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Current Feline Guidelines for the Prevention, Diagnosis, and Management of Heartworm ( immitis) Infection in Thank You to Our Generous Sponsors:

Printed with an Education Grant from IDEXX Laboratories. Photomicrographs courtesy of Bayer HealthCare. © 2014 American Heartworm Society | PO Box 8266 | Wilmington, DE 19803-8266 | E-mail: [email protected] Current Feline Guidelines for the Prevention, Diagnosis, and Management of Heartworm () Infection in Cats (revised October 2014)

CONTENTS Click on the links below to navigate to each section.

Preamble...... 2

EPIDEMIOLOGY...... 2 Figure 1. Urban heat island profile.

BIOLOGY OF FELINE HEARTWORM INFECTION...... 3 Figure 2. The heartworm life cycle.

PATHOPHYSIOLOGY OF FELINE HEARTWORM DISEASE...... 4 Figure 3. Microscopic lesions of HARD in the small pulmonary arterioles. Figure 4. Microscopic lesions of HARD in the alveoli.

PHYSICAL DIAGNOSIS...... 5 Clinical Signs and Findings

DIAGNOSTIC TESTING...... 5 Microfilariae Serology Thoracic Radiography Necropsy Confirmation Figure 5. Summary of feline heartworm diagnostics. Table1. Interpretation of heartworm diagnostic procedures and tests in cats.

TREATMENT...... 8 Medical Options Surgical Options Additional Considerations for Adulticide Therapy Surveillance of Infected Cats

PREVENTION...... 11 Drugs Serologic Testing

2014 Feline Heartworm Guidelines 1 Prepared and approved by the Executive Board of support the transmission of heartworms for brief the American Heartworm Society periods. Thus, the introduction of microfilaremic or wild canids could set up a nidus of infection (Officers:Dr. Stephen Jones, President; Dr. Wallace for local transmission of heartworm in this state. Graham, Past President; Dr. Cristiano von Simson, Such relocation of microfilaremic dogs and Vice President; Dr. Robert Stannard, Secretary- expansion of the territories of microfilaremic wild Treasurer; Dr. Doug Carithers, Editor; Dr. Patricia canids in other areas of the United States continue Payne, Dr. Chris Rehm, Dr. Charles Thomas Nelson, to be important factors contributing to further Dr. Martha Smith-Blackmore, Dr. Elizabeth Clyde dissemination of the parasite, as the ubiquitous and, Dr. Bianca Zaffarano Board Members; presence of one or more species of vector-competent Dr. Matthew Miller, Symposium Chair; Dr. Clarke mosquitoes makes transmission possible wherever Atkins, Symposium Co-Chair; Dr. John McCall, a reservoir of infection and favorable climatic Co-Editor; Dr. Mike Loenser and Dr. Tony Rumschlag, conditions co-exist. Change in any of these factors Ex Officio Members. can have a significant effect on the transmission Preamble potential in a specific geographic location.

These recommendations supersede the previous Environmental changes, both natural climatic edition of these guidelines and are based on the change and those created by , and latest information presented at the 2013 Triennial movement have increased heartworm infection Symposium of the American Heartworm Society and potential. Commercial and residential real estate recently completed studies. The recommendations development of non-endemic areas and areas of for the prevention, diagnosis, and management low incidence has led to the resultant spread and of heartworm infection in dogs are contained in a increased prevalence of heartworms by altering companion document (http://heartwormsociety.org/ drainage of undeveloped land and by providing veterinary-resources/canine-guidelines.html). water sources in new urban home sites. In the western United States, irrigation and planting of EPIDEMIOLOGY trees has expanded the habitat for sierrensis (western knot hole ), the primary vector Heartworm infection has been diagnosed around for transmission of heartworms in those states. the globe, including all 50 of the United States. In (Asian tiger mosquito), which the United States, its territories and protectorates, was introduced into the Port of Houston in 1985, heartworm is considered at least regionally endemic has now spread northward, approaching Canada, in each of the contiguous 48 states, Hawaii, Puerto and isolated populations have been identified in Rico, U.S. Virgin Islands, and Guam. Heartworm areas in the western states. This urban-dwelling transmission has not been documented in Alaska; mosquito is able to reproduce in small containers however, there are regions in central Alaska that such as flowerpots. Urban sprawl has led to the have mosquito vectors and climate conditions to

