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It is caused by parasites surviving in the blood as a result of inadequate or ineffective treatment.

Relapse is when symptoms reappear after the parasites have been eliminated from blood but persist as dormant hypnozoites in liver cells. Reinfection means the parasite that caused the past infection was eliminated from the body but a new parasite was introduced.

In the life cycle of Plasmodium, a female Anopheles mosquito (the definitive host) transmits a motile infective form (called the sporozoite) to a vertebrate host such as a human (the secondary host), thus acting as a transmission vector.

A sporozoite travels through the blood vessels to liver cells (hepatocytes), where it reproduces asexually (tissue schizogony), producing thousands of merozoites.

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.

Several genetic factors provide some resistance to it including sickle cell trait, thalassaemia traits, glucose-6-phosphate dehydrogenase deficiency, and the absence of Duffy antigens on red blood cells.

The impact of sickle cell trait on malaria immunity illustrates some evolutionary trade-offs that have occurred because of endemic malaria.

However, circulating infected blood cells are destroyed in the spleen. 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.

When a fertilized mosquito bites an infected person, gametocytes are taken up with the blood and mature in the mosquito gut.

The male and female gametocytes fuse and form an ookinete—a fertilized, motile zygote.

The merozoites infect red blood cells, where they develop into ring forms, trophozoites and schizonts that in turn produce further merozoites.

Sexual forms are also produced, which, if taken up by a mosquito, will infect the insect and continue the life cycle.

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