Dirofilaria Immitis in Cats: Diagnosis and Management*

CE Article #2

Dirofilaria immitis in Cats: Diagnosis and Management *

C. Thomas Nelson, DVM a 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.

iagnosis is the most challenging part of tions are often single sex. When microfilariae feline heartworm disease because are produced, they are only present for 1 or 2 Dno single test can reliably detect heart - months, at which time the cat’s immune sys - worms at all stages. Veterinarians must be will- tem eliminates them and suppresses further ing to conduct multiple and even repeat tests embryogenesis. 1 (Table 1 and Figure 1 ) to obtain a diagnosis and to correctly interpret and apply the results .b Radiology The most common radiographic finding in DIAGNOSIS feline heartworm disease is an enlargement of Microfilariae the right caudal lobar artery (see Figure 2 in the Filtration tests for microfilariae are virtually companion article beginning on page 382 ). This useless in cats because cats are only transiently is best seen on a ventrodorsal view. A bron - microfilaremic, if at all. To be microfilaremic, a chointerstitial pulmonary pattern (Figure 2) cat must have both a mature male and a may also be noted, but this finding is not mature female worm, and because cats typi - unique to feline heartworm disease. cally only have one or two worms, the infec - The use of radiology has limitations, as only 55% of heartworm antigen −positive cats had *A companion article on prevalence and pathophysi - ology begins on page 382. radiographic signs consistent with heartworm 2 aDr. Nelson discloses that he has received financial sup - disease in one study. Follow-up on some of port from the American Heartworm Society, the Com - these cats showed improvement in radiographic panion Animal Parasite Council, IDEXX Laboratories, scores in 50% of cases and worsened scores in Fort Dodge Animal Health, the KNOW Heartworms 16%. Because cats can tolerate adult worm campaign, Merial, and Pfizer Ani - mal Health. infections fairly well and it is common for clini - bFor the complete American cal signs to either resolve or become intermit - Heartworm Society 2007 Guide - tent, such results are to be expected . •Take CE tests lines for the Diagnosis, Prevention and Management of Heartworm • See full-text articles (Dirofilaria immitis ) Infection Echocardiography CompendiumVet.com in Cats , please visit www.heart In skillful hands, ultrasonography has been wormsociety. org . shown to detect 100% of adult feline heart -

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Table 1. Interpretation of Heartworm DiagnosticTests in Cats Test Purpose Result and Interpretation Limitations

Antibody test Detects antibodies produced • Negative—Decreases index of suspicion Antibodies confirm in response to late L4, recent infection to at juvenile , and adult worms. • Positive—Increases index of suspicion; least late L4 stage May detect infections as early confirms cat is at risk but do not confirm as 8 weeks posttransmission disease causality

Antigen test Detects antigen from an • Negative—Decreases index of suspicion Immature or male- adult female heartworm, >5 only worm infections dying male heartworms, or a • Positive—Confirms presence of are rarely detected dying female heartworm heartworms

Thoracic Detects vascular • Normal—Decreases index of suspicion Radiographic signs radiography enlargement (inflammation are subjective and and hypertrophy caused by a • Signs consistent with feline heartworm affected by clinical juvenile worm), pulmonary disease—Enlarged arteries greatly interpretation parenchymal inflammation, increase index of suspicion and (more rarely) edema

Echocardiography Detects echogenic walls of • No worms seen—No change in index of Accuracy depends in the immature or mature suspicion part on the heartworm residing in the ultrasonographer’s lumen of the pulmonary • Worms seen—Confirms presence of experience with arterial tree (only within the heartworms in the structure heartworm detection visual ultrasonographic window ) © American Heartworm Society

