Heartworm: Disease, Treatment and Prevention

[sscully]

Heartworm:
Disease, Treatment, and Prevention in the Dog and Cat



LIFE CYCLE

The heartworm, Dirofilaria Immitis, is a nematode, or roundworm parasite. It is a member of the family Onchocercidae and the superfamily Filarioidea.

Adult male and female worms mate while in the heart or pulmonary arteries of an infected animal. The females give live birth to first-stage larvae, also known as microfilariae.

Heartworms have five larval stages, “L1,” through “L5”. Microfilariae are L1 stage. They can live in a canine host’s bloodstream for up to 2 years. In order to reach adulthood, however, heartworms must pass through a mosquito, where they develop into L2 and then L3 stage. The temperature must be above 57F for this development to take place. The higher the outside temperature, the faster the larvae will develop. With daily high temperatures of 80F, development from L1 to L3 stage takes around two weeks. In extremely hot climates, it can take as little as 10 days. Once at the L3 stage, larvae can infect a host.

An easy formula to discover if heartworm preventative is necessary (since preventatives work backwards) is to count the degrees above 57F reached each day. Each degree counts as a “Heartworm Development Unit”. If 234 units are reached within a 30-day period, then L3 transmission is possible and heartworm preventative must be administered.

L3s are not transmitted directly to the bloodstream by a mosquito. Instead, they are deposited in the saliva a mosquito leaves behind after biting. The larva swims through the bite into the skin. Within two weeks, it develops to L4 stage. L4s live under the skin of a dog for around 90 days before molting to L5 stage. L5s, immature adults, enter the circulatory system and migrate to the heart or the preferred pulmonary arteries where they undergo the transformation to adult worms.

Adult worms are also known as Dirofilaria Immitis and live in the pulmonary arteries or heart. They are nourished by the blood flow and can grow to over a foot in length. Average female length is 30cm and males are about 23cm with a coiled tail. The female starts producing microfilariae between 5-7 months after initial L3 stage infection. Adult worms can live in a canine host for up to seven years, and can produce thousands of microfilariae a day, who circulate the bloodstream waiting to be picked up by a mosquito.



EPIDEMIOLOGY

Heartworms are present on every continent except Antarctica. They require four conditions to establish a presence in an area:

-A susceptible host population.

-A stable reservoir of the disease.

-A stable population of the vector species.

-A climate that supports their life cycle.

Dogs are considered a host species, although the life cycle cannot complete itself in a dog and the parasite cannot be transmitted between dogs. Dogs also provide a stable reservoir of the disease. Alternate hosts are wolves, foxes, coyotes, domestic cats, ferrets, sea lions and domestic cats. Humans, beavers, bears and raccoons are aberrant, or “dead-end” hosts, meaning they can harbor larvae transmitted by a mosquito bite, but they will not develop into adult worms.

The vector species is the mosquito. More than 70 different species of mosquito can transmit heartworms.

The climate required is one that can support mosquitoes and larval development. In some cases, humans can artificially create such a climate, as has been the case in Salt Lake City and Los Angeles. The desert climate in these cities is hot enough for larval development but normally does not support mosquitoes. However people in these cities have planted trees that provide a suitable habitat for some species of mosquitoes. It has not been routine to test for heartworm or use preventative in these areas, but it’s now becoming necessary.

The southeastern and Mississippi River valley areas of the United States are where heartworm is most prevalent. In the past 30-40 years, there has been a noted increase in the prevalence of heartworm and these parasites are establishing a definite presence in new areas. Previously heartworm infections were concentrated just in the Southeast portion of the United States, but now high rates of infection are seen through the Midwest and eastern coast. This is due to several factors, including urbanization and movements of human populations along with their pets, increased overall canine population (today estimated at 40 million in the US), and the heartworm parasite adapting to wider temperature ranges and using different mosquito species as vectors.



