Multifaceted analysis of equine cystic echinococcosis: genotyping, immunopathology, and screening of repurposed drugs against E. equinus protoscolices

Cystic echinococcosis (CE) is a neglected zoonotic disease that causes significant economic losses in livestock and poses health risks to humans, necessitating improved diagnostic and therapeutic strategies. This study investigates CE in donkeys using a multifaceted approach that includes molecular identification, gene expression analysis, serum biochemical profiling, histopathological and immunohistochemical examination, and in vitro drug efficacy evaluation. Molecular analysis of hydatid cyst protoscolices (HC-PSCs) from infected donkey livers and lungs revealed a high similarity to Echinococcus equinus (GenBank accession: PP407081). Additionally, gene expression analysis indicated significant increases (P < 0.0001) in interleukin 1β (IL-1β) and interferon γ (IFN-γ) levels in lung and liver homogenates. Serum biochemical analysis showed elevated aspartate transaminase (AST), alkaline phosphatase (ALP), and globulin levels, alongside decreased albumin compared to non-infected controls. Histopathological examination revealed notable alterations in pulmonary and hepatic tissues associated with hydatid cyst infection. Immunohistochemical analysis showed increased expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and toll-like receptor-4 (TLR-4), indicating a robust inflammatory response. In vitro drug evaluations revealed that Paroxetine (at concentrations of 2.5, and 5 mg/mL) demonstrated the highest efficacy among repurposed drugs against HC-PSCs, resulting in the greatest cell mortality. Colmediten followed closely in effectiveness, whereas both Brufen and Ator exhibited minimal effects. This study identifies Paroxetine as a promising alternative treatment for hydatidosis and provides a framework for investigating other parasitic infections and novel therapies.