Plasmodium hypnozoite-stage targets

Plasmodium hypnozoite-stage targets represent the molecular machinery of the dormant liver-stage parasites of Plasmodium vivax and Plasmodium ovale. These hypnozoites are a major obstacle to malaria eradication because they can persist in a quiescent state within hepatocytes for extended periods, leading to periodic relapses of symptomatic blood-stage malaria (10). Therapeutic intervention against these targets, known as radical cure, is necessary to eliminate the parasite reservoir in endemic regions (13). Currently, the 8-aminoquinolines primaquine and tafenoquine are the only approved drugs with hypnozoitocidal activity, although their use is limited by safety concerns in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (9, 13). Modern drug discovery efforts are focused on identifying specific molecular targets within the hypnozoite, such as epigenetic regulators (e.g., histone acetyltransferases), RNA-binding proteins (e.g., IESI-1 and IESI-2), and metabolic enzymes, to develop safer and more effective anti-relapse therapies (1, 6, 8).

Other names

Dormant liver stageQuiescent liver stageHypnozoiteRelapse-causing liver stage

Radical cure through the elimination of dormant liver-stage parasites, likely involving the generation of reactive oxygen species or interference with parasite mitochondrial electron transport and metabolic pathways.