Plasmodium vivax latent liver infection is characterized by persistent hypnozoites, hypnozoite-derived schizonts, and time-dependent efficacy of primaquine

• DOI: 10.1016/j.omtm.2022.07.016
• Publication Date: 2022-08-02T08:54:24Z
• Authors: Erika L. Flannery; Niwat Kangwanrangsan; Vorada Chuenchob; Wanlapa Roobsoong; Matthew Fishbaugher; Kevin Zhou; Zachary P. Billman; Thomas Martinson; Tayla M. Olsen; Carola Schäfer; Brice Campo; Sean C. Murphy; Sebastian A. Miko...; Stefan H.I. Kappe; Jetsumon Sattabon...
• Keywords: Primaquine; Vivax malaria

Plasmodium vivax is a malaria-causing pathogen that establishes dormant form in the liver (the hypnozoite), which can activate weeks, months, or years after primary infection to cause relapse, characterized by secondary blood-stage infection. These asymptomatic and undetectable latent infections present significant obstacle goal of global malaria eradication. We use human liver-chimeric mouse model (FRG huHep) study P. hypnozoite latency activation an vivo system. Functional hypnozoites formation schizonts demonstrated first eliminating using schizont-specific antimalarial tool compound, then measuring recurrence tissue increase parasite RNA within liver. also reveal that, while primaquine does not immediately eliminate from liver, it arrests developing prevents hypnozoites, consistent with its clinical activity humans. Our findings demonstrate FRG huHep be used biology assess anti-relapse drugs.