Heartworm

Heartworm is a parasitic roundworm (Dirofilaria immitis) that is spread from host to host through the bites of mosquitoes.

Heartworm is a type of filaria, a small thread-like worm. It can affect dogs, cats, wolves, coyotes, foxes, and some other animals, such as ferrets, sea lions, and even humans. The parasitic worm is called a "heartworm" because the parasite, in the final reproductive stage of its life cycle, resides in the heart of its host where it can live for many years and kill its host through congestive heart failure. Heartworm infestation is extremely serious for the host; infected dogs that go untreated can die and even treated dogs must go through a long period of uncomfortable treatment (sometimes requiring surgery in advanced cases to remove the worms from the right ventricle). The best defense against heartworm is the use of prophylactic treatment given monthly. A course of heartworm prevention begins with a blood test to see if the parasite is present. If the dog is parasite free, a prophylactic medication can be used to prevent heartworm infection. A positive test result usually requires treatment to eradicate the worms.

History of the disease
The first published evidence of heartworm disease in the dog was in The Western Journal of Medicine and Surgery in 1847. Feline heartworm was first described in the 1920s.

Distribution
Although at one time confined to more southern climates, heartworm has now spread to nearly all climates where its vector, the mosquito, is found. Transmission of the parasite from dog to dog occurs in all of the United States (except Alaska) and the warmer regions of Canada. The highest infection rates are found within 150 miles of the Atlantic 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, and Japan.

Course of infestation


Heartworms go through several life stages before they become adults infesting the heart of the host animal. The worms require the mosquito as an intermediate stage in order to complete their life cycle. 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 some 6.5 to 7 months in dogs and is known as the prepatent period.

Heartworms bear live young, known as microfilariae, producing thousands of them every day. The microfilariae then circulate in the bloodstream for as long as two years, waiting for the next stage in their life cycle in the gut of a bloodsucking mosquito. When ingested by a mosquito, the microfilariae undergo a series of molts to the infective, or third, larval stage and then migrate to the head of the mosquito, where they wait to infect another host. These changes can occur in as little as two weeks and as long as six weeks, depending on the warmth of the climate, and generally cease entirely at ambient temperatures below 14° Celsius (57° Fahrenheit).

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, some 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 lodge in the arteries of the lungs. Over the next 3 to 4 months they increase greatly in size. The female adult worms are about 30 cm in length, and males are about 23 cm with a coiled tail. By approximately 6.5 to 7 months after infection the adult worms have mated and the females begin producing microfilariae.

Symptoms of infestation
Dogs show no indication of heartworm infestation during the 6 month long 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.

Many dogs will show little or no sign of infection even after the heartworms have matured. To some degree these dogs may be described as seeming to age slightly faster than normal as the worms slowly damage the lungs, kidneys and liver. These animals usually have a light infection and live a fairly sedentary lifestyle. However, active dogs and those with heavier infections will quickly show the classic symptoms of heartworm disease. Early symptoms include a cough, especially on exercise, and early exhaustion upon exercise. More advanced cases progress to severe weight loss, fainting, coughing up blood, and, finally, congestive heart failure.

Role of Wolbachia
Wolbachia is an intracellular bacteria that is an endosymbiont of heartworms. An endosymbiont is an organism that lives within the cells of another organism, often giving an advantage to both. It is estimated that all heartworms are infected with Wolbachia to some degree. Research indicates that the inflammation that occurs at the die-off of adult heartworms or larvae is in part due to the release of Wolbachia bacteria into the tissues. This may be particularly significant in cats, in which disease seems to be more related to larval death than living adult heartworms (see below). Pretreating heartworm positive animals with an antibiotic such as doxycycline to remove Wolbachia may prove to be beneficial, but further studies are necessary.