Figure 1. Sketch of an urban heat island profile. From http://eetd.lbl.gov/eatIsland/HighTemps/

2 American Heartworm Society formation of “heat islands,” as buildings and parking reflect a shorter transmission season than actually lots retain heat during the day (Figure 1), creating exists. microenvironments with potential to support the development of heartworm larvae in mosquito Once a reservoir of microfilaremic domestic and wild vectors during colder months, thereby lengthening canids is established beyond the reach of veterinary the transmission season. care, the ubiquitous presence of one or more species of vector competent mosquitoes makes transmission As vectors expand their territory, the number possible and eradication becomes improbable. of infected will continue to increase. A BIOLOGY OF FELINE HEARTWORM INFECTION pivotal prerequisite for heartworm transmission is a climate that provides adequate temperature and Significant differences exist between feline humidity to support a viable mosquito population, heartworm disease and its classical canine and also sustain sufficient heat to allow maturation counterpart and these are consistent with of ingested microfilariae into the infective, third- characteristics of partially adapted –parasite stage larvae (L3) within this intermediate host. It relationships. Although cats are susceptible hosts, has been shown that maturation of larvae, within they are more resistant to infection with adult three mosquito species, ceases at temperatures Dirofilaria immitis than are dogs. When dogs not below 57ºF (14ºC). Heartworm transmission does previously exposed to heartworms are injected with decrease in winter months but the presence of 100 L3 larvae, an average of 60 adult worms develop microenvironments in urban areas suggests that in almost 100% of the dogs; in cats, however, 3 to 10 the risk of heartworm transmission never reaches adult worms develop in approximately 75% of the zero. Furthermore, some species of mosquitoes cats. These L3 larvae molt to L4 and juvenile worm overwinter as adults. While heartworm larval (immature adult) with some loss along the way but development in these mosquitoes may cease in cool there is a very high mortality rate of the juvenile temperatures, development quickly resumes with worms as they reach the 3 to 4 months after subsequent warming. infection. Most heartworm infections in cats are comparatively light and consist of less than six The length of the heartworm transmission season adult worms. Although much heavier infections in the temperate latitudes is critically dependent occur occasionally, usually only one or two worms on the accumulation of sufficient heat to incubate are present, and approximately one third of these larvae to the infective stage in the mosquito. The consist of worms of the same sex. Nevertheless, peak months for heartworm transmission in the because of their relatively small body size, cats with Northern Hemisphere are typically July and August. only a few worms are still considered to be heavily Models predict that heartworm transmission in the infected in terms of parasite biomass. Some clinical continental United States is limited to 6 months or surveys and data from experimentally infected less above the 37th parallel at approximately the cats have documented a slight preponderance of Virginia–North Carolina state line. While model- infection in male cats, but it has not been determined based predictions of transmission using climatic conclusively that male cats are at greater risk. No data are academically appealing, they typically fail sex predilection for anti–D immitis host antibody to consider several potentially important factors, seropositivity has been proven within populations such as influence of microclimate, unique biological of naturally exposed cats, nor has a preference by habits and adaptations of the mosquito vectors, vector mosquitoes for either sex, although some variations in time of larval development and data suggest trends for each toward female cats. mosquito life expectancy, year-to-year temperature Host preference by some of the most abundant fluctuations, and global climate change. Predictive vectors does favor the and may contribute to risk maps assume that mosquito vectors live for only the lower prevalence of infection in cats. The one month; however, several significant mosquito spp mosquito, which is the most common species vectors live and breed for much longer periods, in many urban areas, feeds on both cats and dogs including Aedes albopictus (3 months), Aedes without preference. sticticus (3 months), Aedes trivitatus (2 months), (2 months), and The true prevalence of heartworm infection in cats is (several months). There are also documented cases probably understated due to diagnostic limitations, of hibernating Aedes quadrimaculatus surviving and the greater tendency of cats to exhibit only for 4 to 5 months, so the predictive risk maps likely

