Liver hypnozoite-stage Plasmodium spp. and gametocytes

Liver hypnozoite-stage Plasmodium spp. and gametocytes represent critical life stages of the malaria parasite essential for disease persistence and transmission (CDC, 2020). Hypnozoites are dormant forms of Plasmodium vivax and Plasmodium ovale that reside in the liver and can reactivate weeks or months after the initial infection, leading to clinical relapses (White et al., 2014). Gametocytes are the sexual stages of the parasite that circulate in the human bloodstream and are ingested by Anopheles mosquitoes, facilitating the spread of malaria within a population (Bousema & Drakeley, 2011). Targeting these stages is vital for achieving a radical cure and for malaria elimination efforts (MMV, 2023). Currently, 8-aminoquinoline derivatives like primaquine and tafenoquine are the primary drugs used to clear these stages, though their use is limited by safety concerns in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (Ashley et al., 2018). Research continues to focus on identifying specific molecular targets within these stages to develop safer and more effective transmission-blocking and anti-relapse therapies (Wells et al., 2015).

Other names

Dormant liver stagesSexual stages of PlasmodiumRelapse-causing stagesTransmission-blocking targets

Drugs targeting these stages typically act by inducing oxidative stress through the generation of reactive oxygen species, interfering with mitochondrial electron transport, or disrupting parasite-specific metabolic pathways required for survival during dormancy or sexual maturation (Ashley et al., 2018; Wells et al., 2015).