Dirofilaria immitis in Cats: Diagnosis and Management*

CE Article #2
Dirofilaria immitis in Cats:
Diagnosis and Management*
C. Thomas Nelson, DVMa
Animal Medical Centers of Northeast Alabama
Anniston, Alabama
ABSTRACT: Imaging and laboratory studies can help with the diagnosis of heartworm disease in cats,
but no test is definitive. Furthermore, even when the diagnosis can be reliably established, therapy
directed at the heartworms does little to help the cat. Rather, management is directed at alleviating
clinical signs, with an emphasis on prevention for all.
D
iagnosis is the most challenging part of
feline heartworm disease because
no single test can reliably detect heartworms at all stages. Veterinarians must be willing to conduct multiple and even repeat tests
(Table 1 and Figure 1) to obtain a diagnosis and
to correctly interpret and apply the results.b
DIAGNOSIS
Microfilariae
Filtration tests for microfilariae are virtually
useless in cats because cats are only transiently
microfilaremic, if at all. To be microfilaremic, a
cat must have both a mature male and a
mature female worm, and because cats typically only have one or two worms, the infec*A companion article on prevalence and pathophysiology begins on page 382.
aDr. Nelson discloses that he has received financial support from the American Heartworm Society, the Companion Animal Parasite Council, IDEXX Laboratories,
Fort Dodge Animal Health, the KNOW Heartworms
campaign, Merial, and Pfizer Animal Health.
b For the complete American
Heartworm Society 2007 Guidelines for the Diagnosis, Prevention
• Take CE tests
and Management of Heartworm
• See full-text articles
(Dirofilaria immitis) Infection
in Cats, please visit www.heart
CompendiumVet.com
wormsociety. org.
July 2008
393
tions are often single sex. When microfilariae
are produced, they are only present for 1 or 2
months, at which time the cat’s immune system eliminates them and suppresses further
embryogenesis.1
Radiology
The most common radiographic finding in
feline heartworm disease is an enlargement of
the right caudal lobar artery (see Figure 2 in the
companion article beginning on page 382). This
is best seen on a ventrodorsal view. A bronchointerstitial pulmonary pattern (Figure 2)
may also be noted, but this finding is not
unique to feline heartworm disease.
The use of radiology has limitations, as only
55% of heartworm antigen−positive cats had
radiographic signs consistent with heartworm
disease in one study.2 Follow-up on some of
these cats showed improvement in radiographic
scores in 50% of cases and worsened scores in
16%. Because cats can tolerate adult worm
infections fairly well and it is common for clinical signs to either resolve or become intermittent, such results are to be expected.
Echocardiography
In skillful hands, ultrasonography has been
shown to detect 100% of adult feline heartCOMPENDIUM
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CE Dirofilaria immitis in Cats: Diagnosis and Management
Table 1. Interpretation of Heartworm Diagnostic Tests in Cats
Test
Purpose
Result and Interpretation
Limitations
Antibody test
Detects antibodies produced • Negative—Decreases index of suspicion
in response to late L4,
• Positive—Increases index of suspicion;
juvenile, and adult worms.
May detect infections as early confirms cat is at risk
as 8 weeks posttransmission
Antibodies confirm
recent infection to at
least late L4 stage
but do not confirm
disease causality
Antigen test
Detects antigen from an
adult female heartworm, >5
dying male heartworms, or a
dying female heartworm
Immature or maleonly worm infections
are rarely detected
Thoracic
radiography
• Negative—Decreases index of suspicion
• Positive—Confirms presence of
heartworms
Detects vascular
• Normal—Decreases index of suspicion
enlargement (inflammation
and hypertrophy caused by a • Signs consistent with feline heartworm
juvenile worm), pulmonary
disease—Enlarged arteries greatly
parenchymal inflammation,
increase index of suspicion
and (more rarely) edema
Echocardiography Detects echogenic walls of
the immature or mature
heartworm residing in the
lumen of the pulmonary
arterial tree (only within the
visual ultrasonographic
window)
• No worms seen—No change in index of
suspicion
• Worms seen—Confirms presence of
heartworms in the structure
Radiographic signs
are subjective and
affected by clinical
interpretation
Accuracy depends in
part on the
ultrasonographer’s
experience with
heartworm detection
© American Heartworm Society
worm infections, but the technician must be able to follow the caudal pulmonary arteries to their bifurcation
within the lung fields.3 Other reports cite echocardiography as detecting 68% of natural infections4 and 88% of
experimental infections in cats.5
The cuticle of the adult heartworm is strongly
echogenic, producing short, segmented, parallel lines
where the imaging plane crosses the worm. Heartworm
signatures on echocardiography have been described as
equal signs (=; Figure 3). However, the imaging beam
may cross the same worm multiple times, making quantifying the number of worms difficult.
