Plasmodium

Abstract

Plasmodium is a genus of parasitic protozoa which infect erythrocytes of vertebrates and cause malaria. Their life cycle alternates between mosquito and vertebrate hosts. Parasites enter the bloodstream after a mosquito bite, and multiply sequentially within liver cells and erythrocytes before becoming male or female sexual forms. When ingested by a mosquito, these fuse, then the parasite multiplies again to form more invasive stages which are transmitted back in the insect's saliva to a vertebrate. All invasive stages have specialized secretory structures (apical organelles) typical of the protozoan subphylum Apicomplexa, enabling them to invade cells and tissues. Parasites exploit erythrocytes by ingesting haemoglobin and exporting molecules which change erythrocyte membrane properties. Five species infect humans, the most lethal being Plasmodium falciparum which can cause pathology and death by clogging blood vessels in brain, viscera and placenta. Many hundreds more species infect other mammals, birds and lizards.

Key Concepts:

  • Intracellular parasitism. Many apicomplexan protozoa invade and exploit the cells of their hosts, situated in a nutrient‐rich environment and protected from attack by their host's immune system.

  • Alternation of hosts. All parasites of the genus Plasmodium have two different types of host which they parasitize alternately, a vertebrate and a mosquito. This arrangement enables the parasite to multiply numbers greatly in the richly nutrient environment of the vertebrate host, and also to find new hosts via the mosquito vector.

  • The parasitophorous vacuole. Blood stage parasites are enclosed in a cavity within the erythrocyte (parasitophorous vacuole) lined by membrane (parasitophorous vacuole membrane) derived from the erythrocyte surface membrane. The parasite is therefore not in direct contact with the erythrocyte cytoplasm.

  • Life‐cycle stages. The structure, molecular composition and behaviour of Plasmodium parasites change constantly throughout its life cycle, as the expression patterns of its genes vary within both vertebrates and mosquito hosts, enabling parasites to exploit different aspects of the host's biology.

  • Intracellular invasion. Intracellular life requires the ability to selectively capture and enter host cells, seen in the invasion by merozoites into erythrocytes and of sporozoites into liver hepatocytes. In both cases this depends on the secretion of adhesive proteins and membrane‐altering substances by the parasite, and on its actin–myosin driven locomotion.

  • Host cell transformation. Intracellular parasites export various molecules into the host cell to transform its properties. In erythrocytes this increases permeability to nutrients and in some species causes the erythrocyte membrane to adhere to blood vessel walls. The parasite also consumes host cell cytoplasm.

  • Malaria. This is a generic name given to diseases in vertebrates caused by species of Plasmodium. They are typified in mammals by cyclic episodes of fever and may have many other complications including anaemia, spleen pathology, placental dysfunction, neurological complications and in severe malaria, coma and death.

  • Parasite evolution. Molecular studies indicate that the evolution of Plasmodium species is closely linked to the evolution of terrestrial vertebrates and has impacted significantly on the human genome.

Keywords: malaria; apicomplexa; parasite; erythrocyte; Plasmodium; protozoa

Figure 1.

The main features of the life cycle of the malaria parasite Plasmodium falciparum, showing its different phases in vertebrate and mosquito hosts.

Figure 2.

The stages of Plasmodium falciparum in the blood. (a) Light micrographs of infected erythrocytes stained as a blood film with Giemsa's stain are assembled into the major stages of asexual blood cycle and the sexual blood stages. (b) A transmission electron micrograph of a section through a blood sample infected with the simian malaria parasite Plasmodium knowlesi. A number of different stages are visible. To aid interpretation, false colour has been added to the monochrome micrographs, the parasites being coloured blue and the erythrocytes red. The same convention is followed in most other figures in this article. (c) An electron micrograph (EM) of a malaria merozoite, showing its main structural features. (d) Electron micrographs of the main blood stages of Plasmodium falciparum are assembled, coloured as in (b); nuclei are indicated in purple. Light micrographs of cells shown in (a) were provided by Gabriele Margos, Bath University, UK.

Figure 3.

(a)–(d) The merozoite and invasion. (a) A diagram shows the main organelles typical of Plasmodium merozoites. (b) Two merozoites of Plasmodium falciparum (arrows) and two erythrocytes have been imaged by scanning electron microscopy. (c) Depicts the main steps in merozoite invasion of an erythrocyte, related in (d) to three transmission EMs of invading Plasmodium knowlesi merozoites; false colours include green for a mitochondrion and orange for an apicoplast. (d (iv)) is altered from Bannister LH, Mitchell GH, Butcher GA and Dennis ED (1986). Lamellar membranes associated with rhoptries in erythrocytic merozoites of Plasmodium knowlesi: a clue to the mechanism of invasion. Parasitology92: 291–303, with permission of Cambridge University Press.

Figure 4.

(a)–(f) Details of trophozoite and schizont organization. (a) shows major features of a trophozoite stage of P. falciparum imaged by transmission EM. The diagram (b) illustrates the mechanism of haemoglobin uptake, digestion and storage in a trophozoite, related in other panels to electron micrographs of (c) the export of adhesive proteins and knobs to the erythrocyte surface via Maurer's clefts, (d) ingestion of haemoglobin through the cytostome, and (e) formation of the malaria pigment haemozoin, which is left uncoloured to show the high density of individual pigment crystals. (f) shows an EM of a schizont during the process of merozoite budding from the main parasite mass (residual body).

Figure 5.

(a)–(h) Illustrations of Plasmodium mosquito stages. (a) and (b) show ookinetes of Plasmodium berghei, (a) by light microscopy (Giemsa‐stained specimen, left and immuno‐fluorescently stained for myosin, right), and (b) by transmission EM showing numerous micronemes, here coloured red, in the anterior region. (c)–(f) show sporozoites of P. berghei expressing green fluorescent protein after transfection, enabling clear visualization by fluorescence microscopy. (c) a female mosquito containing oocysts in its gut wall shows the presence of parasites by green fluorescence in its abdomen (lower arrow) and also some sporozoites in a drop of saliva at the tip of its proboscis (upper arrow); (d)–(f) show the movement of sporozoites gliding in circular trajectories on a glass surface, imaged to trace the direction of gliding, seen in more detail in (e) and (f). The diagram in (g) shows the major structures visible in a Plasmodium sporozoite, with its anterior end towards the right. For comparison, an EM of the anterior part of a P. berghei sporozoite is shown in H, showing the elongated rhoptries and numerous micronemes crowded in this region. Original images shown in (a) were provided by Dr Inga Siden‐Kiamos and (b) Dr Anton Dluzewski, Institute of Molecular Biology and Biotechnology, Heraklion, Crete. (c), (d), (e), and (f) were provided by Dr Sylvia Münter and Dr Friedrich Frischknecht, University of Heidelberg Medical School, Heidelberg, Germany. (h) is reproduced by permission of Cambridge University Press from Schrével et al..

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http://www.wehi.edu.au/MalDB‐www/intro.html

http://www.who.int/topics/malaria/en/

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Bannister, Lawrence H, and Sherman, Irwin W(Dec 2009) Plasmodium. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001970.pub2]