Rodent-borne cestodes of the genus Raillietina include several poorly characterized species with
potential zoonotic relevance, yet their molecular identity, host–parasite interactions, and susceptibility
to alternative anthelmintic agents remain inadequately understood. Here, we present an integrated
morphological, ultrastructural, molecular, immunopathological, and experimental evaluation of
Raillietina hymenolepidoides naturally infecting the fat sand rat (Psammomys obesus) in Egypt. Adult
cestodes were identified using light microscopy, scanning electron microscopy, and mitochondrial
cytochrome c oxidase subunit I (COI) sequencing, confirming species identity and revealing close
phylogenetic affinity to Raillietina mahnerti. Histopathological analysis of infected hosts demonstrated
severe intestinal epithelial degeneration, necrosis, and Peyer’s patch hyperplasia, accompanied by
pulmonary emphysematous changes. Immunohistochemical profiling revealed increased CD56⁺ natural
killer cell infiltration alongside reduced CD68⁺ macrophage and TGF-β expression, indicating altered
local immune regulation during chronic infection. In parallel, the in vitro anthelmintic activity of
Androctonus crassicauda crude venom was assessed against adult cestodes, revealing time-dependent
tegumental disruption, microtriche erosion, proglottid detachment, and parasite death, as visualized
by scanning electron microscopy. Collectively, these findings provide the first comprehensive molecular
confirmation of R. hymenolepidoides in P. obesus in Egypt and demonstrate the pronounced in vitro
cestocidal effects of scorpion venom. The study highlights the value of integrative approaches and supports further investigation of venom-derived compounds as potential leads for novel anthelmintic development.