CANINE HEARTWORM DISEASE

There is a difference between heartworm infection and heartworm disease. Heartworm infection encompasses a dog who has any stage of heartworm present in his body. A infected dog may only have microfilariae circulating, which does not cause disease or damage. However, most dogs with heartworm infection go on to develop heartworm disease.

Signs and Symptoms: A dog with heartworm disease presents with adult worms in the pulmonary arteries or heart. Worms prefer to live in the pulmonary arteries, but if there are more than about 25 worms (in a medium sized dog) they begin to back up into the right ventricle of the heart. With 50 or more worms, they begin to take over the atrium. If 100 or more worms are present, the entire right side of the heart is full, and little blood can be pumped. At this point a dog will be suffering from what is known as “Caval Syndrome” and will soon die.

Even the presence of one worm can begin to damage the pulmonary arteries. Adult worms stimulate the immune system to overproduce antibodies. The antibody response to heartworms causes inflammation and damage of sensitive tissues in the heart and pulmonary arteries. With advanced heartworm disease, antibodies can travel to and damage the sensitive membranes of the eyes, kidneys, blood vessels and joints, and also cause tremendous pain.

The lining of the artery can become damaged just days after a worm’s arrival, due to the inflammation caused by the immune system’s response. When pulmonary arteries become damaged and clogged with worms, the heart must pump faster and harder, causing a condition called pulmonary hypertension. The arteries dilate to the point where they may be visible on a radiograph, and blood flow is redirected to areas around the heart that are free of worms. Fluid begins to accumulate in around the lungs and heart. With the artery that supplies blood to the lungs partially blocked, the lungs are unable to efficiently provide oxygen to the blood.

At this point the heartworm disease is very advanced and you may see symptoms of congestive heart failure such as exercise intolerance, lethargy, coughing and trouble breathing, dull coat, a swollen abdomen and fainting spells. A non-infectious form of pneumonia can develop because of the inflammation of the lungs, called pulmonary eosinophilic granulomatosis. Arrhythmia may develop as the heart muscle hardens and fails to properly conduct electrical impulses. Symptoms appear sooner and are worse in very active dogs.

Caval Syndrome occurs when worms block the entire right side of the heart. It is usually fatal, with death occurring in one to two days. The only way to effectively treat a dog with Caval Syndrome is to surgically remove enough worms to re-establish blood flow. The worms are removed through the jugular vein using a flexible alligator forceps. In Japan, this method is very popular for treating heartworm even if a dog does not present with Caval Syndrome.

Radiographs and ultrasounds can be indicative of heartworm disease. They may show blunted pulmonary arteries and an enlarged heart. Ultrasounds can measure the thickening of the right side of the heart and in advanced cases it is possible to visualize the worms wiggling in the right ventricle or atrium.

There also appears to be an association between heartworm infection and renal disease, with renal problems clearing up after the infection is treated.

Occasionally worms migrate to sites other than the heart or pulmonary arteries. This is an ectopic infection. Common sites are the eye, central nervous system or systemic arteries, most commonly those in the rear legs. In these cases the treatment is surgical removal and adulticide treatment.


Tests:

There are several types of tests to determine heartworm infection: filter tests, microfilaria tests, antigen tests and antibody tests.

In a filter test, blood is examined under a microscope to check for live microfilariae. In order for this test to detect infection, a large number of microfilariae must be present. A dog with a small number of microfilariae circulating, or with a single-sex adult infection will test negative on a filter test.

The Difil and Knott’s tests are concentration methods to detect microfilariae. A large amount of blood is filtered or centrifuged to concentrate any microfilariae that are present.

These tests are not always accurate. Animals can have adult worms, but no microfilariae present, as in the case of single-sex infections. Further, several brands of heartworm preventative kill microfilariae but not adult worms, so if heartworm preventative is administered to an animal with an active infection, they will test negative on microfilariae tests. Heartworm is also not the only disease with microfilariae as first stage larva. A different parasite called Dipetalonema reconditum, which is transmitted by fleas, can be picked up by microfilariae tests.

Today these tests are usually done in combination with antigen or antibody testing. Many also feel that an animal who tests positive on microfilariae tests should not undergo treatment unless there is also a positive antigen or antibody test, since microfilariae infection can occur without active adult worm infection.

Antigen tests look for antigens, or foreign proteins, in the blood. Females will shed tiny pieces of skin into the bloodstream. With antigen testing, very small infections can be detected as well as some Occult Infections – when there are adult worms but no microfilariae in the bloodstream for various reasons. However, antigen testing cannot detect male-only infections and may not detect infections with one or two female worms, usually at least three must be present.

Antibody tests are the latest innovation in diagnosing heartworms. They test the body’s immune response to heartworms. Antibody tests can detect an infection sooner, as well as single-worm or male-only infections. They are very useful for cats who often only have one or two adult worms.

Testing should be performed annually for animals not on year-round heartworm prevention, who take daily heartworm prevention or if there are concerns about possible missed doses. With missed doses, there is a small possibility of an infection establishing. Dogs who are on year-round preventative should only need to be tested every two to three years.

There is no need to test animals less than seven months of age, as active infection cannot develop before then. Microfilariae can be passed from a mother to fetus, but these will not develop into adult worms unless they first pass through a mosquito. Young puppies who test positive for microfilariae are not at risk for active infection, although preventative treatment should be started.



TREATMENT

Before treatment, a dog is graded into one of four categories:

Group I: Low risk. Young, healthy dogs with minimal disease evident on radiographs, normal bloodwork and no signs of illness.

Group II: Moderately affected. Some coughing, moderate changes on radiographs, normal bloodwork.

Group III: Severely affected. Symptoms of congestive heart failure, damage visible on radiographs, bloodwork shows kidney and liver damage.

Group IV: Caval Syndrome. Collapse or shock, worms visible on ultrasound, very abnormal blood work, dark brown urine. Heartworms must be surgically removed and the dog stabilized enough to qualify for another category before adulticide treatment can take place.


Medications:

THIACETARSAMIDE (Caparsolate by Rhone) – This treatment is no longer in use. At one point it was the only effective treatment for heartworms. It is a derivative of arsenic and often had serious or fatal liver side effects. It is administered intravenously, and a severe erosive reaction occurs if it contacts tissues outside the bloodstream. It was typically given in four doses, two per day for two days. Younger and female worms were somewhat resistant and required the second course. The death of all of the worms at the same time caused abnormal clotting and inflammatory reactions. This was especially evident in the month following treatment. Dogs had to be given a chance to absorb the dead worms. Exercise restriction was very important because strenuous activity could cause a dead worm to dislodge in the lungs.

MELARSOMINE DIHYDROCHLORIDE (Immiticide by Rhone) – The development of Immiticide was a breakthrough in the treatment of heartworms. Like thiacetarsamide, it is a derivative of arsenic, but it is not toxic to the liver and is more effective at killing young and female worms. It is administered in the muscle by injection and typical treatment is two doses, 24 hours apart. An alternative protocol for dogs with large numbers of worms is to give one dose to reduce that number and follow up with the two-dose course several months later. Common side effects are muscle soreness and inflammation. Inflammatory and clotting reactions still occur when the worms die. It is also still necessary to restrict exercise for a month.

Medications to relieve inflammation may also be used. Many veterinarians prefer to use aspirin to ease inflammation during the initial treatment period. Steroids like prednisone reduce inflammation more effectively but appear to protect the heartworms.

Antigen tests should always be given 4-5 months after treatment to ensure all worms have been killed. Sometimes young female worms are resistant to treatment and another dose is required after they age.



PREVENTION

There are many different medications available to prevent heartworm, which can be prescribed by your veterinarian.

DIETHYLCARBAMAZINE (Filbartis by Pfizer) – This was the standard treatment before the advent of monthly heartworm preventative. It must be administered daily, starting immediately at the beginning of mosquito season and continuing until 60 days after the last frost. Just one or two missed doses can put a pet at risk of adult infection. DEC works by killing L3s and L4s before they develop further and migrate. It is very important to test for heartworm immediately before starting DEC because infected animals can develop a potentially fatal anaphylactic reaction. This drug itself does not target other parasites.

