April 25, 2012
A recent study at Auburn University has shown us a new side of feline heartworms.
Dillon and Blagburn, with the financial backing of Pfizer Animal Health of New York, performed an amazing study1. They infected three groups of cats with heartworm larvae.
The first group was untreated to see what would happen from natural exposure.
The second group was given ivermectin at the time in the life cycle that would kill the immature adults but not the adults. This group showed the pathology that occurs when the 2-inch-long immature adults die; the pathology that occurred was only due to immature adults, not to 6-inch-long adult worms.
The third group was infected while receiving selamectin. This group was to demonstrate the efficacy of this drug in preventing heartworm infections; its high efficacy was clearly demonstrated.
The following is a synopsis of what we now know about heartworm disease in cats.
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. The L3 molt within a couple of days to fourth-stage larvae (L4).
L4 migrate subcutaneously in fat and muscle for two months, then molt to become a juvenile or immature adult worm. (Immature adult worms have incorrectly been called L5 larvae.) Immature adult worms enter circulation via a peripheral vein. This occurs about 60 days after infection. An antibody response begins about this time; some cats test antibody positive.
Within the next 15 to 30 days — 75 to 90 days post-infection — the immature adult worms arrive in the pulmonary arteries. The vast majority of the juvenile worms die, are carried by blood flow into the lungs and cause an intense inflammatory response affecting the pulmonary arterioles, bronchi and alveoli.
It is estimated that about 3 to 4 percent of the immature adults become 6-inch-long adult heartworms and live for two to four years before dying spontaneously.
Heartworm associated respiratory disease, or HARD, is unique to the cat. You will not find it by studying heartworm disease in dogs. It is defined as vascular, airway and interstitial lung lesions caused by the death of immature adult worms, and the inflammation may last up to eight months.
If we administer 100 infective larvae to a dog, 75 will mature to adults. If we administer 100 infective larvae to a cat, many will become immature adult heartworms; however, only three to four will mature to adults. A very large number of immature adult worms develop but never make it to adulthood due to the effects of the cat’s immune system. Severe lung lesions are present but:
• No adult worms will be present on necropsy.
• The immature adult worms disintegrate within the lung tissue and are very difficult to find on necropsy.
• Antibodies disappear very quickly.
• Antigen tests will be negative because there have been no adults.
Radiographically, these cats may look similar to cats with allergic bronchitis. Interstitial or bronchial patterns may be present, and the caudal pulmonary arteries may be enlarged and blunted. In some cats, apparent enlargement may be due to periarterial inflammation. Repeated exposure to immature adult heartworms results in severe interstitial and bronchial disease. (See Figures 1,2)
It is no wonder that this disease has eluded detection until the Dillon and Blagburn study.
A large necropsy study in Gainesville, Fla., found that 5 percent of cats had adult heartworms2, virtually the same incidence as FeLV and FIV infections. In the same group of cats, 15 percent were antibody positive. Interestingly, many that did not have adult heartworms present had signs of severe lung disease. In retrospect, what was observed was HARD, but at the time HARD was not understood.
In the 1997 Heska Heartworm Survey3, 15.9 percent of tested cats were heartworm-antibody positive. In the 1998 Miller, et. al. study4, 12 percent of tested cats, many from non-endemic areas, were antibody positive. Because many cats with HARD test antibody negative, the 12 to 16 percent incidence is probably much lower than the true incidence.
For every 10 heartworm-infected dogs in a given locale, one cat has adult heartworms. However, it is likely that only about 10 percent of heartworm-infected cats have an adult worm. That makes the exposure and infection rates of dogs and cats about the same.
Antibodies are produced by the presence of immature adults, and they begin to wane as the immature adult worms die. If the immature adult worms mature to adults, the adult worms suppress the immune system, causing antibodies to dissipate. Most antibody tests turn negative about four months later as long as new infections do not occur.
A positive antibody test means one or more of these possibilities:
• A current infection with late L4.
• A current infection with immature adult heartworms.
• A current infection with adult heartworms.
• A previous heartworm infection. Antibody persists about four months.
Many cats with HARD are antibody positive and antigen negative. However, many test negative on both antigen and antibody tests, making differentiation from cats with allergic bronchitis virtually impossible.
A positive antigen test means (one or both):
• One or more adult female heartworms.
• One or more dying adult female heartworms.
Heartworm tests are inclusionary, not exclusionary. If they are positive, they are meaningful. If they are negative, they are not meaningful.
Antigen or antibody testing is not necessary to begin heartworm prevention because there is not a reaction between current heartworm prevention products and any stage of the heartworm.
In contrast to dogs, very few microfilaria circulate in cats. This test has very poor sensitivity in cats. This also explains why cats are very poor reservoirs for heartworm infections to other cats or to dogs.
• Positive antibody test: This cat is or has been infected with heartworms that progressed at least to the immature adult stage. It is clearly at risk of future infections
• Positive antigen test: This cat is infected with adult heartworms. It is clearly at risk of future infections.
• Microfilaria testing: This test has a very poor diagnostic yield.
Most cats with HARD have mild coughing, but a severe respiratory crisis can occur when a large number of immature adult heartworms die at once. The treatment for the crisis cat is 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 such as terbutaline. Oral prednisolone (1-2 mg/kg) or corticosteroid inhalers can be used prophylactically for inflammation.
These cats should be placed on a heartworm preventive product to prevent new infections.
If we knew nothing about Dirofilaria immitis before the Dillon and Blagburn study, what common name would we have put on this parasite?
I seriously doubt we would call it a “heartworm.” Its normal locations in the cat are the pulmonary trunk and the left and right pulmonary arteries. Immature adults and adults are found in the heart only when the pulmonary arteries are filled with worms.
I was at a meeting of heartworm researchers and interested practitioners a few months ago. I suggested that we rename this parasite to better reflect its location in the cat and to make a break with the misunderstandings of the past. Not surprisingly, my idea was not well received. And I am not now on a campaign to change its name. However, it is important that we realize that this parasite does not follow the pattern of heartworms in dogs.
We all know that “cats are not small dogs.” We need to also appreciate that “cat parasites are not small dog parasites!”
First, we need to appreciate what Dillon and Blagburn, with Pfizer’s financial backing, have done. Their study was one of the blockbusters in feline medicine.
Accolades also need to go to the “KNOW Heartworms” campaign of the American Assn. of Feline Practitioners. However, we must go past singing praises and move into action. This information needs to be shared with our clients, who must be motivated to act on it.
Create a handout for your clients endorsing heartworm prevention for all cats. Use the “KNOW Heartworms” materials in your exam rooms, and proactively use your annual examinations and other opportunities to talk to clients about this very important subject.
Clients need to know:
• Heartworm disease is much more common in cats than we thought. We have missed it because of a lack of understanding that we now have. • Even with our new knowledge, heartworms are difficult to diagnose. Blood tests have severe limits on sensitivity.
• There is no good way to rid the cat of this parasite. It must die on its own.
• All cats should be on heartworm prevention using the same schedule as for dogs in that locale.
• Even indoor cats need to be included because about 25 percent of diagnosed cats are indoors only4.
• By about three months post-infection, 2-inch-long immature adult heartworms are in the pulmonary arteries.
• Most of these are killed by the immune system, never becoming adult heartworms. They are carried by blood flow into the lungs.
• About 3 percent to 4 percent of the immature adults become 6-inch-long adult heartworms.
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