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Canine Heartworm Disease

Canine Heartworm Disease
Dogs are considered the definitive hosts for heartworm infections. In experimental infections of
D. immitis, the percentage of infective larvae developing to adult D. immitis is higher in dogs
(40% to 90%) than cats (0% to 25%). However, the percentage of experimentally-infected dogs
from which adult worms are recovered is virtually 100% of infected dogs, which is different from
cats where adult worms are recovered in approximately 61% to 90% of experimentally-infected
cats. The worm burden in dogs is usually higher than in cats, as the number of worms in dogs
can range from 1 to 250 worms whereas cats typically harbor from 1 to 3 worms. The life span
of the worms in dogs appears to be about 5 to7 years, compared to 2 to 3 years in cats.
The average prepatent period (the time elapsed from when the larvae enter the host until the
adult female worms begin to produce microfilariae) in dogs is about 6-7 months, which is 1 to 2
months shorter than that seen in cats.
Microfilaremia is relatively common in dogs. Not all heartworm infections result in circulating
microfilariae that can be found upon examination of the dog's blood, however. These are
known as occult heartworm infections and can be the result of a number of factors. Single
sex heartworm infections, host immune responses affecting the presence of circulating
microfilariae and the administration of heartworm preventives can be factors which produce
occult infections in dogs.
The onset and severity of disease in the dog is in part a reflection of the number of adult
heartworms present. Dogs with higher numbers of worms are generally found to have more
severe cardiac and pulmonary disease changes. Until the number of heartworms exceeds 50 in
a 25-kg dog, nearly all of the heartworms reside in the caudal pulmonary arteries. Higher
numbers of heartworms will result in their presence in the right ventricle, and possibly the right
atrium, of the dog's heart. The most common pathological changes created by heartworms are
due to inflammatory processes that occur in and around the caudal pulmonary arteries in
response to the presence of heartworms.
Canine heartworm infection is widely distributed in the United States. Heartworm infection has
been found in dogs native to all 50 states, and is considered at least regionally endemic in each
of the contiguous states and Hawaii. All dogs regardless of their age, sex, or habitat are
susceptible to heartworm infection. The highest infection rates (up to 45%) in dogs not
maintained on heartworm preventive are observed within 150 miles of the Atlantic coast from
Texas to New Jersey and along the Mississippi River and its major tributaries. Other areas of
the United States have lower incidence rates (5% or less) of canine heartworm disease, while
some regions have environmental, mosquito, and dog population factors that allow a higher
incidence of heartworm infection. Endemic regions have heartworm infections diagnosed in
dogs as young as 1 year, with most areas diagnosing infections primarily between the ages of 3
and 8 years of age. The infection rate in male dogs is as much as 4 times that of female dogs
and dogs housed outdoors are 4 to 5 times more likely to be infected than indoor dogs.
Although there are differences in frequency of infection for various groups of dogs, all dogs in
endemic regions should be considered at risk and placed on surveillance/prevention programs.
Clinical Signs
D. immitis infection may cause multiple system dysfunction affecting the pulmonary circulation,
heart, liver and kidneys. Heartworm disease may have an acute onset, but it is usually insidious,
resulting from a chronic infection with a combination of underlying pathophysiologic responses.
Dogs with low worm burdens that receive little cardiopulmonary exercise may never have overt
signs of heartworm disease. The heart and lungs are the major organs affected by heartworms
in dogs, and they can have no clinical signs, or can present with mild, moderate or severe
clinical signs.
Clinical Signs Associated with Canine Heartworm Disease
No abnormal clinical signs observed Mild Disease
Moderate Disease
Cough, exercise intolerance, abnormal lung sounds Severe Disease
Cough, exercise intolerance, dyspnea (difficulty breathing), abnormal lung sounds, hepatomegaly (enlargement of the liver), syncope (temporary loss of consciousness due to poor blood flow to the brain), ascites (fluid accumulation in the abdominal cavity), abnormal heart sounds, death
Diagnosis
The diagnosis of canine heartworm disease depends upon an accurate patient history, the
recognition of varied clinical signs, and the use of several diagnostic procedures that may
include radiology, angiography and ultrasonography (echocardiography), serologic testing,
microfilarial detection and differentiation, clinical laboratory tests and, in the worst case
scenario, necropsy.
