Heartworm disease in dogs and related carnivores is caused by a filarial nematode (a very large threadlike white-to-cream colored roundworm), Dirofilaria immitis described by Joseph Leidy in 1856 in Philadelphia. The adult worms live in the right side of the heart (right ventricle) and its blood vessels like the pulmonary arteries.
Human filariasis, mostly in Africa and Asia, is discussed in Filariasis: http://www.pitt.edu/~super1/lecture/lec10971/index.htm
Dirofilaria repens. It also lives in the skin of dogs and most rarely infects man. The female is about 12.0 x 0.5-1.0 cm. The vectors are mosquitoes. See Veterinary Parasitology 105 (2002) 173–178
After mfs are ingested during the blood meal. They migrate from the intestine within 24-36 hours into the Malpighian tubules to develop and molt from the 1st to the 2nd juvenile stage. The parasite becomes immobile, shortens, thickens and develops into the sausage stage in about 4-5 days. This larval form is followed by the 1st stage larva, and the 1st molt occurs in the Malpighian tubules at day 8. During the 2nd larval stage, the internal organs of the worms are formed. After 9 days, they enter the abdominal hemocele, where the 2nd molt occurs. The 2nd molt occurs at 11-12 days, resulting in 3rd stage larvas.
Third stage larvas are about 900 microns long and appear 10-20 days after infecting the mosquito in less than 4 weeks. The 3rd stage juveniles migrate to the mouthparts of the moquito. Infection of dogs occurs while mosquitoes are feeding. Third stage juveniles escape onto the skin and enter it through the feeding site wound. For about 80 days, juveniles are in the subcutaneous tissues and muscles where the 3rd molt takes place 9-12 days after entry. In the tissues. The 4 th stage juveniles attain lengths up to 25 mm. They begin entering the right side of the heart shortly after the 4th molt 60-70 days after infection. During the mosquito’s blood meal, the 3rd stage larvas are deposited on the skin and enter the host by the bite wound. These larvas molt to the 4 th stage and migrate to the dog's abdomen. In several months, they invade the chambers of the heart and the pulmonary arteries. Development to maturity with males 14-19 cm long and females 23-31 cm takes 175-225 days, at which time mfs appear in the blood. The reproductive period may pass 5 years.
Collection of mosquitoes in residential areas in Vero Beach showed that 4 species ( Ae. taeniorhynchus, An. quadrimaculatus, Cx. nigripalpus and Cx. quinquefasciatus ) are natural hosts of D. immitis . At least 7 mosquito species ( An. quadri-maculatus, Ae. taeniorhynchus , Ae. sollicitans, Ae. aegypti , Cx. nigripalpus , Cx. quinquefasciatus and Mansonia titillans ) can be infected with D. immitis when they are fed on an infected dog.
In Florida, about 20/70 species are potential vectors. The main vectors near the coasts are 2 mosquitoes that breed in salt marshes ( Aedes. taeniorhynchus and Ae. sollicitans) and one freshwater species ( Cx. nigripalpus) . The inland vectors that breed in fresh water are Culex. quinquefasciatus , Cx. salinarius, Ae.aegypti, An. quadrimaculatus and Mn. titillans . These mosquitoes breed in a wide variety of habitats including marshes, swamps, ponds, ditches, cans, bottles, old tires and trash piles. See http://www.pitt.edu/~super1/lecture/lec10991/index.htm.
Chronic congestive heart failure, usually right-sided, may ensue with edema of the legs, ascites and weakness. When a mass of worms lodge in the posterior vena cava the obstruction may lead to the vena caval syndrome, characterized by hemoglobinuria, anorexia, icterus and collapse. Death usually ensues within several days. Among the pathologic changes seen in the various manifestations of heartworm disease are: pulmonary embolism, endocarditis of heart valves, glomerulonephritis due to immune complexes, pulmonary endoarteritis and eosinophilia even to pneumonia.
The malaria technique of thick-n-thin slides is applicible. Also, RBC will settle if an equal volume of 6 % dextran is added. Examination of the buffy coat spun in capillary tubes may be the best way to detect mfs. Two percent formalin or paraldehyde will fix mfs suitably for measurements or other tasks. Immunochemistry is not well developed, or not applied, e. g., acid phosphatase test.. Here, there still is enormous room for improvement and much experimental flexibility. Buffy coat as in QBC of B-D can be developed for several diseases. ELISA is available for detection of adult D. immitis antigen both before and after mfs are found in blood. DiroCheck (Symbiotics) and PetCheck (IDEXX) are available as microwell ELISAs. Other rapid tests are: Snap (IDEXX), AbboScreen (Abbot), Solo Step (Heska) and Witness (Symbiotics). These and other serological tests sometimes produce false negatives just as slide examination may produce a false negative. Therefore such tests should be run WITH microscope tests. Might a blood smear be negative during the day and positive at night ? Does this periodicity correlate with the daily cortisol cycle ? Where are the mfs when they are not swimming in the blood stream ? Another direct approach to diagnosis is demonstration of mfs in the blood using Knott’s popular centrifuge concentration test or a filter test.
