Heartworm Biology
Heartworm (Dirofilaria immitis) is a serious threat to dog wellness. Over the last two decades, its recognition worldwide has increased dramatically. Heartworm infection is quite debilitating, even deadly. Furthermore, treatment is costly and difficult. Thus, prevention of heartworm is a key goal of pet wellness. In 1997 it was reported to the University of Guelph that there were 525 heartworm positive dogs in Canada. This number is not alarming in itself, but when it is revealed that 90% (474) of these positive dogs were not on a preventive program, the effectiveness and necessity of a preventive regime is evident. Incidence of heartworm is up from last year. In 1996 there were 443 positives reported in Canada. Increased awareness of the disease prompting an increase in the amount of testing done by veterinarians is partly responsible for the increase this year, but these numbers would certainly be much higher if prevention was not so widely used.
Heartworm is able to infect wild animals such as coyotes, wolves, foxes etc. As a result, once heartworm is introduced in an area it becomes permanent, as wild animals are not able to be treated with a preventive and transmission goes unchecked.
Life Cycle
Infective heartworm larvae are transmitted between animals via mosquitoes, and their continued transmission is directly related to environmental conditions within an area. The correct species of mosquito is necessary (about 70 are known to carry the disease) and a temperature of roughly 21° Celsius for at least 14 days is required for the heartworm larvae to complete the required molts within the mosquito. Typically, during a bloodmeal, a mosquito will pick up 1 or two microfilarie, and rarely 3. A moderate rate of infection, both in the intermediate host (mosquito) and the final host (the dog) is most conducive to heartworm transmission. If there are to many circulating microfilarie the mosquito will be killed by the numbers it ingests.
Adult worms range in size from six to twelve inches and generally live in the right ventricle of the heart and the pulmonary arteries, where their presence damages the arterial walls. Over time, the walls of the blood vessels of infected dogs begin to thicken and expand. Eventually, the dog develops increased blood pressure (hypertension) as a result of damage to its arteries. In very severe cases, the worms can actually enter the right side of the heart. If the number of worms or "worm burden" becomes significant, they can cause congestive heart failure as well as kidney and liver failure (called caval syndrome).
Click here to view the heartworm life cycle.
Legend
1. Adult heartworms in heart and lungs of infected animals (domestic or wild).
2. Fertile female heartworm releases microfilarie (tiny heartworm larvae) into bloodstream.
3. Mosquito swallows microfilarie when it bites dog.
4. Microfilarie grow to infective stage in mosquito.
5. The mosquito serves as an intermediate host for two molts of the larvae.
6. In the infective third stage, the larvae enter the mosquito's mouth parts, ready to be transmitted.
7. The mosquito bites the dog and the larvae are deposited via the saliva.
8. The third molt to L4 occurs 3 to 4 days after infection when the larvae begin their journey under the dog's skin.
9. The fourth molt (to L5) takes place 50 to 70 days after infection. During that time the larvae have been working their way toward the pulmonary arteries.
10. Larvae become adults in heart and lungs.
11. Within 70 to 100 days after infection, the worms arrive in the pulmonary arteries. After an additional 3 months the worms reach sexual maturity (L5 to adult), mate and release microfilarie, completing the life cycle.
The time from infection by a mosquito to an active adult is completed in approximately 6 months.
Incidence
The technical term for canine heartworm disease is dirofilariasis. It is only fairly recently that it was recognized as a serious problem. Until the early 1970s, it was confined primarily to the coastal areas of the southeastern and southern sections of the United States and a few localized areas in the Midwest and Northeast. Since that time the disease has spread so rapidly that it is now found in all but the mountainous and desert areas of the country. This spread is due to human migration from heartworm-endemic parts of the country (with then heartworm infected dogs) to other areas where heartworm was previously rare or unrecognized. The heaviest infestations of heartworm continue to be found along the major waterways and tributaries, due to the high prevalence of mosquitos, but the incidence is increasing across Canada.