Serology
There is an ongoing debate about the accuracy of antigen and antibody testing for feline heartworm disease.
Both tests can provide valuable information, but a thorough understanding of their limitations is essential to
interpreting results correctly.
Antigen tests are considered the gold standard in diagnosing heartworms in dogs. However, they do not detect
COMPENDIUM
early or male-only worm infections. Part of the disease
process in cats is the death of juvenile worms at 3 to 4
months postinfection, which antigen tests cannot detect.
Again, because most infected cats have one or, at most,
two adult worms, single-sex, male-only infections are
common.1 Multiple studies have reported the sensitivity
of antigen testing in mature heartworm infections in cats
to be 50% to 86%.6–9 As a result, a negative antigen test
result does not rule out heartworm infection in cats.
The antibody test was initially very promising. In
experimental studies, it detected 93% to 100% of heartworm infections, including late L4 larvae as well as juvenile and adult worms. 7,10,11 However, a significant
number of cats with adult heartworms are antibody negative. For example, in a retrospective study of 50 cats
with known heartworm disease, there was a 14% falsenegative rate.12 Most of the cats in the study (72%) had
clinical signs indicating active disease.
A necropsy study of shelter cats in Texas6 reported a
50% false-negative rate for one antibody test, and a similar study in Florida had an 11% to 68% false-negative
July 2008
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395
rate on eight different antibody tests.8 Twenty-one of 31
cats with heartworm disease had a negative result on at
least one of the eight antibody tests evaluated. All of
these studies have drawbacks, but collectively they
demonstrate that a negative antibody test result cannot
be used to rule out heartworm infection.
The use of antigen and antibody tests must be tempered by an awareness of these limitations. It is difficult
to establish a diagnosis with a single method unless the
antigen test result is positive or a worm is detected on
ultrasonography. Diagnosis generally requires multiple
tests. If antibody or antigen testing is used for initial
screening, the practitioner should be prepared to conduct additional tests if the results do not support the
clinical suspicions. This is illustrated by the results of a
study of 22 heartworm-infected cats in which thoracic
radiography, echocardiography, and antigen and antibody tests were conducted. Pulmonary enlargement was
seen in 64% of the cats, worms were visualized by
echocardiography in 64%, 55% were antigen positive,
and 82% were antibody positive.13 In a multicenter study
of 215 cats in which clinical signs were correlated to
serology and radiographic findings, 44% of the cats that
presented with coughing or dyspnea and intermittent
vomiting unrelated to eating were antibody positive.14
This was twice the antibody base rate for the area. Of
the cats with radiographic signs consistent with heartworm disease, 60% were antibody positive.
IMPLICATIONS
Because heartworm disease in cats is primarily caused
by juvenile worms, antibody serology data can be used to
estimate the percentage of cats infected at some point in
their life span, thus establishing regional risk. In 1997,
15.9% of the 25,277 cats tested at Heska’s reference laboratory were antibody positive.15 A second study mainly
conducted in the Northeastern and Midwestern states
reported a 12% antibody-positive rate.16 Analysis of data
from IDEXX reference laboratories shows the national
rates of feline heartworm antigen, FeLV, and FIV detection to be 1%, 1.9%, and 1%, respectively, indicating that
heartworm disease is a significant health risk in cats.17
As a result, IDEXX is adding a heartworm antigen spot
to its point-of-care test for FeLV and FIV. This new
format should increase the number of cats tested yearly
for heartworms from tens of thousands to millions. It is
important for practitioners to understand that they will
be testing for the presence of the adult female worm.
