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Heartworm (Dirofilaria immitis) is a parasitic roundworm that is spread from host to host through the bites of mosquitoes. The heartworm is a type of filaria, a small thread-like worm, that causes filariasis. The definitive host is the dog, but it can also infect cats, wolves, coyotes, foxes and other animals, such as ferrets, sea lions and even, under very rare circumstances, humans. The parasite is commonly called "heartworm"; however, that is a misnomer because the adults actually reside in the pulmonary arterial system (lung arteries) for the most part, and the primary effect on the health of the animal is a manifestation of damage to the lung vessels and tissues. Occasionally, adult heartworms migrate to the right heart and even the great veins in heavy infections. Heartworm infection may result in serious disease for the host.
Although at one time confined to the southern United States, heartworm has now spread to nearly all locations where its vector, the mosquito, is found. Transmission of the parasite occurs in all of the United States (cases have even been reported in Alaska), and the warmer regions of Canada. The highest infection rates are found within 150 miles of the coast from Texas to New Jersey, and along the Mississippi River and its major tributaries. It has also been found in South America, southern Europe, Southeast Asia, the Middle East, Australia, Korea, and Japan.
Heartworms go through several life stages before they become adults infecting the pulmonary artery of the host animal. The worms require the mosquito as an intermediate stage to complete their life cycles. The rate of development in the mosquito is temperature-dependent, requiring about two weeks of temperature at or above 27°C (80°F). Below a threshold temperature of 14°C (57°F), development cannot occur, and the cycle will be halted. As a result, transmission is limited to warm months, and duration of the transmission season varies geographically. The period between the initial infection when the dog is bitten by a mosquito and the maturation of the worms into adults living in the heart takes six to seven months in dogs and is known as the "prepatent period".
After infection, the third-stage larval heartworms (L3) deposited by the mosquito grow for a week or two and molt to the fourth larval stage (L4) under the skin at the site of the mosquito bite. Then, they migrate to the muscles of the chest and abdomen, and 45 to 60 days after infection, molt to the fifth stage (L5, immature adult). Between 75 and 120 days after infection, these immature heartworms then enter the bloodstream and are carried through the heart to reside in the pulmonary artery. Over the next three to four months, they increase greatly in size. The female adult worm is about 30 cm in length, and the male is about 23 cm, with a coiled tail. By seven months after infection, the adult worms have mated and the females begin giving birth to live young, called microfilariae.
The microfilariae circulate in the bloodstream for as long as two years, waiting for the next stage in their life cycles in the gut of a bloodsucking mosquito. When ingested by a mosquito, the microfilariae undergo a series of molts to the infective third larval stage, and then migrate to the salivary glands of the mosquito, where they wait to infect another host. The incubation period required to reach the stage where the microfilariae become transmittable to another host can be as little as two weeks or as long as six weeks, depending on the warmth of the climate, and the larval life cycle ceases entirely if the ambient temperature drops below 14°C (57°F).
Hosts of Dirofilaria immitis include:
Dogs show no indication of heartworm infection during the six-month prepatent period prior to the worms' maturation, and current diagnostic tests for the presence of microfilariae or antigens cannot detect prepatent infections. Rarely, migrating heartworm larvae get "lost" and end up in unusual sites, such as the eye, brain, or an artery in the leg, which results in unusual symptoms such as blindness, seizures and lameness. But normally, until the larvae mature and congregate inside the heart, they produce no symptoms or signs of illness.
Many dogs will show little or no sign of infection even after the worms become adults. These animals usually have only a light infection and live a fairly sedentary lifestyle. However, active dogs and those with heavier infections may show the classic signs of heartworm disease. Early signs include a cough, especially on exercise and early exhaustion upon exercise. In the most advanced cases where many adult worms have built up in the heart without treatment, signs progress to severe weight loss, fainting, coughing up blood and, finally, congestive heart failure.
Wolbachia pipientis is an intracellular bacterium that is an endosymbiont of Dirofilaria immitis. All heartworms are thought to be infected with Wolbachia to some degree. Research indicates the inflammation occurring at the die-off of adult heartworms or larvae is in part due to the release of Wolbachia bacteria or protein into the tissues. This may be particularly significant in cats, in which the disease seems to be more related to larval death than living adult heartworms (see below). Treating heartworm-positive animals with an antibiotic such as doxycycline to remove Wolbachia may prove to be beneficial, but further studies are necessary.
