Pathogenesis

Plasmodium falciparum develop diseases in human body by infecting both circulatory and lymphatic system.

The pathogenesis of P.falciparum starts at the stage where the parasites leave liver cells and attack host’s red blood cells (RBSc). Before it leave the liver cell, the parasites wrapping itself in the cell membrane of the infected host liver cell, thus immune system can’t detect it while it in the bloodstream.

Rug et al. (2004) suggested that, prior to invasion of human erythrocytes, the parasites exports proteins beyond its own plasma membrane to modify the properties of the host red cell membrane. These modifications are critical to the pathogenesis of malaria. In order to establish infection in the host, the malaria parasites export remodeling and virulence proteins into the RBCs. These proteins can traverse a series of membranes, including the parasite membrane, the parasitophorous vacuole membrane, and the erythrocyte membrane (Marti et al. 2004). Another research done by Harrison and co-investigators that written by Crown (2003) found that G proteins in the RBCs may be used by the parasites. This is supported by a research by Haldar and co-investigators that found a G protein subunit, called Gs, concentrates around the malaria parasite during infection of the red blood cell.

According to McKerrow et al. (1993), parasites proteases produced by P.falciparum are likely required during both the invasion of RBCs by merozoites and the rupture of RBCs by mature schizonts. It is because in both events, the RBCs cytoskeletal proteins must be hydrolyzed as it is serves as an important barrier to malaria parasites other than erythrocyte plasma membrane. Multiple proteins of mature schizonts and merozoites are proteolytically processed immediately before or during erythrocyte rupture and invasion, suggesting that proteolytic fragments have roles in these processes. Hemoglobin degradation is found occurs predominantly in trophozoites and early schizonts of P.falciparum, the stages at which the parasites are most metabolically active. Trophozoites ingest RBCs cytoplasm via pinocytosis or use the cytostome, a specialized organelle, and then transport the cytoplasm within vesicles to a large central food vacuole. The hemoglobin is then broken down into heme, which is a major component of malarial pigment; while globin is hydrolyzed to its constituent free amino acids.

Picture shows 2 ruptured RBCs surrounded by fresh RBCs

In the RBCs, the multiplying process continue, rupture of host cell to invade fresh RBCs.The amplification cycle occur. The symptoms of Malaria such as fever, chills, headache, muscle aches, joint pain, vomitting, and fatigue occur when infected red blood cells that are “incubating” thousands of P.falciparum literally explode and release more parasites into the blood stream during the “blood stage” of malaria.

The parasite is relatively protected from attack by the body's immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. However, usually infected RBCs will be destroyed in the spleen. To avoid from destruction in the spleen, the adhesive proteins (PfEMP1) display on the surface of the circulating infected blood cells by these parasites. This causes the blood cells and the wall of small blood vessels stick together. Furthermore, this action avoid the parasite of being destroyed in spleen’s circulation. Although PfEMP1 is exposed to the immune system, it can’t be detected as there are at least 60 variation of the protein (PfEMP1). The “stickness” may induces hemorrhagic complication of malaria. Attachment of masses of the infected RBCs block the high endothelial venules and give rises to some symptoms, for example, placental and cerebral malaria. The sequestrated red blood cells can ruptures the blood brain barrier and possess possibility to cause coma in cerebral malaria.