Diagnosis
Blood testing is the most common method of diagnosis. Formerly, ELISA tests were used to detect antibodies to heartworm, but the sensitivity and specificity was low. Current ELISA tests detect female heartworm antigens. The specificity of these tests is close to 100 percent and the sensitivity is about 85 percent. False negative tests can result from low worm counts, immature infections, and all male infections. Heartworm positive dogs should also be tested for the presence of microfilariae, usually using a filter test. X-rays can provide a good estimate of the amount of lung damage caused by the presence of heartworms.

Treatment
If either a blood test or the onset of symptoms betray the presence of heartworms, treatment is indicated. Treatment is highly efficacious if the disease is diagnosed early in the disease process. Before the worms can be treated, however, the dog must be evaluated for good heart, liver, and kidney function to ensure the animal can survive the treatment. Any insufficiencies in these organs must be dealt with first, before treatment, as the eradication process can be taxing on organ function. Usually the adult worms are killed with an arsenic-based compound. The currently recommended compound, melarsomine dihydrochloride, is marketed under the brand name Immiticide. It has a greater efficacy and fewer side effects than previous formulation (thiacetarsamide sodium, sold as Caparsolate) which makes it a safer alternative for dogs with late-stage infestations.

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 come back negative, the treatment is considered a success.

Surgical removal of the adult heartworms is also a treatment that may be indicated, especially in advanced cases with substantial heart involvement.

Long term monthly administration of ivermectin (but apparently not moxidectin, milbemycin or selamectin) year round for at least three years at the dose normally used for heartworm prevention (see "Prevention") also removes most adult heartworms from most dogs. However, this is not the treatment of choice for removal of adult heartworms for two reasons. First, not all dogs are completely cleared of heartworms by this treatment. More importantly, adult heartworms do not begin to die until some 18 months of treatment have elapsed, which is not acceptable under most circumstances. This treatment is normally reserved for dogs that are not likely to tolerate treatment with the harsher, but more effective, melarsomine or instances where the owner cannot afford the more expensive melarsomine treatment.

Some research indicates that monthly preventive use of Ivermectin not only prevents new adult heartworms from developing, but also may kill some adult heartworms within a year of Ivermectin use. Whether these adults are killed by the Ivermectin preventative doses, or just die of old age (they have a limited life span of a few years), or both, is unclear.

From time to time various "homeopathic," "natural" or "organic" products are touted as cures or preventives for heartworm disease. However, such products have never been proven effective by rigorous scientific methods, and the claims should be viewed with skepticism.

Prevention
Prevention of heartworm infection can be obtained through a number of veterinary drugs. Most popular are ivermectin (sold under the brand name Heartgard), milbemycin (Interceptor) and moxidectin (ProHeart) administered as pills or chewable tablets. These drugs are given monthly during the local mosquito season. Moxidectin is also available in a six-month sustained release injection, Proheart 6, administered by veterinarians, but the injectable form of moxidectin was taken off the market in the United States due to safety concerns. ProHeart 6 remains on the market in many other countries including Canada and Japan. Its sister product, ProHeart SR-12 is used extensively in Australia and Asia as a 12 month injectable preventative. Moxidectin has been re-released in the United States as part of Advantage Multi™ (imidacloprid + moxidectin) Topical Solution, which utilizes moxidectin for control and prevention of roundworms, hookworms, heartworms, whipworms, as well as imidocloprid to kill adult fleas. Selamectin (Revolution), on the other hand, is a topical preventive that is likewise administered monthly. Some of these drugs also kill other parasites, including intestinal worms. In addition, selamectin controls fleas, ticks, and mites.

Preventative drugs are highly effective, and when regularly administered will protect more than 99 percent of dogs from infection. Most failures of protection result from irregular and infrequent administration of the drug. However, the monthly preventives all have a reasonable margin for error in their administration such that if a single month's dose is accidentally missed, adequate protection is usually provided so long as the next two monthly doses are administered on schedule.

Cats may be treated with ivermectin (Heartgard for Cats), milbemycin (Interceptor), or the topical selamectin (Revolution for Cats).

