While once considered a disease limited to the southern United States, heartworm infections have now been confirmed in all 50 states. Canines, both the pet dog and some wild canids like the coyote, fox, and wolf, are considered the definitive hosts. But this parasitic, potentially deadly roundworm in the genera Dirofilaria, can also infect cats, ferrets, and other mammal species, such as raccoons, bears, sea lions, and, in rare cases, humans. Due to space limitations, most of this article will be focused on heartworm disease in the canine patient. Additional details can be found on the website for the American Heartworm Society (AHS) (www.heartwormsociety.org). Lifecycle Dirofilaria immitis, the causative agent for canine heartworm disease, is transmitted by the mosquito. There are nearly two-dozen species of mosquitoes that can act as a vector for heartworms. The cycle begins when one of these mosquito species takes a blood meal from an infected host. Only the female mosquito bites and is capable of transmitting the parasite. The environment plays a critical role in this lifecycle, as specific temperatures and humidity are essential for supporting mosquito populations. In addition, the ambient environmental temperatures must be high enough to permit the microfilaria to mature within the mosquito from the ingested larval stage (L1) through the L2 molt, and eventually to the infective L3 stage, which is then transmitted to the next host via the bite from the infected mosquito. This process takes approximately 10 to 14 days and is temperature dependent. Climate change, a mobile society, and global warming has led to northerly spread of this disease, as just a few decades ago heartworm was not seen in northern climes. Although heartworm transmission has not been documented in Alaska, there are microclimates in the center of the state where the conditions are favorable for potential mosquito transmission. As mentioned, heartworm has been documented in the state as a result of heartworm-positive animals that have been relocated from outside endemic regions. Under the right conditions, these translocated animals can act as a source of potential spread of the disease even in remote, northern places like Alaska. Depending on the geographic location, heartworm transmission does decrease (and cease in some locales) during the colder winter months. That stated, the presence of some natural and manmade microclimates in these cooler regions, specifically in urban areas, can keep the door open to possible transmission even over the winter. The lifecycle of D. immitis can range from seven to nine months. After the initial development of the infective stage within the mosquito intermediate host, the next phase begins when the mosquito takes its next blood meal and passes on the infective L3 larva. Once the L3 is injected into the skin of the new definitive host (the canine) the L3 molts to the L4 stage between three to 14 days later. The final molt into the immature adult form, where they are now migrating through the host’s body, occurs between 50 and 70 days, ultimately reaching the host’s pulmonary arteries. At this stage, the young worms are typically 2.5-4 cm in length. Mature female heartworms can reach lengths of 25-30 cm. The worms reach sexual maturity around four months post infection. As early as six months circulating microfilaria can be found, but this typically does not occur until the seventh to ninth month. As the worm burden increases with size and time, the location of the worms, which start out in the smaller pulmonary arteries, progresses to the main pulmonary artery, the right ventricle, right atrium and eventually into the vena cava; where they cause the Caval Syndrome. This is an acute occurrence which rapidly leads to hemolysis, inhibition of blood flow, organ failure, and death. 2019 United States heartworm incidence map.Image courtesy AHS Signs of heartworm disease In early stages many dogs will be asymptomatic. A common question from owners of asymptomatic heartworm-positive dogs is whether or not it is safe to anesthetize them for elective procedures, such as spays or neuters. The answer is yes—providing they are truly asymptomatic. If it is decided to treat positive animals first, then it is best to wait at least six months post-adulticide therapy before any procedures are performed. As the worm burden grows in size, the number of symptoms will start to increase. Typical signs are those commonly seen in cardiac disease: subtle coughing, fatigue, exercise intolerance, hyporexia, and weight loss. As the disease progresses, fulminant heart failure can ensure showing symptoms, such as cyanosis and ascites. With Caval Syndrome, the patient may exhibit labored breathing, ashen mucous membranes, hemoglobinuria, and cardiovascular collapse. Diagnosis of heartworm disease It is always best to prevent rather than treat disease. Prevention will be covered in detail later. Identifying the disease early on is also preferable than waiting until there are severe clinical signs. That said, AHS