Canine Heartworm Disease

12 Canine Heartworm Disease



Clay A. Calvert, Laura Gaye Ridge




1. What is heartworm (HW) disease?

HW disease, or dirofilariasis, is the consequence of parasitic infection by a filarid nematode, Dirofilaria immitis. The dog is the primary host. Adult heartworms reside primarily within the pulmonary arteries but are occasionally found in the right atrium, right ventricle, or vena cava. The adult female worms release a larval form (L1) directly into the bloodstream; transmission of the infection is by mosquitoes, which are an obligatory intermediate host for the parasite.


2. What is the worldwide dissemination of D. immitis infection in dogs?

Mexico, Japan, South America, southern and southeastern Asia, Australia, Italy, and southern European countries are all endemic areas.


3. Are there any areas of the United States and Canada where the HW infection has not been detected?

HW infection is generally uncommon in Canada but has been reported in southern regions adjacent to Washington, Minnesota, New York, and lakes Huron, Ontario, and Erie. HW infection is rare in mountainous regions of the United States and in Alaska, Idaho, Montana, Wyoming, Nevada, Utah, Arizona, and the western parts of the Dakotas.


• A mobile public guarantees that infected dogs will be transported to nonendemic regions and, if the climate is suitable, infections will be established.

• Feral dogs and wild Canidae (principally coyotes and foxes) are reservoirs, making HW infection impossible to eradicate once introduced into a region.

4. What species other than dogs and cats are susceptible to D. immitis infections?

Other Canidae, sea lions, and ferrets are susceptible.


5. What does the term occult HW infection mean?

Occult HW infection refers to infections in which microfilariae are absent or present inconsistently in low numbers in serial venipuncture samples. Possible causes of occult HW infection include the following:


• There may be immune-mediated entrapment and destruction of microfilariae in the pulmonary microcirculation.

• Unisex infections can occur; these are more likely in nonendemic regions when the adult HW burden is low.

• The HW-preventative drugs Interceptor, Heartgard, ProHeart, Iverheart, and Revolution will stop microfilarial production and kill microfilariae over a period of 6 to 12 months.

6. Are all mosquitoes capable of transmitting infective D. immitis larvae?

Many (at least 60) species of mosquitoes can transmit the infection. Culex and Aedes spp. are the primary culprits in dogs, because they prefer to feed on dogs. Culex pipiens and perhaps other species prefer to feed on cats.


7. What are the microfilariae?

Microfilariae are the first-stage larvae (L1) that are produced by gravid female D. immitis.


• It is believed that microfilariae produce little or no disease and are a “dead end” for the parasite unless they are ingested by a mosquito.

• The L1 develop to the infective larval stage (L3) within the mosquito.

8. How long does it take for the Ll to develop to the infective (L3) stage within the mosquito?

The time varies with the ambient temperature. The maturation time is 30 to 130 days for ambient temperatures between 60° F and 64° F. At 80° F (27° C), 10 to 14 days are required for development from the L1 to L3 stage.


9. When can HW infection be transmitted?

Most HW infections are transmitted in the northern hemisphere during July and August. Even along the Gulf coast, transmission in December and January is uncommon.


10. How long after a dog is infected by L3 does it take for microfilariae to appear in the peripheral blood of the host?

Approximately 6 months is required.


11. Which stages of development are found in the pulmonary arteries?

The fifth-stage larvae (L5) develop 50 to 70 days after inoculation with L3 and reach the pulmonary arteries 70 to 110 days after L3 inoculation. Most are found in the caudal lobar pulmonary arteries because these vessels have the highest blood flow. The L5 grow and mature in the pulmonary arteries and are sexually mature 190 to 285 days after L3 inoculation. Thus the L5 (young adults) and adults are found in the pulmonary arteries.


12. Are adult HWs always present when microfilariae are detected?

Usually adult HWs are present, unless an adulticide treatment has been administered.


• It is uncommon (<1% of cases) for microfilariae to be present without adult worms in an untreated dog because the adult HW life span is longer.

• The true life span of adult HW is poorly documented, but microfilariae can live for 2 to 4 years.

13. Microfilariae are occasionally detected in puppies. What is the significance of this finding?

Microfilariae (Ll) can be transmitted via the placenta to the fetus.


• If the puppy is younger than 7 months, the microfilariae cannot represent a patent HW infection.

• The microfilariae do little or no harm but the puppy serves as a reservoir for infection.

• If microfilariae are detected in a puppy that is at least 7 months of age, then an antigen test should be performed.

