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Cell Host Microbe. 2015 Apr 8;17(4):526-35. doi: 10.1016/j.chom.2015.02.011. Epub 2015 Mar 19.

Plasmodium vivax liver stage development and hypnozoite persistence in human liver-chimeric mice.

Author information

1
Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA. Electronic address: sebastian.mikolajczak@seattlebiomed.org.
2
Seattle Biomedical Research Institute, 307 Westlake Avenue North, Suite 500, Seattle, WA 98109, USA.
3
Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
4
Mahidol Vivax Research Center, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
5
Department of Global Health, College of Public Health, University of South Florida, Tampa, FL 33620, USA.
6
Department of Biochemistry and Molecular Biology, Center for Malaria Research, Pennsylvania State University, University Park, PA 16802, USA.
7
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.

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.

PMID:
25800544
PMCID:
PMC5299596
DOI:
10.1016/j.chom.2015.02.011
[Indexed for MEDLINE]
Free PMC Article

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