Radiology
Radiographic abnormalities develop early in the course of the disease. Radiographs of the
heart and lungs are the best tool available to evaluate the severity of the disease. Typical
changes observed are enlargement of the following structures: right-side of the heart, main
pulmonary artery, pulmonary arteries in the lobes of the lung. Blunting and thickening of
pulmonary arteries, along with tortuosity is often noted. Evidence of inflammation in the lung
tissue that surrounds the pulmonary arteries is often found.
Angiography and Ultrasonography
These forms of imaging are rarely used in the diagnosis of canine heartworm infection outside
of referral practices and teaching institutions. Angiography is a technique that permits
visualization of blood vessels in the body by taking radiographs within seconds after injecting a
contrast material (dye) into those blood vessels. In canine heartworm infection, angiography is
used to study changes to the pulmonary arteries. Ultrasonography (echocardiography) has
been used to evaluate right ventricular enlargement and to look for the presence of heartworms
in the right ventricle or main pulmonary artery.
Necropsy
While necropsy is probably the most definitive diagnostic test, most veterinarians will assure
you that this procedure is not regarded as a practice builder. Heartworms are often readily
found in the right ventricle of the heart or in the major pulmonary arteries. The worms can also
be found in the farthest branches of the pulmonary arteries. Ectopic heartworm infections are
rare, with worms detected occasionally in organs other than the heart and lungs or in body
cavities.
Clinical Laboratory Tests
There are no definitive changes to the complete blood count, serum chemistries or urinalysis of
dogs with heartworm disease. Increased number of eosinophils and basophils found on a
complete blood count are regarded as supportive of, but not diagnostic for, heartworm infection.
Microfilarial Detection and Differentiation
The identification of D. immitis microfilaria from a blood sample is indicative of infection with
adult heartworms in over 99% of individuals. Microfilaria identification is equally accomplished
through either of 2 concentration tests: the Knott's test (a technique requiring centrifugation of
the test sample) or the filter test. Practitioners will often do a quick examination of a blood
smear to look for the presence of microfilariae, but this procedure is not sensitive enough to
serve as a final rule out for the absence of microfilariae in a sample.
One other parasite infection of dogs is capable of producing circulating microfilariae that can be
detected on examination of the blood. Dipetalonema reconditum is a non-pathogenic parasite
that localizes in the subcutaneous tissues of dogs. It's microfilariae can be differentiated from
those produced by D. immitis through microscopic examination evaluating size and shape.
Physical Exam
The physical examination may be perfectly normal in heartworm-infected dogs with mild
disease, or severely-affected dogs may present recumbent, in right-sided heart failure. Labored
breathing or crackles may be auscultated in dogs with severe pulmonary hypertension or
pulmonary thromboembolic complications, and a history of chronic cough and exercise
intolerance are some of the earliest detectable abnormalities. Tachycardia, ascites and
hepatomegaly indicate right-sided congestive heart failure. Hemoptysis occasionally occurs and
indicates severe pulmonary thromboembolic complications. There have been reports of
anorexia, cachexia, syncope and jaundice in severely-affected dogs. Occasionally, heartworms
are reported in unusual locations such as the eye, abdominal cavity, cerebral artery and spinal
cord (ectopic locations). Clinical signs and disease experienced in ectopic infections depend
largely on the location of the worm. In dogs, the primary response to the presence of
heartworms occurs in the heart and lungs.
