may consistently get negative results when heartworms are present.

• An antigen test detects a protein produced by the adult heartworm. However, this protein is primarily present in female worms. Therefore, a positive test means the cat has adult heartworms, but, a negative test may result when only larvae are present or when an infection with adult worms is all male.

• Although it is helpful and important to perform these blood tests for heartworms, unfortunately interpretation of the results may not always be easy.

2. Radiographs (x-rays) are an important part of heartworm testing. There are changes in the major blood vessels (the caudal pulmonary arteries) that are typical of heartworm disease. However, many of the important findings are in the lungs because the amount of lung disease is often more severe than the changes in the heart and blood vessels. Unfortunately, the lung changes are usually identical to other recognized feline lung diseases.

3. Ultrasound of the heart (echocardiogram) can be helpful if there are adult heartworms in the heart. Finding them gives us a firm diagnosis. However, they are only there if the pulmonary arteries no longer have room for the worms. This is often not the case so a negative finding on an ultrasound study may be misleading.

Treatment

There is a safe and effective drug for killing heartworms in dogs. However, this drug is not safe for use in cats. Furthermore, if we kill a large number of juvenile adults or adults, they may cause severe, and even fatal, lung reactions. Therefore, "treatment" is based on the cat's immune system's ability to kill the larvae and adults. This is typically a slow process, which is actually an advantage to the cat. Although most cats kill their worms within about 2 years, some may take up to 4 years.

The second part of "treatment" is to relieve the inflammation caused by the worms with corticosteroids ("steroids"). They may be given orally and continuously at a low dose, or they may be injected when a breathing crisis arises.

The third step in "treatment" is to prevent further infections by using one of the heartworm prevention products. Topical products and oral products are available for once monthly dosing. Our choices are: