Heartworm disease, so named because the adult worms live in the right side of the heart, continues to be a major problem for many species of animals. Heartworms are spread by mosquitoes, and thus are found throughout the world. In the United States the prevalence is highest along the southeastern Atlantic and Gulf Coasts, but heartworm has been found in all 50 states. The disease is less prevalent at higher elevations.
The highest infection rates (up to 45 percent) in dogs not maintained on heartworm preventive are observed within 150 miles of the Atlantic Coast from Texas to New Jersey and along the Mississippi River and its major tributaries. Other areas of the United States have lower incidence rates (5 percent or less) of canine heartworm disease, while some regions have environmental, mosquito, and dog population factors that combine for a higher incidence of heartworm infection. The infection rate in male dogs is as much as four times that of female dogs, and dogs housed outdoors are four to five times more likely to be infected than indoor dogs.
Although there are differences in frequency of infection for various groups of dogs, all dogs in endemic regions should be considered at risk and placed on prevention programs.
Heartworm life cycle:
A knowledge of the life cycle of this parasite (Dirofilaria immitis) is needed to understand how to prevent and treat it. Infection begins when L3 infective larvae in the mouthparts of a mosquito enter the dog’s skin at the site of a bite. The larvae burrow beneath the skin and undergo two molts that eventually lead to the development of small immature worms. The first molt (L3 to L4) occurs one to 12 days after the dog is bitten by the mosquito. The larvae remain in the L4 stage for 50 to 68 days, and then molt into the L5 stage (immature worms).
It is only during the brief L3 stage, 1 to 12 days after the larvae enter the dog’s body, that they are susceptible to the killing effects of diethylcarbamazine. However, throughout the L3 and L4 stages the larvae are susceptible to three other drugs: ivermectin, selamectin, and milbemycin.
Immature worms make their way into a peripheral vein and are carried to the right ventricle and the pulmonary arteries. Approximately six months after entering the dog’s body, they mature into adults. Adults can grow to 4 to 12 inches (10 to 30 cm) long and live up to five years. As many as 250 worms may be found in a heavily infested dog.
Sexual reproduction occurs if worms of both sexes are present. Females give birth to live young called microfilaria; 5,000 microfilariae can be produced in one day by a single worm. Microfilaria are able to remain alive in the dog’s circulatory system for up to three years.
Before the microfilariae can become infective to another dog, the Li larvae must go into a secondary host, the mosquito. This occurs when the mosquito bites the dog. The LI larvae in the mosquito molt to L3 larvae. In warm southern climates this process takes less than 10 days; in northern climates it can take up to 17 days. The L3 larvae then move to the mouthparts of the mosquito and are ready to infect a new host.
When there are fewer than 50 adult worms in the average-size dog, the worms live primarily in the pulmonary arteries and the right ventricle of the heart. When the numbers are greater than 75, the worms usually extend into the right atrium. With a heavier infestation, the worms may migrate into the superior and inferior vena cavae and the veins of the liver.
Worms in the lungs can migrate into the terminal branches of the pulmonary arteries, where they obstruct the flow of blood and cause the vessels to clot. This is known as pulmonary thromboembolism. Even after treatment, dead worms can be carried by the bloodstream into the pulmonary circulation, resulting in a similar severe and sometimes fatal reaction. Chronic pulmonary thromboembolism causes loss of lung tissue and right-sided congestive heart failure. Dogs with thromboembolism may cough up bloody sputum.
Worms entwined about the heart valves can interfere with the mechanics of the heart and produce effects similar to those of chronic valvular disease.
Worm clumps in the vena cava or hepatic veins are responsible for a condition called vena cava syndrome, which causes liver failure with jaundice, ascites, spontaneous bleeding, and anemia. Collapse and death can occur in two to three days.
The signs of heartworm disease depend on the number of worms and the size of the dog. Dogs with a light infestation involving only a few worms may remain asymptomatic.
