Heartworm

Heartworm is a parasitic roundworm ("Dirofilaria immitis") that is spread from host to host through the bites of mosquitoes. The heartworm is a type of filaria, a small thread-like worm. 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 humansFact|date=August 2008. The parasite is commonly called "heartworm" because the adult reproductive stage of its life cycle resides primarily in the pulmonary artery of its host where it can live for many years. Heartworm infection may result in serious disease for the host; infected dogs that are untreated may die and treatment also has risks. The best defense against heartworm disease is the use of prophylactic treatment given monthly.

History of the disease

The first published evidence of disease in the dog in the United States was in "The Western Journal of Medicine and Surgery" in 1847. Feline heartworm was first described in the 1920s.cite web | title = General Heartworm Disease Information | work = American Heartworm Society | url = http://www.heartwormsociety.org/GeneralInfo.htm | accessdate = 2007-02-26 ]

Distribution

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 (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.cite book|author=Ettinger, Stephen J.;Feldman, Edward C.|title=Textbook of Veterinary Internal Medicine|edition=4th ed.|publisher=W.B. Saunders Company|year=1995|id=ISBN 0-7216-6795-3] It has also been found in South America, [cite journal |author=Vezzani D, Carbajo A |title=Spatial and temporal transmission risk of Dirofilaria immitis in Argentina |journal=Int J Parasitol |volume=36 |issue=14 |pages=1463–72 |year=2006 |pmid=17027990 |doi=10.1016/j.ijpara.2006.08.012] southern Europe,cite web | title = Heartworm Disease: Introduction | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/11300.htm | accessdate = 2007-02-26 ] Southeast Asia, [cite web | last = Nithiuthai | first = Suwannee | title = Risk of Canine Heartworm Infection in Thailand | work = Proceedings of the 28th World Congress of the World Small Animal Veterinary Association | year = 2003 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2003&PID=6702&O=Generic | accessdate = 2007-02-26 ] the Middle East, [cite web | last = Rafiee | first = Mashhady | title = Study of Prevalence of "Dirofilaria immitis" Infestation in Dogs were Examined in Veterinary Clinics of Tabriz Azad University (Iran) during 1992–2002 | work = Proceedings of the 30th World Congress of the World Small Animal Veterinary Association | year = 2005 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2005&PID=11172&O=Generic | accessdate = 2007-02-26 ] Australia, and Japan.

Course of infection

Heartworms go through several life stages before they become adults infecting 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 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 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 salivary glands 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 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 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. [cite web | last = Johnstone | first = Colin | title = Heartworm | work = Parasites and Parasitic Diseases of Domestic Animals | publisher = University of Pennsylvania | year = 1998 | url = http://cal.vet.upenn.edu/merial/hrtworm/hw_1a.htm | accessdate = 2007-02-26 ] By approximately 6.5 to 7 months after infection the adult worms have mated and the females begin producing microfilariae.

Clinical signs of infection

Dogs show no indication of heartworm infection 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. These animals usually have 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. 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 "Dirofilari immitis". An endosymbiont is an organism that lives within the cells of another organism, often giving an advantage to both. It is thought 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.cite journal | last = Todd-Jenkins | first = Karen | coauthors = | title = The Role of "Wolbachia" in heartworm disease | journal = Veterinary Forum | volume = 24 | issue = 10 | pages = 28–30 | publisher = Veterinary Learning Systems |month=October | year=2007]

Diagnosis

A blood test to detect the antigens released from the female reproductive tract is the most common method of diagnosis. The specificity of these tests is close to 100 percent and the sensitivity is more than 90%. [cite web | last = Atkins | first = Clarke | title = Heartworm Disease in Dogs: An Update | work = Proceedings of the 30th World Congress of the World Small Animal Veterinary Association | year = 2005 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2005&PID=10900&O=Generic | accessdate = 2007-02-26 ] 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 concentrating filter test. X-rays are used to evaluate the amount of lung damage caused by the presence of heartworms.

Treatment

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". [cite web | title = Product Information | url = http://ph.merial.com/pet_owners/dogs/product_immiticide.asp| accessdate = 2008-07-01] It has a greater efficacy 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 is also a treatment that may be indicated, especially in advanced cases with substantial heart involvement. [cite web | title = 2005 GuidelinesFor the Diagnosis, Prevention and Management of Heartworm (Dirofilaria immitis) Infection in Dogs | work = American Heartworm Society | year = 2005 | url = http://www.heartwormsociety.org/article.asp?id=48 | accessdate = 2008-07-01 ]

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") may 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 at melarsamine. More importantly, adult heartworms do not begin to die until some 18 months of treatment have elapsed, which is not acceptable under most circumstances.

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. The drugs approved for use in the US are ivermectin (sold under the brand name "Heartgard" and several other generic versions), milbemycin ("Interceptor" and "Sentinel") and moxidectin ("ProHeart") administered as pills or chewable tablets. These drugs should be given monthly throughout the entire year. Even to indoor only pets. Moxidectin is also available in both a 6-month and 12-month sustained release injection, ProHeart 6, ProHeart 12, administered by veterinarians. The injectable form of moxidectin was taken off the market in the United States due to safety concerns [ [http://www.fda.gov/cvm/PH6QA.htm Questions and Answers regarding the FDA Recall of ProHeart®6] U.S. Food and Drug Administration, updated June 10, 2008, 3:46 PM ET. ] . 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, which utilizes moxidectin for control and prevention of roundworms, hookworms, heartworms, whipworms, as well as imidocloprid to kill adult fleas. Selamectin ("Revolution"), is a topical preventive that is likewise administered monthly and also controls fleas, ticks, and mites.

