Unravelling malaria latency: parasite intrinsic and environmental factors influencing dormant liver stages

Hypnozoites - dormant Plasmodium parasites in the liver - can cause relapse infections and form a major obstacle to malaria eradication. The mechanisms controlling dormancy remain poorly understood, but hypnozoite formation and reactivation is likely regulated by a combination of parasite intrinsic factors and external stimuli. We reviewed current knowledge of Plasmodium dormancy and drew parallels with dormancy in other parasites and life-cycle stages. Epigenetic, post-transcriptional, or post-translational regulation probably jointly control hypnozoite dormancy at the intrinsic level. Additionally, environmental factors, such as vector availability, host wellbeing, and tissue microenvironment, could be instrumental to hypnozoite reactivation. A better understanding of how external stimuli influence the intrinsic reactivation switch at a mechanistic level will be required to expand the limited toolset to combat relapsing malaria.