2014 Feline Heartworm Guidelines 3 transient clinical signs or die without confirmation shorter than that in dogs (Figure 2). Nevertheless, of infection. Necropsy surveys of shelter cats have heartworms are capable of causing severe disease in placed the prevalence of adult heartworm infections cats. at 5% to 15% of the rate in unprotected dogs in a PATHOPHYSIOLOGY OF FELINE HEARTWORM given area. Circulating microfilariae are seldom DISEASE found in infected cats. When microfilaremias do develop in cats, they appear only about one week The clinical importance of heartworms is amplified later than in dogs (195 days post infection at the in cats because even a small number of heartworms earliest) and seldom persist beyond 228 days post are potentially life-threatening. Although live adult infection. Heartworms transplanted from cats are worms in the pulmonary arteries cause a local capable of resuming production of circulating arteritis, some cats never manifest clinical signs. microfilariae in dogs; thus it appears that feline When signs are evident, they usually develop during infections become occult due to host immune- two stages of the disease: 1) arrival of heartworms mediated clearance of the microfilariae and perhaps in the pulmonary vasculature and 2) death of adult a reversible suppression of microfilariae production. heartworms. The first stage coincides with the arrival of immature adult worms in the pulmonary There are other indications that the is an arteries and arterioles approximately 3 to 4 months imperfect host for heartworms. Aberrant migration post infection. These early signs are due to an acute occurs more frequently in cats than in dogs. vascular and parenchymal inflammatory response to Although uncommon, heartworms are found the newly arriving worms and the subsequent death disproportionately often in the body cavities, of most of these same worms. This initial phase is systemic arteries, and central nervous system of often misdiagnosed as asthma or allergic bronchitis cats. Additionally, the life span of the parasite in cats but in actuality is part of a syndrome known as is thought to be 2 to 4 years, which is considerably

Figure 2. The heartworm life cycle in cats (right).

4 American Heartworm Society heartworm-associated respiratory disease (HARD). right ventricular hypertrophy and right Clinical signs associated with this acute phase are less common in heartworm-infected cats subside as the worms mature but demonstrable than in dogs. Even when narrowing of a lumen histopathologic lesions are evident even in those is compounded by worm-induced thrombosis, cats that clear the infection. The most notable bronchopulmonary collateral circulation usually is microscopic lesion is occlusive medial hypertrophy adequate to prevent infarction of the . of the small pulmonary arterioles (Figure 3), but PHYSICAL DIAGNOSIS other changes are also noted in the bronchi, bronchioles, alveoli (Figure 4), and pulmonary Clinical Signs and Physical Findings arteries. Once the pulmonary infection is established, evidence suggests that live heartworms are able Many cats tolerate their infection without any to suppress immune function. This allows many noticeable clinical signs, or with signs manifested cats to tolerate their infection without apparent ill only transiently. Clinical signs associated with effects—until the mature worms begin to die, which feline heartworm disease may be only a vague initiates the second stage of disease expression. malaise or can consist of predominantly respiratory, The degenerating parasites result in pulmonary gastrointestinal (e.g., emesis), or occasionally inflammation and thromboembolism, which often neurologic manifestations, either chronically or leads to fatal acute lung injury. Such reactions in acutely. Signs of chronic respiratory disease such cats can occur even in single-worm infections as the as persistent tachypnea, intermittent coughing, and result of the death of that worm. increased respiratory effort are most common. A systolic heart murmur may be present in cats when In dogs, the caval syndrome (dirofilarial worms reside in the right atrioventricular junction hemoglobinuria) results partly from large numbers interfering with tricuspid valvular function. Anorexia of heartworms relocating to the cavae and right and weight loss occur in some cats. Intermittent atrioventricular junction, interfering with tricuspid vomiting unrelated to eating is reported frequently valve function. Caval syndrome occurs rarely in cats and in endemic areas when no other cause is evident because infections are usually light; however, even should raise suspicion of heartworm infection. one or two worms may cause tricuspid regurgitation Other abnormalities, such as ascites, hydrothorax, and resultant heart murmur. chylothorax, pneumothorax, ataxia, , and , have been reported but are uncommon. A Arterial intimal proliferation resembling the peracute syndrome consisting of some combination characteristic heartworm arteritis found in dogs of signs including respiratory distress, ataxia, also develops in the major lobar and peripheral collapse, seizures, hemoptysis, or sometimes sudden pulmonary arteries of cats. Because heartworm death may arise without warning. infections in cats usually have a small number of worms and are of relatively short duration, DIAGNOSTIC TESTING these lesions are localized and ordinarily fail to cause sufficient obstruction to produce clinically Heartworm infection in cats is a more elusive significant pulmonary hypertension. Consequently, diagnosis than in dogs and can be overlooked easily.

