guidelines for clinical management of feline … · infection of cats with dirofilaria immitishas...

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Infection of cats with Dirofilaria immitis has been diag- nosed in many European countries and is spreading. These guidelines, developed by the European Society for Dirofilaria and Angiostrongylus, are based on the latest information and include up-to-date recommendations for the prevention, diagnosis, and clinical management of feline heartworm disease (HWD). Life cycle of Dirofilaria immitis in cats Cats are considered a susceptible, but not ideal, host for Dirofilaria immitis. Increased host resistance is reflected by the relatively low adult worm burden in natural in- fections (cats generally harbour 1 to 6 worms with 2 to 4 worms being the usual burden), the low number of heartworms that develop after experimental inoculation with infective larvae, the prolonged pre-patent period (8 months), the low level (< 10/ml of blood) and short du- ration (approximately 7 months)of microfilaremia (in only 20% of cats with mature male and female heart- worms), and the short life span of adult worms (2-4 years). Finally, adult worms in cats are shorter than those in dogs. European prevalence The prevalence of feline heartworm infection is not well known because ante-mortem diagnosis is difficult. It is generally considered to be 5% to 20% that of the in- fected canine population in the same area. Cats are like- ly less attractive to mosquito vectors, but Culex spp. and Aedes albopictus, among the most common mosquitoes, 1 GUIDELINES FOR CLINICAL MANAGEMENT OF FELINE HEARTWORM DISEASE Prepared for and approved by the Executive Board of ESDA

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Page 1: GUIDELINES FOR CLINICAL MANAGEMENT OF FELINE … · Infection of cats with Dirofilaria immitishas been diag- nosed in many European countries and is spreading. These guidelines, developed

Infection of cats with Dirofilaria immitis has been diag-nosed in many European countries and is spreading.These guidelines, developed by the European Society forDirofilaria and Angiostrongylus, are based on the latestinformation and include up-to-date recommendationsfor the prevention, diagnosis, and clinical managementof feline heartworm disease (HWD).

Life cycle of Dirofilaria immitisin cats

Cats are considered a susceptible, but not ideal, host forDirofilaria immitis. Increased host resistance is reflectedby the relatively low adult worm burden in natural in-fections (cats generally harbour 1 to 6 worms with 2 to4 worms being the usual burden), the low number ofheartworms that develop after experimental inoculationwith infective larvae, the prolonged pre-patent period (8months), the low level (< 10/ml of blood) and short du-ration (approximately 7 months)of microfilaremia (inonly 20% of cats with mature male and female heart-worms), and the short life span of adult worms (2-4years). Finally, adult worms in cats are shorter thanthose in dogs.

European prevalence

The prevalence of feline heartworm infection is not wellknown because ante-mortem diagnosis is difficult. It isgenerally considered to be 5% to 20% that of the in-fected canine population in the same area. Cats are like-ly less attractive to mosquito vectors, but Culex spp. andAedes albopictus, among the most common mosquitoes,

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GUIDELINES FOR CLINICAL MANAGEMENTOF FELINE HEARTWORM DISEASEPrepared for and approved by the Executive Board of ESDA

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feed regularly on cats. Given the epidemiology andpathophysiology of the disease, every cat living in arewhere the infection is present in dogs should be consid-ered at risk. For canine prevalence rates in Europe,please see the ESDA Guideline for canine heartwormdisease (www.esda.vet)

Clinical presentationof Feline Heartworm Disease(HWD)

The clinical signs of D. immitis infection in cats are verydifferent compared to dogs. Most cats seem to supportthe infection well for long periods of time. These catsmay have spontaneous self-cure due to the natural deathof parasites without any clinical manifestations or maysuddenly show dramatic, acute symptoms, includingsudden death.When present, the most common clinical signs observedin cats are cough and dyspnoea, sometimes associatedwith vomiting, unrelated to food intake. Rarely, catswill present with vomiting alone. Chronic coughing,vomiting, diarrhoea, weight loss can also be observed.Contrary to that seen in dogs, symptoms associated withright ventricular heart failure are not considered consis-tent with heartworm infection in cats. Even thoughchanges in the pulmonary arteries and lungs seem to besimilar in cats and dogs, the feline right cardiac cham-bers support pulmonary hypertension well and right car-diac heart failure is an unusual finding.Sudden death in apparently healthy cats is a further,typical event.The pathogenesis of D. immitis infection in cats hasbeen the subject of intense study in recent years. The on-set of symptoms in most cases seems to be related to thenatural death of adult parasites, but it has been more re-cently hypothesized that the disease develops along sev-eral stages. The first phase is associated with the arrivalof young, immature worms in the caudal pulmonary ar-teries approximately 3 months after the infection. Themajority of these young parasites die and this causes anacute vascular and parenchymal response, with severemuscular hypertrophy of the medium and small size ar-teries. Therefore, cats can present pulmonary diseasewithout the presence of fully mature adult worms (seeHARD, below).It is now known that adult worms suppress the activityof pulmonary vascular macrophages, the main compo-nent of the feline reticuloendothelial system. Thus, whenand if young worms develop to the adult stage, suppres-sion of the immune response, together with resolution ofclinical signs, can occur in a second phase of the infec-tion. Once adult worms die (spontaneously or followingmedical treatment), immune suppression ceases and themost severe forms may appear. Thus, the third phase ofdisease appears with the degeneration of dead parasitesthat cause a dramatic inflammatory and thromboem-bolic response that can lead to sudden or acute death inup to 20% of cats. Finally, in the fourth and final stage,in cats that have survived worm death, hyperplasia oftype II alveolar cells replaces the normal type I cells andthis may cause permanent respiratory dysfunction and