The rate of transmission of heartworm is directly proportional to the number of mosquitoes in the area. It is also dependent on the number of infected dogs. Dogs are increasingly susceptible if they live outdoors, and susceptibility increases with years of exposure. Numerous mosquito species have demonstrated the ability to carry the heartworm larvae.
Dogs with an extremely high concentration of microfilaria (20,000 per milliliter or greater) are actually less efficient disease carriers than dogs with lower concentrations, because the mosquito can take in so many microfilaria that it dies.
For the past 65 years, heartworm disease has also been known to occur in cats, although only in the past 20 years has it been diagnosed with any regularity. The incidence is believed to be 10% or less of that of unprotected dogs living in the same area. Cats are less susceptible to heartworm than are dogs; however, arterial damage and clotting can be severe in some cats and may be a cause of sudden death.
Generally, infections in cats consist of a very light worm burden (1 to 3 adult worms), which may be of the same sex; therefore, no microfilarie are generated. Diagnosis of heartworm infection in cats is difficult due to ambiguous test results. However, chronic vomiting and coughing can be signs of an infection. Significant pulmonary disease can be identified from radiographs.
Heartworm infection also occurs in wild canines, ferrets, muskrats, raccoons, bears, horses, foxes, coyotes and the California sea lion. In many species, however, the life cycle of the worm ends at the adult stage. It is due to infestation in the wild animals of an area that heartworm becomes a permanent problem once introduced, as wild animals are not treated with preventives and the transmission by mosquitos is allowed to go unchecked.
Heartworm infection in humans usually consists of a single worm, often located just under the skin, although some do reach the pulmonary artery. The incidence in humans is probably far greater than what has been reported, primarily because only countries with advanced medical services are likely to recognize the problem.
Clinical Signs
The worms generally make a home for themselves in the pulmonary arteries. In the living dog, heartworms are not found in the right side of the heart except when the dog is very heavily infected. They may also be present in the veins connecting to the liver, where large numbers can cause severe damage.
Normal Progression of Clinical Signs
Adult heartworms living in the pulmonary arteries cause inflammation inside the vessels. Blood clots also may form within these arteries, which may completely obstruct segments of the vessels. As the damage progresses, smaller branches of arteries become affected. The inflammation and occlusion of blood vessels leads to increased blood pressure (pulmonary hypertension).
As the pressure increases, the pulmonary arteries try to expand to circulate needed blood. In addition, the right ventricle of the heart must strain to pump blood through the affected arteries. Eventually, the right side of the heart usually enlarges and may fail. Normally, 3 to 5 years is required for clinical pulmonary hypertension to develop as a result of heartworm disease. However, clinical signs may develop more quickly in active dogs.
Unfortunately, much of the internal damage to the dog occurs before any clinical signs are evident. When clinical signs do develop, they resemble signs of general heart failure consisting of sporadic coughing and lowered exercise tolerance. As time passes, the cough becomes chronic and is accompanied by noticeably difficult respiration.
In advanced cases of the disease, a dog will often collapse after even light physical exertion. Most dogs develop congestive heart failure and ascites (an accumulation of fluid in the abdomen). When infection becomes this severe, normal health may not be fully restored even after an effective treatment program. Thus, early detection of infection is of critical importance.
Liver Failure or Caval Syndrome
A fatal condition called caval syndrome is encountered in dogs exposed to a massive infection over a short period of time. Caval syndrome occurs when a large mass of worms cluster in the vena cava (the large blood vessel leading to the heart from the liver, kidneys and abdominal organs). These worms restrict blood flow to the heart and cause anemia and extensive liver and kidney damage. Two US studies have shown that 16 to 20% of dogs with heartworm disease develop caval syndrome. Most commonly found in young dogs who have acquired little or no protective immunity, the clinical signs include sudden weakness, rapid breathing, and brown urine. If the worms are not eliminated, death occurs in 24 to 72 hours. In these severe cases, immediate surgical removal is the only option for survival.
