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heartworm infection with this protocol, providing evidence of macrocyclic lactone resistance (Pulaski, 2014). Later studies, however, have failed to confirm the presence of this resistance. Earlier studies conducted on L3 heartworm larvae from apparently resistant microfilarial isolates and heartworm larvae from nonresistance microfilarial isolates show similar macrocyclic lactone susceptibility in vitro (Moorhead, Evans, & Wolstenholm, 2011). These findings underscore the current controversy and need for further research on the topic of macrocyclic lactone resistance. It has been documented that some currently used macrocyclic lactones have single-dose efficacy of less than 100% (Snyder, 2011). Due to genetic variation seen in heartworms, even a Frequently asked questions about heartworm disease I have a heartworm-positive patient who needs to be spayed. Is it safe to spay her, even if her owner declines adulticide treatment for heartworms? Yes, it is safe to go ahead with surgery if she is exhibiting little to no clinical signs. A 2014 study demonstrated no increase in perioperative complications in heartworm-positive dogs, with only mild signs of heartworm disease, assuming that cardiovascular-sparing drugs are used (Peterson et al., 2014). If a dog is showing signs of more advanced heartworm disease, elective surgical procedures should be avoided until adulticidal treatment has been performed. Are heartworms a public health concern? Yes. Although the number of reported human cases is low, heartworms are a public health concern. In the last fifty years, over 100 human cases of pulmonary dirofilariasis have been reported. Pulmonary dirofilariasis in humans results in nodular lung inflammation. These nodules may be mistaken for lung tumors or tuberculosis on thoracic x-rays, leading to unnecessary surgery in affected individuals. Additionally, aberrant location has resulted in human infections involving the eye, skin, testicle, and other tissues. Reducing the risk of human heartworm disease involves the use of mosquito repellants and protective clothing, as well as reducing the prevalence of heartworm infection in the local dog population (Companion Animal Parasite Council, 2016). Conclusion Heartworm is a significant infection that poses a risk for dogs throughout the United States. Ideally, all dogs should remain on year-round heartworm prevention to prevent heartworm infection. Additionally, these dogs should receive annual antigen and microfilarial tests, so that any cases of heartworm References Š Adolph, C. (2015). Canine Heartworm Disease: Where Are We in 2015? Atlantic Coast Veterinary Conference. Atlantic City, NJ. Š American Heartworm Society. (2013). Heartworm Incidence. Retrieved June 4, 2019 from https://www.heartwormsociety.org/images/incidence- maps/IncidenceMap2013.pdf. Š American Heartworm Society. (2014). Current Canine Guidelines for the Prevention, Diagnosis and Management of of Heartworm (Dirofilaria immitis) Infection in Dogs. Retrieved June 4, 2019 from https://www.heartwormsociety.org/images/pdf/2014-AHS- Canine-Guidelines.pdf. Š Atkins, C. (2012). Treating Heartworm Infection: Ancillary Corticosteroid Therapy in Dogs. Today's Veterinary Practice , Nov/Dec: 85-87. Š Atkins, C. (2014). Heartworm "lack of effectiveness" claims in the Mississippi delta: computerized analysis of owner compliance 2001–2011. Veterinary Parasitology , 206(1- 2):106-13. Š Atkins, C. (2015). Canine Heartworm Disease - What Has Changed? American College of Veterinary Internal Medicine Forum. Indianapolis, IN. Š Blagburn, B. (2013). Heartworms and Heartworm Disease: They Will Find a Way to Fool You! Atlantic Coast Veterinary Conference. Atlantic City, NJ. Š Bowman, D. (2013). The Great Heartworm Resistance Controversy. Western Veterinary Conference. Las Vegas, NV. Š Companion Animal Parasite Council. (2016). CAPC Recommendations: Canine Heartworm. Retrieved June 4, 2019 from http://www.capcvet.org/. Š Drake, J. (2015). False negative antigen tests in dogs infected with heartworm and placed on macrocyclic lactone preventives. Parasites and Vectors , 8:68.