Monthly heartworm prevention should be administered beginning within a month of the onset of the local mosquito season and continued for a month after the cessation of local mosquito activity. In warm climates, such as the warm temperate climate along the immediate Gulf Coast of the United States and in tropical and subtropical regions, heartworm prevention must be administered year round. Some authorities recommend year round administration even in colder climates on the theory that mosquito activity may occur during the occasional unseasonable warm spell, but others argue that computer models indicate heartworm transmission is highly unlikely under such circumstances.

Feline heartworm disease
While dogs are a natural host for D. immitis, cats are an atypical host. Because of this there are significant differences between canine and feline heartworm disease. The majority of heartworm larvae do not survive in cats, so unlike in dogs, a typical infestation in a cat is only a few worms. The life span 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 infection rate in cats is 5 to 20 percent of that in dogs in endemic areas. Although most infected cats are outdoors, one study showed that one-third of infected cats have an indoor lifestyle.

Pathology
The vascular disease in cats that occurs when the L3 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 die-off of the L3 larvae in the vessels. The subsequent inflammation of the pulmonary vasculature and lungs can be easily misdiagnosed as feline asthma or allergic bronchitis.

Obstruction of pulmonary arteries due to HARD or emboli is more likely to be fatal in cats than dogs because of less collateral circulation and fewer vessels.

Signs and symptoms
Acute heartworm disease in cats can result in shock, vomiting, diarrhea, fainting, and sudden death. Chronic infection and HARD 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
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 when there are female worms, an antigen test will usually only become positive seven to eight months post-infection. Therefore, a cat may be symptomatic 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. The antibody test is more sensitive than the antigen test but is also much less specific for detecting an 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.

Treatment and prevention
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 generally not recommended.

Treatment typically consists of putting the cat on a monthly heartworm preventative and a short term corticosteroid. Surgery has also been used successfully to remove adult worms. Three drugs commonly used as preventatives are ivermectin, milbemycin, and selamectin. The prognosis for feline heartworm disease is guarded.

Human health considerations
The dog heartworm is a 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 at that time, the granuloma may resemble lung cancer on the X-ray and require a biopsy to rule out the life threatening condition. This may well be the most significant medical consequence of human infection by the dog heartworm.

At one time it was thought that the dog heartworm infected the human eye, with most cases reported from the southeastern United States. However, these cases are now known to be caused by a closely-related parasite of raccoons, Dirofilaria tenuis. Several hundred cases of subcutaneous (under the skin) 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.

Heartworm Society
American Heartworm Society information for pet owners: American Heartworm Society information for veterinarians. (Every three years the American Heartworm Society holds an international symposium. Following each triennial symposium, the Society updates its guidelines for veterinarians to incorporate any new discoveries. The following guidelines are widely considered "best practices" and should be closely followed by veterinarians in dealing with this parasite.)
 * American Heartworm Society Founded in 1974, the American Heartworm Society is internationally recognized as the definitive authority with respect to heartworm disease in dogs and cats.
 * What Is Heartworm?
 * Frequently Asked Questions
 * Heartworm Disease in Dogs
 * Heartworm Disease in Cats
 * Guidelines for the Diagnosis, Prevention and Management of Heartworm (Dirofilaria immitis) Infection in Dogs
 * Guidelines for the Diagnosis, Prevention and Management of Heartworm (Dirofilaria immitis) Infection in Cats

Other resources

 * Moxidectin Facts, Usage, and Safety Information
 * Feline Heartworm Disease (from Auburn University)
 * Heartworm Topics (from the University of Pennsylvania)
 * Mosquito-borne Dog Heartworm Disease (University of Florida Extension Bulletin)
 * What You Should Know About Heartworm Disease (from the American Veterinary Medical Association)
 * Case Study of Canine Heartworm Disease (from the University of California, Davis)
 * Case Study of Feline Heartworm Disease (from the University of California, Davis)
 * Case Study of Canine Heartworm Disease (from the University of California, Davis)
 * Heartworm Prevention Resources for Dog Owners (from Drs. Foster & Smith's Veterinary Staff)

Dirofilariose Dirofilariosis Canina דירופילריאזיס フィラリア