Diagnostic Options
A combination of methods, including physical examination, diagnostic tests and the history of the dog are combined when making a determination. Two extremely important factors are:
The local incidence of disease.
The accuracy of the tests used.
The American Heartworm Society recommends that dogs being seen for the first time should be both Antigen and Microfilarial tested. After the first year they should be antigen tested only and this is done every two or three years. Your veterinarian will tell you the recommendation for your area. Depending on the climate of the area of Canada you are in, it may not be necessary to test the dog if it was born after the previous mosquito season ended. If it has never been exposed to mosquitos, it can not have heartworm.
An antigen test is used to detect the presence of adult heartworm in the dog. Adult worms release a substance called an "Antigen" and when combined with elements of a test kit their presence produces a change in the color of the test medium. This involves taking your dog to the veterinarian for a blood sample, usually a month or so before heartworm season begins in your area. The blood is analyzed and a determination made that the dog is either positive or negative for the presence of adult worms. False positives are rare and are usually the result of operator error. A false negative may occur if there are less than 3 adult worms present, (not enough antigen generated to be detected) or if there are only male worms in the heart (as the test only reacts to the antigen of the female).
Another type of test is a microfilaria screening test. This is where the blood is examined for microfilaria under a microscope for the actual microfilarie. This test is usually done as a confirmation if the antigen test shows positive. A false positive may occur with this test if the microfilarie detected are actually D. reconditum
A microfilarie screen test may show a false negative if:
Only a single worm is present or all worms are of the same sex;
The adults are too old or too young to reproduce;
The dog's immune system is eliminating microfilarie as they are produced.
A microfilaricidal drug such as SENTINEL® or INTERCEPTOR® has destroyed the microfilarie.
The accuracy of the microfilarie tests is vital because there are other filarial worms that may infect a dog. The most important of these is Dipetalonema reconditum . It is a harmless species (transmitted by the flea) that can be mistaken for D. immitis. D. reconditum typically resides in the subcutaneous and peri-renal (area around the kidney) tissues and releases its microfilaria from there. In comparing the two species, D. reconditum has a smaller body size and will travel across a microscope field, while D. immitis will undulate vigorously in place. There is also a difference in the shape of the head of the worms that your veterinarian will be able to use to speciate the parasite. With D. reconditum , there will also be fewer microfilarie on the microscope slide. These distinctions are important because failure to distinguish between the two can result in:
A "false-positive" reading where the dog is thought to have heartworm microfilarie or D. immitis when it really doesn't and may undergo expensive treatment.
A case where D. immitis is mistaken for the relatively harmless D. reconditum. The outcome would be either an inappropriate treatment regimen or, perhaps, no treatment at all leaving the dog at risk.
X-rays are sometimes taken to confirm heart enlargement due to the presence of adult worms. Radiographs can confirm the presence of heartworm disease, but not whether heartworms are still present. They are best used to assist in assessing the degree of damage that has occurred and the extent to which the lung may be able to cope with the blood vessel blockage that inevitably follows the destruction of adult worms.
Treatment
Treatment of heartworm infection is a three stage process because there is no product available which is effective against both adult worms and microfilaria. The treatment program recommended by the American Heartworm Society is to:
1. Remove the adult worms (with an adulticide or surgery).
2. In 3 to 4 weeks, administer a product to kill the microfilarie (a microfilaricide such as SENTINEL or INTERCEPTOR).
3. Prevent future re-infection.
Eliminating Adult Worms
Thiacetarsamide (Caparsolate®) and Melarsomine (Imidicide®) are the two products approved for adult heartworms. However, because both are arsenic compounds, they are potentially dangerous and can have serious side effects. Your veterinarian will be able to detail the benefits of each drug and will establish the treatment regime for your dog should it become necessary.
