Clinical application of milbemycin D as a prophylactic agent against Dirofilaria immitis infection in dogs: Reactions in uninfected and infected dogs.

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Abstract
A dose of 1 mg/kg or 5 mg/kg of milbemycin D, a new prophylactic agent for Dirofilaria immitis (heartworm), was given to 201 dogs orally and the reaction was investigated by symptomatic, hematological and biochemical examinations. Dogs were divided into 3 groups: uninfected by heartworm (unifected group), infected without circulating microfilaria (mf negative group), and infected with circulating mf (mf positive group). The incidence and degree of clinical signs were not clearly different with either dose. Vomiting and arrhythmia, which were noted to show about the same incidence in 3 groups, were seen in a total of 5 (2%) and 22 (11%) dogs, respectively. Body temperature and blood pressure fell slightly, and RBC count, serum total protein concentration, osmolality and sodium concentration were also slightly deceased 3 and/or 6 hr after administration in the uninfected and mf negative groups. Almost all of these changes remained within the normal ranges, and tended to cover 24 hr after administration. No other reactions were seen in the uninfected group. Loss of appetite, pale visible mucous membanes, shock-like reaction and dirofilarial hemoglobinuria (caval syndrome) were noted in a total of 5 (2%), 9 (5%), 9 (5%) and 8 (4%) dogs, respectively, which were seen mainly in the mf positive group. A significant decrease of circulating mf count, rise in body temperature, serum GOT, GPT and ALP activities were also observed 24 hr after administration in the mf positive group. Shock-like reaction was seen in a dog of the mf negative group, but in this case a small number of microfilariae were detected in the liver and lungs on histopathological examination. The effects of dead mf might be involved in the reaction of the mf positive group. From these results, it is considered that clinical application of milbemycin D for uninfected and mf negative dogs present no risks, but adverse reactions may occur in dogs with microfilaremia.