Dose-dependent efficacy of oral lincomycin and associated host immune responses in Streptococcus agalactiae-infected Nile tilapia

In Nile tilapia aquaculture, infections caused by Streptococcus agalactiae are among the most significant bacterial diseases, for which effective therapeutic options remain limited. This study evaluated the dose–response relationship and efficacy of orally administered lincomycin, with emphasis on immunopharmacological responses, in experimentally infected Nile tilapia ( Oreochromis niloticus ). A total of 180 fish weighing approximately 100 g were used. The median lethal dose (LD 50 ) of the bacterial strain was first determined, after which fish were assigned to four treatments: an infected untreated control and infected groups treated with lincomycin at 10, 20, and 40 mg/kg body weight (mg/kg BW; 30 fish per treatment, with three tank replicates per treatment). A non-infected group was included as a descriptive naive reference group. Infected fish were intraperitoneally challenged with approximately 4.96 × 10⁷ CFU/fish of S. agalactiae . Fish in the control and 10 mg/kg BW group exhibited clinical signs consistent with streptococcosis, whereas no evident clinical or behavioral alterations were observed in the 20 or 40 mg/kg BW groups, although some mortality was observed in the 20 mg/kg BW group. Survival was 43.34% in the infected untreated control group, 80.00% in the 10 mg/kg BW group, 83.34% in the 20 mg/kg BW group, and 100.00% in the 40 mg/kg BW group, with corresponding relative percent survival values of 64.70%, 70.59%, and 100.00% for the treated groups, respectively. A dose–response pattern was observed, with 40 mg/kg BW associated with the highest survival and attenuation of infection-associated hematological disturbances, leukocyte activation, and reactive oxygen species production. This group also showed higher specific antibody levels, a pattern consistent with more effective infection control rather than direct immunomodulation. Overall, orally administered lincomycin demonstrated a clear dose-dependent treatment response against experimental streptococcosis under an early-intervention challenge model, providing experimental evidence to support future dose-optimization studies and the rational evaluation of antimicrobial use in tilapia aquaculture.