Trichinellosis is a common zoonosis due to different species of Trichinella that infect the small intestine and muscles of human and several mammalian host species. Trichinella spiralis (T. spiralis), one of the most frequent species, is transmitted mainly by eating undercooked or raw pork containing the encysted infective larvae (Bai et al., 2022). The cycle of T. spiralis infection in the human host passes through dual phases: adults in the intestinal phase and encysted larvae in the muscular phase (Gherman et al., 2022). Notably, the invading T. spiralis newborn larvae produce severe inflammatory and oxidative stress damage of the skeletal muscle fibers that initiates proliferation and re-differentiation of the satellite cells hence nurse cell formation and encapsulation of the larvae with great vascular capillary rete (Abou Rayia et al., 2022). Nurse cell formation is actually a highly complex process that is mainly initiated by increasing angiogenesis and vascular permeability around the collagen capsule shelter to ensure complete nutrition and to guard them from the host immune responses (Elmehy et al., 2021a, 2021b). Such complicated pathology always results in severe, aching, and handicapping muscular dysfunction (Abou Rayia et al., 2022).

The most common approach for treating trichinellosis as a public health issue is drug administration of Ivermectin (IVM) and albendazole (Elmehy et al., 2021a, 2021b). Ivermectin is frequently used in control programs against human lymphatic filariasis, onchocerciasis, ectoparasites as Pediculus and Sarcoptes scabiei and veterinary deworming (Laing et al., 2017; Ashour, 2019; Sharaf et al., 2020). There have been concerns mentioned about the possible emergence of ivermectin resistance since its use in a variety of fields and illnesses. Nevertheless, regarding the results of the anti-Trichinella spiralis effect of IVM on the encysted muscle larvae, they were nearly disappointing (Ashour, 2019). Such results triggered the enthusiasm of the researchers to focus their attention upon alternative treatments against encysted larvae.

One of the eminent drugs in the anti-nematodal era today is moxidectin (MOX) which is a semi-synthetic macrocyclic lactone of the milbemycin class of the macrolide antibiotics (Hürlimann et al., 2023). MOX is used as an antiparasitic, like IVM. It was approved by the US Food and Drug Administration in 2018 to treat onchocerciasis in individuals who are more than 12 years old (Prichard and Geary, 2019). MOX may be an appropriate option for combination treatment against infections caused by soil-transmitted helminths, according to data from earlier trials (Hofmann et al., 2021). Also, MOX revealed a powerful efficacy against adult cyathostomes, Strongylus spp., Triodontophorus spp. and Habronema muscae (Nielsen et al., 2022). Also, it is worth mentioning that MOX showed a prophylactic effect at various doses and regimens against macrocyclic lactone-resistant heartworm (Dirofilaria immitis) strains in dogs (McTier et al., 2019). Thus, the present study's aim was to evaluate MOX versus IVM in the prevention and treatment of different stages of T. spiralis infection in experimental mice especially against the chronic inflammatory muscular phase to pave the way for the avoidance of the severe forms of myopathy and myositis.