IVERMECTIN (Heartgard by Merial) – The development of Ivermectin was a breakthrough in heartworm prevention. Instead of daily, it is administered monthly in moist chewable tablets. It contains a very low dose of Ivermectin that is sufficient to kill any L4s in the skin. It is not truly “prevention”, rather an animal is infected but medication stops the progression of the parasite before it reaches adulthood. This drug also kills L1s and young L5s and suppresses female worm reproduction. It is safe to use in infected animals, although not yet approved by the FDA for such use, it is often used to clear L1s in animals with active infections. It is also safe for puppies and kittens 6 weeks or older, and for pregnant or lactating females.
Ivermectin also has a “reach back effect” and in studies has been shown to prevent some infections even if not used for up to four months. There is a certain grace period of 15 days, meaning it is effective for any larvae acquired in the 45 days before it is given.

Ivermectin is not strong enough to kill intestinal parasites, but it is paired with Pyrantel (Heartgard Plus) which kills hookworms and roundworms in dogs, and hookworms in cats.

Some collies and herding breeds have proven to be “ivermectin sensitive” and toxic reactions have been reported. The signs of toxicosis are salivation, dilated pupils, vomiting, tremors, ataxia, and in severe cases recumbency, weakness, or coma. . In clinical studies the dose contained in Heartgard has not caused toxic reactions in collies, but when warning were removed from the label, reactions were reported.

MILBEMYCIN OXIME (Interceptor and Sentinel by Novartis) – Sentinel and Interceptor both contain milbemycin oxime to kill heartworms, but sentinel also has lufenuron, which controls fleas, whipworms, hookworms and roundworms. It also effectively treats demodectic mange. It is administered monthly and comes in flavored tablet form. Milbemycin works by killing L3s and L4s and it also eliminates L1s. It is not approved for use in cats, but is safe for puppies over 8 weeks and pregnant or lactating female dogs. It has a probable grace period of about 2-3 weeks. However, it can cause shock if given to a dog with a high microfilariae count, so it is important to perform a test for this. There are no breed related sensitivities with milbemycin oxime.

SELAMECTIN (Revolution by Pfizer) – This drug is administered topically once a month and works by killing L4 stage larvae. It is also effective against hookworms, roundworms, ear mites, fleas, sarcoptic mange and the American Dog Tick. It is approved for use in cats, puppies and kittens 6 weeks or older, and pregnant or lactating females. It has an up to two-month grace period for heartworm infection. Selamectin is FDA approved for use in heartworm positive animals.

Selamectin is effective in about 80% of animals for treating and preventing fleas, mites, mange and intestinal parasites. However it is 100% effective in clinical studies for preventing heartworm infection.

MOXIDECTIN (ProHeart and ProHeart 6 by Fort Dodge) – Moxidectin is a derivative of ivermectin, and the same rules apply for the monthly tablet, including possible increased sensitivity in collies. It is not approved for cats or puppies under 8 weeks.

Moxidectin is also available in an slow-release injection administered by a veterinarian that gives six months of protection against heartworms and hookworms. It is not to be used in sick, underweight or otherwise compromised animals, or puppies under six months, and is not approved for cats. A higher risk of complications and side effects has been reported with ProHeart 6 than with the monthly preventatives, including anaphylactic reactions and death. The FDA is currently investigating the matter.


-There are no proven effective herbal remedies that prevent heartworm infection.




FELINE HEARTWORM

Many people do not know that heartworm infection can occur in cats. In fact, wherever dogs are infected with heartworm, cats also get the disease, but at a lesser rate (estimates are between 5-20% of the infection rate of dogs). Cats seem to react differently to the heartworm parasite and evidence suggests that heartworms are not well suited to living in a feline host. The infection is much more short-lived than in dogs- adult worms live 2-3 years and microfilariae for 2-3 weeks only. Cats also typically present with a lower worm burden, often only one or two adult worms. Ectopic infections are more common than in dogs.