The typical early signs of heartworm infestation are tiring easily, exercise intolerance, and a soft, deep cough. As the disease progresses these symptoms become more severe and the dog loses weight, breathes more rapidly, and may cough after exercise to the point of fainting. The ribs become prominent and the chest starts to bulge. Acute vena cava syndrome or episode of thromboembolism can lead to collapse and death.
A number of blood tests are available to diagnose heartworms. The most accurate is the heartworm antigen test, which identifies an antigen produced by the adult female heartworm. False negatives occur in dogs with early infections (before the appearance of mature worms), in light infections with fewer than five adult worms, and in infections in which only males are present. False positives are rare.
Another important heartworm test is the microfilarial concentration test, in which parasites in a sample of blood are identified under the microscope. Although a positive test definitely indicates heartworms, a negative test does not rule out the diagnosis because typically 10 to 25 percent of infected dogs do not have microfilariae circulating in the peripheral blood.
Dogs with a negative microfilarial concentration test who do have heart- worms are said to be suffering from an occult infection. There are a number of explanations for occult infection. One is that the dog is receiving a heartworm preventive. Preventives kill microfilaria but not adult worms. Thus these dogs will have a positive heartworm antigen test and a negative microfilarial concentration test. Also, a dog could be infected with adult heartworms of just one sex, which means no reproduction is taking place.
There is yet another type of microfilaria that can be present in dogs tested for heartworms. It is called Dipetalonema. It is a harmless worm living under the skin. Its importance lies in the fact that its microfilaria may be mistaken for those of heartworm. This can be differentiated from heartworm microfilaria by careful examination under a microscope.
A chest X-ray is the best test for determining the severity of the infection. Dogs with a heavy burden of worms in the pulmonary artery have X-rays that show enlargement of the right ventricle and/or pulmonary arteries.
An ECG may show right ventricular enlargement and cardiac arrhythmias. An echocardiogram may show worms in the main pulmonary artery or the right ventricle. In dogs with vena cava syndrome, heartworms can be seen in the vena cava. Blood and urine samples are obtained to check for anemia and assess kidney and liver function.
Treating Heartworm Disease:
When and how to treat depends on the number of heartworms, their location, any medical complications (such as congestive heart failure or liver or kidney disease), the age and condition of the dog, and the presence of circulating microfilariae. After a thorough medical examination, your veterinarian will discuss these options and recommend a treatment program based on the findings.
For dogs with uncomplicated heartworm disease, the objectives are to eliminate all adult worms, kill the microfilariae (if present), and initiate preventive measures. At the same time, it is important to avoid complications associated with drug toxicity and the passage of dead worms into the lungs. Some veterinarians may choose to reduce the microfilaria numbers first, then go after the adult worms.
If you and your veterinarian decide to eliminate the adult worms first, the first step in dealing with uncomplicated heartworm infection is to administer an agent that will poison the worms. Two drugs that are FDA-approved and commonly used are thiacetarsamide (Caparsolate) and melarsamine (Immiticide). Both contain arsenic. Caparsolate is given intravenously twice a day for two days. Significant toxic reactions can occur, and include loss of appetite, vomiting, diarrhea, jaundice, kidney failure, and death. Caparsolate does not always kill all the worms. Immature worms, especially females, are relatively resistant. Treatment with Caparsolate must be followed by treatment for microfilaria. The drug is not safe to use on high-risk dogs with congestive heart failure, liver failure, or kidney impairment.
Immiticide eliminates more than 90 percent of worms, making it more effective than Caparsolate. It has a higher margin of safety and can be given to dogs at high risk. Immiticide is given by intramuscular injection once a day for two days. If the dog is severely debilitated by heartworms, the drug can be given in divided doses 30 days apart. Complications are similar to those of Caparsolate, but occur less often. Both drugs can cause a local reaction at the site of injection. Thromboembolism is a complication associated with the death of adult worms, and can occur with either drug.
Approximately 10 percent of dogs are poor candidates for immediate drug treatment because of severe pulmonary artery infestation and congestive heart failure. These dogs will benefit from complete rest and confinement for a minimum of two to three weeks before and after drug therapy. Aspirin, a mild anticoagulant, is given to help prevent respiratory failure due to worm thromboembolism.
