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However, limited understanding of infection dynamics in human LS exists due to species-specificity challenges. Reported here is a reproducible, easy-to-manipulate, and moderate-cost <jats:italic>in vivo<\/jats:italic> model to study human Plasmodium LS in mice; the ectopic huLiver model. Ectopic huLiver tumors were generated through subcutaneous injection of the HC-04 cell line and shown to be infectible by both freshly dissected sporozoites and through the bite of infected mosquitoes. Evidence for complete LS development was supported by the transition to blood-stage infection in mice engrafted with human erythrocytes. Additionally, this model was successfully evaluated for its utility in testing antimalarial therapeutics, as supported by primaquine acting as a causal prophylactic against <jats:italic>P<\/jats:italic>. <jats:italic>falciparum<\/jats:italic>. Presented here is a new platform for the study of human <jats:italic>Plasmodium<\/jats:italic> infection with the potential to aid in drug discovery.<\/jats:p>","DOI":"10.1371\/journal.pone.0279144","type":"journal-article","created":{"date-parts":[[2023,3,16]],"date-time":"2023-03-16T17:57:27Z","timestamp":1678989447000},"page":"e0279144","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of an ectopic huLiver model for Plasmodium liver stage infection"],"prefix":"10.1371","volume":"18","author":[{"given":"Gabriela","family":"Samayoa-Reyes","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siobhan M.","family":"Flaherty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristina 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