A B C Figure 3. Small pulmonary arterioles. A, Adult heartworm and antibody (Ab) negative. B, Adult heartworm negative and antibody positive. C, Adult heartworm positive. 2014 Feline Heartworm Guidelines 5 A B C Figure 4. Alveolus, A, Adult heartworm and antibody (Ab) negative. B, Adult heartworm negative and antibody positive. C, Adult heartworm positive

A conscious awareness of its existence is critical. A most commonly when infections are light, female willingness to pursue this high index of suspicion worms are still immature, only male worms are frequently entails application of multiple diagnostic present, and/or the test kit instructions have not tests, some of which may need to be repeated on been followed. There are also documented cases of several occasions. Of these, heartworm serology, antigen‒antibody complexes interfering with antigen thoracic radiography, and echocardiography are the testing resulting in false-negative tests. Laboratory most useful methods of clinical confirmation. studies have shown that heating the sample test- tube to 104°C for 10 minutes will break these Microfilariae complexes down, releasing any antigen, resulting Cats are seldom microfilaremic when examined. In in more accurate test results. The routine heating the Americas, only Dirofilaria immitis microfilariae of blood samples IS NOT RECOMMENDED at this have been identified in cats but in northern Italy, time as this is contrary to the label instructions for microfilariae ofDirofilaria repens also have been these tests. It also could interfere with the results of identified. Since few microfilariae are ever present, combination tests that include an antibody test for the chances of finding them are improved by using detection of other infectious agents. Due to this and concentrations techniques (modified Knott or other mentioned considerations, heartworm test millipore filter). results should only be recorded as “positive” or “no antigen detected” (NAD) and should not be written Serology as “negative.”

Interpretation of antibody and antigen test results Antibody tests have the advantage of being able to is complicated and a thorough understanding of detect infection as early as 2 months post infection. the limitations of both tests is necessary in order Antibody tests do not offer an indication of the to use these assays in a clinical setting with any continued existence of an infection, however, just confidence. The antigen test is the “gold standard” that an infection occurred. Initial research reported in diagnosing heartworms in dogs but because the sensitivity and specificity of the feline antibody unisex infections consisting of only male worms or tests to be as high as 98% in experimentally symptomatic immature infections are more common infected cats with adult worms. Necropsy surveys in cats, none of the presently available antigen tests of naturally infected cats from shelters, however, can be relied upon to rule out heartworm disease in have indicated a lower sensitivity ranging from 32% cats. The current generation of heartworm antigen to 89%. The different antibody tests vary in their tests identify most “occult” infections (adult worms sensitivity to each stage of larval development, present but no circulating microfilariae) consisting thus discordant results between test methods of at least one mature female worm and are nearly are common. In a necropsy survey in which six 100% specific. In the cat, detectable antigenemia different antibody tests were evaluated, 21 of 31 develops at about 5.5 to 8 months post infection. heartworm-infected cats were negative on at least Necropsy surveys of shelter cats have shown one antibody test. These tests were performed on that 50% to 70% of infected cats have at least one postmortem samples, which may have some effect female worm. False-negative test results occur on the sensitivity; but in another necropsy survey

