Comparison of two doxycycline dosages on inflammatory and stress response in dogs naturally infected with Dirofilaria immitis

BACKGROUND: Canine heartworm disease, caused by Dirofilaria immitis, is characterized by a marked inflammatory response largely driven by its endosymbiotic bacterium Wolbachia pipientis. Doxycycline is routinely incorporated into treatment protocols to reduce Wolbachia burden and the associated pathology. Although the standard recommended dosage is 10 mg/kg every 12 h for 28-30 days, evidence comparing lower dosages under clinical conditions remains limited. This study aimed to compare the effects of two doxycycline dosages on inflammatory and immune markers in dogs naturally infected with D. immitis during the pre-adulticidal phase of treatment. METHODS: Seventy-seven dogs naturally infected with D. immitis were randomly allocated to receive doxycycline at either 10 mg/kg (n = 39) or 5 mg/kg (n = 38) every 12 h for 30 days, in combination with a single oral dose of ivermectin (6 µg/kg) administered at treatment initiation. Serum concentrations of C-reactive protein (CRP) and cortisol were measured at baseline (day 0) and after treatment completion (day 30). Anti-recombinant Wolbachia surface protein (rWSP) antibody levels were determined by ELISA. Intra- and intergroup comparisons were performed using non-parametric statistical tests. RESULTS: Both doxycycline regimens resulted in a significant reduction in CRP concentrations from day 0 to day 30 (p < 0.05), indicating a decrease in systemic inflammation. No significant differences were observed between dosages in the magnitude of CRP reduction. Cortisol concentrations showed a non-significant downward trend in both groups, while anti-rWSP antibody levels remained stable throughout the study period. No significant intergroup differences were detected for any evaluated parameter. CONCLUSIONS: Doxycycline administered at 5 mg/kg every 12 h for 30 days showed a comparable short-term biomarker response to the standard 10 mg/kg regimen during the pre-adulticidal phase. Lower doxycycline dosages may represent a potential alternative with possible benefits in terms of tolerance, compliance, and antimicrobial stewardship, although these aspects were not directly evaluated in the present study.