Avian trichomonosis: An innovative approach in drug redirection with Ciprofloxacin, Norfloxacin, and Nitrofurantoin.

Abstract

Trichomonas gallinae is the protozoan that causes avian trichomonosis, a disease affecting the upper digestive tract of birds and leading to proliferative lesions. The 5-nitroimidazoles, especially metronidazole, are the only recommended treatment, but emerging resistance highlights the need for alternatives. Ciprofloxacin (CP) and norfloxacin (NOR) are fluoroquinolones, and nitrofurantoin (NF) is a nitrofuran; all of which show broad-spectrum activity against bacterial and parasitic infections. This study evaluated the in vitro antiparasitic activity of these antibiotics on T. gallinae trophozoites and determined the mean inhibitory concentration (IC), the minimum inhibitory concentration (MIC), and the mortality curve, in addition to demonstrating the morphological changes caused in the trophozoites. The antibiotics were tested at the following concentration ranges: 5-0.1 mg/mL (CP), 10-0.25 mg/mL (NOR), and 5-0.03 mg/mL (NF). Efficacy was observed at the highest concentrations (5 mg/mL for CP and NF; 10 mg/mL for NOR) after 24 h, with approximately 100 % inhibition of trophozoite growth. In the determination of IC₅₀ values, NF showed the lowest value (0.069 mg/mL), followed by CP (0.27 mg/mL) and NOR (0.71 mg/mL). The activity of antibiotics against T. gallinae began in the first hour of incubation, with over 98 % inhibition for NOR compared to approximately 65 % for CP and NF. After 12 h, inhibition of >95 % was observed, reaching 100 % in 48 h for all antibiotics. These results demonstrated that CP, NOR, and NF were promising antibiotics for the in vitro treatment of avian trichomonosis. All tested antibiotics induced significant morphological changes in trophozoites, including flagellar internalization, vacuolization, and pseudocyst-like formations. In silico studies were carried out with relevant Trichomonas proteins which showed potential mechanistic pathways of CP and NOR.