Blocking Dirofilaria immitis transmission by treatment of heartworm microfilaremic dogs with doxycycline

Abstract Background This study was conducted to determine whether heartworm infective larvae (L 3 ) from mosquitoes fed earlier on blood from dogs during daily administration of doxycycline at various dosages and treatment schedules and a single prophylactic dose of ivermectin could develop normally in dogs. Methods A total of 20 heartworm microfilaremic Beagles in a separate study allocated to four groups ( n = 5/group) of five dogs were used as blood donors for mosquito infection. These donor dogs in groups 4, 5, and 6 had received doxycycline orally at 5.0, 7.5, or 10.0 mg/kg twice daily (BID) × 14 or 21 days, and ivermectin orally (minimum 6 mcg/kg) on day 0. Group 2 served as the untreated control. To produce infective larvae for each study, two sets of four groups of Aedes aegypti mosquitoes fed on blood from these four groups of dogs on day 14 (study A) or 21 (study B), respectively, and, infective third-stage larvae (L 3 ) were recovered 14 days later. In each study, 8 heartworm-naive dogs (4 groups of 2) were inoculated subcutaneously with 50 L 3 /dog originating from mosquitoes fed on the corresponding donor group, for a total of 16 recipient dogs. Recipient dogs were monitored by antigen testing and microfilaria counts and necropsied for adult heartworm recovery and enumeration. Necropsies were performed on the same day at 252 days postinfection for study A and 245 days postinfection for study B. Results Overall, 11 of the 12 dogs that had received L 3 from mosquitoes fed on blood from treated dogs had no heartworms at necropsy; however, 1 dog that was administered doxycycline orally at the lowest dosage of 5.0 mg/kg BID daily and for the shorter treatment period of 14 days allowed only 1 adult female heartworm to reach the pulmonary arteries. All control dogs had male and female heartworms at necropsy. Conclusions Treatment of microfilaremic dogs with doxycycline administered daily at 10.0 or 7.5 mg/kg BID for 14 days and one monthly dose of a heartworm preventive (macrocyclic lactone [ML]) renders the L 3 incapable of normal development in recipient dogs, which could potentially widen the scope of a multimodal prevention approach to reduce the spread of heartworm disease.