6 American Heartworm Society involving 10 heartworm positive cats, 50% were Correct interpretation of antibody test results antibody negative on antemortem samples. A third requires additional information and thoughtful report of 50 clinical cases from a university referral analysis. When infection with adult female worms center had a 14% antibody false-negative rate. These actually exists, however, antigen tests are more four studies reported a wide range in sensitivity; to reliable than generally credited. Since both juvenile understand the differences, the population tested and adult worms are capable of causing clinical and the timing of the test must be examined. In disease in the cat, both antibody and antigen tests the first study on experimentally infected cats, 50 are useful tools and when used together increase to 100 L3 were injected into heartworm-naïve cats the probability of making appropriate diagnostic and the cats were followed for 6 months. This is a decisions. much larger challenge than occurs in nature and no Thoracic Radiography data are available on whether the antibody level will decrease over the expected 2- to 4-year life span of Independent of serologic test results, radiography an adult worm in a naturally infected cat. The two may provide strong evidence of feline heartworm necropsy studies represent cat populations more disease and is valuable for assessing the severity typical of those encountered in clinical practice. In of disease and monitoring its progression or the last study from a university referral center, 72% regression. The most characteristic radiographic of the cats had clinical signs of disease. Limited features of heartworm disease in cats, as in evidence from these studies suggest that the dogs, are a sometimes subtle enlargement of the antibody level in cats decreases with time as the main lobar and peripheral pulmonary arteries, parasite matures and that heartworm-infected cats characterized by loss of taper, and sometimes with clinical signs are more likely to be antibody tortuosity and truncation in the caudal lobar positive than asymptomatic infected cats. Necropsy branches. These vascular features are visualized studies of shelter cats indicate a distinct correlation best in the ventrodorsal view and may be visible to antibodies and occlusive medial hypertrophy of only in the right caudal lobar artery, where substantial numbers of small pulmonary arterioles. heartworms are found most often. The characteristic These pathologic changes are evident in 79% of morphology of the pulmonary arteries in infected necropsy-confirmed adult worm infections and 50% cats, unlike dogs, tends to normalize and may of adult heartworm-negative but antibody-positive disappear completely, leaving no residual evidence cats. These findings have been confirmed in a study of infection. Enlargement of the main pulmonary utilizing an experimental model and are significant artery segment may occur in heavily infected cats as they indicate pulmonary disease occurs even but is not a reliable marker because most cats do not in those cats that do not develop adult worm develop pulmonary hypertension and because the infections. In the model cats were infected with 100 main is obscured by the cardiac L3 and were then treated with at 150 µg/ silhouette. The cardiac silhouette itself is seldom kg every 2 weeks starting at day 84 post infection enlarged. A bronchointerstitial lung pattern that to abbreviate the infection. The study revealed may clear spontaneously within a few months is a 50% of the cats were antibody negative 8 months common secondary feature suggestive of, but not later when necropsied. These cats developed unique to, feline heartworm disease. Other less radiographic and histopathologic changes indicative commonly associated pulmonary findings include of HARD. A second group of cats using the same hyperinflation of the lungs with flattening of the protocol but necropsied 16 months later were all diaphragm, focal parenchymal radiodensities, antibody negative even though radiographic and consolidated lung lobes, pleural effusion, and histopathologic changes could still be detected. pneumothorax. In some cases of feline heartworm Additional studies have shown that precardiac disease, thoracic radiographs provide no evidence of stages of D immitis also elicit pathology in bronchial, infection. bronchiole, alveolar-interstitial, and pulmonary arteries. It has been shown that cats placed on Radiographic features suggestive of feline or heartworm preventives heartworm disease can be found in about half prior to infection with L3 had significantly fewer of the cats suspected of being infected based on pulmonary lesions. historical and physical signs. Also, about half of those cats with pulmonary arterial enlargement

2014 Feline Heartworm Guidelines 7 indicative of feline heartworm disease are antibody heartworm infection of at least 5 months’ duration. positive. Temporal differences in the development Quantification of worm burden is, nevertheless, of the parasite, host immune responses and organic difficult because the potential serpentine positioning disease, as well as spontaneous regression of allows echo beams to transect the worm in multiple lesions, may account for discrepancies between sites, giving multiple echo images and potentially radiographic, clinical and serologic findings. overestimating worm burden.

