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This study aimed to conduct a multidisciplinary investigation integrating detailed morphology, oxidative stress, immunology, and histopathology alteration to advance our understanding of Clinostomum infection. In this annual study, 400 Nile tilapia (<jats:italic>Oreochromis niloticus<\/jats:italic>) were collected from the Nile River at Al Bahr Al Aazam, Giza Governorate to assess <jats:italic>Clinostomum<\/jats:italic> infection prevalence. Of the examined fish, 160 individuals (40.0%) harboured larval <jats:italic>Clinostomum<\/jats:italic> infections. <jats:italic>Clinostomum<\/jats:italic> metacercariae were observed in various anatomical locations, with 135 fish (33.8%) in buccal cavities, 21 fish (5.25%) in gill chambers, and 4 fish (1.0%) on the skin. Infection intensity ranged from 2 to 12 cysts per fish, averaging 5 cysts, notably with skin infections characterized by a single cyst in each fish. Macroscopic encysted metacercariae were collected from buccal cavities, gills, and skin. Micro-morphology revealed distinct features in <jats:italic>C. complanatum<\/jats:italic>, including an elliptical oral sucker with collar-like rings and large sensory papilla-like structures, contrasting with the absence of these features in <jats:italic>C. phalacrocoracis<\/jats:italic>. Oxidative stress, assessed through malondialdehyde (MDA) and nitric oxide levels, revealed an elevation in MDA to 35.13\u2009\u00b1\u20096 nmol\/g and nitric oxide to 25.80\u2009\u00b1\u20093.12 \u00b5mol\/g in infected fish. In infected fish, MHC-I gene expression increased approximately 13-fold, MHC-II peaked at 19-fold, and IL-1\u03b2 significantly upregulated by 17-fold, compared to control levels. Histopathology detailed associated lesions, such as cyst encapsulation and eosinophilic infiltration. Clinstomiasis and its impacts on fish hosts offer crucial insights to control this emerging fish-borne zoonotic disease, threatening wildlife, aquaculture, and human health.<\/jats:p>","DOI":"10.1186\/s12917-024-03901-7","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T10:02:39Z","timestamp":1708423359000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A multidisciplinary study on Clinostomum infections in Nile tilapia: micro-morphology, oxidative stress, immunology, and histopathology"],"prefix":"10.1186","volume":"20","author":[{"given":"Olfat A.","family":"Mahdy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar Z.","family":"Abdel-Maogood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Abdelsalam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai A.","family":"Salem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,2,20]]},"reference":[{"key":"3901_CR1","doi-asserted-by":"crossref","unstructured":"Mahdy OA, Abdelsalam M, Salem MA. 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It\u2019s important to note that the fish samples used in this research were purchased, and therefore, no specific permissions were required for their collection. The study strictly adhered to institutional, ethical, and animal welfare guidelines as outlined in the Laboratory Animal Care and Use Guide (Vet-CU-11112018019).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no conflict of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"60"}}