Plasmodium vivax latent liver infection is characterized by persistent hypnozoites, hypnozoite-derived schizonts, and time-dependent efficacy of primaquine
Issued Date
2022-09-08
Resource Type
eISSN
23290501
Scopus ID
2-s2.0-85136183072
Journal Title
Molecular Therapy - Methods and Clinical Development
Volume
26
Start Page
427
End Page
440
Rights Holder(s)
SCOPUS
Bibliographic Citation
Molecular Therapy - Methods and Clinical Development Vol.26 (2022) , 427-440
Suggested Citation
Flannery E.L., Kangwanrangsan N., Chuenchob V., Roobsoong W., Fishbaugher M., Zhou K., Billman Z.P., Martinson T., Olsen T.M., Schäfer C., Campo B., Murphy S.C., Mikolajczak S.A., Kappe S.H.I., Sattabongkot J. Plasmodium vivax latent liver infection is characterized by persistent hypnozoites, hypnozoite-derived schizonts, and time-dependent efficacy of primaquine. Molecular Therapy - Methods and Clinical Development Vol.26 (2022) , 427-440. 440. doi:10.1016/j.omtm.2022.07.016 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/83607
Title
Plasmodium vivax latent liver infection is characterized by persistent hypnozoites, hypnozoite-derived schizonts, and time-dependent efficacy of primaquine
Other Contributor(s)
Abstract
Plasmodium vivax is a malaria-causing pathogen that establishes a dormant form in the liver (the hypnozoite), which can activate weeks, months, or years after the primary infection to cause a relapse, characterized by secondary blood-stage infection. These asymptomatic and undetectable latent liver infections present a significant obstacle to the goal of global malaria eradication. We use a human liver-chimeric mouse model (FRG huHep) to study P. vivax hypnozoite latency and activation in an in vivo model system. Functional activation of hypnozoites and formation of secondary schizonts is demonstrated by first eliminating primary liver schizonts using a schizont-specific antimalarial tool compound, and then measuring recurrence of secondary liver schizonts in the tissue and an increase in parasite RNA within the liver. We also reveal that, while primaquine does not immediately eliminate hypnozoites from the liver, it arrests developing schizonts and prevents activation of hypnozoites, consistent with its clinical activity in humans. Our findings demonstrate that the FRG huHep model can be used to study the biology of P. vivax infection and latency and assess the activity of anti-relapse drugs.