Adult heartworms cause pathology, but the elimination of worms with adulticide therapy can also create pathology. Recent investigation has shown that pretreatment with ivermectin and doxycycline may minimize the damage from dying worms by decreasing the antigenic mass of circulating microfilariae and reducing Wolbachia, an endosymbiotic bacterial organism found in the reproductive tract of the female heartworm. This study evaluated the use of doxycycline alone and with ivermectin before treatment with melarsomine dihydrochloride. Twelve adult dogs (male and female) were each infected with 8 adult male and 8 adult female heartworms by intravenous transplantation. Approximately 6 weeks later they were ranked within gender by microfilarial counts and randomly allocated into 3 groups of 4 dogs. Group 1 dogs were given doxycycline (10 mg/kg Q 12 H PO) from weeks 0 to 4 and were then treated with melarsomine (2.5 mg/kg IM) at week 12, followed 1 month later by 2 injections of melarsomine at the original dose given 24 hours apart. Dogs in group 2 were given doxycycline as described for the group 1 dogs, along with monthly doses of ivermectin (6 mcg/kg PO) for 24 weeks. They were then treated with melarsomine as described for group 1. Group 3 dogs received only melarsomine as described for groups 1 and 2. All the dogs were humanely euthanized and necropsies were performed. Sections from the right caudal lung of each dog were prepared for histology, coded to ensure blinding, and evaluated independently by 2 pathologists. Perivascular inflammation and endothelial proliferation were scored. Dogs in group 3 showed typical lesions associated with thromboembolism as well as severe alveolar wall thickening and hepatization. Dogs in group 1 showed moderate reduction in interstitial inflammation as compared with dogs in group 3 and mild improvement in their arterial lesions. Dogs in group 2 showed milder arterial lesions and the virtual absence of thrombi. Treatment with doxycycline appears to reduce the population of Wolbachia organisms and in combination with ivermectin can markedly reduce the potentially harmful effects of adulticidal therapy.

Commentary:
A previous study1 showed similar results but the long-term antibiotic treatment and weekly administration of ivermectin used in that study may not be as feasible in a clinical setting. The protocol used in group 2 dogs could be instituted to reduce the harmful effects of treating adult heartworms. Of course reducing the number of dogs that have heartworm disease should be the number one goal.—Patricia Thomblison, DVM, MS

Evaluation of lung pathology in Dirofilaria immitis experimentally infected dogs treated with doxycycline or a combination of doxycycline and ivermectin before administration of melarsomine dihydrochloride. Kramer L, Grandi G, Passeri B, et al. VET PARASITOL doi: 10.1016/j.vetpar.2011.01.021.

1 Wolbachia and its influence on the pathology and immunology of Dirofilaria immitis infection. Kramer L, Grandi G, Leoni M, et al. Vet Parasitol 158:191-195, 2008.