The life cycle of malaria

29th Apr 2021

Let’s talk about what happens when someone is infected with malaria. Remember, malaria results from infection with one of the various species of the parasite Plasmodium. Malaria-causing Plasmodia are carried by a special type of mosquito, the anopheline mosquito. 

 

Exposure to the malaria sporozoites through a mosquito's bite

To become infected, a person has to be bitten by a female mosquito that carries immature malaria cells called sporozoites. As the mosquito finishes feeding, she injects the crescent-shaped sporozoites into her victim’s bloodstream where they make their way to the liver.

Mosquito on skin. Sporozoite traveling in blood vessel between skin and liver. Illustration.

Figure 1. When a mosquito finishes feeding, immature malaria cells, or sporozoites, are injected into the bloodstream and filtered out in the liver.  

 

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Replication and formation of merozoites inside the liver

As the blood carrying the sporozoites passes through the liver, specialized white blood cells—fixed-tissue macrophages called Kupffer cells—filter the foreign sporozoites from the blood. But, the sporozoites are able to escape destruction by the macrophages and migrate into the cells of the liver. 

 

In the hepatocyte, the sporozoites are able to begin an asexual reproduction process called schizogony. This occurs when a sporozoite divides and fills the liver cell—now known as a liver schizont—with many smaller, identical copies of itself called merozoites. Eventually, the liver schizont ruptures and releases the merozoites into the bloodstream.

4 panels. Malaria sporozoites in Kupffer cell. Sporozoite in hepatocyte. Liver schizont. Schizont ruptures to release merozoites. Illustration.

Figure 2. a) Malaria parasites, or sporozoites, in the bloodstream travel to the liver where they are picked up by Kupffer cells, b) and escape into the hepatocytes, c) the sporozoites divide through schizogony, filling the hepatocyte to create a liver schizont, d) the liver schizont bursts to release immature parasite cells called merozoites into the bloodstream. 

At the time of hepatocyte invasion, the patient has not yet shown any clinical signs of malaria.

Invasion of red blood cells (RBCs) is essential for survival and continued reproduction of malaria parasites

Once in the bloodstream, the merozoites find and invade red blood cells (RBCs) where they have two fates: asexual reproduction or sexual reproduction.

Asexual reproduction of the malaria parasite

Inside the RBC, the merozoite will continue the process of schizogony creating an RBC schizont that eventually bursts, releasing more of these merozoites, which will find and invade other RBCs and the process will start all over again. 

Merozoite in bloodstream, entering red blood cell, red blood cell schizont. Illustration.

Figure 3. Asexual life cycle of malaria in the blood. 

This red blood cell infection cycle causes the periodic fever and chills that are the classic early manifestations of malaria. Every time merozoites are released into the blood stream, the immune system is activated, causing fever and chills.

Sexual reproduction and the formation of malaria gametocytes

Some of those merozoites do not undergo schizogony in the RBC. Instead, they become sexual structures called gametocytes which hang around until a mosquito bites.

Red blood cell with merozoite. Male and female gametocytes. Illustration.

Figure 4. Plasmodium merozoites enter red blood cells (RBCs) and may become gametocytes. 

Formation of new malaria sporozoites in the mosquito vector (sporogony)

Then, when a mosquito bites the infected individual, it ingests the gametocytes. And, once taken in by a mosquito the female and male gametocytes form a kinetic egg called an ookinete. The egg eventually becomes an oocyst that releases sporozoites as it matures. And when the mosquito bites another person, these sporozoites are transferred, infecting them with malaria. And the cycle continues.

The pathway gametocytes follow in a mosquito. Gametocytes. Oocyst. Ookinete. Sporozoites in mosquito. Sporozoites outside mosquito. Illustration.

Figure 5. Malaria gametocytes are picked up when a mosquito bites an infected individual. Inside the mosquito, the female and male gametocytes form a kinetic egg, or ookinete, which develops into an oocyst that releases sporozoites as it matures. These sporozoites are transferred when the mosquito bites another person, infecting them with malaria.

 

We know that can be a lot to remember, so we've created this handy summary of the key points:

Infographic depicting the stages of the malaria life cycle.

 

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Recommended reading

  • Ashley, EA, Phyo, AP, and Woodrow, CJ. 2018. Malaria. Lancet391:1608­–1621. PMID: 29631781
  • Fairhurst, RM and Wellems, TE. 2014. “Malaria (Plasmodium Species)”. In: Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, edited by Bennett, JE, Dolin, R, Blaser, MJ. 8th edition. Philadelphia: Elsevier Saunders. (Fairhurst and Wellems 2014, 3070–3090)
  • Phillips, MA, Burrows, JN, Manyando, C, et al. 2017. Malaria. Nat Rev Dis Primers3: 17050. PMID: 28770814
  • World Health Organization. 2019. World malaria report 2019. World Health Organizationhttps://www.who.int