Three methods can be used for the diagnosis:
Microfilarial detection was accomplished most commonly in the past by the microscopic identification of microfilariae on a direct blood smear, above the buffy coat in a microhematocrit tube, using the modified Knott test, or after millipore filtration. The accuracy of these tests, typically used for routine screening or diagnosis of heartworm infection, is improved by multiple testing. The modified Knott test and millipore filtration are more sensitive because they concentrate microfilariae, improving the chance of diagnosis. The direct smear technique allows examination of larval motion, helping in the distinction of D. immitis from Acanthocheilonema reconditum. This distinction is important because the presence of the latter parasite does not require expensive and potentially harmful therapy. However, the potential for amicrofilaremic infections is 5-67%. The number of circulating microfilariae does not correlate with the number of adult heartworms, so is not an indicator of disease severity.
Antigen testing, in most practices, has supplanted or supplemented microfilarial detection. Combining the microfilaria and adult antigen test is most useful in dogs receiving diethylcarbamazine or no preventative (as macrolides as for example ivermectin or moxidectin typically render the dog amicrofilaremic). Up to 1% of infected dogs are microfilaria-positive and antigen-negative. Immunodiagnostics (ELISA, lateral flow immunoassay, rapid immunomigration techniques) to detect heartworm antigen in the host's blood are now regularly used. The weakness of these tests is they only detect the antigens released from the adult female worm's reproductive tract, so will produce negative results during the first five to eight months of infection. The specificity of these tests is close to 100%, and the sensitivity is more than 80%. A recent study demonstrated a sensitivity of only 64% for infections of only one female worm, but improved with increasing female worm burden (85%, 88%, and 89% for two, three and four female worms, respectively). Specificity in this study was 97%. False-negative test results can be due to low worm counts, immature infections and all male infections.
X-rays are used to evaluate the amount of lung damage caused by the presence of heartworms.
If an animal is diagnosed with heartworms, treatment may be indicated. Before the worms can be treated, however, the dog must be evaluated for heart, liver, and kidney function to evaluate the risks of treatment. Usually, the adult worms are killed with an arsenic-based compound. The currently approved drug in the US, melarsomine dihydrochloride, is marketed under the brand name Immiticide. It has a greater efficiency and fewer side effects than previously used drug (thiacetarsamide sodium, sold as Caparsolate) which makes it a safer alternative for dogs with late-stage infections.
After treatment, the dog must rest (restricted exercise) for several weeks so as to give its body sufficient time to absorb the dead worms without ill effect. Otherwise, when the dog is under exertion, dead worms may break loose and travel to the lungs, potentially causing respiratory failure and death. According to the American Heartworm Society, use of aspirin in dogs infected with heartworms is no longer recommended due to a lack of evidence of clinical benefit and may be contraindicated. It had previously been recommended for its effects on platelet adhesion and reduction of vascular damage caused by the heartworms.
The course of treatment is not completed until several weeks later, when the microfilariae are dealt with in a separate course of treatment. Once heartworm tests are negative, the treatment is considered a success.
Surgical removal of the adult heartworms as a treatment also may be indicated, especially in advanced cases with substantial heart involvement.
Long-term monthly administration of ivermectin year-round at three times the dose normally used for heartworm prevention (see "Prevention") will eventually kill adult heartworms. However, this is not the treatment of choice for removal of adult heartworms for two reasons. First, this treatment is not as effective as melarsamine. More importantly, adult heartworms do not begin to die until 18 months of treatment have elapsed, which is not acceptable for dogs with high-volume infections. Long-term treatment over a year with doxycycline daily and Heartguard Plus has been shown to be effective in early heartworm patients which are asymptomatic.
Prevention of heartworm infection can be obtained through a number of veterinary drugs. The drugs approved for use in the US are ivermectin (sold under the brand names Heartgard, Iverhart, and several other generic versions), milbemycin (Interceptor Flavor Tabs and Sentinel Flavor Tabs) and moxidectin (ProHeart) administered as pills or chewable tablets. Moxidectin is also available in both a six-month and 12-month, sustained-release injections, ProHeart 6 or ProHeart 12, administered by veterinarians. The injectable form of moxidectin was taken off the market in the United States due to safety concerns in 2004, but the FDA returned a newly formulated ProHeart 6 to the market in 2008. ProHeart 6 remains on the market in many other countries, including Canada and Japan. Its sister product, ProHeart 12, is used extensively in Australia and Asia as a 12-month injectable preventive. Topical treatments are available, as well. Advantage Multi (imidacloprid + moxidectin) Topical Solution, uses moxidectin for control and prevention of roundworms, hookworms, heartworms, and whipworms, as well as imidacloprid to kill adult fleas. Selamectin (Revolution) is a topical preventive likewise administered monthly; it also controls fleas, ticks, and mites.