recommends annual testing of all dogs older than seven months with both an antigen and microfilaria test. Heartworm antigen and microfilaria are not detectable for the first five to six months post-infection, hence, the reason to wait until the patient is at least seven months old. Diagram showing the cycle of how Dirofilaria immitis spreads in dogs. (Click to enlarge.) Microfilaria are tested for using the Modified Knott’s Test, a blood smear or a spun microhematocrit tube. All of these are easily done in the clinic setting. Testing protocols and details are found on the AHS website. Note the most accurate of these tests is the Modified Knott’s test. It is generally recommended to do at least a Knott’s test and a smear when screening for microfilaria. The Knott’s test is also the preferred test to differentiate between the pathogenic D. immitis and nonpathogenic species such as Acanthocheilonema [Dipetalonema] reconditum. The antigen test detects proteins secreted by the mature female D. immitis worm. These tests are highly accurate and specific, approaching 100 percent, in detecting heartworm disease, even when it is occult—meaning there is at least one adult female worm present, but no microfilaria. The male worm is not detectable via antigen testing. All positive antigen tests should be confirmed with microfilaria screening such as with a Modified Knott’s Test, or using a different type of antigen testing prior to starting a patient on adulticide therapy. Be aware a negative antigen test does not guarantee a dog is truly heartworm-free. It means that antigen was not detected in that sample. This can happen if the females are immature at the time of testing, or there is a “male-only” infection. In addition, if the in-house antigen test kit instructions are not followed exactly, it is possible to get false negative results. The AHS recommends yearly testing for all dogs, even if they are on regular preventives. Additional or ancillary heartworm diagnostics Radiography and echocardiography are excellent adjunctive diagnostic aids. Common radiographic findings include enlarged, tortuous peripheral intra- and interlobar branches of the pulmonary arteries. Parenchymal changes may accompany vascular pathology and as the disease progresses, right heart enlargement, enlargement of the main and peripheral pulmonary arteries, and typical changes associated with right heart failure such as hepatomegaly, loss of serosal detail in the abdomen, and ascites. An experienced sonographer may be able to pick up heartworms due to their highly echogenic body walls. Depending on the angle of view, “O’s” or “parallel lines” may be seen with the ultrasound in the pulmonary arteries, crossing the tricuspid valve, the right ventricle, right atrium and in severe cases, the vena cava. Treatment of heartworm disease: Wolbachia Wolbachia sp. is an obligate, intracellular, gram-negative endo-symbiotic bacteria of the filarial nematode D. immitis. It has been demonstrated that Wolbachia may contribute to the complications secondary to treatment of heartworm disease. The bacterium contains surface proteins (WSP) that induce an IgG response in the host. These WSP can trigger renal and pulmonary inflammation during adulticide therapy. Doxycycline (or minocycline if doxycycline is not available) should be administered to reduce the Wolbachia burden for at least four weeks prior to initiating adulticide therapy with melarsomine. Doxycycline is given at 10mg/kg, PO BID for four weeks. A four-week wait period post doxycycline therapy is recommended to wash out remaining WSPs and other metabolites from the dead Wolbachia prior to starting the adulticide. Adulticide therapy Table 1: AHS-recommended heartworm management protocol. (Click to enlarge.)Image reprinted courtesy AHS If the patient is clinical, showing any signs of cardiac disease, it must be stabilized and treated for that first. The goal of heartworm treatment is to help the patient return to normal and to eliminate all life stages of the parasite. That stated, the patient must be in stable condition before therapy is initiated. As soon as the patient is diagnosed, even in subclinical cases, the animal should be started on the doxycycline and its activity levels severely restricted. This limited exercise should continue throughout the treatment and six to eight weeks thereafter. In addition, a macrocyclic lactone (ML) should also be initiated. This should be given for at least two months prior to the administration of the adulticide therapy with melarsomine. The ML eliminates existing susceptible larvae and reduces new infections from arising. Once this is accomplished, the practitioner should follow closely the AHS guidelines as listed in Table 1. Pulmonary Thromboembolism is a common sequela of adulticide therapy. Pyrexia, cough, hemoptysis, and worsening of right-sided heart failure may develop anywhere from one to several weeks post treatment. Activity restriction is essential to minimizing these complications. A tapering, anti-inflammatory dose of glucocorticoids