The developmental changes which the malaria parasite, Plasmodium (q.v.) undergoes as it is transmitted from a vector to a host, and back to a vector. The life cycle of P. falciparum, the major parasite causing human malaria, is shown in the illustration. The saliva of an infected Anopheles (q.v.) female transmits the parasite in the sporozoite form when it bites a human being. Each sporozoite synthesizes a circumsporozoite (CS) protein (q.v.), which serves as an immune decoy. The sporozoites reach the liver, where they invade hepatocytes. They then undergo schizogony, a replicative process involving multiple rounds of rapid mitoses without cytokinesis (q.v.). Subsequently, the cytoplasm segments within the multinucleate mass to form hundreds of uninucleate merozoites. Following rupture of the hepatocyte, the merozoites enter the circulatory system and invade red blood cells.
Within the erythrocyte the parasite transforms into the trophozoic or feeding stage, ingesting massive mounts of hemoglobin (q.v.) from the cytoplasm of its host. The trophozoite hydrolyzes the globin into small peptides and releases the heme, which is converted in the food vacuole (q.v.) to a non-toxic crystalline form, called hemozoin. Shortly after its infection the erythrocyte forms thousands of projections on its surface, which contain adhesion molecules produced by the parasite. The infected cells can now adhere to the walls of the blood vessels and avoid being swept into and destroyed by the spleen. The trophocyte stage ends when the cells undergo schizogony. The host erythrocyte then ruptures, releasing merozoites which invade new erythrocytes. Erythrocytic schizogony is synchronized, causing cells to rupture in synchrony. This is the reason for the cyclic fever paroxysms experienced by humans suffering from malaria.
The merozoites in some of the erythrocytes differentiate into male and female gametocytes, and the erythrocytes containing these do not rupture. These gametocytes can be taken up by mosquitoes in the next blood meal, and it is in the mosquito that the sexual phase of the parasite life cycle occurs. Here male and female gametes fuse, resulting in the only diploid stage, the ookinete. This motile cell transverses the midgut epithelium of the mosquito and comes to rest between the epithelial cells and the basal lamina (an acellular membrane surrounding the outside of the gut). The ookinete now completes meiosis to form haploid nuclei, which divide within a sporocyst to form thousands of sporozoites. When the mature sporocyst ruptures, the motile sporozoites penetrate the basal lamina and enter the hemocoel.
The sporozoites now migrate to the salivary glands, traverse the epithelial cells of the gland, and come to rest in the lumen. The life cycle is completed when the mosquito transfers sporozoites to a human during a blood meal. See Chronology, 1880, Laveran; 1898, Ross; 1899, Grassi; 1948, Shortt and Garnham; hemoglobin C, sickle cell trait, vacuoles.
Plasmodium life cycle. From D. F. Wirth, The parasite genome: biological revelations. Nature419 (3 October 2002): 495–496.
Subjects: Genetics and Genomics.