worm infections, but the technician must be able to fol - early or male-only worm infections. Part of the disease low the caudal pulmonary arteries to their bifurcation process in cats is the death of juvenile worms at 3 to 4 within the lung fields. 3 Other reports cite echocardiog - months postinfection, which antigen tests cannot detect. raphy as detecting 68% of natural infections 4 and 88% of Again, because most infected cats have one or , at most, experimental infections in cats. 5 two adult worms, single-sex, male-only infections are The cuticle of the adult heartworm is strongly common. 1 Multiple studies have reported the sensitivity echogenic , producing short, segmented, parallel lines of antigen testing in mature heartworm infections in cats where the imaging plane crosses the worm. Heartworm to be 50% to 86%. 6–9 As a result, a negative antigen test signatures on echocardiography have been described as result does not rule out heartworm infection in cats. equal signs (=; Figure 3). However, the imaging beam The antibody test was initially very promising. In may cross the same worm multiple times, making quan - experimental studies, it detected 93% to 100% of heart - tifying the number of worms difficult. worm infections, including late L4 larvae as well as juve - nile and adult worms. 7,10,11 However, a significant Serology number of cats with adult heartworms are antibody neg - There is an ongoing debate about the accuracy of anti - ative. For example, in a retrospective study of 50 cats gen and antibody testing for feline heartworm disease. with known heartworm disease, there was a 14% false- Both tests can provide valuable information, but a thor - negative rate .12 Most of the cats in the study (72%) had ough understanding of their limitations is essential to clinical signs indicating active disease. interpreting results correctly . A necropsy study of shelter cats in Texas 6 reported a Antigen tests are considered the gold standard in diag - 50% false-negative rate for one antibody test, and a sim - nosing heartworms in dogs. However, they do not detect ilar study in Florida had an 11% to 68% false-negative

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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 tem - pered 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 con - duct 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 anti - body 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 heart - worm 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 lab - oratory 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 detec - tion 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 heartworm-

July 2008 COMPENDIUM 396 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 heartworms 6,8 ) are anti - body negative 8 months after infection. 18 Based on these num - Antibody Test Antigen Test or bers, it could be argued that the or Radiography Echocardiography percentage of cats at risk for • Positive result • Positive result is HARD in a given area is twice the increases index diagnostic base antibody rate (32%). At the of suspicion • Negative result lowers same time, Browne et al 19 have • Negative result index of suspicion showed that half of antibody-posi - lowers index of tive cats (50% of 16% = 8%) have suspicion lung lesions consistent with HARD. If, at a conservative esti - mate, 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 diag - TREATMENT 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 veterinari - clinical 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 cular, bronchointerstitial, or parenchymal disease. Cats information about cats at risk for HARD. exhibiting clinical or radiographic signs of disease The 1% heartworm antigen –positive rate will proba - should be given antiinflammatory doses of glucocorti - bly emerge as just the “tip of the iceberg” (Figure 4) of costeroids (prednisone , 1 to 2 mg/kg/day ), reduced cats with or at risk for HARD because only cats with weekly over a 3 - to 4 -week period. If clinical signs recur adult female heartworms test positive for antigen. Also, or persist, alternate -day glucocorticosteroids should be a significant number of cats infected with heartworms at given at the lowest effective dose. Radiography and any stage are missed due to the limitations of current serology are then repeated every 6 months to monitor testing modalities. Although the nationwide antibody- the course of the disease. A monthly heartworm preven -

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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 (dex - amethasone 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. Retro - spective studies indicate that 10% to 20% of cats with adult heartworm infections die as a result of complica - tions from a dead or dying heartworm. 20 Owners of cats

July 2008 COMPENDIUM 398 CE Dirofilaria immitis in Cats: Diagnosis and Management