Infection with and Aelurostongylus Necropsy Confirmation species can cause similar radiographic patterns and Making an antemortem diagnosis of heartworm must be considered in a differential diagnosis. infection may be difficult and thus necropsy Echocardiography confirmation should be attempted in cats suspected of dying of the disease or in which the cause of The chambers of the right side of the feline heart death is unexplained. A thorough search of the can be thoroughly interrogated by two-dimensional vena cavae, right side of the heart, and pulmonary ultrasonography. Limited access also can be gained arteries must be performed because one or two to the main pulmonary artery and a long segment worms easily can be overlooked, particularly if of the right and a short portion of the left pulmonary immature, dead, or fragmented. Special attention arteries. Although heartworms are found most should be paid to examining the distal extremities often in the main and right lobar branch of the of the pulmonary arteries as any dead worms would pulmonary artery, it is necessary to methodically be forced and compressed, by blood flow, into the probe all of these locations because worms in a most distal and smallest possible space. Because typical light infection may occupy only one or two heartworms occasionally are restricted to ectopic sites and may escape detection. The body wall sites, the systemic arteries, body cavities, and, if of an adult heartworm is strongly echogenic and neurologic signs were present, the brain and spinal produces short, segmented, parallel linear artifacts canal should also be examined thoroughly. where the imaging plane transects the parasite’s body, producing the signature signs of live worms. Feline heartworm diagnostics are illustrated in Sometimes dead heartworms can be recognized Figure 5 and heartworm diagnostic procedures and by collapse of the parallel sides of the body wall. tests are summarized in Table 1. An adult heartworm is relatively long compared TREATMENT with the length of the pulmonary arteries in cats. Therefore, there is a better chance in cats than Medical Options in dogs of finding heartworms extending from peripheral branches into proximal segments where If a cat displays no overt clinical signs despite they can be visualized. An experienced sonographer radiographic evidence of pulmonary vascular/ has a very good chance of making a definitive interstitial lung disease consistent with feline diagnosis in cats that are actually infected with adult heartworm disease, it may be prudent to allow heartworms, particularly when there are several time for a spontaneous cure to occur. The course worms. In suspected cases, the high specificity of of infection in these subclinical cases can be this examination generally allows for confirmation of monitored periodically at 6- to 12-month intervals

Figure 5. Summary of feline heartworm diagnostics

8 American Heartworm Society Table 1. Interpretation of Heartworm Diagnostic Procedures and Tests in Cats

Test Brief Description Result Interpretation Limitations

Antibody Test Detects antibodies Negative Lower index of suspicion Antibodies confirm produced by the cat in infection with response to presence of heartworm larvae, heartworm larvae. May Positive Increasing index of suspicion; but do not confirm detect infections as early 50% or more cats will have disease causality. as 8 weeks post trans- pulmonary arterial disease; mission by mosquito confirms cat is at risk

Antigen Test Detects antigen produced Negative Lower index of suspicion Immature or male- by the adult female heart- only worm infections worm or from the dying are rarely detected. male (>5) or female heart- Positive Confirms presence of worms heartworms

Thoracic Detects vascular enlarge- Normal Lower index of suspicion Radiographic signs Radiography ment (inflammation caused are subjective and by juvenile worms and, Signs Enlarged arteries greatly affected by clinical later, hypertrophy), consistent increase index of suspicion interpretation. pulmonary parenchymal with inflammation, and edema feline [the latter only in acute heartworm respiratory distress disease syndrome (ARDS)-like syndrome]

Echocardiography Detects echogenic walls of No worms No change to index of Ultrasonographer the immature or mature seen suspicion experience with heartworm residing in the heartworm detection lumen of the pulmonary Worms Confirms presence of appears to influence arterial tree, if within the seen heartworms in the structure accuracy rate. visual window of the ultrasound

Note: In the cat, no single test will detect all heartworm cases. While the antigen tests are highly specific for detecting adult heartworm antigen, they will not detect infections with only live male worms. The clinician must use a combination of test results to determine the likelihood of heartworm disease as the etiology of the cat’s symptoms. by repeat antibody and antigen testing and thoracic signs. An empirical oral regimen is 2 mg/kg body radiography. In those cats destined to recover, weight/day, declining gradually to 0.5 mg/kg every regression of radiographic signs and especially other day by 2 weeks and then discontinued after seroconversion of a positive antigen test to negative an additional 2 weeks. At that time the effects of status provide evidence that the period of risk treatment should be reassessed based on the clinical probably has passed. response and/or thoracic radiography. This treatment may be repeated in cats with recurrent clinical signs. Prednisone in diminishing doses often is effective medical support for infected cats with radiographic Cats that become acutely ill need to be stabilized evidence of lung disease whether or not they appear promptly with supportive therapy appropriate for ill. Prednisone also should be initiated whenever treating . Depending on the circumstances, antibody- and/or antigen-positive cats display clinical this may include intravenous corticosteroids,