Preventive drugs are highly effective, and when regularly administered, will protect more than 99% of dogs and cats from heartworm. Most compromises in protection result from failure to properly administer the drugs during seasonal transmission periods. In regions where the temperature is consistently above 14°C (57°F) year-round, a continuous prevention schedule is recommended.
Lapses of up to four months between doses of ivermectin-based products still provides 95% protection from adult worms. This period is called the reach-back effect. Annual heartworm testing is highly recommended for pet owners who choose to use minimal dosing schedules.
Heartworm prevention for cats is available as ivermectin (Heartgard for Cats), milbemycin (Interceptor), or the topical selamectin (Revolution for Cats) and Advantage Multi (imidacloprid + moxidectin) topical solution.
While dogs are a natural host for D. immitis, cats are an atypical host. Because of this, differences between canine and feline heartworm diseases are significant. The majority of heartworm larvae do not survive in cats, so unlike in dogs, a typical infection in cats is two to five worms. The lifespan of heartworms is considerably shorter in cats, only two to three years, and most infections in cats do not have circulating microfilariae. Cats are also more likely to have aberrant migration of heartworm larvae, resulting in infections in the brain or body cavities.
The vascular disease in cats that occurs when the L5 larvae invade the pulmonary arteries is more severe than in dogs. A syndrome related to this inflammatory reaction has been identified in cats: heartworm-associated respiratory disease (HARD). HARD can occur three to four months after the initial infection, and is caused by the presence of the L5 larvae in the vessels. The subsequent inflammation of the pulmonary vasculature and lungs can be easily misdiagnosed as feline asthma or allergic bronchitis.
Acute heartworm disease in cats can result in shock, vomiting, diarrhea, fainting, and sudden death. Chronic infection can cause loss of appetite, weight loss, lethargy, exercise intolerance, coughing, and difficulty breathing. The signs of HARD can persist even after complete elimination of the heartworm infection.
Diagnosis of heartworm infection in cats is problematic. Like in dogs, a positive ELISA test for heartworm antigen is a very strong indication of infection. However, the likelihood of a positive antigen test depends on the number of adult female worms present. If there are only male worms, the test will be negative. Even with female worms, an antigen test will usually only become positive seven to eight months after infection. Therefore, a cat may have significant clinical signs long before the development of a positive test. HARD can be found in cats that never develop adult heartworms and therefore never have a positive antigen test.
An antibody test is also available for feline heartworm infection. It will be positive in the event of exposure to D. immitis, so a cat that has successfully eliminated an infection may still be positive for up to three months. The antibody test is more sensitive than the antigen test, but it does not provide direct evidence of adult infection. It can, however, be considered specific for diagnosing previous larval infections, and therefore fairly specific for HARD.
X-rays of the chest of a heartworm-infected cat may show an increased width of the pulmonary arteries and focal or diffuse opacities in the lungs. Echocardiography is a fairly sensitive test in cats. Adult heartworms appear as double-lined hyperechoic structures within the heart or pulmonary arteries.
Arsenic compounds have been used for heartworm adulticide treatment in cats, as well as dogs, but seem more likely to cause pulmonary reactions. A significant number of cats develop pulmonary embolisms a few days after treatment. The effects of melarsomine are poorly studied in cats. Due to a lack of studies showing a clear benefit of treatment and the short lifespan of heartworms in cats, adulticide therapy is not recommended, and no drugs are approved in the US for use in cats.
Treatment typically consists of putting the cat on a monthly heartworm preventive and a short-term corticosteroid. Surgery has also been used successfully to remove adult worms. Three drugs are approved for use in cats in the US: ivermectin, milbemycin, and selamectin. The prognosis for feline heartworm disease is guarded.
The dog heartworm is of negligible public health risk, because it is unusual for humans to become infected. Additionally, human infections usually are of little or no consequence, although rarely an infected human may show signs of respiratory disease. In most cases, however, the heartworm dies shortly after arriving in the human lung, and a nodule, known as a granuloma, forms around the dead worm as it is being killed and absorbed. If an infected person happens to have a chest X-ray following granuloma formation, the nodule may be large enough to resemble lung cancer on the X-ray and require a biopsy for a pathologic assessment. This may well be the most significant medical consequence of human infection by the dog heartworm.
At one time, the dog heartworm was thought to infect the human eye, with most cases reported from the southeastern United States. However, these cases are now thought to be caused by a closely related parasite of raccoons, Dirofilaria tenuis. Several hundred cases of subcutaneous infections in humans have been reported in Europe, but these are almost always caused by another closely related parasite, Dirofilaria repens, rather than the dog heartworm.