14. Is there any significance to the concentration of microfilariae in the peripheral blood?

The concentration of microfilariae detected in small samples of blood collected at various times varies throughout the day. Sometimes there are midday peaks but the periodicity is unpredictable.


• The concentration of microfilariae does not correlate strongly with the adult HW burden.

• The incidence of acute adverse reactions following the administration of Interceptor is increased when the microfilarial counts are high.

15. What actually causes the pulmonary artery disease associated with HW infection?

Sloughing of strips of endothelium occurs quickly after HW contact. Endothelin levels increase and platelets and leukocytes adhere to the damaged endothelium and growth factors are released. Multiplication and migration of smooth muscle cells and interstitial fibrosis result. There is villus hypertrophy characterized by protuberances consisting of smooth muscle covered by a healed endothelium. The healed endothelium of a villus may be damaged and then a secondary villus develops. Thickening of artery and arteriole walls leads to decreased blood flow, thromboembolism, and decreased compliance (relaxation) of the artery wall. Pulmonary hypertension can develop.


16. Do all dogs with HW infection have pulmonary hypertension?

Not all dogs have pulmonary hypertension, or at least it is mild in most cases.


• Some degree of pulmonary hypertension exists in most dogs with radiographic evidence of HW infection.

• Artery size apparent on radiographs does not necessarily correlate with the degree of hypertension.

• Two thirds of the pulmonary circulation must be obstructed before severe hypertension develops.

• The arterioles cannot dilate when severely diseased, and recruitment of collateral vessels does not occur because the vessels are already in use or are obstructed.

• Hypertension is exacerbated by exercise.

• There may be exercise-induced symptoms, including right-sided congestive heart failure and syncope.

17. Why is HW damage worse in some dogs than in others?

High adult HW burden (increased contact with endothelium) and immune-mediated responses cause severe damage. Longer duration of infection and higher levels of exercise also lead to more damage.


• Lobar arterial dilation, tortuosity, and obstruction tend to be more severe in dogs with HW disease that come from regions where HW disease is highly prevalent.

• Higher worm burden

• Higher incidence of immune-mediated occult infections

• Loss of pulmonary arterial compliance resulting from a thickening of the walls, fibrosis, embolism, and obstruction leads to pulmonary hypertension with the following results:
• Right ventricular dilation and hypertrophy

• Exercise intolerance

• Syncope

18. When should dogs be tested for HW infection?

The recommendations for testing dogs for HW infection are as follows:


• Antigen testing should begin about 7 months after the end of the previous transmission season. This could be in April in northern states and June in the southern states and tropical regions.

• Young dogs should be tested 7 months after possible exposure.

• Annual antigen testing is recommended but is controversial and not necessary if an appropriate preventative program is maintained.

• An adult dog that is not or may not have been on an adequate HW preventative program should be tested 7 months after possible exposure.

• A microfilarial test is mandatory prior to initiating diethylcarbamazine prophylaxis.

• Antigen testing is advisable before initiating prophylaxis.

19. Is it really necessary to test annually?

It is well documented that client compliance with oral administration of HW preventative drugs is often poor. However, if Heartgard, Interceptor, Iverheart, or Revolution is given at least every 2 months, the likelihood of infection is small. Annual testing is recommended.


20. Has serologic (antigen) testing supplanted microfilarial detection as the preferred method of diagnosis?

Yes; however, a microfilarial test is mandatory before initiating diethylcarbamazine prophylaxis.


21. What is the best antigen test for the detection of HW infection?

There are numerous tests available and all are sensitive and specific. The two types of tests are the “stat” tests, which provide a quick answer while the client is at the clinic, and those more suitable for batching numerous samples to be run later in the day. Antigen tests are used for the following:


• Screening

• As part of the clinical evaluation of a dog with signs, radiographic findings, and laboratory findings consistent with HW infection

• Monitoring adulticide efficacy

22. False-positive test results are not supposed to happen, but they do. Why?

Theoretically, HW antigen tests have absolute specificity. The primary causes for false-positive results are cross-contamination and improper methods.


• Inadequate washing

• Excess time between test setup and test assessment

• Difficulty of interpreting weak reactions. HW antigen test kit manufacturers provide a confirmatory test service

23. Can false-negative test results occur?

Yes. There are several situations that can lead to a false-negative result, including the following:


• Only the female worm contributes to a positive result.
• An all-male-worm infection will give a negative test result.

