Biologic Characteristic

The malaria parasite Plasmodium falciparum belongs to the phylum Apicomplexa, which includes intracellular pathogens such as Toxoplasma, Cryptosporidium, Eimeria, Babesia, and Theileria species. All Apicomplexa are intracellular parasites, with most growing and replicating within a nonphagosomal parasitophorous vacuole, a compartment bound to the membrane and segregated from most intracellular traffic routes.

Some Apicomplexa have a group of organelles (called rhoptries, micronemes, the apical polar ring, and conoids) that form their apical complex. The rhoptries and micronemes are the only secretor organelles that contain products required for mobility, adhesion, host cell invasion, and parasitophorous vacuole formation. The Apicomplexa have another unique structural characteristic, called the apicoplast (similar to a chloroplast), which is an essential organelle for parasite survival. P.falciparum are surrounded by a pellicle, which is a structure formed by the plasma membrane and an internal membrane complex (IMC) found within the cell, intimately associated with several cytoskeleton elements such as actin, myosin, microtubules, and a network of filament-like proteins involved in sporozoite mobilization. Apicomplexan proliferation occurs due to host cell invasion followed by parasite growth and cell division until the host cell is lysed. Parasites become liberated and do not show growth or extracellular division, meaning that they must speedily invade other host cells.

Life cycle of Plasmodium in mosquitoes and humans

All Plasmodium species has a complex life cycle. Infection in humans begins with the bite of an infected female Anopheline mosquito. Sporozoites released from the salivary glands of the mosquito enter the bloodstream during feeding quickly invade liver cells (hepatocytes). Sporozoites are cleared from the circulation within 30-60 minutes.

Some evidence indicates that sporozoites are first trapped by Kupffer cells before it transported to hepatocytes; though, there are other findings suggest that sporozoites home to hepatocytes directly. Circumsporozoite (CS) protein, the primary protein antigen found on the surface of sporozoites, binds to the basolateral domain of hepatocytes. Other sporozoite surface proteins, such as sporozoite surface protein (SSP2), are believed to be involved in hepatocyte invasion.

During the next 14 days in the case of P.falciparum, the liver-stage parasites differentiate and undergo asexual multiplication resulting in tens of thousands of merozoites which burst from the hepatoctye.

-Ring Stage Parasites-
Fig. 1: Normal red cell; Figs. 2-10: Increasingly mature ring stage parasites

-Trophozoites-
Figs. 11-18: Increasingly mature trophozoites

-Schizonts-
Figs. 19-25: Increasingly mature schizonts; Fig. 26: Ruptured schizont

The merozoites are extracellular for only 1-2 minutes before they rapidly invade red blood cells (erythrocytes). Individual merozoites invade erythrocytes and undergo an additional round of multiplication producing as many as 36 merozoites within a schizont. In the erythrocyte the merozoite goes through ring, trophozoite, and schizont stages. The trophozoites are generally ring shaped, 1-2 microns in size, although other forms (ameboid and band) may also exist. The length of this erythrocytic stage of the parasite life cycle depends on the parasite species: 48 hours for P.falciparum, P.vivax, and P.ovale and 72 hours for P.malariae. The clinical manifestations of malaria, fever and chills, are associated with the synchronous rupture of the infected erythrocyte. The released merozoites go on to invade additional erythrocytes.

-Gametocytes-
Figs. 27, 28: Mature macrogametocytes (female); Fig. 29, 30: Mature microgametocytes (male)

Not all of the merozoites divide into schizonts, some differentiate into sexual forms, male and female gametocytes. This sexual forms are much larger than trophozoites and 7-14 microns in size. P. falciparum is the largest and is banana shaped while others are smaller and round. These gametocytes are taken up by a female Anopheline mosquito during a blood meal.

Within the mosquito midgut, the male gametocyte undergoes a rapid nuclear division, producing 8 flagellated microgametes which fertilize the female macrogamete. The resulting ookinete traverses the mosquito gut wall and encysts on the exterior of the gut wall as a oocyst. Soon the oocyst ruptures, releasing hundreds of sporozoites into the mosquito body cavity where they eventually migrate to the mosquito salivary gland. Then the infectious cycle of malaria continuously repeat itself.

Click here to view animation of the life cycle of P.falciparum.