Statistically, an infected cat is most likely to be between 3-6 years and male. This may be because a young male cat is more likely to roam outside where they have a higher chance of being bitten by a mosquito with the parasite.
Symptoms of heartworm in cats are coughing, weight loss, vomiting, and lethargy. Some cats die suddenly when a worm dies and becomes lodged in the lungs – heartworm may be the culprit in many sudden deaths of seemingly healthy cats.

Heartworm is difficult to diagnose in cats. Often there are few or no microfilariae circulating in the blood. Antigen testing is not reliable because of the likelihood of single-worm or male-only infections. The best test for heartworms in cats is the ELISA antibody test.

Often no direct treatment is attempted in cats with heartworm, because of the low worm load and shorter average lifespan of the adult worms. Adulticide treatments also have a high rate of complications in cats. In many cases it is best to let the cat clear the infection itself, and monitor for complications. Surgical removal of the worms is an option for cats that develop complications.

Several monthly preventative treatments are approved for cats, including Revolution and Heartgard. If you live in a high-risk area and especially if your cat goes outside, preventative may be a good choice.

[Aroura]

I live in an area with no heart worm, I've been told before, I can't remember who by, that if you give a dog heart worm tablets I think 3 days before visiting a heart worm area they will be protected. Is this right? I'm not sure of the exact information I was given. I'm taking Montie to the coast for his birthday and don't want him to pick up heartworm! :o

[TDG]

you do not need to give a dog heartworm meds in advance at all since they are not really preventives as in that they prevent infestation so it can not happen. sadly there is still no drug that has that kind of capability.

all these products do is kill off microfilariae a dog may have gotten infested with. so for example in a dog who gets a heartworm drug every 30 days, what the product does is kill off any microfilariae accummulated since the last dose was given. if there are no microfilariae present, you are essentially pumping pesticides into your dog for no reason.

here's a link to a page that compares how long different heartworm products have been on the market and how many adverse reactions (and sadly, deaths) they have caused. choose wisely what you subject your dog to. the newest products are not always the best or safest.

[url]http://www.dogsadversereactions.com/moxidectin/comparison2.html[/url]

[sscully]

Since HW preventatives really "work backwards" by preventing larvae from advancing to L5 (or immature adult) stage and migrating to the heart, you would have to give him a preventative after (preferably less than 30 days) your trip to the coast. You need a prescription for HW preventative, so your vet can advise you on the best choice. I would probably use a single Heartgard monthly tablet (they are chewable and liver flavored, most dogs like them :). The Proheart6 injection would definitely not be needed.

[TDG]

[quote name='sscully']The Proheart6 injection would definitely not be needed.[/quote]

i can not mention often enough that people should [b]not[/b] let their vet administer proheart 6., unless they are prepared to risk their pet's health and life, even if it is 6 months or a year down the road. many, many dogs have died after getting their second or third injection, showing no problems at all after the first or second.

please stick with true and tried products rather than one that has not even been sufficiently tested.
[url]http://www.dogsadversereactions.com/moxidectin/moxidectinpage.html[/url]

vets have knowingly witheld information from clients and some have even administered this injection without consent of owners, only telling them afterwards that "they don't have to worry about heartworms for 6 months now".

be educated. don't just go for the "most convenient thing". :D

[sscully]

I do not like the Proheart6 injection, although it works fine in the majority of dogs. I would not give it to my dog until a lot more is known about the actual risks. I don't have a problem remembering the monthly pills, anyway. Moxidectin doesn't seem to have the same effects when administered monthyl (Proheart tablets) so I wonder if there are some "kinks" that have to be worked out in the way the medicine is released w/ the injection. Tragically, a lot of dogs have become ill or died due to the Proheart6 injection... clinical trials can't always predict these things. It is a good concept for the pet owners who have trouble remembering the monthly pills. I hope that what specifically is causing the adverse reactions in so many dogs can be resolved, so that this option is as safe as the monthly preventatives.