Malaria Parasite Liver Stages

Background Malaria, caused by Plasmodium (P.) parasite species, poses a significant global health burden. There were 229 million ma-laria cases reported in 2019 and 95% of the 409,000 global malaria-caused fatalities occurred in sub-Saharan Africa (World Malaria Report 2020). Infection of the human host begins with a Plasmodium-infected mosquito bite that deposits sporozoites in the skin. Sporozoites enter blood vessels, are transported to the liver and invade hepatocytes. Within a hepatocyte, each sporozoite transforms into a liver stage (LS), which differenti-ates into tens of thousands of exo-erythrocytic merozoites. The hepatocyte takes center stage throughout this asymptomatic phase of infection; it initiates with hepatocyte surface in-teractions that mediate sporozoite entry, it continues with the complex remodeling of the infected hepatocytes and the de-fense mechanisms that have evolved to alert the immune sys-tem against the silent invader and ends with hepatocyte death and exo-erythrocytic merozoite release. Only recently, robust in vivo and in vitro models have been developed to study liver infection by the two most important human malaria parasites, P.falciparum (Pf) and P.vivax (Pv). Thus, we highlight our general knowledge of LS biology and immunology, mainly garnered from rodent malaria research but also insights directly gained from human parasite LS research.