• This is not truly a false-negative test result.

• Currently no test will detect early (up to 5 to 6 months after L3 inoculation) infections.
• There is 100% sensitivity when three or more female worms 8 months old or older are present.

• If only one female is present, negative results are possible.

• The test kit or sample is not warmed to room temperature. Some newer test kits do not require refrigeration.

Dogs with few worms resulting from a recent infection are unlikely to have clinical signs and thus the false-negative test result is not really a problem as long as the dog is receiving prophylaxis.


• Prophylaxis will prevent superinfection.

• Heartgard will kill the few worms within 2 years.

24. What tests are used to detect circulating microfilariae and which are the best?

Microfilariae can be detected through examination of a direct blood smear. However, tests that concentrate the microfilaria are more sensitive.


• The modified Knott test uses centrifugation to concentrate microfilariae; the sediment is stained and examined microscopically.

• Filter tests rely on a small-pore filter to concentrate the microfilariae.

• Both the concentrating filter tests and modified Knott test are equally sensitive (75%).

• The direct blood smear, while quick and facilitating the identification of microfilariae (D. immitis compared with Dipetalonema reconditum), is at least 25% less sensitive than the concentration tests.

• Depending on the geographic region, 15% to 50% of all HW infections in dogs are not associated with circulating microfilariae if they are not receiving prophylaxis.

• The higher incidences of occult infections occur in highly endemic regions. It is estimated that in the southeastern United States 20% to 30% of all infections are occult, while in tropical areas the incidence may be as high as 50%.

25. Do we need to worry about a weakly positive HW antigen test in an asymptomatic dog?

A weakly positive antigen test indicates a low antigen burden, provided it is a true positive test result.


• Reevalute with a different test if the first test result is equivocal.

• It is difficult to differentiate between red blood cell (RBC) sedimentation and weak hemagglutination (Vetred). Repeat testing with a different method is recommended.

• The risk of symptomatic HW disease developing from a recent infection in such an animal is relatively low.

• The results of a Knott or filter test will probably be negative.

• Thoracic radiographs will probably appear normal or equivocal.

26. Should asymptomatic dogs with low-level antigenemia be treated?

The risk of serious adverse reactions in recently acquired, low-worm-burden infections treated with Immiticide is low. Because disease severity and rate of progression are usually limited, some clinicians initiate Heartgard prophylaxis to kill the adult worms over a period of about 24 months. This course is controversial.


• Our recommendation is to treat with Immiticide.

27. Are D. reconditum infections of any significance?

D. reconditum is a benign subcutaneous parasite commonly found in regions where D. immitis is endemic. The microfilariae of D. reconditum tend to be of lower concentration than those of D. immitis, can cause profound eosinophilia, and closely resemble those of D. immitis (Table 12-1).


• On a direct smear, the microfilariae of D. reconditum progress across the microscopic field while those of D. immitis tend to undulate in place without steady progression.

• D. reconditum have a more rounded or blunt “nose” and a hooked tail.

• Differentiation is best accomplished by measuring the organism’s length and width.

• Neither Interceptor nor Heartgard kills the microfilariae of D. reconditum.

• The 50 μg/kg dose of ivermectin kills both the D. immitis and the D. reconditum microfilariae.

28. Can HW serologic tests be of value in determining the severity of infection?

Table 12-1 Differentiation of the Microfilariae of D. immitis from D. reconditum



























  D. IMMITIS D. RECONDITUM
Filter test
Length (μm) 235-285 215-240
Width (μm) >6 <6
Knott test
Length (μm) >290 <275
Width (μm) >6 <6

Yes. All enzyme-linked immunosorbent assay (ELISA) antigen tests, but not immunochromatographic tests, provide a crude estimate of the HW burden. However, recent spontaneous death of worms will cause an antigen concentration spike. When an antigen concentration spike is due to a high worm burden, there will also be:


• More severe clinical signs

• The emergence of signs in an asymptomatic dog

• Increased likelihood of thromboembolic complications following Immiticide treatment.

Semiquantitation of the HW burden can be done by serial dilution (with phosphate-buffered saline) of the serum and determining to which titer (dilution) a positive result persists. A titer of more than 1:32 is associated with greater risk of thromboembolic disease. The severity of disease as determined by antigen level, the dog’s history, and the results of the physical examination and thoracic radiography are used to select the appropriate therapy.

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Jul 31, 2016 | Posted by in INTERNAL MEDICINE | Comments Off on Canine Heartworm Disease

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