Serology
Antigen Tests
Antigen tests detect specific antigens from adult female heartworms, and are used successfully
to detect canine heartworm infection. Currently, tests are available as in-clinic tests, as well as
at many veterinary reference laboratories. Most commercial tests will accurately detect
infections with 1 or more mature female heartworms that are at least 7 or 8 months old, but
they generally do not detect infections of less than 5 months duration.
Antibody Tests
In the late 1970's and early 1980's, several canine heartworm antibody tests were developed
and introduced. These tests relied on detection of antibodies using a crude mixture of
heartworm antigens from adult worms, and while they were very sensitive (i.e. they were able to
detect very early infections and infections with small numbers of heartworms), the tests were
non-specific and were believed to cross-react to the common gastrointestinal parasites found in
dogs. These tests were never very popular as screening tests in dogs.
An IFA detecting antibodies to microfilarial cuticular antigen has been used for the diagnosis of
occult infections that result from immune-mediated clearance of microfilariae in dogs. The
presence of sterile worms, worms of only one sex or the absence of a host response to
microfilarial surface antigen does not produce a diagnostic titer. A variation on this test includes
lysing the microfilariae to assess antibody to somatic antigens. This somatic IFA is nonspecific
and not clinically useful in dogs.
Treatments
Most dogs infected with heartworm can be successfully treated. The goal of treatment is to kill
all adult worms with an adulticide and all microfilariae with a microfilaricide. It is important to try
to accomplish this goal with minimal drug toxicity and a tolerable degree of complications
created by the dying heartworms. Heartworm infected dogs which are normal or have mild
disease have a high treatment success rate. Patients with evidence of more severe heartworm
disease can be successfully treated, but the incidence of post-adulticide complications and
mortality are greater. Certainly there are patients whose severity of heartworm disease, or
presence of other concomitant life-threatening diseases, prevent treatment of the heartworm
infection.
Adulticide Therapy
There are currently 2 drugs approved by the FDA for use in dogs for the elimination of adult
heartworms. Both drugs are organic arsenical compounds. Dogs receiving these drugs will
typically have had a thorough pretreatment evaluation of their condition and will be hospitalized
during the administration of the drugs.
Melarsomine dihydrochloride
Melarsomine (Immiticide®; Merial) is the first new adulticide for canine heartworm
to become available in the U.S. in over 25 yrs. It has demonstrated a higher level
of efficacy and safety than what has previously been available. It is administered
by deep IM injection into the lumbar muscles. An important new feature of this
drug is the potential ability to minimize post-adulticide complications in dogs with
more severe heartworm disease. For more complete information on Classification
and Treatment Regimens for heartworm infected dogs using this product, please
consult the drug package insert.
Thiacetarsamide sodium
Thiacetarsamide (Caparsolate®; Merial) must be administered by intravenous
injection. Leakage of the drug around the vein can result in intense perivascular
inflammation. The incidence of side effects due to the systemic toxicity of this
drug can interfere with its use in many patients. Thiacetarsamide's efficacy is dependent upon a full dosage schedule being administered. Male worms are more susceptible to treatment than female worms. Post-adulticide Complications
The primary post-adulticide complication is the development of severe pulmonary
thromboembolism. Pulmonary thromboembolism results from the obstruction of blood flow
through pulmonary arteries due to the presence of dead heartworms. If heartworm adulticide
treatment is effective, some degree of pulmonary thromboembolism will occur.
When dead worms are numerous, widespread obstruction of arteries can occur. Clinical signs
most commonly observed include fever, cough, hemoptysis (expectoration of blood). These
patients require strict reduction in exercise and anti-inflammatory doses of corticosteroids.
Elimination of Microfilariae
Microfilaricide treatment is typically administered 3 to 6 weeks following completion of the
adulticide treatment. This allows an adequate amount of time to pass for the adult worms to die
and to have ceased production of additional microfilariae. The most effective drugs for this
purpose are the macrolide anthelmintics - ivermectin and milbemycin. These drugs are the
active ingredients in the commonly use heartworm preventives. However, their usage in this
application has not been approved by the FDA, but there are no approved microfilaricidal drugs
currently recognized. It is recommended that microfilariae positive dogs being treated with
these drugs be hospitalized for 8 hours following treatment for observation of possible adverse
reactions resulting from rapid death of the microfilariae.
