3^rd Edition of Infectious Diseases World Conference 2026

Abstract

The traditionally used antibabesial monotherapies (diminazene aceturate (DA), imidocarb dipropionate (ID), and atovaquone (AV)) cause toxic side effects to the animals and resistance from the parasite toward these compounds are detected in vitro. Besides, parasite remnants were detected after the treatment. Subsequently, searching for more effective and safer alternatives becomes necessary. In this regard, combination therapy might solve the problem of treating such infections. The present study evaluated combination therapies of pyronaridine tetraphosphate (PYR) and other antibabesial drugs against Babesia in vitro and in vivo. Bioinformatic analysis was performed using atom pair fingerprints. In vitro combination test was performed against Babesia bovis and Theileria equi. Accordingly, the in vivo chemotherapeutic efficacy of oral doses from pyronaridine tetraphosphate (PYR) combined with subcutaneous doses of DA on the growth of Babesia microti (B. microti) in mice was investigated using fluorescence inhibitory assay. PYR and AV exhibited maximum structural similarity and a nearly similar molecular weight with an AP Tanimoto value 0.20. They were followed by an almost identical molecular weight between PYR and DA. The in vitro combination of PYR and DA was synergistic on B. bovis, and additive T. equi. 5 mg/kg PYR combined with 10 mg/kg DA exhibited inhibition in B. microti growth higher than those observed after treatment with 25 mg/kg DA from day six post-inoculation (p.i) till day 12 p.i. The hematological parameters of mice treated with low doses of PYR/DA were comparable to those given a total dosage of the DA-monotherapy approach. In conclusion, the results revealed that an oral dose of PYR combined with a subcutaneous amount of DA might be a new paradigm for babesiosis.