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+) Nationwide heartworm rate in cats is approximately 16%. Browne et al 19 antigen–positive rate. 17 1% have showed that half of Ab+ cats have lung lesions consistent with HARD; therefore, it is possible Of the 16% of cats that are Ab+ without HARD that, nationwide, 8% of cats have HARD. If 50% adult worms, half, or 8%, have pulmonary 8%+2%=10% of cats with known HARD lesions (including parenchymal lesions (HARD). 19 25% to 30% of cats with adult heartworms 6,8 ) are antibody negative (Ab –) 8 months after Nationwide heartworm 18 16% Ab+ infection, it is possible that the 16% Ab+ rate antibody–positive rate. 15 represents only half of the cats at risk for HARD, for a total of 32% of cats potentially at risk. If, at a The 16% Ab+ rate may represent only conservative estimate, an additional 2% of these 32% of cats at risk half of the cats at risk for HARD. Ab – cats have HARD, as many as 10% of cats may In one study, 50% of cats with known have HARD from juvenile infections. This makes HARD lesions were Ab– within 8 the 1% antigen-positive rate 17 merely the tip of 19 months after infection. the iceberg. with an adult heartworm infection diagnosed either by before administering adulticidal medication reduces the antigen testing or echocardiography should be informed pathology associated with worm death ,24 but similar about this risk and instructed to seek prompt medical studies have not yet been completed in cats . attention at any sign of respiratory distress. It may be pru - dent to give the owner a syringe containing 10 mg of PREVENTION dexamethasone sodium phosphate with instructions to All indoor and outdoor cats in endemic areas should administer in the event of a respiratory crisis to initiate receive heartworm prevention because the risk for treatment, but it must be emphasized that this does not indoor cats has been shown to be similar to that for out - eliminate the need for emergency veterinary care. door cats. 12,14,16 There are four products on the market There is anecdotal evidence that antileukotrienes labeled for cats that are safe and virtually 100% effective (e.g., montelukast , 2 mg/day) may help to thwart an in preventing heartworm infection . Ivermectin is avail - acute, fatal lung injury when an adult worm dies. Dil - able 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. lon 21 has been using this approach for more than 6 years , and selamectin and moxidectin as topical applications. and no cat so treated has yet presented in acute respira - Spectra vary among products , but all control multiple tory distress. There is also interest in the use of doxycy - parasites in addition to heartworms . cline in heartworm -positive cats. Heartworms harbor an intracellular endosymbiont of the genus Wolbachia , CONCLUSION which is found in many of the filarial nematodes that Although the promise of universal heartworm antigen test - cause disease in humans and animals (including ing in cats will not translate into universal detection, the Onchocerca volvulus, Wuchereria bancrofti, Brugia malayi , concept of monthly prevention in all cats should be readily and Dirofilaria immitis ). Doxycycline is now being used understandable to owners. With veterinarians leading the to treat some filarial nematode infections in humans .22,23 way in public education, preventive measures for cats may Studies indicate that pretreating a dog with doxycycline 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 heart - worms 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 diagno - sis of feline heartworm disease: a review of published reports. In: Seward RL , ed. Recent Advances in Heartworm Disease: Symposium ’98. Batavia, IL: Ameri - can Heartworm Society; 1998:103-105. 5. Atkins CE, Arther RG, Ciszewski DK, et al. Echocardiographic quantifica - tion 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 south - east Texas. In : Seward RL , ed. Recent Advances in Heartworm Disease: Sympo - sium ’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 Heart - worm 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;40:376- 384. 10. Bestul KJ, McCall JW, Nonglak S, et al. Evaluation of the Assure FH anti - body assay for the detection of feline heartworm infection. In : Seward RL , ed. Recent Advances in Heartworm Disease: Symposium ’98. Batavia, IL: Ameri - can Heartworm Society ; 1998:179-186. 11. Donoghue AR, Mondesire RR, Porter JP. Detection of antibodies to Dirofi - laria 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 heart - worm disease: correlation of clinical signs, serology, and other diagnostics. Results of a multicenter study. In: Seward RL , ed. Recent Advances in Heart - worm 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 diag - nostic 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 Dirofi - laria immitis in multiple areas of the United States. In: Seward RL , ed. Recent Advances in Heartworm Disease: Symposium ’98. Batavia, IL: American Heart - worm Society ; 1998:161-166. 17. Lorentzen L, Caoloa A. Incidence of positive heartworm antibody and anti - gen tests at IDEXX Laboratories: trends and potential impact on feline heartworm awareness and prevention. Vet Parasitol 2008. Accepted for publi - cation .

