The Prevalence and Diagnosis of Feline Heartworm Infection

Within the past few decades, it has become apparent that infection with Dirofilaria immitis, more commonly known as heartworm, can cause serious and even fatal disease in cats as well as dogs. Although the prevalence of heartworm infection in cats is admittedly lower than that observed in dogs, its occurrence is likely underestimated, in part due to difficulty in making an accurate diagnosis in cats.

Multimodal diagnostics can enhance detection and help to differentiate between the clinical manifestations of feline heartworm infection: heartworm-associated respiratory disease (HARD) and adult heartworm infection.

Clinical Aspects of Feline Heartworm Infection

Heartworm infection begins when third-stage D immitis larvae are deposited by a mosquito onto the host’s skin during blood feeding and invade the host through the bite wound. During their subsequent migration to the pulmonary arteries, they molt twice, to the fourth larval stage and then the immature adult stage. Immature adults arrive in the pulmonary arteries 70 to 90 days after infection; here, they complete sexual maturation and begin to reproduce.¹

Dogs are usually permissive hosts and tolerate the initial arrival to the pulmonary arteries relatively well, thus allowing the heartworms to persist and complete development into mature adults. Clinical heartworm disease in dogs is most often due to mature heartworms and cumulative, chronic damage within the pulmonary arteries.¹

In cats, however, the arrival of immature adult worms in the pulmonary system induces a sizable inflammatory response. While the feline immune system is often capable of eliminating the immature worms without therapeutic intervention (sometimes called “self-curing”), the death of the parasites and resulting inflammation can cause heartworm-associated respiratory disease (HARD), a serious condition.² The most common pathological findings associated with HARD are eosinophilic infiltration of the lungs, villous endarteritis (often worst within the caudal lung lobes), and thoracic radiograph abnormalities.^3-5 Clinically, HARD most often manifests with coughing, dyspnea, and vomiting,⁶ with an onset approximately 3 months postinfection, coinciding with arrival and death of immature parasites in the pulmonary system.

Less frequently, immature parasites survive the cat’s immune response and adult heartworm infection develops. Presence of adult worms induces pathology in the lungs and pulmonary vessels similar to that observed with HARD. Interestingly, it has been demonstrated that mature, living heartworms are immunosuppressive in cats and that they downregulate pulmonary intravascular macrophage activity.⁷ It is unclear why immature stages are more immunogenic than adult heartworms in cats.

It is not uncommon for a cat infected with adult heartworms to suffer acute collapse and death (FIGURE 1), regardless of whether it previously exhibited signs associated with heartworm infection.^8,9 This scenario is likely attributable to death of an adult heartworm and a sudden inflammatory response or thromboembolism caused by adult worms.⁸ Many canine and feline heartworm infections exist in the absence of clinical signs, although failure to develop overt clinical signs does not necessarily indicate less severe pathology.

Figure 1. Photo taken at necropsy demonstrating natural heartworm infection in a cat that died suddenly after sharing a household with a dog with heartworm disease. Courtesy Dr. Sarah Morar Schneider, University of Georgia

Feline heartworm infections rarely become microfilaremic, and when microfilaremia has been observed in cats, it has been only transiently detectable, with low numbers of microfilariae.¹⁰ This would indicate that cats do not routinely contribute to the transmission of heartworm to mosquitoes and subsequently other hosts.

Optimizing Diagnosis: A Multimodal Approach

Recommendations regarding diagnostic testing and screening for heartworm infection in dogs are straightforward: Perform an antigen test and a microfilaria test for every dog, every year.¹¹ The tendency for heartworm-infected cats to develop clinical disease in the absence of detectable antigen or microfilariae (or despite elimination of the parasite altogether) makes diagnosis and formulating feline diagnostic guidelines difficult. No sole test performs sufficiently for diagnosing feline heartworm infection. Utilizing multiple diagnostic tests both dramatically improves the likelihood of diagnosis and aids in differentiating the type of heartworm infection—HARD or adult heartworms (FIGURE 2).

Antibody Testing

Cats initially infected with third-stage larvae can seroconvert as early as 1 to 2 months postinfection, and it was demonstrated under experimental conditions that all cats seroconverted by 5 months postinfection.¹² In the same study, at least 90% of cats seroconverted by 3 months postinfection, coinciding with the typical time for the onset of HARD symptoms.¹²

The primary limitation of antibody testing is that it cannot delineate between historical and current infection, and the longevity of antibody titer persistence is not well established and likely varies between individuals. However, antibody positivity in the presence of consistent clinical signs and history should strongly increase the suspicion for HARD or adult heartworm infection. A positive antibody test result in a clinically healthy cat indicates both exposure risk and the possibility of current infection. In these cases, the cat should be started on heartworm prevention and the owner should be educated regarding not only the importance of continued year-round prevention but also the possibility that clinical signs could develop and what to look for. Conversely, a negative test drastically lowers, but does not completely eliminate, the index of suspicion and helps to lessen the probability of heartworm as the cause of respiratory signs.

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For these reasons, and because it is relatively inexpensive, antibody testing can be very beneficial as a first step in the diagnostic workup for suspected feline heartworm infection. However, it is possible for cats with other evidence of heartworm infection (e.g., positive antigen test result, worms visualized on echocardiography, adult worms recovered at necropsy) to have negative antibody test results.^6,13-15 Although uncommon, this finding underscores the importance of a multimodal approach for diagnosis of feline heartworm infection.