has been shown to help reduce signs of thromboembolism. There is no indication for the use of NSAID therapy pre- or post adulticide therapy as it has not been shown to be effective. Caval Syndrome Dogs with heavy worm burdens, where the parasites interfere with the tricuspid valve, can suffer from life-threatening Caval Syndrome. Patients experience passive congestion of the liver, jugular pulses, sudden onset of lethargy, hemoglobinuria, and hemoglobinemia. Death can ensue within a few days if the worms are not immediately surgically removed. This procedure can often be done with minimal sedation and local analgesia. A rigid or flexible grasping tool is inserted through the right jugular vein, preferably with fluoroscopic guidance, and as many adult worms as possible are removed. A few weeks after the patient has recovered from the procedure adulticide therapy following the AHS guidelines to eliminate any remaining worms should be initiated. Alternative therapies Some clients are ill-afforded to pursue standard protocols involving doxycycline, ML, and melarsomine plus all of the associated hospitalization costs. As a result, heartworm treatment is often attempted using long-term therapy with only macrocyclic lactones. The AHS does not recommend this protocol as the older worms are less susceptible to the drug and may take as long as two years to die off. This means the parasite burden persists and pathologic changes to the internal organs may progress. Also, during this entire time it would be imperative the patient’s activity is severely restricted. Heartworm prevention Since heartworm is a vector-borne disease, control should begin with an effort to diminish or eliminate the intermediate host—the mosquito. Environmental mosquito control is beyond the scope of this article, but pet owners should do their part in trying to eliminate places where mosquitoes like to breed—like standing water, rain gutters, old water filled tires, etc. There are commercially available repellents and ectoparasiticides that can be applied directly to the pet. Controlled laboratory studies have shown efficacy >95 percent. As stated, heartworm is present in all 50 states. The AHS recommends year-round preventives. Currently, the FDA approves four macrocyclic lactones (ML) for use in dogs: ivermectin, milbemcin oxime, moxidectin, and selamectin. The prescription of FDA-approved heartworm medications requires authorization by a licensed veterinarian. A veterinarian-client-patient relationship must exist before the prescription is written. A patient must be tested for heartworm prior to dispensing any preventives. All puppies should be started on ML by age eight weeks. If the ML is started after eight weeks, they need to be tested six months after the initial dose, then, annually thereafter. In dogs older than seven months of age, antigen and microfilaria testing is mandatory prior to starting any preventives. ML can be administered in three ways: Oral—Ivermectin and milbemycin oxime (both monthly dosing) Topical—Moxidectin and selamectin (both monthly dosing) Injectable—Slow-release moxidectin-impregnated microspheres (dosing every six to 12 months, age dependent) Considerations Heartworm is a serious and potentially deadly disease now found throughout the U.S. Fortunately, it is also a disease that is preventable, and, if diagnosed in time, treatable. Veterinary practitioners are encouraged to stay current on the latest research and recommendations regarding this disease. The best way to do this is to visit heartwormsociety.org. There is a plethora of information available to veterinarians at no charge, including information that can be shared with pet owners. In addition, there are also well-written pet owner pages that help educate and inform, making the job of the veterinarian that much easier. Veterinarians are encouraged to join the AHS. Members are entitled to more benefits and special deals. In addition, they receive a quarterly newsletter focused at the practitioner. This newsletter contains reports of published and unpublished information on current techniques and changes in heartworm disease management. Douglas R. Mader, MS, DVM, Diplomate ABVP (canine/feline), Diplomate, ABVP (reptile/amphibian), Diplomate, ECZM (herpetology), Fellow, Royal Society of Medicine, received his DVM from the University of California, Davis in 1986. In addition, he completed a residency in primate and zoo animal medicine. He is a consulting veterinarian for the Monroe County Sheriff’s Zoo, the Key West Aquarium, Dynasty Marine, the Sea Turtle Hospital, the Everglades Alligator Farm, and the Theater of the Sea. Dr. Mader is an internationally acclaimed lecturer and is on the review boards of several scientific journals. He has published numerous articles in scientific and veterinary journals, national magazines, and, is an author-editor and coeditor of three textbooks on reptile medicine and surgery. The author wishes to thank Jorge Guerrero, DVM, MSc, PhD, DACVM (parasitology), DEVPC (retired), for reviewing this manuscript.
