Dirofilaria immitis
Dirofilaria immitis, also known as heartworm or dog heartworm, is a parasitic roundworm that is a type of filarial worm, a small thread-like worm, and which causes dirofilariasis. It is spread from host to host through the bites of mosquitoes. Four genera of mosquitoes transmit dirofilariasis, Aedes, Culex, Anopheles, and Mansonia. The definitive host is the dog, but it can also infect cats, wolves, coyotes, jackals, foxes, ferrets, bears, seals, sea lions and, under rare circumstances, humans.
Adult heartworms often reside in the pulmonary arterial system as well as the heart, and a major health effect in the infected animal host is damage to its lung vessels and tissues. In cases involving advanced worm infestation, adult heartworms may migrate to the right heart and the pulmonary artery. Heartworm infection may result in serious complications for the infected host if left untreated, eventually leading to death, most often as a result of secondary congestive heart failure.
Course of infection
Heartworms go through several life stages before they become adults infecting the pulmonary artery of the host animal. The worms require the mosquito as an intermediate host to complete their lifecycles. The rate of development in the mosquito is temperature-dependent, requiring about two weeks of temperature at or above 27 °C. Below a threshold temperature of 14 °C, development cannot occur, and the cycle is halted. As a result, transmission is limited to warm weather, and duration of the transmission season varies geographically. 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 pulmonary arteries takes six to seven months in dogs and is known as the "prepatent period".The first larval stage and second larval stage of heartworm development occurs within the body of a mosquito. Once the larvae develop into the infective third larval stage, the mosquito locates and bites a host, depositing the larvae under the skin at the site of the bite. After a week or two of further growth, they molt into the fourth larval stage . Then, they migrate to the muscles of the chest and abdomen, and 45 to 60 days after infection, molt to the fifth stage. 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 three to four months, they increase greatly in size. The female adult worm is about 30 cm in length, and the male is about 23 cm, with a coiled tail. By seven months after infection, the adult worms have mated and the females begin giving birth to live young, called microfilariae. Heartworms can live for 5 to 7 years in a dog.
The microfilariae circulate in the bloodstream for as long as two years, and are ingested by bloodsucking mosquitos, where development occurs and the cycle repeats.
Clinical signs of infection in dogs
Dogs show no indication of heartworm infection during the six-month 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 aberrant sites, such as the eye, brain, or an artery in the leg, which results in unusual symptoms such as blindness, seizures, and lameness, but normally, until the larvae mature and congregate inside the heart, they produce no symptoms or signs of illness.Many dogs show little or no sign of infection even after the worms become adults. These animals usually have only 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 during or after exercise, and exercise intolerance. In the most advanced cases where many adult worms have built up in the heart without treatment, signs progress to severe weight loss, fainting, coughing up blood, and finally, congestive heart failure.
There are four different classes of symptoms:
- Class 1 – no or mild symptoms with occasional cough.
- Class 2 – mild symptoms with occasional cough and tiredness after moderate activity.
- Class 3 – more severe symptoms, including a generally sick appearance, persistent cough, difficulty breathing, and tiredness after mild activity. Heart and lung changes may be seen with a chest x-ray.
- Class 4 – also called caval syndrome. The blood flowing back to the heart is blocked due to the large mass of worms. This is life-threatening and the only treatment option is surgery.
Role of ''Wolbachia pipientis''
Diagnosis in dogs
Microfilarial detection is accomplished by the using one of the following methods:Direct blood smear
A blood sample is collected and viewed under the microscope. The direct smear technique allows examination of larval motion, confirming the presence of microfilaria. It also helps in the distinction of D. immitis from Acanthocheilonema reconditum. This distinction is important because the presence of the latter parasite does not pose a health risk to the host. D. immitis usually has stationary body movement, while A. reconditum has progressive movement. However, this method often misses light infections because only a small amount of blood sample is used.Hematocrit tube method
This method uses a microhematocrit filled with a blood sample that has been centrifuged, separating the plasma from the red blood cells. These layers are divided by the buffy coat. The buffy coat consists of the leukocytes and platelets that are in the sample. The tube is snapped at the buffy coat and added to a slide for microscopic examination. Adding methylene blue stain to the sample may allow greater visibility of any microfilariae. However, the hematocrit tube method will not allow for species differentiation.Modified Knott's test
The modified Knott's test is more sensitive because it concentrates microfilariae, improving the chance of diagnosis. A blood sample is mixed with 2% formalin and centrifuged in a tube. The supernatant is removed and methylene blue stain is added to the pellet remaining in the tube for microscopic examination. It allows microfilariae species differentiation based on morphology. Microfilariae can be differentiated between D. immitis and Acanthocheilonema reconditum because of small differences in morphology. The Modified Knott's test is the best method of visual examination when determining presence of microfilaria because it preserves their morphology and size. It is easy to perform, quick, and inexpensive.The potential for a microfilaremic infection is 5 – 67%. The number of circulating microfilariae does not correlate with the number of adult heartworms, so is not an indicator of disease severity.
Antigen testing
In most practices, antigen testing has supplanted or supplemented microfilarial detection. Combining the microfilaria and adult antigen test is most useful in dogs receiving diethylcarbamazine or no preventive. Up to 1% of infected dogs are microfilaria-positive and antigen-negative. Immunodiagnostics to detect heartworm antigen in the host's blood are now regularly used. They can detect occult infections, or infections without the presence of circulating microfilariae. However, these tests are limited in that they only detect the antigens released from the sexually mature female worm's reproductive tract. Therefore, false-negative results may occur during the first five to eight months of infection when the worms are not yet sexually mature. The specificity of these tests is close to 100%, and the sensitivity is more than 80%. A recent study demonstrated a sensitivity of only 64% for infections of only one female worm, but improved with increasing female worm burden. Specificity in this study was 97%. False-negative test results can be due to low worm counts, immature infections, and all-male infections.X-rays
X-rays are used to evaluate the severity of the heartworm infection and develop a prognosis for the animal. Typically, the changes observed are enlargement of the main pulmonary artery, the right side of the heart, and the pulmonary arteries in the lobes of the lung. Inflammation of the lung tissue is also often observed.Treatment in dogs
If an animal is diagnosed with heartworms, treatment may be indicated. Before the worms can be treated, however, the dog's heart, liver, and kidney function must be evaluated to determine the risks of treatment. Usually, the adult worms are killed with an arsenic-based compound. The currently approved drug in the US, melarsomine, is marketed under the brand name Immiticide. It has a greater efficacy and fewer side effects than the previously used drug thiacetarsamide, sold as Caparsolate, which makes it a safer alternative for dogs with late-stage infections.After treatment, the dog must rest, and exercise is to be heavily reduced for several weeks so as to give its body sufficient time to absorb the dead worms without ill effect. Otherwise, if the dog is under exertion, dead worms may break loose and travel to the lungs, potentially causing respiratory failure and sudden death. According to the American Heartworm Society, the administering of aspirin to dogs infected with heartworms is no longer recommended due to a lack of evidence of clinical benefit, and aspirin may be contraindicated in several cases. Aspirin had previously been recommended for its effects on platelet adhesion and the 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 and no surviving worm is detected, the treatment is considered a success, and the patient is effectively cured.
Surgical removal of the adult heartworms as a form of treatment may also be indicated, especially in advanced cases with substantial heart involvement and damage.