2014 Feline Heartworm Guidelines 9 balanced electrolyte solutions, bronchodilators, alternative to symptomatic support or adulticide and oxygen via intranasal catheter or closed cage. treatment of cats that are heavily infected and/or in Diuretics are inappropriate, even for infected cats critical condition. Surgery is specifically indicated in with severe interstitial or patchy alveolar lung those few cases that develop the caval syndrome. patterns. and other nonsteroidal anti- Care must be taken to remove the worms intact inflammatory drugs (NSAIDs) have failed to produce because partial or complete traumatic transection of demonstrable benefit and actually may exacerbate a worm may result in acute circulatory collapse and the parenchymal pulmonary disease. death.

Adulticide administration is considered the Additional Considerations for Adulticide Therapy treatment of last resort for cats in stable condition Wolbachia that continue to manifest clinical signs that are not controlled by empirical corticosteroid therapy. Most filarial , includingD immitis, harbor There is insufficient experience with melarsomine obligate, intracellular, gram-negative dihydrochloride at this time; thus melarsomine is belonging to the Wolbachia (Rickettsiales). not recommended for use in cats. Preliminary data In infections with other filarial parasites, treatment suggests that melarsomine is toxic to cats at doses with tetracyclines during the first month of infection as low as 3.5 mg/kg. was lethal to some Wolbachia-harboring filariae, but not to filariae that did not harborWolbachia , Ivermectin at a dose of 24 µg/kg monthly given for 2 and treatment of Wolbachia-harboring filariae years has been reported to reduce worm burdens by suppressed microfilaremia. Similar prophylaxis 65% as compared with untreated cats. Because most studies with D immitis have not been reported, but cats have small worm burdens, it is not worm mass in one study, tetracycline treatment of heartworm- alone that is problematic but the “anaphylactic” type infected dogs resulted in infertility in the female reaction that results when the worms die. This will worms. These bacteria also have been implicated likely also occur when the ivermectin-treated worms in the pathogenesis of filarial diseases, possibly die but the extent of the reaction is unknown. through their endotoxins. Recent studies have To date, there are no studies that indicate any form shown that a major surface protein of Wolbachia of medical adulticidal therapy increases the survival (WSP) induces a specific IgG response in hosts rate of cats harboring adult heartworms. infected by D immitis. It is hypothesized that Wolbachia contributes to pulmonary and renal Surgical Options inflammation through its surface protein WSP, In principle, it is preferable to remove heartworms independently from its endotoxin component. rather than destroy them in situ. This can be Studies to determine the effects of suppressing accomplished successfully by introducing brush Wolbachia populations with doxycyline prior to strings, basket catheters, or loop snares via right adulticide therapy are in progress to determine the jugular venotomy or, after left thoracotomy, clinical utility of this therapeutic approach. alligator forceps can be inserted through a right Surveillance of Infected Cats ventricular purse-string incision. Before attempting either approach, heartworms should be identified Serologic retesting at 6- to 12-month intervals ultrasonographically in locations that can be reached for the purpose of monitoring infection status with these inflexible instruments. When probing is recommended for all infected cats whether from the right jugular vein, worms must be present or not they have clinical signs that are treated within the cavae or right atrium because achieving empirically or are given medical/surgical adulticide access to the right ventricle is difficult with these therapy. Once adult heartworm infection has been instruments. Both atria and ventricles as well as diagnosed, monitoring will be most informative if the main pulmonary artery can be reached through both antibody and antigen testing are performed. a ventriculotomy incision with straight alligator The retesting interval should be consistent with forceps. the clinical circumstances. For asymptomatic cats, an annual retest may be adequate. Spontaneous Although it may not be possible to retrieve every or adulticide-induced elimination of infection in worm, the surgical option may be a reasonable antigen-positive cats ordinarily will be followed

