{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T06:54:47Z","timestamp":1792652087493,"version":"4.5.0"},"reference-count":28,"publisher":"American Veterinary Medical Association (AVMA)","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["javma"],"published-print":{"date-parts":[[2018,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n<jats:p><jats:bold>OBJECTIVE<\/jats:bold> To evaluate the safety of PO administration of a milbemycin oxime (MBO) and spinosad product to heartworm (<jats:italic>Dirofilaria immitis<\/jats:italic>)-positive microfilaremic dogs.<\/jats:p>\n<jats:p><jats:bold>DESIGN<\/jats:bold> Randomized, blinded, complete block trial.<\/jats:p>\n<jats:p><jats:bold>ANIMALS<\/jats:bold> 32 purebred Beagles with a patent heartworm infection.<\/jats:p>\n<jats:p><jats:bold>PROCEDURES<\/jats:bold> Dogs ranked by sex and microfilaria counts (range, 398 to 1,980 microfilaria\/mL) were assigned to 4 groups of 8 to receive 3 treatments PO at 28-day intervals beginning on day 0: placebo (control group) or spinosad-MBO tablets containing MBO at the upper end of the label dose range (0.75 to 1 mg\/kg [0.34 to 0.45 mg\/lb]; 1\u00d7 group) or 3 (3\u00d7 group) or 5 (5\u00d7 group) times that dose. Blood samples were collected at various points for adult heartworm antigen and Knott tests. Necropsies were performed on day 65, and recovered adult heartworms were counted.<\/jats:p>\n<jats:p><jats:bold>RESULTS<\/jats:bold> 1 control dog died from heartworm-associated complications. Other adverse events included mild, transient emesis (1 dog in each of the 1\u00d7 and 5\u00d7 groups and 3 dogs in the 3\u00d7 group). Similar adult heartworm counts (range, 13 to 41) were obtained for all 4 groups. Results of blood antigen and microfilaria tests were positive throughout the study, with 1 exception in each of the 3\u00d7 and 5\u00d7 groups. Mean microfilaria counts increased with time in the control group, whereas reductions from baseline in treated groups ranged from 61.5% to 96.4%.<\/jats:p>\n<jats:p><jats:bold>CONCLUSIONS AND CLINICAL RELEVANCE<\/jats:bold> The evaluated MBO-spinosad formulation caused no severe adverse events when administered PO to microfilaremic dogs. Although microfilaria counts decreased following treatment, repeated monthly MBO treatments were incompletely microfilaricidal, suggesting MBO should not be used as a microfilaricide.<\/jats:p>","DOI":"10.2460\/javma.252.9.1084","type":"journal-article","created":{"date-parts":[[2018,4,11]],"date-time":"2018-04-11T19:52:41Z","timestamp":1523476361000},"page":"1084-1089","source":"Crossref","is-referenced-by-count":7,"title":["Effects of milbemycin oxime, combined with spinosad, when administered orally to microfilaremic dogs infected with adult heartworms (Dirofilaria immitis)"],"prefix":"10.2460","volume":"252","author":[{"given":"Tyre","family":"Grant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Wiseman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel E.","family":"Snyder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1272","reference":[{"key":"ref1","article-title":"Current canine guidelines for the prevention, diagnosis, and management of heartworm (Dirofilaria immitis) infection in dogs","year":"2016"},{"key":"ref2","series-title":"Parasit Vectors","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1186\/1756-3305-5-138","article-title":"Heartworms, macrocyclic lactones, and the specter of resistance to prevention in the United States","volume":"5","author":"Bowman","year":"2012"},{"key":"ref3","series-title":"Vet Parasitol","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.vetpar.2015.04.002","article-title":"Macrocyclic lactone resistance in Dirofilaria immitis: failure of heartworm preventives and investigation of genetic markers for resistance","volume":"210","author":"Bourguinat","year":"2015"},{"key":"ref4","first-page":"108","article-title":"Dirofilaria immitis: 1. 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