chronic respiratory disease (in absence of worms).As stated above, cats may experience acute episodes ofcoughing, dyspnea or intermittent vomiting, known asfeline heartworm-associated respiratory disease(H.A.R.D.), at around three months post-infection.Since most immature worms do not survive in cats afterthey reach the caudal pulmonary arteries, it is thoughtthat this acute disease is related to the death and em-bolization of worms or worm fragments. This induces astrong inflammatory response in the vessels and pul-monary parenchyma with subsequent infarction of thepulmonary parenchyma and circulatory collapse. Othersigns of H.A.R.D. may include neurological signs (e.g.,ataxia, head tilt, blindness, circling or seizures) and sud-den death.Cats infected with heartworm often self-cure. In a recentstudy of naturally infected cats with subclinical disease,28 (82%) self-cured, and 21 of these showed no clinicalsigns during the study. However, it should be noted thatfour of the six cats that died during the study showed noovert clinical signs before death.Aberrant migration, which occurs more frequently incats than in dogs, is a further indication that the cat isan imperfect host for heartworms. Occasionally, adultworms will migrate to sites other than the heart and thepulmonary arteries, and cause s.c. ectopic infections.Localization of D. immitis has been reported in the eye,CNS (cerebral arteries and lateral ventricles), systemicarteries and subcutaneous tissue.

Thoracic Radiographs (both latero-lateral and dorsoventral views)Thoracic radiographs are an important tool for the di-agnosis of feline heartworm disease. Despite the factthat thoracic abnormalities are often absent or transient,typical findings such as enlargement of the peripheralbranches of the pulmonary arteries, accompanied byvarying degrees of pulmonary parenchymal disease, arestrongly consistent with heartworm infection.Enlargement of the main pulmonary artery cannot beobserved in dorsoventral or ventrodorsal views becausethis tract of artery is obscured by the cardiac silhouette.Right sided cardiomegaly is not considered a typicalfinding in the cat.

B mode, M mode and Doppler EchocardiographyCardiac ultrasound allows the direct visualization ofparasites in the right atrium and ventricle, main pul-monary artery and proximal tract of both its peripheralbranches as floating typical double linear parallel hy-perechoic structures.The sensitivity of echocardiography for the detection ofheartworm infections in cats is highly operator-depen-dent and ranges between 88 and 100%. The pulmonaryarteries should be evaluated carefully to increase thelikelihood of detection of heartworms. Only a short por-tion of caudal pulmonary arteries, compared with thelength of the parasite, cannot be thoroughly examinedbecause of the acoustic impedance of the air-inflatedlungs.Diagnostic specificity is virtually 100%. It is howeverpossible to gain false-positive results when scanning catsat risk for heartworm infection. False positive results are

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thought to be caused by the right ventricular chordaetendineae or to the occasional presence of linear echoesthat mimic adult heartworms in the main pulmonary ar-tery branches, probably due to reflections from the ar-tery wall. Quantification of worm burden is, neverthe-less, difficult because the potential serpentine position-ing allows echo beams to transect the worm in multiplesites, giving multiple echo images and potentially overor underestimating worm burden.Even if most of heartworm-infected cats have histologi-cal evidence of pulmonary artery damage, pulmonaryhypertension is considered extremely unusual, therefore,echocardiographic signs of right atrial and right ventric-ular enlargement following pressure overload, as well asthe high velocity tricuspid regurgitation on Doppler ex-amination commonly observed in dogs are consideredextremely rare in cats.

Clinical PathologyIn cats, no significant changes in erythrocytes, plateletsand leucocytes concentrations are strictly associatedwith heartworm infection except for absolute peripher-al eosinophilia, which is reported as starting approxi-mately 70 days after infection in experimental condi-tions. Despite this experimental finding, absoluteeosinophilia cannot be considered a good marker ofheartworm disease as the percentage of naturally infect-ed cats showing eosinophilia is not known. Moreover,eosinophilia in cats is not a specific alteration but acommon finding secondary to several parasitic and al-lergic diseases.