The mfs of the nonpathogenic nematodes Dipetalonema recondita and D. repens parasites of the subcutis must be differentiated from the mfs of D. immitis . The cephalic end of D. repens mfs is round, short and clear, whereas the head of D. immitis mfs is cone-shaped and dark.
Concentrate living mfs by adding 2% saponin and centrifuge at 1000 rpm for 3-5 minutes in an ordinary clinical centrifuge. A 2nd centrifuge method as in QBC by B-D is to use a standard 75 mm heparinized microcapillary tube as used for hematocrit determination. This requires only a drop of blood. Mfs may be present just above the buffy coat. Concentration techniques which kill the mfs are required to prepare them for measurement and morphologic examination. Measurements vary with the different methods of preparation. When fixed in 2 % formalin (modified Knott's method), they shrink a little.
Red azo spots are conspicuous against a pale green background at both the anal and excretory pores of D. immitis , whereas D. reconditum shows no such spots but stains pale-to-dark pink in the anterior 3rd of the body and a bright red in the posterior 2/3rds. Unfortunately, the solutions are unstable and must be made fresh every time. It is effective, but possibly impractical in routine practice.
Adult heartworms are killed with a drug called an adulticide, which is often given through a series of injections. A few days after treatment, the adult heartworms die and are carried by the bloodstream to the lungs where they lodge in small vessels, decompose and are usually absorbed by the body over a period of several months. Heartworm disease in dogs and cats is a serious and potentially fatal disease. If the dog has normal signs, the drug thiacetarsanide may be administered IV in 2 doses per day for 3 days. The dog should be caged or penned up for several weeks. Embolism resulting from dying heartworms sometimes occurs. Of course there are optional treatments.
Thiacetarsamide (2.2 mg/kg, 4 IV doses over 2 days) will kill most male and some female worms but has poor efficacy against immature and young female worms. Melarsomine (2.5 mg/kg, 2 IM doses over 24 hr) has improved efficacy (>95 % kill). However, increased worm death can cause serious complications. One IM dose followed 1 month later by 2 IM doses is a safer alternative.
About 6 weeks after treatment the dog is treated to eliminate circulating mfs. Ivermectin or milbemycin are highly effective. Place the dog or cat in a heartworm preventive program unless there are large numbers of mfs. Because of possible toxic reactions to treatment, animals should be carefully monitored after treatment and appropriate support and care provided. The efficacy of treatment can be determined by another test for the presence of mfs. The owner must understand the risk that treatment imposes on the dog.
Diethylcarbamazine (Hetrazan) is given daily while ivermectin, selamectin, moxidectin and milbemycin are given monthly during the mosquito season. Determine the status of animals by adult antigen tests before using prophylactic medication. Animals that test positive should be treated before starting preventive medication.
The parasite is usually found in the lung (pulmonary dirofilariasis), and less often in the heart. Although the worm forms a &quot;coin lesion&quot; in the lung, which may be confused with other diseases on x-rays, such as carcinoma, its clinical significance in man has not been fully determined. During the last 30 years about 100 cases of human pulmonary dirofilariasis have been reported from Florida.
Life Cycle. Cats like dogs are infected by mosquitoes. The cat is a deadend host, because there are not usually enough adult worms to breed and produce mfs. Larvas migrate to the heart and pulmonary arteries where they mature. Mismigration of mfs to sites like the brain occurs occasionally. The lesions of endarteritis caused by adult heartworms are similar to those seen in the dog. The immune response which appears to be much str onger in the cat than in the dog may be sufficient in many cats to destroy the invading mfs and thus prevent spreading infection. Clinical Features. Clinical signs are absent to severe. A small worm burden can cause chronic vomiting, coughing, dyspnea, respiratory failure and weight loss. The infection is sometimes confused with bronchial asthma. Six to 10 worms may cause right side heart failure. When the disease is acute there may be convulsions, diarrhea, tachycardia and collapse. Diagnosis - This is sometimes more difficult in the cat because of the absence of mfs. ELISA procedures are available for detection of antigen and antibodies. As in the dog radiography and echocardiography are useful. Treatment. The use of an adultacide such as thiacetarsamide IV may be accompanied by pulmonary thromboembolism and a mortality of 20-30 %. Various drugs are used for supportive therapy including prednisone or prednisolone to reduce inflamation, theophyline for bronchial dilation and inflamation reduction and lifesaving supplemental oxygen. Control. Cats are usually tested for antigens before beginning prophylactic medication which involves monthly administration of ivermectin in tablet form to cats 6 weeks or older, or selamectin (Revolution) applied topically. These and several other drugs kill the larvas of D. immitis.