Elderly dogs with heartworms are at high risk of death from therapy to kill the adult worms. Some old dogs may be better off without treatment. An acceptable alternative is to restrict exercise and administer a low dose of aspirin daily to prevent further damage to the lungs. Give the dog a monthly heartworm preventive to prevent new worms from being acquired.
Surgical removal of worms is reserved for critically ill dogs with vena cava syndrome who are not candidates for drug therapy because of the risk of liver failure or thromboembolism. To remove the worms this way, an incision is made over the jugular vein in the neck. The vein is opened and a long grasping instrument is passed down through the superior vena cava into the right atrium and the inferior vena cava. The worms are grasped one by one and removed. The procedure requires X-ray equipment and special skills. Residual worms are eliminated with drug therapy after the dog improves.
A heartworm antigen test should be performed three to five months after drug therapy. If all worms have been eliminated, the test will be negative. If the test is positive, consider retreatment.
The next step is to kill circulating microfilaria. This step is omitted if parasites are not found on a microfilaria concentration test. Most veterinarians wait four weeks to allow the dog to recover from the effects of killing the adult worms before beginning therapy to kill the microfilaria. Currently there are four drugs used – although none is licensed for this purpose. They are ivermectin, selamectin, moxidectin, and milbemycin. Ivermectin is considered the most effective and has the fewest complications, except in dogs with drug sensitivity.
Currently many veterinarians choose to simply give the monthly preventive drugs to dogs with circulating microfilaria, knowing that the microfilaria will slowly die off over six to nine months. Since the dogs are heartworm carriers during that time, they should be kept indoors during times of high mosquito activity and wear bug repellant when outside.
If the veterinarian decides the microfilaria must be eliminated as quickly as possible, the dog is admitted to the hospital on the morning of treatment. Ivermectin is given orally and the dog is observed for 10 to 12 hours for signs of toxicity, including vomiting, diarrhea, lethargy, weakness, and shock. Most reactions are mild and respond to intravenous fluids and corticosteroids. Shock and death have occurred in Collies, Shetland Sheepdogs, Australian Shepherds, Old English Sheepdogs, and other herding breeds and their crosses with the genetic defect that allows these drugs to pass into the brain. Ivermectin should not be used in these dogs.
Dramatic declines in microfilaria counts occur over the next few days. Ninety percent of dogs are free of all microfilaria at three weeks. At this time the dog should return for a microfilaria concentration test. If positive, the protocol is repeated. If negative, begin heartworm prevention.
A positive microfilaria concentration test after two treatments strongly suggests that adult worms are still present in the dog. Confirm this with a heartworm antigen test and treat accordingly.
As the previous section on treatment illustrates, treating a heartworm infestation is difficult and dangerous. It is far easier and more effective to prevent the problem in the first place. In theory, the best way to prevent heartworms is to keep your dog from being bitten by a mosquito. Unfortunately, preventing mosquito bites can never be 100 percent effective. Dogs can be reasonably protected if they remain indoors in the late afternoon and evening, when mosquitoes are feeding.
Areas of most frequent heartworm infestation are along coastal regions, where swamps or other brackish water provide ideal conditions for mosquitoes to breed. Since mosquitoes have a flight range of one quarter mile, spraying around the yard and kennel and removing standing water can be partially effective, but they will never eliminate the threat.
If you live or travel with your dog in an area where heartworm is endemic, your dog should be on a heartworm prevention program. Ask your veterinarian about local prevalence and follow their recommendations for prevention. Most dogs should be on a heartworm preventive program.
