Malaria - Pathogenesis

Pathogenesis

Further information: Plasmodium falciparum biology

Malaria infection develops via two phases: one that involves the liver (exoerythrocytic phase), and one that involves red blood cells, or erythrocytes (erythrocytic phase). When an infected mosquito pierces a person's skin to take a blood meal, sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver where they infect hepatocytes, multiplying asexually and asymptomatically for a period of 8–30 days.

After a potential dormant period in the liver, these organisms differentiate to yield thousands of merozoites, which, following rupture of their host cells, escape into the blood and infect red blood cells to begin the erythrocytic stage of the life cycle. The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.

Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their host cells to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells.

Some P. vivax sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead produce hypnozoites that remain dormant for periods ranging from several months (7–10 months is typical) to several years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in P. vivax infections, although their existence in P. ovale is uncertain.

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, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen. The blockage of the microvasculature causes symptoms such as in placental malaria. Sequestered red blood cells can breach the blood–brain barrier and cause cerebral malaria.

Although the red blood cell surface adhesive proteins (called PfEMP1, for P. falciparum erythrocyte membrane protein 1) are exposed to the immune system, they do not serve as good immune targets because of their extreme diversity; there are at least 60 variations of the protein within a single parasite and even more variants within whole parasite populations. The parasite switches through a broad repertoire of PfEMP1 surface proteins, thereby avoiding detection by protective antibodies.

Read more about this topic:  Malaria

Other articles related to "pathogenesis":

Progressive Massive Fibrosis - Pathogenesis and Causes
... The pathogenesis of PMF is complicated, but involves two main routes - an immunological route, and a mechanical route ... as an effect of this, as well as reduced motility of cells, is fundamental to the pathogenesis of pneumoconiosis and the accompanying inflammation, fibrosis ... There are also some mechanical factors involved in the pathogenesis of Complex Pneumoconiosis that should be considered ...
Huntingtin-associated Protein 1 - Function
... have since been characterised, thus elucidating a possible role for this protein in HD pathogenesis ... indicated HAP1 in pre-aggregate related HD pathogenesis ... The role of HAP1 in HD pathogenesis may involve aberration of cell cycle processes, as high immunostaining of HAP1 during the cell cycle has been ...
Serum Sickness-like Reaction - Pathogenesis
... Although the exact pathogenesis is poorly understood, serum sickness-like reactions are thought to originate from an abnormal inflammatory reaction that occurs in response to defective metabolism ...
Pathogenesis

The pathogenesis of a disease is the mechanism by which the disease is caused. The term can also be used to describe the origin and development of the disease and whether it is acute, chronic or recurrent. The word comes from the Greek pathos, "disease", and genesis, "creation".

Types of pathogenesis include microbial infection, inflammation, malignancy and tissue breakdown.

Most diseases are caused by multiple pathogenetical processes together. For example, certain cancers arise from dysfunction of the immune system (skin tumors and lymphoma after a renal transplant, which requires immunosuppression).

Often, a potential etiology is identified by epidemiological observations before a pathological link can be drawn between the cause and the disease.