Although all cats with adult worms have heartwormJuly 2008
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CE Dirofilaria immitis in Cats: Diagnosis and Management
positive rate is 16%, 50% of cats
with known HARD lesions
(including 25% to 30% of cats
with adult heartworms6,8) are antibody negative 8 months after
infection.18 Based on these numbers, it could be argued that the
Antibody Test
Antigen Test or
or Radiography
percentage of cats at risk for
Echocardiography
HARD in a given area is twice the
• Positive result
• Positive result is
base antibody rate (32%). At the
increases index
diagnostic
same time, Browne et al 19 have
of suspicion
• Negative result lowers
showed that half of antibody-posi• Negative result
index of suspicion
tive cats (50% of 16% = 8%) have
lowers index of
suspicion
lung lesions consistent with
HARD. If, at a conservative estimate, an additional 2% of cats that
are negative on all tests have
HARD, there may be as many as
10 cats with HARD for every one
Figure 1. Summary of interpretation of heartworm diagnostic tests in cats.
cat identified as having adult
heartworms. Given that the adult
heartworm infection rate in cats is
associated respiratory disease (HARD), not all cats with
10% of the rate in unprotected dogs and that for every
HARD have adult worms. The clinical signs associated
cat with an adult infection there may be 10 cats with
with most cases of HARD are the result of juvenile
HARD from juvenile infections, it is possible that cats
worm infections and are not detected by antigen testing.
are infected at the same rate as dogs.
Nonetheless, it is likely that, in the first year of the new
test’s availability, more than 25,000 cats will be diagTREATMENT
nosed with adult heartworm infections that previously
Because no form of medical adulticidal therapy has been
would not have been detected.
shown to increase the survival rate of cats harboring
What are the implications of increased testing? In
adult heartworms, treatment is aimed at controlling
addition to the “rude awakening” in store for veterinariclinical signs. On diagnosis, thoracic radiographs should
ans and cat owners who did not believe heartworms
be obtained or reviewed to look for any evidence of vas-
Treatment is also difficult because no form of medical adulticidal therapy has been shown
to increase the survival rate of cats harboring adult heartworms.
existed in cats in their area, it should provide more
information about cats at risk for HARD.
The 1% heartworm antigen–positive rate will probably emerge as just the “tip of the iceberg” (Figure 4) of
cats with or at risk for HARD because only cats with
adult female heartworms test positive for antigen. Also,
a significant number of cats infected with heartworms at
any stage are missed due to the limitations of current
testing modalities. Although the nationwide antibodyCOMPENDIUM
cular, bronchointerstitial, or parenchymal disease. Cats
exhibiting clinical or radiographic signs of disease
should be given antiinflammatory doses of glucocorticosteroids (prednisone, 1 to 2 mg/kg/day), reduced
weekly over a 3- to 4-week period. If clinical signs recur
or persist, alternate-day glucocorticosteroids should be
given at the lowest effective dose. Radiography and
serology are then repeated every 6 months to monitor
the course of the disease. A monthly heartworm prevenJuly 2008
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Figure 2. Radiographic evidence of heartworm
infection. Bronchointerstitial pattern.
Figure 3. Heartworm signatures of echocardiography
(arrows). (Image courtesy of Clarke Atkins, DVM, DACVIM
[Internal Medicine and Cardiology], North Carolina State
University)
tion regimen should be initiated for all cats; because
microfilaremia is typically rare or marginal in cats
(unlike dogs), it is safe to administer preventive agents
to heartworm-positive cats.
