Cause : infection with nematode parasite, dirofilaria immitis .
Signs : variable with no pathognomonic signs. If present, vary from subclinical to respiratory signs, and sudden death.
Diagnosis : detection of circulating antigens or microfilariae +/- circulating antibodies +/- clinical signs.
Treatment : supportive treatment only; manual extraction in some cases.
Prevention : any formulations of macrocyclic lactones. Disease can be easily prevented.
Prognosis : if truly infected, risk of sudden death exists. Median survival is approximately 4 years.
Presenting signs
Often asymptomatic.
Coughing.
Sudden death.
Vomiting.
Dyspnea.
Acute presentation
Sudden death.
Vomiting or coughing.
Geographic incidence
D immitis infections described in all continents.
Adequate temperature and humidity necessary to support viable mosquito population and sustain sufficient heat to allow maturation of ingested microfilariae to infective, third-stage larvae (L3) within vector.
Reported throughout USA, endemic in 49 states.
Growing prevalence reported in Mexico, Puerto Rico and the Caribbean.
Well established in Southern Canada, Australia and Japan.
Endemic in Southern Europe with scattered reports from Greece, Turkey and some eastern European countries.
Most of S America.
70 + spp of mosquitoes capable of supporting development of larvae to infective stage (L3). Approximately 12 spp are major vectors. Microfilariae from cats develop poorly in mosquitoes.
Once D immitis is introduced into a geographical area its transmission is virtually assured.
Age predisposition
Antigenemia and microfilaremia appear 5-6.5 m post-infection, at the earliest. Both are transient in most cats, even with patent infections.
Clinically affected animals encountered as early as 3 months after infection with L3 larvae .
Breed predisposition
None, all cats exposed to mosquito bites may be infected.
Public Health considerations
Human infection infrequent.
Encapsulated pulmonary dirofilaria infections have been diagnosed in humans. Usually recognized by radiographic examinations .
Cost considerations
Diagnosis be expensive because few tests are definitive.
Dirofilaria immitis, large nematode parasite usually located in lumen of pulmonary arteries, or occasionally right ventricle.
Predisposing factors General
Infection common where parasite is endemic and if patients are not receiving chemoprophylactics.
Much lower prevalence than in the dog population (10-40% of the canine prevalence in any particular area). This depends on many factors.
Pathophysiology
Clinical disease depends on:
Number of worms present - usually only a few worms are found in cats.
Microfilariae.
Number of dead worms present.
Arteriopathy
A few days after arrival, parasite causes mechanical damage to walls of pulmonary arteries.
Endothelial cells are separated and appear inflamed. WBCs accumulate and intima thickens.
Endothelium grows villous-like structures made of smooth muscle and intima.
Heartworms cause lining of heart and pulmonary arteries to become rough and disrupt blood flow.
Growth is stimulated by a platelet derived growth factor.
Endothelial damage and inflammatory reaction produce perivascular edema.
Experimental evidence suggests arteriopathy is caused by Wolbachial antigen (wolbachia surface protein).
Arteriopathy is more severe and acute in cats than dogs, so cats can show clinical signs before worms fully mature.
Pulmonary hypertension
Increase of peripheric resistance of pulmonary arteries occurs.
Arteries become hard and can not expand when more oxygen is needed for exercise, resulting in hypertension .
Can also be caused by:
Vasoconstriction which can be due to inflammatory reaction, attempts to compensate local hypoxia, reduction of modulation of smooth muscle tone caused by parasite metabolites.
Anatomical obstruction of vessels by reduction of arterial lumen due to villous proliferations, emboli caused by live or dead parasites or even microfilariae, secondary thrombi due to endothelial damage and parasite tissue.
Requires a substantial portion of the lung to be affected before hypertension can be detected – in most cases, cats do not have measurable hypertension.
Cardiac lesions
Pulmonary hypertension may occasionally produce a dilation of right ventricle with a compensatory hypertrophy of the myocardium.
Right heart failure secondary to heartworm disease is rare in cats.
Lesions in the pulmonary parenchyma
Increased vascular permeability expands inflammatory reaction to alveolar or interstitial perivascular tissue.
Epithelial cells type I and also type II affected with a consequent fibrosis and reduction of exchange of gases and capillary fragility.
Shock/sudden death
Experimental inoculation of extracts of adult parasites induce massive pulmonary hypertension and sudden death apparently with immunological basis.
Death of a worm within pulmonary artery can also produce severe pulmonary hypertensive response and death.
Lesions caused by microfilariae
Induce immune mediated pathology in pulmonary vessels.
Heartworm associated respiratory disease (HARD)
Recent studies suggest that dirofilarial larve (L5) can induce a vaso-interstitial immune-mediated reaction, resulting in pulmonary parenchymal damage, arteriopathy and clinical signs indistinguishable from feline asthma .
May be the result of Wolbachia surface protein (wsp), released by an endosymbiont found in all dirofilaria - the specific pathophysiology remains undetermind. Studies have shown immunoreactivity in cats to wsp, consistent with this hypothesis.
Timecourse (incubation, duration)
Disease has insidious onset - from months to years after infection.
Adult worms survive for 2-3 years in cats, compared to longer survival in the definitive host (dog).
Epidemiology (population dynamics)
Transmitted by many spp of mosquitoes but mainly members of the family, Culicidae.
Microfilariae (L1), L2 and L3's are found in mosquitoes.
