The malaria parasite life cycle. Sporozoites infect liver cells and mature into schizonts, which rupture and release merozoites. (Of note, in P. vivax and P. ovale a dormant stage [hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years later.) After this initial replication in the liver (exo-erythrocyticschizogony ), the parasites undergo asexual multiplication in the erythrocytes (erythrocyticschizogony ). Merozoites infect red blood cells ]. The ring stage trophozoites mature into schizonts, which rupture releasing merozoites ]. Some parasites differentiate into sexual erythrocytic stages (gametocytes) . Blood stage parasites are responsible for the clinical manifestations of the disease. The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal. The parasites' multiplication in the mosquito is known as the sporogonic cycle. While in the mosquito's stomach, the microgametes penetrate the macrogametes generating zygotes. The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts . The oocysts grow, rupture, and release sporozoites, which make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle. (Source: https://www.cdc.gov/malaria/about/biology/index.html).

Timeline of important events in the development of humanized mice (adapted and modified from Shultz et al. ().

Schema of “creation” for human liver chimeric mice to study LS infection of P. falciparum and subsequent transition to blood-stage infection.