Diagnosis

Diagnosis of feline heartworm infection is challenging.Due to the differences in the biology of the parasite inthe cat, many of the diagnostic methods that are useful,sensitive and specific in the dog are not so in the cat. Itis therefore necessary to use a multifaceted approachand to interpret the results of several tests together: tho-racic radiography and serum antibody tests to raise theindex of suspicion, echocardiography and testing for

both microfilariae and serum antigens to confirm or ex-clude the presence of adult parasites.

Blood test for microfilariaeCats are rarely microfilariaemic and sensitivity of detec-tion of is very low. However, when present, specificity isconsidered 100%, as in dogs.For information on how to perform a Knott test, go towww.esda.vet

Test for adult heartworm antigens Tests detecting adult heartworm antigens can provide adefinitive proof of infections in cats because of the veryhigh specificity. Unfortunately, worm burden is usuallyvery low in cats, infections caused only by male heart-worms are not infrequent and often symptomatologymay be due to immature worms. Thus, these tests havea very high specificity for mature infections but sensitiv-ity can be lower in case of low burden or singleworm/sex infection. A negative test cannot therefore beconsidered sufficient to rule out infection. The resultshould be recorded only as positive or “No Antigen De-tected (NAD)”, but it should not be considered negativefor heartworm infection”.It has been reported that heat treatment of serum sam-ples (in a heat block at 103°C for 10 minutes, the re-sultant coagulum centrifuged, and the supernatant usedin each commercial assay) may increase the sensitivity ofantigen tests in cats by disrupting immune complexesthat are often found in infected cats (Antigen masking).Some laboratories are now offering this service thatcould be useful in case of strong suspicion (i.e. antibodypositive cats with no echocardiographic evidence owadult worms).

Test for antibodies to adult heartwormDue to the low sensitivity of tests for circulating micro-filariae and adult antigens in cats, tests for detection ofantibodies to adult heartworm can be useful to decreasethe index of suspicion, and can be specifically very help-ful in case of HARD as they are the only test that can bepositive 3-4 months post infection.Antibody tests have high sensitivity, but only moderatespecificity due to cross reactivity with other parasitesor due to the presence of antibodies to abortive infec-tions. Sensitivity is high in recent infections and de-creases with the time due the reduced antibody re-sponse. Consequently, antibody tests should be inter-preted carefully, taking other relevant clinical informa-tion into consideration.

Treatment

To date, there are no studies that indicate any form ofmedical adulticidal therapy increases the survival rate ofcats harbouring adult heartwormsFor these reasons and because heartworm infection incats is often self-limiting, infected cats are managed on-ly with supportive treatment, although conservativemanagement is not without risk, as the acute death syn-drome may occur without premonitory signs and in thepresence of only one worm.

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Cross section (typical double linear parallel hyperechoic struc-tures) of an adult Heartworm into the pulmonary artery of a nat-urally infected cat.

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Wait and seeMedical treatment of feline heartworm disease is typi-cally symptomatic. Indeed, specific, adulticidal therapyis associated with a high rate of complications. Further-more, cats frequently self-cure. Therefore, if a cat doesnot show clinical signs or radiographic evidence of pul-monary vascular/interstitial lung disease consistent withthe infection, the best choice seems to allow time for aspontaneous self-cure to occur.These asymptomatic cases must be monitored periodi-cally every 4-6 months by repeating antibody and anti-gen testing, thoracic radiography and echocardiography.

CorticosteroidsInjectable prednisolone administered at 2 mg/kg, taper-ing down over a four-week period, is effective medicalsupport for infected cats with radiographic evidence oflung disease whether or not they appear ill. This treat-ment has to be repeated in cats with recurrent clinicalsigns. Oral administration of prednisone in cats is notadvised due to decreased hepatic conversion of pred-nisone to prednisolone and injectable corticosteroids arepreferred because of variability of gastrointestinal ab-sorption. In some cases following the acute treatment orin cats with recurrent clinical signs the administration oflasting corticosteroids (methylprednisolone acetate, 20mg s.c. cat once in a month) may be a reasonable choice.

Cats with severe clinical signs of heartworm diseaseshould be stabilized by administration of intravenous flu-ids, intravenous corticosteroids, bronchodilators andoxygen supplementation. Diuretics should be absolutelyavoided, even if radiographs show severe interstitial orpatchy alveolar lung patterns. Aspirin and other nons-teroidal anti-inflammatory drugs (NSAIDs) have failed toproduce any benefit and may exacerbate the parenchymalpulmonary disease. Once stabilized, treatment can con-tinue as described above based on clinical signs.

