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Background: The East Route Project (ERP) of the South-to-North Water Diversion Project (SNWDP) stretches across schistosomiasis endemic and non-endemic areas in China, which may lead to the dispersal of Oncomelania hupensis, the intermediate host of Schistosoma japonicum, from permissive areas along the Yangtze River Basin to non-permissive areas in northern China. A previous survey demonstrated that O. hupensis could survive and breed for 13 years (12 generations) after being transferred to a non-permissive area, and could be infected by S. japonicum. However, it is not clear if the migrated snails will change their ability to transmit S. japonicum. Methods: We infected mice with the cercariae released from the infected transferred snails bred in Jining city of Shandong Province (non-permissive areas) for 13 years. The mice in the control group were infected with cercariae derived from the snails collected in their original habitat (Jiangdu county of Jiangsu Province, permissive areas). Then, we explored the pathogenicity to mice including worm burden, liver egg count and pathology. Additionally, the gene expression profiles of the adult male and female worms recovered from the infected mice were analyzed by RNA sequencing. Results: The worm burden, liver egg count and pathology of the mice infected with cercariae released from transferred snails bred in non-permissive areas for 13 years showed no significant differences, when compared with the control cercariae. Slight changes occurred at the transcription level between adult male and female worms recovered from mice infected with cercariae derived from snails bred in permissive and non-permissive areas. Only fourteen genes were significantly differentially expressed in the comparison of adult female worms, and no significantly differentially expressed gene was found in the comparison of adult male worms. Conclusions: Our findings strongly suggest that transferred snails did not change their schistosomiasis transmission ability and the worms derived from them retained the original pathogenicity, even after migrating from permissive to non-permissive areas for 13 years. Therefore, a long-term surveillance system of snails along the SNWDP is urgently needed to prevent the diffusion of O. hupensis and reduce the risk of transmission of schistosomiasis. [ABSTRACT FROM AUTHOR]