Despite renewed eradication efforts from the international community, malaria still exerts an enormous disease burden, with nearly half the planet's population at risk of infection. Within the human host, the disease-causing Plasmodium parasites pass through two distinct lifecycle stages, each in a different cellular environment.
During the liver stage, a single Plasmodium sporozoite will invade a hepatocyte, and while sheltered there gives rise to thousands of new parasites, which will go on to initiate the subsequent blood stage of infection. While only 10-20 new parasites will be generated inside an erythrocyte, consecutive cycles of cell lysis and reinfection causing a potent host response, as well as the symptoms of malaria. It is becoming consensual that malaria control or elimination will never be feasible until we gain a better understanding of the complex interactions occurring between its main players: Plasmodium, the causative agent of disease, and its hosts.
Our ongoing work indicates that the web of host-Plasmodium interactions is densely woven, with liver stage-mediated innate immune system activation (Liehl et al., 2014. Nature Medicine), host nutritional status (unpublished), and an antagonistic relationship between the two parasite stages themselves (Portugal et al., 2011. Nature Medicine) all working to modulate the balance between parasite replication and human health. Altering this balance will be required if we aim to efficiently control this deadly parasite.