Life Cycle. Eggs are laid in the pulmonary arteries and are trapped in capillaries where they hatch. The larvas emerge into alveoli and move up the trachea to the pharynx where they are swallowed and passed in the feces. Larvas enter snails or slugs and undergo 2 molts. Dogs become infected by ingesting infected snails, slugs or their hosts. The 3rd stage larvas migrate from the intestine into lymph nodes and to the pulmonary arteries. The prepatent period is 7 weeks and adults may live in the host for over 2 years.. Clinical Features. Obstruction of pulmonary arteries by adult worms and obstruction of arterioles and capillaries by larvas lead to perivascular fibrosis and endocarditis of the tricuspid valve. Sequels can be congestive cardiac failure and cardiac insufficiency. Signs may include anorexia, coughing and dyspnea. Diagnosis. Demonstration of larvas in feces and saliva. Treatment and Control. Levamisole, fenbendazole and mebendazole have been effective. Many other deparasitizing drugs against nematodes work well.
Dog Heartworm Paul R Earl Facultad de Ciencias Biológicas Universidad Autónoma de Nuevo León San Nicolás, NL 66451, Mexico
Dog heartworm disease (dirofilariasis) of dogs and other canids like foxes also infects cats but to a much lesser extent. It is almost worldwide and often common in humid areas that support mosquitoes as in the entire Mississippi valley. Rarely as in Florida, it can infect man causing pulmonary infarction with granuloma formation. Before the 1960s, Dirofilaria immitis (Leidy, 1856) Railliet & Henry, 1911 was best known along the northern Gulf of Mexico, Florida and along the entire east coast of the US. D. immitis is still colonizing northern Europe and England, perhaps in search for suitable local mosquito vectors. Note that its larvas = microfilarias = mfs have a marked nocturnal periodicity in the peripheral blood.
The taxonomic groups are Genus & Species Dirofilaria immitis of Family Onchocercidae of Order Spirurida of Subclass Spiruria of Class Secernentea. Mosquito-borne D. repens inhabits the skin of dogs. Transmitted by fleas, Dipetalonema (= Acanthocheilonema ) recondita also inhabits the dog's subcutaneous tissues. However, some of this kind have biting midges Culicoides spp. as vectors. Perhaps Dirofilaria, Dipetalonema and Acanthocheilonema are synonyms. The proper systematics for Dirofilaria awaits nucleotide sequencing using the polymerase chain reaction (PCR). The complete mitochondrion squence is already known for D. immitis.
By clogging the main blood vessels, the blood supply to other organs of the body is reduced, particularly the lungs, liver and kidneys. Of course, much more work for the heart results. Therefore, tachycardia (rapid pulse) and dysnea (shortness of breath) are typical. Blockage of major blood vessels can cause the animal to collapse suddenly and die within a few days. Sudden destruction of large numbers of mfs occasionally causes severe shock-like symptoms that may kill the dog. Most dogs can be treated successfully if heartworm disease is detected early by blood tests. Other diagnostic tests include radiography and electro/echo-cardiography.
Dipetalonema recondita. The adult worms measure 13 mm (male) to over 25 mm (female). Fleas as Ctenocephalides felis and lice as Heterodoxus spiniger are the intermediate hosts. The flea ingests mfs when feeding on an infected dog. The mfs develops into infective larvas in 7-14 days. When the flea again feeds on a dog, the larvas are injected into the skin. The female worm lays mfs which find their way into the bloodstream. The prepatent period is about 60-65 days. As the host is asymptomatic, there is no real treatment!
Heartworm disease in dogs & cats and Angiostrongylus infection Etiology. The nematode Dirofilaria immitis infects mainly dogs but also cats, ferrets and some other animals, including--rarely--man. The mfs in the blood can be about 315 long by 6-7 microns in diameter. Distribution. It has a worldwide distribution, and the disease is most common in dogs in humid areas like Florida. The distribution follows that of the mosquito vector. See the map above ! Life Cycle. The worms mature in dogs in 6-7 months, adults living in the chambers of the heart and the pulmonary arteries. Adults mate and large numbers of mfs are discharged into the blood stream. Mfs can survive for 1 - 3 years. The mfs are ingested by a mosquito.
