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13 NOVEMBER/DECEMBER 2017 ■ TVPJOURNAL.COM HEARTWORM HOTLINE study, the following questions should be asked: • Are the Wolbachia completely eliminated after 1 month of doxycycline, or is further time needed? • Even if Wolbachia are killed during this 1-month time period, have the WSPs, a cause of host inflammation, been completely eliminated? • Are the clinical benefits of doxycycline dependent on the amount of time (ie, 0, 1, or 2 months) between the end of the doxycycline regimen and the first melarsomine injection? Further research is needed to answer these questions and to determine whether different doxycycline protocols are effective. CAN DOXYCYCLINE BE USED IN ALTERNATIVE TREATMENT REGIMENS? The AHS does not recommend the use of multiple doses of macrocyclic lactone heartworm preventives for adulticidal treatment of heartworm infection. 11 Nonetheless, in clinical situations where treatment with melarsomine is not feasible, doxycycline and macrocyclic lactones have been used as an alternative treatment. Only studies combining prophylactic doses of ivermectin or topical moxidectin with doxycycline have been reported in the literature. • In naturally infected dogs, administration of ivermectin (6 mcg/kg q15d for 180 days) plus doxycycline (10 mg/kg q24h) resulted in 8 of 11 (72.7%) dogs becoming antigen negative after 300 days. 10 • In an experimental study using 16 dogs (8 treated and 8 controls) that received transplanted adult heartworms, the treated dogs received topical moxidectin (2.5%) plus imidacloprid (10%) for 10 months. Doxycycline (10 mg/kg q12h) was administered concurrently during the first month of moxidectin/imidacloprid treatment. At the end of the study, dogs were necropsied. An average of 10.6 heartworms were found in control dogs compared with 0.6 heartworms in experimental dogs. Furthermore, 5 of the 8 experimental dogs had no heartworms. 14 Although these regimens have shown some efficacy, the AHS recommends melarsomine in heartworm treatment except when melarsomine administration is not feasible. These alternative treatment studies do, however, reinforce that doxycycline is extremely important in the treatment of adult heartworm infection. CONCLUSIONS AND LINGERING QUESTIONS Several important questions remain regarding the use of doxycycline in heartworm treatment: • Is minocycline a viable alternative to doxycycline ( Box 1 )? • Is a full month of doxycycline needed for it to have an effect during heartworm treatment? In other words, what is the minimum dose needed for elimination of Wolbachia from heartworms? BOX 1. Minocycline Versus Doxycycline in Heartworm Treatment Anecdotally, minocycline has been used in the place of doxycycline for treatment of heartworm, typically at the standard dose of 10 mg/kg q12h for 30 days. Although no formal studies have been published on the effect of minocycline on heartworm, efficacy has been demonstrated in vitro against a related filarial parasite. 15 Recent modeling work also suggests that minocycline will be effective as a substitute for doxycycline in the AHS treatment protocol. Papich 16 used pharmacokinetic/ pharmacodynamic analysis to determine potentially effective doses of minocycline for use in heartworm treatment. Results of this analysis suggest that a q12h dose of 5 mg/kg minocycline in dogs will have an effect on Wolbachia in heartworms. Furthermore, minocycline is more lipophilic and binds less easily to proteins, suggesting that it could have superior tissue penetration compared with doxycycline. More research is needed, but the hope is that minocycline can be used for heartworm treatment when doxycycline use is not possible for cost or availability reasons. Andy Moorhead Andy Moorhead, DVM, MS, PhD, is an associate research scientist in the Department of Infectious Diseases at the University of Georgia College of Veterinary Medicine and the director of the Filariasis Research Reagent Resource Center. He received his DVM from North Carolina State University, his MS from Purdue University, and his PhD from Columbia University. His research interests include the potential development of macrocylic lactone resistance in Dirofilaria immitis.