Adults, microfilariae, L3's, L4's and young adults are found in cats. <10% of inoculated L3 larvae mature to adult worms in cats.
Estimates of clinical signs are difficult because of diagnostic difficulties in cats.
Vomiting (may be associated with vigorous coughing).
Often similar to signs of asthma .
Atypical clinical signs may be associated with aberrant migration of larvae - in these cases, signs are dependent on the organ/tissue affected (eg CNS, ocular etc).
Diagnostic investigation
Antigen testing is not very sensitive in cats because (A) single sex infections are more common (antigen is produced most strongly by a gravid uterine epithelium) (B) worms may fail to mature or reproduce. Transient antigenemia is common. However, newer antigen tests are becoming more capable of detecting even infections with a single female worm.
Microfilarial testing is complementary but usually negative in cats.
Antibody tests are not diagnostic of feline heartworm infection - they simply document prior exposure to heartworm larvae, most of which fail to mature to adult stages. Most cats in endemic areas will have antibody titers to Dirofilaria immitus. Additionally, the test has a high incidence of false positive findings in cats NEVER exposed to heartworms (ie cross-reactivity with unknown antibodies). A negative test result suggests that clinical signs are not due to heartworm disease, although false negative results can occur.
Echocardiography is specific, but not sensitive. Worms may be seen within the pulmonary arteries, potentially more easily than in dogs because of the relative size of worm and vessel.
Thoracic radiography is helpful in identifying pulmonary parenchymal (and less often vascular) changes, but these often resemble changes seen with feline asthma (HARD) or other pulmonary parasitic infections.
Cardiac changes are uncommon.
Definitive Diagnostic features
Diagnosis of feline heartworm disease is challenging and is often obtained as a diagnosis of exclusion.
With sudden death, finding heartworms in the pulmonary arteries is diagnostic.
Gross autopsy findings
Adult worms in pulmonary arteries or right ventricle.
Endothelial lesions in pulmonary arteries.
Histopathology findings
Thickening of smooth muscle and intima of pulmonary arteries.
Pulmonary parenchymal changes can be seen with patent infections and with HARD.
Adulticide therapy is not recommended in cats because dying worms are likely to create severe pulmonary reactions resulting in death of the cat.
Microfilaria treatment
Most cats are amicrofilaremic or only transiently microfilaremic, so microfilaricidal therapy is not necessary.
Manual extraction
In rare cases, manual extraction via jugular access can be attempted. Rupture of the worm during extraction results in acute death of the patient. It is generally considered a heroic procedure.
Subsequent management
Treatment
Most clinical signs appear to respond to corticosteroids (prednisolone ) at anti-inflammatory doses.
Signs compatible with asthma may respond to bronchodilators.
The filarial endosymbiont Wolbachia is susceptible to doxycycline therapy (5mg/kg BID for 3-4 weeks PO). Whether killing the Wolbachia reduces clinical signs is unknown.
Cats in heartworm endemic areas should be treated with one of the macrocyclic lactones available in several types of preventive formulations:
Heartgard (ivermectin ) and Heartgard Plus (ivermectin and pyrantel pamoate ) available from Merial. Cats require higher doses of ivermectin than dogs for prevention.
Interceptor (milbemycin oxime ) and Sentinel (milbemycin oxime plus lufenuron ) available from Novartis.
Selamectin is available as Revolution or Stronghold (Pfizer) in a topically applied heartworm preventive liquid.
True prognosis is difficult to assess, since the incidence of subclinical infections is unknown in cats (due to difficulty of accurate diagnosis).
In one study, cats with a known positive diagnosis that lived longer than 1 day after diagnosis (ie those not presenting with sudden death), had a median survival of 4 years.
Lister A L & Atwell R B (2007) Feline heartworm disease: a clinical review. J Feline Med SurgPubMed.
Atkins C E (2007) Reassessing the definition of heartworm infection in cats. JAVMA231 (9), 1338 PubMed.
Nelson C T, McCall J W, Rubin S B, Buzhardt L F, Dorion D W, Graham W, Longhofer S L, Guerrero J, Robertson-Plouch C, & Paul A (Executive Board of the American Heartworm Society) (2005) 2005 Guidelines for the diagnosis, prevention and management of heartworm (Dirofilaria immitis) infection in cats. Vet Parasitol 133 (2-3), 267-275 PubMed.
Berdoulay P, Levy J K, Snyder P S, Pegelow M J, Hooks J L, Tavares L M, Gibson N M, Salute M E (2004) Comparison of serological tests for the detection of natural heartworm infection in cats. J Am Anim Hosp Assoc 40, 376-384 PubMed.
Morchón R, Ferreira A C, Martín-Pacho J R, Montoya A, Mortarino M, Genchi C, Simon F (2004) Specific IgG antibody response against antigens of Dirofilaria immitis and its Wolbachia endosymbiont bacterium in cats with natural and experimental infections. Vet Parasitol 125, 313-321 PubMed.
Bandi C, Trees A J, Brattig N W (2001) Wolbachia in filarial nematodes: evolutionary aspects and implications for the pathogenesis and treatment of filarial diseases.Vet Parasitol 98, 215 PubMed.
DeFrancesco T C, Atkins C E, Miller M W, Meurs K M, Keene B W (2001) Use of echocardiography for the diagnosis of heartworm disease in cats: 43 cases (1985-1997). JAVMA218, 66-69 PubMed.
Cats require higher doses of ivermectin than dogs for prevention.
