title: Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice.
abstract: Plasmodium vivax malaria is characterized by periodic relapses of symptomatic blood stage parasite infections likely initiated by activation of dormant liver stage parasites-hypnozoites. The lack of tractable P. vivax animal models constitutes an obstacle in examining P. vivax liver stage infection and drug efficacy. To overcome this obstacle, we have used human liver-chimeric (huHep) FRG KO mice as a model for P. vivax infection. FRG KO huHep mice support P. vivax sporozoite infection, liver stage development, and hypnozoite formation. We show complete P. vivax liver stage development, including maturation into infectious exo-erythrocytic merozoites as well as the formation and persistence of hypnozoites. Prophylaxis or treatment with the antimalarial primaquine can prevent and eliminate liver stage infection, respectively. Thus, P. vivax-infected FRG KO huHep mice are a model to investigate liver stage development and dormancy and may facilitate the discovery of drugs targeting relapsing malaria.
authors: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA. Electronic address: sebastian.mikolajczak@seattlebiomed.org.
authors: Sebastian A
authors: SA
authors: Mikolajczak
authors: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors: Ashley M
authors: AM
authors: Vaughan
authors: Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors: Niwat
authors: N
authors: Kangwanrangsan
authors: Mahidol Vivax Research Center, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
authors: Wanlapa
authors: W
authors: Roobsoong
authors: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors: Matthew
authors: M
authors: Fishbaugher
authors: Mahidol Vivax Research Center, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
authors: Narathatai
authors: N
authors: Yimamnuaychok
authors: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors: Nastaran
authors: N
authors: Rezakhani
authors: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors: Viswanathan
authors: V
authors: Lakshmanan
authors: Department of Global Health, College of Public Health, University of South Florida, Tampa, FL 33620, USA.
authors: Naresh
authors: N
authors: Singh
authors: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors: Alexis
authors: A
authors: Kaushansky
authors: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors: Nelly
authors: N
authors: Camargo
authors: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
authors: Michael
authors: M
authors: Baldwin
authors: Department of Biochemistry and Molecular Biology, Center for Malaria Research, Pennsylvania State University, University Park, PA 16802, USA.
authors: Scott E
authors: SE
authors: Lindner
authors: Department of Global Health, College of Public Health, University of South Florida, Tampa, FL 33620, USA.
authors: John H
authors: JH
authors: Adams
authors: Jetsumon
authors: J
authors: Sattabongkot
authors: Mahidol Vivax Research Center, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
authors: Jetsumon
authors: J
authors: Prachumsri
authors: Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA; Department of Global Health, University of Washington, Seattle, WA 98195, USA. Electronic address: stefan.kappe@seattlebiomed.org.
authors: Stefan H I
authors: SH
authors: Kappe
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage; D018890:Chemoprevention / Q000379:methods; D002678:Chimera; D004195:Disease Models, Animal; D006801:Humans; D008099:Liver / Q000469:parasitology* / Q000473:pathology*; D016780:Malaria, Vivax / Q000188:drug therapy / Q000469:parasitology* / Q000473:pathology* / Q000517:prevention & control; D018345:Mice, Knockout; D016513:Mice, SCID; D010966:Plasmodium vivax / Q000254:growth & development / Q000502:physiology*; D011319:Primaquine / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D011319:Primaquine