Mouse Models for Pre-Erythrocytic-Stage Malaria

The erythrocytic stages of the malarial parasites were first observed in man by Laveran in 1880 (1 ) and in birds by Danilevsky in 1884 (2 ). This was followed by the discovery and elucidation of the sporogonous cycle by Ross (1897) (3 ) and Grassi (1900) (4 ). Schaudinn produced an apparent link between these two phases, as he claimed to have observed the penetration of a sporozoite into an erythrocyte (5 ). However, this observation could never be repeated, and scientists remained puzzled by the latency between sporozoite injection and the appearance of parasites in the blood. They, therefore, suspected that there was a tissue phase. This phase was not identified until 40 yr later, first in birds (6 ,7 ), and then in monkeys and men (8 ,9 ). It was demonstrated that subcutaneous macrophages were the target of avian malaria sporozoites and that hepatocytes were the target of mammalian sporozoites.