small number of heartworm larvae with the ability to tolerate heartworm prevention could contribute to a resistance issue. It is also important to note that canine heartworm preventions were designed to stop infection by D. immitis by killing third- stage larvae (L3), as well as young and maturing fourth-stage larvae (L4). At no point in their testing or development are these drugs expected to suppress microfilaria. If heartworm preventions are given at labelled doses to dogs infected with adult heartworms (i.e., the “slow-kill” method), microfilariae may still survive this treatment. These microfilariae, which have been drug-selected for macrocyclic lactone resistance, will then be able to be transmitted to other dogs, leading to macrocyclic lactone resistance (Bowman, 2013). What is reach-back? Reach-back is a term used to describe the efficacy of heartworm prevention against young heartworms. Continuous monthly administration of ivermectin for 12-14 months has been demonstrated to be highly effective against 3- and 4-month-old heartworms, meaning that the risk of even four missed doses can be mitigated by consistent dosing for a one-year period following the missed dose. Additionally, continuous monthly administration of ivermectin for 18 months has been shown to be 56% effective against 8-month-old heartworms, providing some protective benefit after even an eight-month lapse in prevention (McCall et al., 2001). Other products have similar reach-back benefits, though less pronounced than ivermectin. Milbemycin oxime, for example, is approximately 50% effective against 3- and 4- month old heartworms when administered continuously for one year, while only one or two doses of milbemycin is nearly 100% effective against 2- month old heartworms. Selamectin is highly effective against heartworms up to three months post-infection, when used continuously for one year. Moxidectin is approximately 90% effective against heartworms up to four months post-infection. These statistics demonstrate varying reach-back effects between products, but show that a single missed dose of any given product is unlikely to be of clinical relevance as long as doses are not missed regularly (McCall, 2008) infection can be promptly detected and treated. When treating heartworms, the split-dose adulticide treatment protocol is optimal, in conjunction with microfilaricidal treatment and doxycycline treatment initiated two months prior to adulticidal therapy. Š E Carretón, R. M.-M.-A. (2014). Evaluation of cardiopulmonary biomarkers during classic adulticide treatment versus the American Heartworm Society recommended treatment protocol in dogs infected by Dirofilaria immitis. Veterinary Parasitology , 206(1-2):55-9. Š McCall, J. (2008). Heartworm and Wolbachia: Therapeutic implications. Veterinary Parasitology , 158:204-214. Š McCall, J., Guerrero, J., Roberts, R., Supakorndej, N., Mansour, A., Dzimianski, M., & McCall, S. (2001). Further Evidence of Clinical Prophylactic, Retroactive (Reach Back) and Adulticidal Activity of Monthly Administrations of Ivermectin (Heartgard PlusTM) In Dogs Experimentally Infected with Heartworms. Recent Advances in Heartworm Disease Symposium. Š Moorhead, A., Evans, C., & Wolstenholm, A. (2011). In vitro bioassay for measuring anthelmintic susceptibility in Dirofilaria immitis [abstract]. Procedings AAVP 56th Annual Meeting , (p. 109). Š Peterson, K., Chappel, D., & Lewis, B. (2014). Heartworm-positive dogs recover without complications from surgical sterilization using cardiovascular sparing anesthesia protocol. Veterinary Parasitology , 206(1-2):83-85. Š Pulaski, C. (2014). Establishment of macrocyclic lactone resistant Dirofilaria immitis isolates in experimentally infected laboratory dogs. Parasites and Vectors , 7:494. Š Snyder, D. (2011). Assessment of the effectiveness of a combination product of spinosad and milbemycin oxime on the prophylaxis of canine heartworm infection. Veterinary Parasitology , 180(3-4):262–266. Š Velasquez, L. (2014). Increased prevalence of Dirofilaria immitis antigen in canine samples after heat treatment. Veterinary Parasitology , 206(1-2):67–70.

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