Preventive drugs are highly effective and when regularly administered will protect more than 99 percent of dogs and cats 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.

Heartworm prevention for cats is available as ivermectin ("Heartgard for Cats"), milbemycin ("Interceptor"), or the topical selamectin ("Revolution for Cats").

Monthly heartworm prevention should be administered every month throughout the entire year. No matter what the season,it is essential for all pet owners to continue heartworm preventative every month. Mosquitos can bite at any time and remember that it only takes one bite.

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 infection in a cat is 2 to 5 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.cite web | title = 2007 Guidelines For the Diagnosis, Treatment and Prevention of Heartworm ("Dirofilaria immitis") Infection in Cats | publisher = American Heartworm Society | year = 2007 | url = http://www.heartwormsociety.org/article.asp?id=47 | accessdate = 2007-07-26 ]

The infection rate in cats is 1 to 5 percent of that in dogs in endemic areas. [cite journal |author=Berdoulay P, Levy JK, Snyder PS, "et al" |title=Comparison of serological tests for the detection of natural heartworm infection in cats |journal=Journal of the American Animal Hospital Association |volume=40 |issue=5 |pages=376–84 |year=2004 |pmid=15347617 |doi=] Both indoor and outdoor cats are infected. The mosquito vector is known to enter homes. [cite journal |author=Atkins CE, DeFrancesco TC, Coats JR, Sidley JA, Keene BW |title=Heartworm infection in cats: 50 cases (1985–1997) |journal=J. Am. Vet. Med. Assoc. |volume=217 |issue=3 |pages=355–8 |year=2000 |pmid=10935039 |doi=]

Pathology

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 3 to 4 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.cite journal | last = Yin | first = Sophia | title = Update on heartworm infection | journal = Veterinary Forum | volume = 24 | issue = 6 | pages = 42–43 | publisher = Veterinary Learning Systems |month=June | year=2007]

Obstruction of pulmonary arteries due to emboli from dying worms is more likely to be fatal in cats than dogs because of less collateral circulation and fewer vessels.cite book|editor=August, John R. (ed.)|chapter=Heartworm Disease|author=Atkins, Clarke E., Litster, Annette L.|title=Consultations in Feline Internal Medicine Vol. 5|publisher=Elsevier Saunders|year=2005|id=ISBN 0-7216-0423-4]

igns and symptoms

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

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 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 3 months. The antibody test is more sensitive than the antigen test but it does not provide direct evidence of adult infection. [cite journal |author=Atkins C |title=The diagnosis of feline heartworm infection |journal=Journal of the American Animal Hospital Association |volume=35 |issue=3 |pages=185–7 |year=1999 |pmid=10333254 |doi=] 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. [cite journal |author=DeFrancesco TC, Atkins CE, Miller MW, Meurs KM, Keene BW |title=Use of echocardiography for the diagnosis of heartworm disease in cats: 43 cases (1985–1997) |journal=J. Am. Vet. Med. Assoc. |volume=218 |issue=1 |pages=66–9 |year=2001 |pmid=11149717 |doi=]

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 not recommended and there are no drugs 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.

Human health considerations

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 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 thought 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.

References

Resources and external links

Heartworm Society

* [http://www.heartwormsociety.org 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. American Heartworm Society information for pet owners:
* [http://www.heartwormsociety.org/article.asp?id=17 What Is Heartworm?]
* [http://www.heartwormsociety.org/article.asp?id=14 Frequently Asked Questions]
* [http://www.heartwormsociety.org/article.asp?id=11 Heartworm Disease in Dogs]
* [http://www.heartwormsociety.org/article.asp?id=16 Heartworm Disease in Cats] 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.)
* [http://www.heartwormsociety.org/article.asp?id=48 Guidelines for the Diagnosis, Prevention and Management of Heartworm (Dirofilaria immitis) Infection in Dogs]
* [http://www.heartwormsociety.org/article.asp?id=47 Guidelines for the Diagnosis, Prevention and Management of Heartworm (Dirofilaria immitis) Infection in Cats]

Other resources

* [http://www.moxidectinfacts.com Moxidectin Facts, Usage, and Safety Information]
* [http://www.vetmed.auburn.edu/distance/cardio/page1.html Feline Heartworm Disease] (from Auburn University)
* [http://cal.vet.upenn.edu/merial/hrtworm/hw_top.htm Heartworm Topics] (from the University of Pennsylvania)
* [http://edis.ifas.ufl.edu/MG100 Mosquito-borne Dog Heartworm Disease] (University of Florida Extension Bulletin)
* [http://www.avma.org/communications/brochures/heartworm/heartworm_brochure.asp What You Should Know About Heartworm Disease] (from the American Veterinary Medical Association)
* [http://www.vmth.ucdavis.edu/cardio/cases/case27/case27.htm Case Study of Canine Heartworm Disease] (from the University of California, Davis)
* [http://www.vmth.ucdavis.edu/cardio/cases/case31/case31.htm Case Study of Feline Heartworm Disease] (from the University of California, Davis)
* [http://www.vmth.ucdavis.edu/cardio/cases/case33/case33.htm Case Study of Canine Heartworm Disease] (from the University of California, Davis)
* [http://www.drsfostersmith.com/general.cfm?gid=262 Heartworm Prevention Resources for Dog Owners] (from Drs. Foster & Smith's Veterinary Staff)