Inability of Dirofilaria immitis infective larvae from mosquitoes fed on blood from microfilaremic dogs during low-dose and short-treatment regimens of doxycycline and ivermectin to complete normal development in heartworm naïve dogs

BACKGROUND: This study was conducted to determine whether heartworm infective larvae (L(3)) collected from mosquitoes fed on dogs during low-dose, short-treatment-regimen doxycycline and ivermectin could develop normally in dogs. METHODS: Twelve Beagles in a separate study were infected with 10 pairs of adult male and female Dirofilaria immitis by IV transplantation and randomly allocated to three groups of four dogs. Starting on Day 0, Group 1 received doxycycline orally at 10 mg/kg sid for 30 days plus ivermectin (min., 6 mcg/kg) on Days 0 and 30; Group 2 received doxycycline orally at 10 mg/kg sid until individual dogs became microfilaria negative (72–98 doses) and ivermectin every other week for six to seven doses. These dogs served as microfilaremic blood donors for the current mosquito studies. Aedes aegypti were allowed to feed on group-pooled blood samples from treated Groups 1-M and 2-M and untreated control Group 3-M on Days 22 (Study M-A) and 42 (Study M-C) and from Groups 1-M and 2-M on Day 29 (Study M-B) after treatment was started. From the Day 22 mosquito feeding, two dogs in Groups 1-M and 2-M and one dog in Group 3-M were given 50 L(3) by SC inoculation. From the Day 29 feeding, two dogs in Groups 1-M and 2-M were given 50 L(3). From the Day 42 feeding, two dogs in Group 1-M received 30 L(3), while two dogs in Group 2-M and one dog in Group 3-M received 40 L(3). All 14 dogs were necropsied for recovery and enumeration of adult heartworms 163–183 days PI. RESULTS: None of the 12 dogs that received L(3) from mosquitoes fed on blood from treated dogs 22, 29 or 42 days after treatment started had any adult heartworms at necropsy, while the two control dogs had a total of 26 and 43 heartworms, respectively. CONCLUSIONS: Treatment of microfilaremic dogs with doxycycline plus an ML, which later renders the L(3) incapable of normal development in the animal host, widens the scope of the multimodal approach to heartworm prevention in reducing the spread of heartworm disease. GRAPHICAL ABSTRACT: [Image: see text]