A prevention program should be started at 6 to 8 weeks of age in endemic areas, or as soon thereafter as climate conditions dictate. In the Deep South, where mosquitoes are a year-round problem, dogs should be kept on preventive drugs all year long. In areas where it is not necessary to administer the drug year round, start one month before the mosquito season and continue one month beyond the first frost (generally from May or June to November or December). Heartworm prevention is important for the dog’s whole life. Some owners may elect to give heartworm preventives year round for zoonotic parasite protection and to reduce the risk of breakthrough heart-worm disease in case they miss a monthly dose. All dogs 7 months and older should have an antigen test for heartworms before starting a prevention program. If the test is positive, a microfilaria concentration test should be performed. The antigen test should be repeated annually or as frequently as your veterinarian recommends – even if the dog is on a heartworm prevention pro- gram. Many heartworm preventives can cause illness if given to a dog with circulating microfilaria.
There are a number of drugs currently in use as heartworm preventives. They include ivermectin (Ivomec, Heartgard), milbemycin oxime (Interceptor), and selamectin (Revolution).
Heartgard is an effective preventive that is given once a month. This drug acts on the L4 larvae. It has the advantage that dogs do not have to be heart-worm-free to initiate therapy; dogs infected for as long as two months before treatment will not develop heartworms. If a monthly dose is missed, restart the drug and obtain a heartworm antigen test seven months later. Heartgard is marketed in chewable tablets of different sizes, depending on the weight of the dog. The recommended dose is generally considered to be safe to use on Collies and other herding breeds. However, with safer alternatives available, most owners avoid this for the breeds with the genetic defect that causes sensitivity to ivermectin.
Heartgard Plus is a popular chewable tablet that combines ivermectin with pyrantel pamoate. This combination prevents heartworms and also controls roundworms and hookworms.
Interceptor (milbemycin oxime) is another orally administered once-a-month heartworm preventive that also acts on the L4 larvae. Like Heartgard, this drug is marketed in different dosages based on the weight of the dog. Interceptor also controls hookworms, roundworms, and whipworms. This drug is safer to use on Collies and Collie crosses.
The injectable form of ProHeart, called ProHeart 6, was considered to provide protection for six months. However, it has been removed from the market due to potential side effects. The FDA is still considering a final decision about this medication.
Selamectin (Revolution) is a once-a-month liquid heartworm preventive applied to the skin of the dog’s neck between the shoulder blades. It is available from your veterinarian in premeasured doses based on the dog’s size and age. A principal advantage of selamectin is that it also controls adult fleas and prevents flea eggs from hatching for one month. In addition, it treats ear mites and the mites that cause scabies.
Diethylcarbamazine (DEC) has proven over many years to be extremely safe and effective when given daily. It is less convenient than the drugs just described, and unlike them it does not protect if two or three days are missed. DEC is currently unavailable because so many dog owners have switched to the convenient monthly medications. If it should become available again, the following precautions must be taken.
Dogs over 6 months of age must be tested for microfilaria before starting on DEC. If microfilaria are found in the blood, the drug should not be given because anaphylactic reactions of varying severity, including death, may develop.
DEC kills L3 infective larvae before they molt to L4. Since molting can occur in as little as 24 hours, DEC must be given daily to be effective. If more than two days of treatment are missed, stop the drug and consult your veterinarian for further instructions.
Medications containing DEC have an extremely bitter taste and need to be mixed with flavoring agents to be given in chewable form.
Some breeds show an increased susceptibility to the potential toxicity of ivermectin and similar drugs. In these dogs, there is a defect of the gene MDR-1. This is a multidrug transporter gene that influences the movement of drugs across the blood brain barrier. Dogs who are homozygous for this autosomal recessive trait will have severe, potentially fatal reactions to some drugs, including ivermectin. Dogs who are heterozygous may be able to safely take the medications, but may pass on the defective trait to their offspring.
A genetic test for this defect is available through Washington State University’s Veterinary Laboratory of Clinical Pharmacology. A cheek swab can be sent to determine if your dog has the gene. This testing is recommended for Collies, Border Collies, Shetland Sheepdogs, Australian Shepherds, Old English Sheepdogs, and longhaired Whippets. In breeds such as the Collie, more than 70 percent of the dogs tested are either homozygous for this defect or carry it.