Life cycle of Plasmodium. [Human Liver Stages] 1 – Mosquito take a blood meal and injects Plasmodium into a human. 2 – Plasmodium infects liver cell. 3 – Plasmodium multiplies in liver cell. [Human Blood Stages] 4 – Plasmodium enters blood. An immature ring stage looks like a signet ring in a red blood cell. This becomes a mature ring stage and undergoes mitosis to produce schizonts which are released by rupturing the red blood cells. 5 – Gametes (1n) produced by meiosis. [Mosquito Stages] 6  - Moquito takes a blood meal and ingests gametes. 7 – Microgametes fertilizes macrogamete. 8 – Zygote (2n) forms. 9 – Zygote undergoes mitosis. 10 – Parasite differentiates and enters the saliva of the mosquito.
The life cycle of Plasmodium. (credit: modification of work by Centers for Disease Control and Prevention)

OpenStax Microbiology

Despite more than a century of intense research and clinical advancements, malaria  remains one of the most important infectious diseases in the world today. Its widespread distribution places more than half of the world’s population in jeopardy. In 2015, the WHO estimated there were about 214 million cases of malaria worldwide, resulting in about 438,000 deaths; about 88% of cases and 91% of deaths occurred in Africa. Although malaria is not currently a major threat in the US, the possibility of its reintroduction is a concern. Malaria is caused by several protozoan parasites in the genus PlasmodiumP. falciparum, P. knowlesi, P. malariae, P. ovale, and P. vivax. Plasmodium primarily infect red blood cells and are transmitted through the bite of Anopheles mosquitoes.

Currently, P. falciparum is the most common and most lethal cause of malaria, often called falciparum malaria. Falciparum malaria is widespread in highly populated regions of Africa and Asia, putting many people at risk for the most severe form of the disease.

The classic signs and symptoms of malaria are cycles of extreme fever and chills. The sudden, violent symptoms of malaria start with malaise, abrupt chills, and fever (39–41° C [102.2–105.8 °F]), rapid and faint pulse, polyuria, headache, myalgia, nausea, and vomiting. After 2 to 6 hours of these symptoms, the fever falls, and profuse sweating occurs for 2 to 3 hours, followed by extreme fatigue. These symptoms are a result of Plasmodium emerging from red blood cells synchronously, leading to simultaneous rupture of a large number of red blood cells, resulting in damage to the spleen, liver, lymph nodes, and bone marrow. The organ damage resulting from hemolysis causes patients to develop sludge blood (i.e., blood in which the red blood cells agglutinate into clumps) that can lead to lack of oxygen, necrosis of blood vessels, organ failure, and death.

In established infections, malarial cycles of fever and chills typically occur every 2 days in the disease described as tertian malaria, which is caused by P. vivax and P. ovale. The cycles occur every 3 days in the disease described as quartan malaria, which is caused by P. malariae. These intervals may vary among cases.

Plasmodium has a complex life cycle that includes several developmental stages alternately produced in mosquitoes and humans. When an infected mosquito takes a blood meal, sporozoites in the mosquito salivary gland are injected into the host’s blood. These parasites circulate to the liver, where they develop into schizonts. The schizonts then undergo schizogony, resulting in the release of many merozoites at once. The merozoites move to the bloodstream and infect red blood cells. Inside red blood cells, merozoites develop into trophozoites that produce more merozoites. The synchronous release of merozoites from red blood cells in the evening leads to the symptoms of malaria.

In addition, some trophozoites alternatively develop into male and female gametocytes. The gametocytes are taken up when the mosquito takes a blood meal from an infected individual. Sexual sporogony occurs in the gut of the mosquito. The gametocytes fuse to form zygotes in the insect gut. The zygotes become motile and elongate into an ookinete. This form penetrates the midgut wall and develops into an oocyst. Finally, the oocyst releases new sporozoites that migrate to the mosquito salivary glands to complete the life cycle.

Diagnosis of malaria is by microscopic observation of developmental forms of Plasmodium in blood smears and rapid EIA assays that detect Plasmodium antigens or enzymes. Drugs such as chloroquine, atovaquone , artemether, and lumefantrine may be prescribed for both acute and prophylactic therapy, although some Plasmodium spp. have shown resistance to antimalarial drugs. Use of insecticides and insecticide-treated bed nets can limit the spread of malaria. Despite efforts to develop a vaccine for malaria, none is currently available.

A micrograph showing red blood cells. A dark ring in the center of one cell is labeled ring form. A larger dark region in another cell is labeled schizont.
A blood smear (human blood stage) shows an early trophozoite in a delicate ring form (upper left) and an early stage schizont form (center) of Plasmodium falciparum from a patient with malaria. (credit: modification of work by Centers for Disease Control and Prevention)


Parker, N., Schneegurt, M., Thi Tu, A.-H., Forster, B. M., & Lister, P. (n.d.). Microbiology. Houston, Texas: OpenStax. Access for free at:


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