Cats presenting in acute respiratory distress should be
given oxygen, “shock” doses of glucocorticosteroids (dexamethasone sodium phosphate, 1 to 2 mg/kg IM or IV,
or prednisolone sodium succinate, 50 to 100 mg/kg/cat
IV), and a bronchodilator (e.g., aminophylline, 6.6 mg/kg
IV). Supportive therapy (IV fluids and thermal support)
is maintained until the cat’s condition is stabilized. Retrospective studies indicate that 10% to 20% of cats with
adult heartworm infections die as a result of complications from a dead or dying heartworm.20 Owners of cats
July 2008
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CE Dirofilaria immitis in Cats: Diagnosis and Management
1%
Nationwide heartworm
antigen–positive rate.17
HARD
8%+2%=10%
16% Ab+
32% of cats at risk
Of the 16% of cats that are Ab+ without
adult worms, half, or 8%, have pulmonary
parenchymal lesions (HARD).19
Nationwide heartworm
antibody–positive rate.15
The 16% Ab+ rate may represent only
half of the cats at risk for HARD.
In one study, 50% of cats with known
HARD lesions were Ab– within 8
months after infection.19
with an adult heartworm infection diagnosed either by
antigen testing or echocardiography should be informed
about this risk and instructed to seek prompt medical
attention at any sign of respiratory distress. It may be prudent to give the owner a syringe containing 10 mg of
dexamethasone sodium phosphate with instructions to
administer in the event of a respiratory crisis to initiate
treatment, but it must be emphasized that this does not
eliminate the need for emergency veterinary care.
There is anecdotal evidence that antileukotrienes
(e.g., montelukast, 2 mg/day) may help to thwart an
acute, fatal lung injury when an adult worm dies. Dil-
Figure 4. Heartworm antigen and antibody
test results versus potential numbers of cats
at risk for HARD. According to the study
conducted at Heska’s reference laboratory,15 the
nationwide heartworm antibody–positive (Ab+)
rate in cats is approximately 16%. Browne et al19
have showed that half of Ab+ cats have lung lesions
consistent with HARD; therefore, it is possible
that, nationwide, 8% of cats have HARD. If 50%
of cats with known HARD lesions (including
25% to 30% of cats with adult heartworms6,8)
are antibody negative (Ab–) 8 months after
infection,18 it is possible that the 16% Ab+ rate
represents only half of the cats at risk for HARD,
for a total of 32% of cats potentially at risk. If, at a
conservative estimate, an additional 2% of these
Ab– cats have HARD, as many as 10% of cats may
have HARD from juvenile infections.This makes
the 1% antigen-positive rate17 merely the tip of
the iceberg.
before administering adulticidal medication reduces the
pathology associated with worm death,24 but similar
studies have not yet been completed in cats.
PREVENTION
All indoor and outdoor cats in endemic areas should
receive heartworm prevention because the risk for
indoor cats has been shown to be similar to that for outdoor cats.12,14,16 There are four products on the market
labeled for cats that are safe and virtually 100% effective
in preventing heartworm infection. Ivermectin is available as a chewable treat, milbemycin as a flavored tablet,
Heartworm disease in cats can be difficult to diagnose because
no single test can detect heartworms at all stages.
lon21 has been using this approach for more than 6 years,
and no cat so treated has yet presented in acute respiratory distress. There is also interest in the use of doxycycline in heartworm-positive cats. Heartworms harbor an
intracellular endosymbiont of the genus Wolbachia,
which is found in many of the filarial nematodes that
cause disease in humans and animals (including
Onchocerca volvulus, Wuchereria bancrofti, Brugia malayi,
and Dirofilaria immitis). Doxycycline is now being used
to treat some filarial nematode infections in humans.22,23
Studies indicate that pretreating a dog with doxycycline
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and selamectin and moxidectin as topical applications.
Spectra vary among products, but all control multiple
parasites in addition to heartworms.
CONCLUSION
Although the promise of universal heartworm antigen testing in cats will not translate into universal detection, the
concept of monthly prevention in all cats should be readily
understandable to owners. With veterinarians leading the
way in public education, preventive measures for cats may
soon be as acceptable as they currently are for dogs.