Adulticide treatmentPharmacological elimination of adult parasites is associ-ated with significant risk and is considered the last re-sort for cats in unstable condition with clinical signs thatare not controlled by corticosteroids.Melarsomine dihydrochloride treatment is not recom-mended for use in cats. Data suggests that melarsomine is

toxic to cats at doses as low as 3.5 mg/kg and that its effi-cacy is only about 36% against adult heartworms in cats.Ivermectin at a dose of 24 µg/kg monthly given for 2years has been reported to reduce worm burdens by 65%as compared with untreated cats. In cats it is not theworm mass alone that is dangerous but the “anaphylac-tic” type reaction resulting when even a single worm dies,this will likely also occur when the ivermectin-treatedworms die but the severity of the reaction is unknown.There is still debate on the usefulness of doxycycline ininfected cats in order to target Wolbachia. It is notknown if it has the same beneficial effect as has been re-ported in dogs and there is no data on the adulticidal ef-fect of the macrocyclic lactone/doxycycline combinationin cats. Therefore, doxycycline is not recommended asan adjunctive therapy in cats at this time.

Minimally invasiveSurgical Heartworm removal

Surgical removal of heartworms may be attempted insymptomatic cats when the parasites are echocardio-graphically visualized in the right heart and main pul-monary arteries, with thin horsehair brush or basketcatheters or other intravascular retrieval snare intro-duced via the right jugular vein into the right cardiacchambers. Surgical extraction of worms can also be at-tempted via thoracotomy and right atriotomy or ven-triculotomy and main pulmonary arteriotomy for re-moving them from pulmonary arteries. Care should betaken to remove worms intact, because the frequent ac-cidental damage to worms during extraction can resultin acute circulatory collapse and death mainly when par-asites are removed via jugular vein because the smallsize of the vessel compared to the worms. The inciden-tal rupture of worms during the procedure may result inthe dead of the cat (till 30% of cases). Heartworm sur-gical removal in cats for this reason is not considered incats as safe as in dogs.

Prognosis

The prognosis for heartworm-infected cats should beconsidered guarded. Approximately 80% of naturally

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Asymptomatic cats

Due to incomplete sensitivity of tests for the detection of antigens and antibodies, using both is strongly advised for screening cats.If both are negative infection is unlikely. If one of them is positive see below

Symptomatic cats

Antibody test POSCat infected

Antigen test POS

Antibody test NEGCat infected

Antigen test POS

Antibody test POS POS Cat infected

POS Cat infected

Antigen test NEG NEG Monitor the catNEG and recheck

4 months later

Possible HARD orAntigen masking

Ask for Antigentest on heat

treated serumsample

High suspicionPlan

Echocardiography

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infected cats self-cure and 20% die often very suddenly.Prognosis is better for cats surviving beyond the day ofpresentation.

Prevention

The best approach to feline heartworm disease is pre-vention through the regular monthly administration ofdrugs that kill the infective larvae in the L3-L4 stage.Monthly heartworm preventives are a safe and effectiveoption for cats living in or travelling to areas whereheartworm infection is considered endemic in dogs andexposure to infective mosquitoes is possible. Even theso-called “indoor” cats may also be considered at risk,even in low endemic areas. When monthly heartwormprevention is chosen, it should at least be administeredwithin 30 days following the estimated onset of trans-mission and continued within 30 to 90 days after thatperiod has ended. Preventives should be started in kit-

tens at 8 weeks of age and be administered to all cats inheartworm-endemic areas during the heartworm trans-mission season.There are currently five macrocyclic lactone drugs regis-tered for feline heartworm prophylaxis, alone or in com-bination with other active principles (see Table 1).Additionally, depending on the active ingredients, theseproducts protect cats from a variety of common endo-and ectoparasitic infections.These drugs can be administered in cats that are anti-gen/antibody positive. Therefore, screening of cats be-fore administration is less useful than in dogs. Many, ifnot most, cats that are antibody positive have onlybeen transiently infected to the L4 stage and antibodypositivity confirms the potential risk of developingHARD and giving more justification for recommend-ing preventives.Given the incomplete sensitivity of tests in cats, testingbefore starting prevention in adult cats is suggested, butnot mandatory.

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All rights reserved.No part of this publication may be reproduced, stored in a retrieval system, or internet communication system

or transmitted in any form, or by any means, electronic, mechanical, photocopying, recording or otherwise,without the prior permission, in writing, from the publisher.

© Copyright 2017 - EV/ESDA

TABLE 1 - MACROCYCLIC LACTONES USED FOR THE PREVENTION OF FELINE HWD

Drug Administration Dose Interval Efficacy against otherESDA parasites #

Ivermectin Oral 24 mg/kg Monthly D. repens

Milbemycin Oral 2 mg/kg Monthly

Selamectin Spot on 6 mg/kg Monthly

Moxidectin Spot on 1 mg/kg Monthly D. repens

Eprinomectin Spot on 0.48 mg/kg Monthly

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