Microfilarias (mfs) of D. immitis in a lysed blood slide
Mosquito Vectors. Many mosquitoes worldwide have been identified as capable of sustaining the development of dog heartworm mfs to the infective stage. Examples are Aedes aegypti, Ae. albopictus, Ae. canadensis , Ae. cantator, Ae. excrucians, Ae. sollicitans, Ae. sticticus, Ae. stimulans, Ae. taeniorhynchus, Ae. vexans, Anopheles bradleyi , A. punctipennis, An. quadrimaculatus , Culex nigripalpus , Cx. quinquefasciatus , Cx. salinarius and Psorophora ferox have been identified as natural hosts of D. immitis in the US east of the Mississippi River. Among these, 11 species are found in abundance in Florida.
Clinical signs and pathology Dogs with low numbers of adult worms may be asymptomatic and also produce false negatives. Chronic disease may develop in more infected dogs. Coughing, reluctance to exercise, weight loss, weakness and dypsnea are clinical signs. With heavy infections, there may be circulatory distress-dypsnea due to reduction of blood flow and pulmonary hypertension. Typically, signs include coughing, labored breathing, weakness and tiring with exercise. Since the signs vary, the disease may be well advanced before the dog begins to show problems. In advanced stages, the heart, lungs, liver and kidneys may be severely damaged. Eventually, heart failure can occur involved with overwork by the heart.
Diagnosis Heartworm disease should be suspected in dogs a year or more of age with some of the signs mentioned above in endemic regions. This disease is usually detected by finding mfs in a blood sample by either 1/ looking for mfs with a microscope at 20-100 x or 2/ using one of several serological diagnostic tests which can detect of heartworm antibodies even when mfs cannot be found with a microscope. A drop of blood is smeared on a slide, dried, fixed with 95 % ethanol and stained with Giemsa or Wright's, as in standard hospital procedure. Very simple. However, unstained fresh blood or blood with anticoagulant can reveal mfs by their writhing movement at very low power.
D. recondita mfs stain rather solidly with acid phosphatase, whereas D. immitis mfs produce a few spots.
The respective mfs have these sizes: D. recondita 264 x 4.4, D. immitis 300 x 5.0 and D. repens 325 x 7.2 microns. Length difference 12 % between D. recondita and D. immits, and D. recondita and D. repens of 19 % are sufficient to differentiate these mfs, whereas the other differences are not. The differential diagnosis of D. Immitis & D. recondita has been worked out using PCR with primers for the internal transcribed spacer region 2 (Vet Parasit 106: 243-252, 2002). In a fresh thin blood smear the mfs of D. immitis undulate in one place while those of D. recondita move across the field of the microscope.
Knott's technique: A/ 1.0 ml freshly drawn blood added to 10.0 ml of 2 % formalin, B/ Shake to help lyse the RBC, C/ Centrifuge 5 min at 1000-1500 rpm, D/ Decant, E/ Stir residue with wooden applicator to free the mfs from the walls of the tube and F/ to sediment on a slide, add an equal volume of 1/1000 (or less) methylene blue or acridine orange; after a few minutes mount a drop under a coverslip. D. recondita has a characteristic button-hook tail.
The acid phosphatase test is the most accurate method for differentiating the mfs of D. immitis, D. repens and D. recondita . Mfs from serum, after clotting the blood, are air-dried on a slide. The slides are then incubated for 1 hour in a substrate of Michaelis vernal acetate buffer (pH 10.0), naphthal AS-TR phosphate, pararosaniline and 4.0 % sodium nitrate. After rinsing in distilled water, it is counterstained with methyl green, rinsed successively in 95% ethanol and absolute ethanol, and mounted in Permount.
Treatment. Thiacetarsamide (Caparsolate) and melarsamine (Immiticide) are arsenical type compounds that consistently kill the adults. Mfs can be killed with ivermectin. This drug is supreme. Many other drugs are very successful, the problem being dead worms & mfs whose presence in the dog's lungs is downright dangerous.
Ivermectin: (Heart Guard, Iverhart, Stromectol, Mectizan)--Macrocyclic lactone derivative of avermectin (22, 23-dihydro-avermectin). Binds selectively with glutamate-gated chloride ion channels in invertebrate nerve and muscle cells, causing cell death. Half-life is 16 h; metabolized in liver. Exerts its antiparasitic action by acting as a potent agonist at GABA receptors and potentiating the inhibitory signals sent to motor neurons, which paralyses the parasite. As GABA is confined to the central nervous system in humans and ivermectin does not cross the mammalian blood-brain barrier, the drug has no paralytic action in humans . Adult Dose: 150-200 mcg/kg administered orally.