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REFERENCES
1. McCall JW, Dzimianski MT, McTier TL, et al. Biology of experimental
heartworm infection in cats. In: Soll MD, ed. Proceedings of the Heartworm
Symposium ’92. Batavia, IL: American Heartworm Society; 1992:71-79.
2. Brawner WR, Dillon AR, Robertson-Plough CK, Guerrero J. Radiographic
diagnosis of feline heartworm disease and correlation to other clinical criteria:
results of a multicenter clinical case study. In: Seward RL, ed. Recent Advances
in Heartworm Disease: Symposium ’98. Batavia, IL: American Heartworm
Society; 1998:91-95.
3. Venco L, Morini S, Ferrari E, Genchi C. Technique for identifying heartworms in cats by 2-D echocardiography. In: Seward RL, ed. Recent Advances
in Heartworm Disease: Symposium ’98. Batavia, IL: American Heartworm
Society; 1998:97-102.
4. Defrancesco TC, Atkins CE. The utility of echocardiography in the diagnosis of feline heartworm disease: a review of published reports. In: Seward RL,
ed. Recent Advances in Heartworm Disease: Symposium ’98. Batavia, IL: American Heartworm Society; 1998:103-105.
5. Atkins CE, Arther RG, Ciszewski DK, et al. Echocardiographic quantification of Dirofilaria immitis in experimentally-infected cats. Vet Parasitol 2008.
Accepted for publication.
6. Nelson CT, Self TS. Incidence of Dirofilaria immitis in shelter cats in southeast Texas. In: Seward RL, ed. Recent Advances in Heartworm Disease: Symposium ’98. Batavia, IL: American Heartworm Society, 1998:63-66.
7. McCall JW, Guerrero J, Supakorndej P, et al. Evaluation of the accuracy of
heartworm antigen and antibody test for cats. In: Seward RL, ed. Recent
Advances in Heartworm Disease: Symposium ’98. Batavia, IL: American Heartworm Society; 1998:127-134.
8. Snyder PS, Levy JK, Salute ME, et al. Performance of serologic tests used to
detect heartworm infection in cats. JAVMA 2000;216:693-700.
9. Berdoulay P, Levy JK, Snyder PS, et al. Comparison of serological tests for
the detection of natural heartworm infection in cats. JAAHA 2004;40:376384.
10. Bestul KJ, McCall JW, Nonglak S, et al. Evaluation of the Assure FH antibody assay for the detection of feline heartworm infection. In: Seward RL,
ed. Recent Advances in Heartworm Disease: Symposium ’98. Batavia, IL: American Heartworm Society; 1998:179-186.
11. Donoghue AR, Mondesire RR, Porter JP. Detection of antibodies to Dirofilaria immitis in the cat using a highly specific recombinant antigen. Presented
at the North American Veterinary Conference, Orlando, FL, January 11-15,
1997.
12. Atkins CE, DeFrancesco TC, Coats JR, et al. Heartworm infection in cats:
50 cases (1985-1997). JAVMA 2000;217:355-358.
13. DeFrancesco TC, Atkins CE, Miller MW, et al. Use of echocardiography for
the diagnosis of heartworm disease in cats: 43 cases (1985-1997) JAVMA
2001;218(1):66-69.
14. Dillon AR, Brawner WR, Robertson-Plough CK, Guerrero J. Feline heartworm disease: correlation of clinical signs, serology, and other diagnostics.
Results of a multicenter study. In: Seward RL, ed. Recent Advances in Heartworm Disease: Symposium ’98. Batavia, IL: American Heartworm Society;
1998:153-158.
15. Piche’ CA, Cavanaugh MT, Donoghue AR, Radecki SV. Results of antibody
and antigen testing for feline heartworm infection at Heska® veterinary diagnostic laboratories. In: Seward RL, ed. Recent Advances in Heartworm Disease:
Symposium ’98. Batavia, IL: American Heartworm Society; 1998:139-143.
