Reevaluating doxycycline dosage in canine heartworm disease: isless more?

Abstract

Several aspects of heartworm disease adulticide treatment require further investigation, particularly regarding Wolbachia pipientis elimination. This study evaluated the acute phase response, specifically C-reactive protein (CRP) concentrations and anti-Wolbachia surface protein (r-WSP) antibody response, before (D0) and after (D30) treatment with oral ivermectin (6-12 μg/kg, monthly) and doxycycline for 30 days at three dosages: Group A (n=10, 10 mg/kg BID), Group B (n=16, 10 mg/kg SID), and Group C (n=13, 5 mg/kg BID). CRP concentrations were generally elevatedat D0 (Group A: 15.3±22.7 mg/L; Group B: 27.6±45.3 mg/L; Group C: 13.9±14.2 mg/L) and slightly decreased at D30 except in Group A (Group A: 25.9±63.3 mg/L; Group B: 17.7±15.7 mg/L; Group C: 12±9.4 mg/L). Anti-rWSP antibody response remained stable in Group A but significantly increased in Groups B and C at D30 (p<0.05). The increase in anti-WSP antibody optical densities may result from Wolbachia release during microfilarial death following ivermectin administration at D0 in microfilaremic dogs. Additionally, lower doxycycline doses in Groups B and C may have resulted in a minor Wolbachia reduction over 30 days. Also, it should be noted that the immune response is not well known and the serological persistence of these antibodies is unknown. Elevated CRP values at D0 confirm the strong inflammatory component of heartworm disease. By D30, slight CRP reductions in Groups B and C suggest decreased vascular inflammation due to Wolbachia elimination and microfilariae reduction. However, Group A showed increased CRP levels at D30, which may be due to other inflammatory factors or spontaneous adult worm death induced by antibiotic and macrocyclic lactone treatment. These findings support previous studies suggesting lower doxycycline doses may be sufficient for Wolbachia elimination in Dirofilaria immitis-infected dogs, and encourage further studies in this line of research.