Antigen Testing

Due to the interplay of heartworms and the feline immune system, antigen testing alone is generally considered a less reliable diagnostic method in cats. Combining antigen detection with antibody testing increases the diagnostic value. A positive antigen test is highly suggestive of adult heartworm infection, especially if other diagnostic tests and/or the case history fit with the positive result. However, a negative antigen test result should be interpreted as inconclusive. It is possible that the cat may be truly negative. Alternatively, the result could be falsely negative due to low worm burden, immature worms, male-only infection (commercial tests target an antigen primarily expressed by the reproductive tract of mature female worms), or immune-complex formation binding any available antigen and rendering it undetectable. Because cats typically mount a strong antibody response to immature adult heartworms early in infection, antibody binding of antigen likely reduces test sensitivity and results in false negatives.¹⁶

When heartworm infection is suspected in a cat, heating the samples prior to antigen testing should be considered, as it causes immune-complex dissociation and improves test performance^17,18; however, this recommendation is contrary to label indications of the diagnostic tests. A negative antigen test result in conjunction with a positive antibody test result and associated clinical signs is highly indicative of HARD.

Thoracic Radiography

Thoracic radiography may provide useful supportive evidence for diagnosis of both HARD and adult heartworm infection (FIGURE 3). Multiple studies have sought to establish a conclusive relationship between specific radiographic changes and heartworm infection status in cats, as this has been a successful diagnostic approach in dogs.^3,5,14,19 However, radiographic changes in cats are variable, have not been able to consistently predict heartworm infection status, and are often indistinguishable from those caused by other respiratory disease. Nonetheless, in cats with suspicion of heartworm infection based on serologic findings and history, thoracic radiography may help to support diagnosis and evaluate lesion severity.

Figure 3. Thoracic radiographs demonstrating abnormalities associated with heartworm infection in a domestic shorthair shelter cat. (A) Dorsoventral radiographic view showing diffuse bronchointerstitial pattern with enlargement of the caudal lobar pulmonary artery (arrowhead).

Figure 3B. Right lateral radiographic view showing a diffuse bronchointerstitial pattern within the lung area. The cat was heartworm antigen–positive and had variable heartworm antibody test results depending on the assay used. Radiographic analysis showed an arteriole wall to lumen ratio of 96.76% (occlusive hypertrophy) and a radiographic score of 2 (0–3 scale). One female heartworm was recovered at necropsy.

The most common radiographic findings in heartworm-infected cats are pulmonary arterial enlargement and increased bronchointerstitial pattern, particularly in the caudal lung lobes.^3,5,14,19 Radiographic changes in cats with heartworm infection have not been found to differ significantly.³

Echocardiography

Echocardiography has proven to be a useful tool for visualizing and diagnosing adult heartworm infection in cats.^20,21 Adult worms within the pulmonary arteries or cardiac chambers appear as characteristic double-lined structures, sometimes called “train tracks.” Enumerating worms via echocardiography is possible, although the accuracy of this method for determining worm burden is not consistent.²¹ Accurate enumeration of worms may not be of much clinical relevance since even a single worm can be of serious consequence for a cat.

It was previously thought that visualization of worm structures on echocardiography was conclusively diagnostic; however, false positives can occur even with a trained eye.²¹ Visualization of supposed worm structures on echocardiography in conjunction with a positive antigen test result is as close to a definitive antemortem confirmation of adult heartworm infection as can be achieved.

Conflicting results, such as a positive antigen test result in the absence of echocardiographic evidence or, conversely, echocardiographic evidence of adult worms with a negative antigen test result, present a more complex diagnostic picture but do not necessarily rule out infection. It is possible that the infection is undetectable by echocardiography or that antigen is below the detectable threshold, bound by antibody complexes, or absent (i.e., the infection is immature or there are male worms only).

Microfilaria Testing

Since microfilaremia is rare or transient in cats infected with heartworm,¹⁰ tests for the recovery or detection of microfilariae are unlikely to be accurate diagnostic methods. The modified Knott’s test and polymerase chain reaction testing do offer the advantages of being relatively sensitive as well as allowing species-level identification of microfilariae, which is important as other filarial infections that result in microfilaremia have been reported in cats in the United States.¹⁵ If microfilariae are recovered, the possibility of infection with a filariid other than heartworm should not be ruled out until the species is definitively identified.

Prevalence And Risk Trends

Evaluating feline heartworm prevalence is difficult for the same reason as is making a confident diagnosis: lack of a single, reliable test that is commonly used and easily available. It is estimated that feline heartworm infection prevalence is 5% to 20% of the canine infection prevalence in the same geographic area.²² Most studies comparing canine and feline prevalence among similar populations have corroborated this estimate.^15,23 In a nationwide study comparing antigen prevalence among shelter-housed and owned cats (n = 34 975), prevalence in both populations was found to be 0.4%, with outdoor access increasing risk of infection threefold.²⁴ Although outdoor exposure is a major risk factor for infection, the perception that indoor cats are protected from heartworm infection is a myth debunked by several studies that found strictly indoor cats to be infected with heartworms.^6,8,24 A separate nationwide study that evaluated healthy pet cats found an antigen prevalence of 0.3% but a substantially higher antibody prevalence of 3.5%.²⁵

Summary

Although adult heartworm infection seems relatively uncommon in cats, even among high-risk populations, antigen prevalence is not a completely accurate metric for assessing true risk of infection or prevalence of clinical disease caused by heartworms. Additionally, housing cats indoors does not completely protect them from infection with or disease related to heartworm. Regardless of lifestyle, year-round heartworm prevention is a necessity to completely protect cats from both HARD and adult heartworm infection.