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18. Dillon AR, Blagburn BL, Tilson DM, et al. Immature heartworm infection 4. Antigen testing has limited value in cats because produces pulmonary parenchymal, airway, and vascular disease in cats. Pre - a. it primarily detects only mature, female worms. sented at the 12th Triennial Heartworm Symposium, Washington, DC, July 2007. b. cats seldom have an immune reaction to the pres - 19. Browne LE, Carter TD, Levy JK, et al. Pulmonary arterial disease in cats ence of worms. seropositive for Dirofilaria immitis but lacking adult heartworms in the heart c. it has a low sensitivity in both cats and dogs. and lungs. Am J Vet Res 2005;66:1544-1549. d. it is effective only in the microfilaremic stage. 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 . 5. Antibody testing cannot be used to rule out 21. Heartworm-Associated Respiratory Disease in Cats. Pfizer Animal Health; heartworm infection in cats because 2007 . Accessed May 2008 at http://www.advanstarvhc.com/c9 . a. it cannot detect all stages of the worm’s life cycle. 22. Hoerauf A, Mand S, Adjei O, et al. Depletion of Wolbachia in Onchocerca b. it has a high false-negative rate. volvulus by doxycycline and microfilaridermia after ivermectin treatment. c. frequent false-positive results can lead to overtreat - Lancet 2001;357:1415-1416. ment. 23. Taylor MJ, Bandi C, Hoerauf AM, Lazdins J. Wolbachia bacteria of filarial nematodes: a target for control? Parasitol Today 2000;16:179-180. d. all of the above 24. McCall JW, Genchi C, Kramer L, et al. Heartworm and Wolbachia : therapeu - tic implications. Vet Parasitol 2008. Accepted for publication. 6. When diagnostic tests were compared in the same group of infected cats, heartworm infection was most consistently detected by ARTICLE #2 CE TEST a. thoracic radiography. This article qualifies for 2 contact hours of continuing CE b. echocardiography. education credit from the Auburn University College c. antibody testing. of Veterinary Medicine. Subscribers may take d. antigen testing. individual CE tests or sign up for our annual CE program . Those who wish to apply this credit to 7. Data from a group of reference laboratories fulfill state relicensure requirements should consult their show similar infection rates for feline heartworm respective state authorities regarding the applicability disease and of this program . CE subscribers can take CE tests online a. FeLV . and get real-time scores at CompendiumVet.com . b. feline infectious peritonitis. c. FIV . 1. Because heartworm infection in cats typically d. Lyme disease. involves only one or two juvenile worms, it rarely causes 8. The primary advantage of increased antigen a. pulmonary symptoms. testing is the identification of cats b. a host reaction. a. that need adulticidal therapy. c. microfilaremia. b. that should be quarantined. d. vascular inflammation. c. with compromised immunity. d. at risk for HARD. 2. Radiographic signs of heartworm infection in cats 9. The mainstay of symptomatic therapy for cats a. are present in only about 55% of cases. with heartworm disease is b. generally improve in about 50% of cats that have a. glucocorticosteroids . them. b. bronchodilators. c. often appear as an enlargement of the right caudal c. NSAIDs . lobar artery . d. parasiticidal agents. d. all of the above 10. A heartworm disease prevention regimen should 3. The echocardiographic signature of feline heart - be initiated worm disease consists of a. only in cats found to be antigen negative on two con - a. an equal (=) sign. secutive tests. b. a wavy (~) sign. b. only in cats younger than 6 months. c. aV sign. c. in all cats that show no signs of HARD. d. a C sign. d. in all cats, regardless of infection status.

COMPENDIUM July 2008