In thiacetarsamide treatment, a dog is injected intravenously twice a day for two days. The dosage kills most male and many female heartworms, but less than 50% of infections are eliminated completely. Researchers have found that increasing the recommended dosage by 10% improves the efficacy of the treatment, although the risk of toxic reactions is slightly higher. Occasionally, treatment is suspended before the entire series of injections has been completed if a reaction occurs. Most dogs can be given a full series of injections at a later time without incident.
After thiacetarsamide therapy, adult worms begin to die in 5 to 7 days, but complete elimination of the heartworms may not occur for 30 to 60 days. The dog's activity is severely restricted during this time to prevent blood vessel blockage as the worms break up into the lungs. Some veterinarians also prescribe other supportive therapy such as aspirin, steroids and antibiotics; however, studies are not conclusive about the effectiveness of such treatment.
Melarsomine is a newer arsenic compound that is more effective than thiacetarsamide in eliminating adult heartworms at a lower dosage. It is given via intramuscular injection; either two injections 24 hours apart or a single injection followed in 30 days by the normal two injection schedule.
Melarsomine is thought to be more effective for adult heartworms, but the resulting side effect from greater numbers of dying worms means a slightly higher chance of reaction due to the fragmenting adults and may be potentially more severe than with thiacetarsamide.
In dogs with caval syndrome, surgery is sometimes necessary if the dog's life is to be saved. In these cases the worms are extracted by inserting a long forceps through the right jugular vein into the vena cava (the large blood vessel leading to the heart) where a large number of worms are usually found. Once the dog is stable, thiacetarsamide is administered to remove any remaining worms.
Eliminating Microfilarie
When all danger of post-treatment reaction has passed, usually in 4 to 6 weeks, the elimination of microfilarie is begun. There are no approved microfilaricides available on the market but The American Heartworm Society has recommended Milbemycin oxime (INTERCEPTOR or SENTINEL) for this purpose.
Although not labeled as a microfilaricide, findings from laboratory trials indicate the regular monthly dose of milbemycin oxime that is used to prevent heartworm has significant microfilaricidal properties, and its use is recommended by the American Heartworm Society for this purpose.
In studies with heartworm infected dogs, microfilaricidal counts showed a marked decrease, with no severe reactions as a result of the microfilaricidal effects. Side effects that do occur are generally slight to moderate and can include abdominal respiration, pale mucous membranes, shock, vomiting and decreased activity.
Prevention
Heartworm prevention is the goal of every veterinarian and pet owner. Pet "wellness" has thankfully begun the transition from treatment to prevention of most common ailments facing pets today.
Once a dog has been tested for heartworm it's important that a prevention program suitable for the climate/region of the pet be put in place.
There are several preventive products on the market. Most are simple to administer, although their spectrum of activity may vary. Preventives like milbemycin oxime are effective against a broad parasite spectrum.
SENTINEL & INTERCEPTOR (Milbemycin Oxime)
Milbemycin oxime was introduced by Novartis Animal Health in 1990. Highly effective in preventing heartworm, milbemycin oxime also treats and controls adult hookworm (Ancylostoma. caninum) , adult whipworm (Trichuris Vulpis) and two types of adult roundworm (Toxascaris Leonina and Toxocara Canis) . All with one monthly dose. It is now a component of INTERCEPTOR (A monthly heartworm preventive and dewormer) and SENTINEL (A heartworm preventive combined with PROGRAM for flea control) And both of these products are GUARANTEED by Novartis Animal Health.
For more information on these products and their spectrum of activity please follow the links.
As an example, rabies is almost never encountered in domestic animals these days. A regular regime of vaccines has gone a long way to reduce the incidence of this disease. Novartis has taken this concept of prevention to improve pet wellness, and acted on it by introducing a single compound that not only prevents heartworm disease, but also deworms your dog with each monthly dose. Your pets remain parasite free and huggable all year long, and you don't need to worry about anything other than enjoying time spent with your dog. Milbemycin is safe in all breeds of dog, and in puppies as young as 2 weeks of age and 1 kg in body weight. It is available only by prescription from your veterinarian.
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