16. Miller MW, Atkins CE, Stemme K, et al. Prevalence of exposure to Dirofilaria immitis in multiple areas of the United States. In: Seward RL, ed. Recent
Advances in Heartworm Disease: Symposium ’98. Batavia, IL: American Heartworm Society; 1998:161-166.
17. Lorentzen L, Caoloa A. Incidence of positive heartworm antibody and antigen tests at IDEXX Laboratories: trends and potential impact on feline
heartworm awareness and prevention. Vet Parasitol 2008. Accepted for publication.
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18. Dillon AR, Blagburn BL, Tilson DM, et al. Immature heartworm infection
produces pulmonary parenchymal, airway, and vascular disease in cats. Presented at the 12th Triennial Heartworm Symposium, Washington, DC, July
2007.
19. 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.
20. Genchi C, Venco L, Ferrari N, et al. Feline heartworm (Dirofilaria immitis)
infection: a statistical elaboration of the duration of the infection and life
expectancy in asymptomatic cats. Vet Parasitol 2008. Accepted for publication.
21. Heartworm-Associated Respiratory Disease in Cats. Pfizer Animal Health;
2007. Accessed May 2008 at http://www.advanstarvhc.com/c9.
22. Hoerauf A, Mand S, Adjei O, et al. Depletion of Wolbachia in Onchocerca
volvulus by doxycycline and microfilaridermia after ivermectin treatment.
Lancet 2001;357:1415-1416.
23. Taylor MJ, Bandi C, Hoerauf AM, Lazdins J. Wolbachia bacteria of filarial
nematodes: a target for control? Parasitol Today 2000;16:179-180.
24. McCall JW, Genchi C, Kramer L, et al. Heartworm and Wolbachia: therapeutic implications. Vet Parasitol 2008. Accepted for publication.
ARTICLE #2 CE TEST
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1. Because heartworm infection in cats typically
involves only one or two juvenile worms, it rarely
causes
a. pulmonary symptoms.
b. a host reaction.
c. microfilaremia.
d. vascular inflammation.
2. Radiographic signs of heartworm infection in
cats
a. are present in only about 55% of cases.
b. generally improve in about 50% of cats that have
them.
c. often appear as an enlargement of the right caudal
lobar artery.
d. all of the above
3. The echocardiographic signature of feline heartworm disease consists of
a. an equal (=) sign.
b. a wavy (~) sign.
c. a V sign.
d. a C sign.
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4. Antigen testing has limited value in cats because
a. it primarily detects only mature, female worms.
b. cats seldom have an immune reaction to the presence of worms.
c. it has a low sensitivity in both cats and dogs.
d. it is effective only in the microfilaremic stage.
5. Antibody testing cannot be used to rule out
heartworm infection in cats because
a. it cannot detect all stages of the worm’s life cycle.
b. it has a high false-negative rate.
c. frequent false-positive results can lead to overtreatment.
d. all of the above
6. When diagnostic tests were compared in the
same group of infected cats, heartworm infection
was most consistently detected by
a. thoracic radiography.
b. echocardiography.
c. antibody testing.
d. antigen testing.
7. Data from a group of reference laboratories
show similar infection rates for feline heartworm
disease and
a. FeLV.
b. feline infectious peritonitis.
c. FIV.
d. Lyme disease.
8. The primary advantage of increased antigen
testing is the identification of cats
a. that need adulticidal therapy.
b. that should be quarantined.
c. with compromised immunity.
d. at risk for HARD.
9. The mainstay of symptomatic therapy for cats
with heartworm disease is
a. glucocorticosteroids.
b. bronchodilators.
c. NSAIDs.
d. parasiticidal agents.
10. A heartworm disease prevention regimen should
be initiated
a. only in cats found to be antigen negative on two consecutive tests.
b. only in cats younger than 6 months.
c. in all cats that show no signs of HARD.
d. in all cats, regardless of infection status.
July 2008