heartworm prevention. This method is inferior to adulticide therapy, but may be used if no other options are available. “Slow-kill” heartworm treatment The “slow-kill” method of heartworm treatment involves placing dogs on monthly macrocyclic lactone therapy, without the use of adulticidal therapy. Continuous ivermectin administration for a period of two to three years has been shown to be nearly 100% effective in eradicating infections consisting of young adult heartworms (American Heartworm Society, 2014). Although this treatment is convenient and affordable, it does carry risks. Heartworms treated via the “slow-kill method” die gradually over a period of years, causing further, irreversible damage to the cardiopulmonary system prior to death (Adolph, 2015). Also, the period for exercise restriction is unknown. For many owners, it is impractical to restrict exercise for a period of two to three years. For these reasons, the “slow-kill” method of heartworm treatment should only be attempted when patient age, concurrent medical problems, or owner financial constraints prohibit adulticide treatment. Finally, while some clients and veterinarians feel, based on previous experience, that this method kills adult worms relatively quickly, recent information has called that into question. Many of the dogs that test negative on antigen tests while on heartworm prevention may not truly be free of heartworms, due to antigen-antibody complexes. This phenomenon can complicate diagnosis and decrease the likelihood of these dogs receiving appropriate treatment. Approximately 50% of dogs receiving monthly macrocyclic lactone therapy in the absence of appropriate adulticidal treatment will test negative for heartworms, yet be positive when samples are heat-treated (Drake, 2015). Therefore, it is important to remember that even dogs who test negative after a year of “slow-kill” treatment should still be regarded as having heartworm disease. Adulticide therapy The recommended treatment for adult heartworms is melarsomine. This is the only FDA- approved adulticide. Melarsomine is administered via a series of injections in the epaxial muscles, between the 3rd and 5th lumbar vertebrae. These injections should be initiated as soon as heartworm infection is detected, in order to minimize cardiac and pulmonary effects. Common side effects of melarsomine include mild injection-site swelling and discomfort, but these effects can be minimized with correct delivery. Injections should be administered deep in the muscle belly. Additionally, a new needle should be used for administration, instead of using the same needle that had been used to draw up the injection (American Heartworm Society, 2014). Additionally, corticosteroids or non-steroidal anti- inflammatory drugs may be used to minimize inflammation and discomfort. Melarsomine can be administered in either of two dosing methods: ● Standard two-dose protocol : The standard melarsomine dosing protocol involves two injections of melarsomine (2.5 mg/kg IM in the epaxial muscles), given 24 hours apart. Advantages of this protocol include its low cost, brief period of exercise restriction, and rapid clearance of adult heartworms. Disadvantages of the standard two-dose protocol include a low efficacy, with approximately 70% of dogs clear of heartworms after one two-dose treatment. This method is commonly used for shelter dogs and many dogs seen in general practice. Although this method is far superior to the “slow-kill” method, it is no longer regarded as the most effective method of heartworm treatment (Atkins, 2014). ● Split-dose protocol : This protocol is currently recommended for all dogs, but is considered especially important for dogs who are severely affected with heartworm disease or those at high risk for pulmonary thromboembolism. In this protocol, a patient first receives a single dose (2.5 mg/kg
IM in the epaxial muscle) of melarsomine. This single dose kills approximately 50% of the adult worms, allowing a small reduction in worm burden without a massive die-off. One month later, the patient returns for two additional doses of melarsomine (2.5 mg/kg IM in the epaxial muscles) 24 hours apart, to clear the remaining adult heartworms (Atkins, 2014). The split dose protocol is considered superior to the standard adulticide protocol, because a more gradual worm die-off decreases some of the pathological effects of heartworm death. A 2014 study compared cardiopulmonary biomarkers in dogs treated with the standard two- dose protocol and dogs treated with the split-dose protocol and found that dogs treated with the split-dose protocol showed lower levels of D-dimer, indicating a lesser degree of pulmonary thromboembolism (Carretón, 2014). Microfilaricidal therapy Although adulticide treatment kills the adult heartworms, microfilaricidal treatment still must be performed to kill circulating microfilariae. Traditionally, microfilaricidal therapy has been initiated 4-6 weeks after adulticide administration. Recently, it has been advocated to begin microfilaricidal heartworm prevention prior to adulticide treatment. This recommendation is based on the fact that melarsomine is less effective against young adult worms. In theory, this could lead to incomplete clearance of young adult heartworms and be a cause of treatment failures. Administering a macrocyclic lactone for two months prior to initiating adulticide treatment can reduce new infections and allow young adult worms to mature to a stage where they will be more susceptible to melarsomine (American Heartworm Society, 2014). The administration of ivermectin or milbemycin efficiently and rapidly clears microfilariae. The chances of adverse reaction are low with these products, but owners should still be cautioned to administer the medication on a day that someone will be home to observe the dog (Atkins, 2014). Wolbachia Wolbachia is a rickettsial organism that exists in a symbiotic relationship with heartworms. Wolbachia was first discovered in 1975, seen in developing D. immitis embryos under electron microscopy, but the organism was not identified until 1995. Wolbachia plays a role in allowing D. immitis to develop, thrive, and infect new hosts. When Wolbachia is eliminated, through the use of doxycycline, D. immitis is unable to thrive. Many of the adult heartworms deteriorate and die. Without Wolbachia , adult heartworms are also less capable of reproduction – they produce reduced numbers of microfilariae and these microfilariae are less infective than those produced by untreated adult heartworms (Atkins, 2014). Additionally, there is evidence that eliminating Wolbachia will stop the progression of infective larvae to adulthood when administered within the first 30 days of infection (McCall, 2008). Wolbachia is treated with doxycycline, at a dose of 10 mg/kg every 12 hours. If a dog does not tolerate this dose, doses can be reduced to 5 mg/kg every 12 hours. This therapy should be initiated as soon as possible upon detection of heartworm infection. Steroid usage Steroid usage during the course of heartworm treatment is a controversial topic, due to steroid risks and side effects. A 2014 study showed that dogs receiving prednisone during adulticide therapy demonstrate higher D-dimer levels, indicating an increased degree of pulmonary thromboembolism than dogs who did not receive prednisone (Carretón, 2014). Prednisone can, however, have an important adjunct role in the treatment of heartworm disease under certain circumstances. The use of prednisone in heartworm disease should be limited to two classes of dogs. The first class is dogs with pulmonary parenchymal complications. These complications may include allergic pneumonitis, eosinophilic granulomatosis, and pulmonary thromboembolism. Prednisone, either alone or
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