Professor of Veterinary Medicine, School of Veterinary Medicine, Hebrew University, Rehovot, Israel
Filariasis in dogs and cats can be caused by a number of species that vary from one geographic region to another. At least 8 different filarial spp. have been described to cause persistent microfilaremia in dogs. Some of the filarial species can be highly pathogenic and cause a life-threatening disease, whereas other species are associated with asymptomatic infection. Dirofilaria immitis and Dirofilaria repens are two filarial species infecting dogs and cats that are often found in the same area but cause different clinical syndromes.
Dirofilaria repens Infection
Filariasis caused by Dirofilaria repens is prevalent in several regions in the world including: the Mediterranean basin, southeastern Europe, Africa and southeast Asia. Due to the recent elevation in the number of human infections in Spain and Italy, it is considered an emerging zoonosis in these countries. Dogs, foxes and cats are the reservoir for this infection and people are accidental "dead end" hosts in which the life cycle is not completed.
The mosquito vectors of D. repens vary in different geographic regions and include species belonging to the genera Culex, Anopheles and Aedes. Microfilariae taken up in the blood meal by Ae. aegpyti mosquitoes migrate to the malpighian tubules where they develop to stage 3 (L3) larvae that reach the proboscis. Larvae injected during the mosquito bite into the skin of the dog migrate through the subcutaneous tissues, develop to L4, L5 and adult worms and shed microfilariae in the blood. Canine infection is often an incidental hematological finding, or accompanied by mild clinical signs including skin swelling, hyperpigmentation or subcutaneous granulomas containing adult worms.
In humans, immature D. repens migrate in connective tissues and elicit an inflammatory response resulting in the formation of nodules around the worms that are frequently confused with tumors and treated by surgical excision. The manifestations of D. repens infection in people are associated with nodules that have been described from the lung, subcutaneous tissues, epididymis, spermatic cord, omentum, conjuctiva, and the breast. Infections have been recorded to persist for 8 years and can be detected in tourists that have visited endemic areas.
In contrast to the relatively non-pathogenic D. repens, D. immtis is a major pathogen in many parts of the world. Dirofilaria immitis causes heartworm disease in domestic and wild canine and feline spp. in warm and temperate regions. It is present in southern Europe, North and South America, Africa, Asia and Australia. The life cycle of D. immitis is basically similar to that of D. repens. The main difference is that the larvae injected into the skin migrate through the muscles to the lung blood vessels reaching the pulmonary arteries where they continue to mature. Adult worms are found primarily in the pulmonary arteries and in severe infections also in the right side of the heart and occasionally in the vena cava. The pre-patent period, e.g., the time from infection to the appearance of microfilaremia, is approximately 6-7 months and the life expectancy of the worm in the dog is approximately 5 years.
Chronic heartworm disease results from progressive proliferative endarteritis and thromboembolism of the pulmonary artery caused mostly by adult worms, and not by juvenile migrating worms. The progressive vascular changes lead to pulmonary hypertension, right ventricular hypertrophy or dilation and cor pulmonale. The first clinical signs of disease typically include exercise intolerance and cough. This is followed by signs of chronic right heart failure including ascites, hepatomegaly, syncope and respiratory signs such as dyspnea, tachypnea, cough and hemoptysis. More acute heartworm disease with a heavy worm burden causes vena caval syndrome with erythrocyte membrane disruption and a hemolytic crisis. Humans can become infected with D. immitis but the worm does not complete its life cycle in people.
Wolbachia and Dirofilariasis
Wolbachia are gram-negative bacterial endosymbionts of arthropods and filarial worms. Wolbachia have been demonstrated to be transovarially transmitted in the human filarial pathogens Onchocerca volvulus and Brugia malayi. Hosts with filarial infection come into contact with Wolbachia following the death of the filarial parasite. Dogs infected with D. immitis have been shown to mount a specific immune response to Wolbachia antigens.
Diagnosis of Dirofilariasis
The diagnosis of dirofilariasis can be achieved by detection of microfilaremia with microscopic examination of blood smears when microfilaremia is high. The Knott's concentration method allows detection of lower numbers of microfilaria. Failure to detect circulating microfilariae does not rule out infection. There are several D. immitis ELISA tests employing monoclonal antibodies for the detection of circulating D. immitis antigen useful also for the detection of occult infection. Serology for infection of cats is usually aimed at the detection of anti-D. immitis antibodies.
The filarial species that have been reported to cause persistent microfilaremia in dogs include D. immitis, D. repens, Acantocheilonema reconditum (formerly Dipetalonema), Acantocheilonema dracunculoides, Brugia malayi, Brugia ceylonensis, Brugia phangi and Cercopithifilaria grassi. The geographic distribution of some fliarial spp. is limited and therefore some spp. can be expected to be found only in certain parts of the world. PCR diagnosis of filariasis in canine blood is available in several laboratories. A recent publication has described an assay that can discriminate between 6 species of canine microfilariae by a single PCR.
Treatment and Prevention
Treatment of infected dogs usually includes the adulticide drug melarsomine hydrochloride injected intramuscularly on two consecutive days followed by microfilaricidal treatment with ivermectin or a related drug.
There are several prophylactic drug formulations for the prevention of infection. These include preparations of ivermectin, moxidectin, milbemycin, spot on selamectin and more.
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