10 American Heartworm Society within 4 to 5 months by disappearance of detectable kg, oxime 2.0 mg/kg, moxidectin 1.0 antigenemia. Once cats become antigen negative mg/kg, and selamectin 6 mg/kg of body weight. and are clinically normal, further antibody retesting Administration of these drugs in cats is not becomes optional because antibodies may persist precluded by antibody or antigen seropositivity. for an indefinite period after the parasites are Serologic Testing gone and because continued exposure, even with preventive therapy, will result in a positive test. Seroepidemiologic data for most communities is Radiography and ultrasonography also may be very presently meager; thus, it behooves veterinarians useful for monitoring the course of infection and to become familiar with the local risk potential disease in those cats with pulmonary vascular and/or by testing cats before initiating heartworm parenchymal lung disease, or in which heartworms chemoprophylaxis. While guidelines are still being have been identified with echocardiography. developed and evaluated, it is considered prudent to establish this serologic benchmark for future PREVENTION reference, in the event it becomes necessary to retest a cat receiving chemoprophylaxis. Monthly chemoprophylaxis is a safe and effective option for cats living in areas where heartworm Although testing cats before starting infection is considered endemic in dogs and chemoprophylaxis is recommended, there is less exposure to infective mosquitoes is possible. Many utility in doing so than is the case for dogs. This cats live more sheltered lives than do most dogs apparent contradiction reflects the differences in and are often confined indoors. Unless the home testing methods and test performance in the two environment provides an effective barrier to the hosts. Pretesting (screening) dogs is limited to entrance of mosquitoes, these so-called “indoor” documenting either heartworm antigenemia or cats also may be at risk. In one retrospective study, circulating microfilariae, both of which are specific approximately 25% of cats diagnosed with adult indicators of adult worm infection in a host that heartworms were considered indoor cats. Caregivers is significantly more likely to become infected. should be advised objectively of the potential risk of Many, if not most, cats that are antibody positive heartworm infection in their community and for their have only been transiently infected to the fourth cat’s living conditions. When monthly heartworm larval stage. Evidence of exposure of a cat to at chemoprophylaxis is elected, it should at least be least fourth-stage larvae confirms the potential risk administered within 30 days following the estimated of developing heartworm-associated respiratory seasonal onset of transmission and be continued disease (HARD) and reinforces justification for within 30 days after that period has ended. recommending chemoprophylaxis. The use of an Administering a preventive year-round also has antigen test to screen healthy cats is also an option merit for the following reasons: 1) activity against if one is fully aware of its limitations. (Refer to Table some common intestinal parasites and in the case 1 in Diagnostic Testing section for limitations of both of selamectin and topical moxidectin + imidacloprid, antibody and antigen test.) The preferred method external parasites; 2) increased compliance, and 3) for screening, however, includes the use of both an retroactive efficacy as a safeguard for inadvertent antigen and an antibody test. missed doses. (For a more detailed explanation, consult the Canine Guidelines under the heading Since microfilaremia in cats is uncommon, Macrocyclic Lactones.) transient, and below concentration levels that might trigger an adverse reaction to microfilaricidal Drugs chemoprophylactic drugs, pretesting for Heartworm chemoprophylaxis can be achieved microfilariae is unnecessary. Furthermore, in cats with monthly doses of either ivermectin or antibody retesting of cats already committed to orally, or topical moxidectin or chemoprophylaxis provides no assurance of efficacy selamectin. Preventives should be started in because sensitization from repetitive aborted at 8 weeks of age and be administered to all cats in precardiac larval infections is possible in cats that heartworm endemic areas during the heartworm are repetitively exposed. Therefore, the primary transmission season. The individual minimum reasons for heartworm testing in cats are: monthly prophylactic dose of ivermectin is 24 µg/

2014 Feline Heartworm Guidelines 11 1. To establish an etiologic diagnosis in those individuals that, based on other clinical evidence, are suspected of being infected;

2. To monitor the clinical course of those cats that have already been diagnosed with feline heartworm disease;

3. To establish a baseline reference prior to initiating chemoprophylaxis.

These guidelines are based on the latest information on heartworm disease. In keeping with the objective of the Society to encourage adoption of standardized procedures for the diagnosis, treatment, and prevention of heartworm disease, they will continue to be updated as new knowledge becomes available.

12 American Heartworm Society