Management can consist of the following: 1/ diagnostic evaluations (before therapy) to determine subclinical disease, especially of the liver and kidneys; 2/ adulticidal therapy to eliminate mature worms; 3/ a rest period of 4-6 weeks to allow the dog to recover from the lung injury associated with worm death; 4/ mf therapy; 5/ a test for mfs to determine success of mf therapy; 6/ an antigen test to determine success of adulticidal therapy and 7/ preventive medication. The death of the worms is associated with parenchymal lung damage. Shock from dead mfs is another hazard. Limitation of exercise is critical after adulticidal therapy.
Complications of worm death often include impaired pulmonary function and vessel damage, which may initiate disseminated intravascular coagulation (DIC). A platelet count <100,000/ml is not uncommon, but an activated clotting time should be performed to determine if DIC is present. If so, the prognosis is poor. Antigen assays 12-16 weeks after successful adulticidal therapy should be negative. However, low worm burdens and immature worms can still be present with a negative antigen test. Positive antigen tests should be rechecked in 1 month before initiating a 2nd adulticidal regimen. This is deluxe treatment.
Surgery avoids embolism and other ills. Rather than destroy heartworms with arsenicals and other drugs, it is sometimes better to physically remove them from the pulmonary arteries. This treatment allows for removal of most of the worms without risking complications due to thromboembolism . Then, dogs with severe cor pulmonale or caval syndrome will benefit greatly. As worms are removed from the pulmonery artery with forceps, more will come up from the heart. Close your incision in the artery with a clamp to minimize escaping blood. Remove it. Then fish out more worms in the artery. However , there are several ways this operation can be conducted, using alligator flexible forceps and so on.
Control. Mosquito control depends upon public health (PH) measures per district and per season. PH protects the public by indoor & outdoor spraying, and by mosquito larva control, not by killing the parasite. Repelents are hardly common. Deet repelent is good for you and bad. for your dog. Is heartworm disease effectively prevented by once monthly medication beginning at about 2 months of age? Yes. In tropical regions, medication is administered throughout the year; in temperate areas prophylaxis is begun about one month before the mosquito season and concluded about a month after.
Flea collars as preventing heartworm disease have never been studied ! They contain organophosphates and protect against leishmaniasis and all other insect borne diseases. They kill fleas, mosquitoes, triatomid bugs, ticks, etc. Flea collar insecticides have a VERY SLOW evaporation that is PERFECT for ridding the dog's kennel and your home from these pests. Vaporizers that plug into an electric outlet. are also PERFECT for clearing houses of vectors and pests like cockroaches. Still, even perfect has limits !
Eradication. This requires a level of cooperation by no means evinced! All dogs & cats in animal shelters must be dosed at least once as well as all licenced animals to clear mfs. Organophosphates go after vectors, whereas a great variety of drugs attack the parasites. Should the financing be raised in some area like highly infected Florida to successfully eradicate heartworm? Would infected endemic wild animals bring back dirofilariasis ? Veterinary epidemiology does not concentrate on vector control and surveillance, possibly because these underinvestigated fields are not financed. For example, no vaccine development is based on low profits. The motivation to eradicate dirofilariasis has not yet arisen.
Public Health Significance Infection results from mosquito bites. The worms lodge in the pulmonary artery causing vascular occlusion, coagulation, necrosis and fibrosis. Symptoms include chest pain, coughing and in some cases hemoptysis. In some patients radiographs have disclosed an asymptomatic, fibrotic nodule 1-3 cm in diameter.
Heartworm disease of cats Cats are susceptible yet are poorer hosts than dogs. The most prominent clinical signs include coughing, dyspnea, vomiting, lethargy and anorexia. Acute collapse and death can occur. As less than 20% of infected cats have mfs in the blood, diagnosis is best confirmed by either X-rays, echocardiograhy or serologic tests. Etiology. Heartworm disease caused by Dirofilaria immitis is a significant disease of cats. It is found worldwide and in many states in the US where the canine disease occurs. Prevalence rates in cats are estimated to be about 10 % of that of local dogs. The average worm burden is 1-5. The mean age of affected cats is 3-6 years.
Angiostrongylus infection Etiology. This parasite is the nematode Angiostrongylus vasorum, up to 2.5 cm long. Distribution. With the exception of North and South America, it is found worldwide. Because of the infection’s frequency in France, it is called the "French heartworm." Dogs are the definitive host and adults are found in pulmonary vessels. It has been reported in dogs imported into the US.
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