A microfilaria concentration test is performed 3 weeks after microfilaricide treatment. Pets that
are microfilaria negative have completed the treatment for canine heartworm infection and are
ready to start a heartworm preventive program.
Confirmation of Adulticide Efficacy
The goal of adulticide treatment is the elimination of all adult heartworms. However, clinical
improvement in dogs treated for heartworm infection is possible without completely eliminating
the adult heartworms. Heartworm antigen testing is the most reliable method of confirming the
efficacy of adulticide therapy. If all the adult worms have been destroyed or very few survive,
heartworm antigen should be undetectable by 16 weeks post-adulticide. Dogs that remain
antigen positive at that time should only be considered as candidates for repeat treatment with
an adulticide after a full review of each case.
Preventives
While treatment of canine heartworm disease is usually successful, prevention of the disease is
much safer and more economical. There are currently 4 products approved for use in the US
for the prevention of canine heartworm infection. Prevention of heartworm disease in dogs can
be accomplished through the routine administration of either diethylcarbamazine or one of the
macrolide anthelmintics. These drugs are highly effective when administered at the appropriate
doses and intervals. Due to the temperature dependent nature of the heartworm life cycle, use
of heartworm preventives is seasonal in the majority of the U.S. The heartworm preventive
season which veterinarians will employ depends upon their knowledge of the heartworm life
cycle in their region. Before starting a preventive program, all dogs that could possibly be
infected with mature heartworms should be tested for the presence of circulating antigen.
Diethylcarbamazine
Diethylcarbamazine requires daily oral administration throughout the heartworm season in
order to be effective in preventing heartworm infection. The drug is available in several
formulations and has a history of being reliable, safe, and efficacious. The primary drawback to
the usage of this drug is the necessity of strict client compliance to its daily administration in
order for it to be effective.
Macrolide Anthelmintics
Macrolide anthelmintics are highly effective in preventing heartworm infections. Their primary
benefits lie in their safety at the prescribed doses and the fact that only monthly administration
is required during the heartworm prevention season.
Ivermectin
Ivermectin (Heartgard®; Merial) was the first in this family of drugs to be approved
for use in preventing heartworm infection. Infection with larvae as long as 2
months prior to initiation of ivermectin treatment will be blocked from development.
Milbemycin
Milbemycin (Interceptor®; Novartis) has benefits which are similar to ivermectin. A
key additional feature of milbemycin is it's ability to control hookworm, roundworm,
and whipworm infections as well.
Moxidectin
Moxidectin (ProHeart™; Fort Dodge) is an extremely potent preventive compound
that differs from the other macrolides in that it is not microfilaricidal at preventive
dose levels.
Selamectin
Selamectin (Revolution®; Pfizer) is the newest preventive approved by the FDA. It
is applied topically and includes fleas in its spectrum of activity.

Dogs vs. Cats
Parasite
Dirofilaria immitis Dirofilaria immitis Susceptibility to infection
Very high - virtually 100% Lower than dogs - 61% to of dogs exposed to 90% of cats exposed to infective larvae become infective larvae become Longevity of worms
Ectopic infections
not uncommon to find more usually less than 6, 1-2 Number of worms
worms most common Single-sex infections in
meso- to high-endemic
areas
Microfilaremia
• very common (80%-90%) • seen in only 20% of cats • can last years, even after • lasts about 1 month death of adult worms Organ with greatest
pathology
little clinical importance, Clinical importance of small depending upon size of dog potentially fatal
worm burdens
and exercise level Diagnosis
relatively simple Treatment
• 2 compounds approved • none approved • complications • high risk of complications Compounds for prevention
4 approved in US 1 approved in US

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