Malaria

Lawrence H Bannister, King's College London, London, UK
Irwin W Sherman, University of California, Riverside, California, USA

Published online: February 2013

DOI: 10.1002/9780470015902.a0001927.pub2

Malaria is a disease of the blood resulting from infection by protozoan parasites of the genus Plasmodium, transmitted by female Anopheline mosquitoes. Five species of Plasmodium infect humans, Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, Plasmodium malariae and Plasmodium knowlesi. The parasite life cycle includes stages in the mosquito and in human liver cells and red blood cells, which they penetrate and feed on. Plasmodium falciparum is the main cause of malaria deaths, especially of young African children. Cerebral malaria, renal and pulmonary failure are major pathologies. Frequent infections gradually confer immunity over several years, but this is rarely complete. Many antimalarial drugs are available for prophylaxis and treatment, but emerging parasite resistance limits their use. Several vaccines are being tested, with some moderate success. Efforts to control malaria include breeding grounds drainage, insecticide sprays and use of insecticide-impregnated bednets. With the help of several major global initiatives, there are reports of significant reductions of malaria cases.

Key Concepts:

  • Malaria is a disease caused by infection of red blood cells (erythrocytes) by protozoan parasites of the genus Plasmodium.
  • Malaria is a major global disease affecting many millions worldwide and causing up to a million or more deaths a year, mostly children under 5 years in sub-Saharan Africa.
  • Malaria is caused by five species of Plasmodium, the most lethal being Plasmodium falciparum.
  • Malaria parasites are transmitted to humans by the bite of infected female mosquitoes, and then the parasite multiplies first in the liver and later in the bloodstream before passing back to the mosquito as it feeds.
  • Malaria has many symptoms, which include cyclic episodes of fever, the frequency depending on malaria parasite species.
  • Severe malaria is frequently fatal if not treated rapidly.
  • The pathology of malaria is related to blood infections, either by destroying erythrocytes or by blocking small blood vessels (sequestration) as occurs in cerebral malaria.
  • Acquired immunity builds up gradually and its maintenance depends on repeated infections; innate immunity is often associated with genetic diseases of the blood.
  • Numerous antimalarial drugs have been developed including those related to quinine and more recently artmesinin, but parasites have developed resistance to most of these in some parts of the world; several vaccines are now under trial.
  • Other efforts to control malaria include elimination of mosquitoes and draining their breeding grounds plus the use of insecticide-impregnated bednets to minimise transmission.

Keywords: malaria; Anopheles; mosquito; parasite; disease; Plasmodium; pathology; immunity; antimalarials

Figure 1. Current global maps showing the spatial limits of distribution of P. falciparum in 2010 and P. vivax in 2009. The values represent the annual parasite incidence for (a) P. falciparum (PfAPI) and (b) P. vivax (PvAPI), representing the percentage of people with detectable parasitaemias in random samples of global populations. The distributions of the two species are colour-coded in the same way (see boxes, lower picture); grey areas are those where previously endemic malaria has been cleared; pink indicates regions where the API is less than 0.1% though present; dark red areas have APIs equal to or exceeding 0.1%; the oblique hatching on the P. vivax map indicates areas where the Duffy-negative (Fy–) gene is present in more than 90% of the population, coinciding with low P. vivax infection. Both maps are reproduced from the Malaria Atlas Project (2012). Plasmodium falciparum map is cited from Gething et al. (2011) and the P. vivax map is from Guerra et al. (2010).
Figure 2. Female feeding A. gambiae, showing the abdomen distended with a blood meal. Photograph provided by Jim Gathany, Centers for Disease Control and Prevention, USA.
Figure 3. Diagrams illustrating the major stages of the P. falciparum life cycle. In (a) the female mosquito commences feeding by injecting anticoagulant saliva containing sporozoites into the skin and these enter blood vessels to be taken to the liver (b). Here they penetrate hepatocytes lining the liver sinusoids, transforming into a feeding stage which then multiplies and releases large numbers of merozoites into the circulation. These merozoites enter erythrocytes (c) where they feed (ring and trophozoite stages) then multiply (schizont stage) before a new set of merozoites is released into the circulation. Here they invade fresh erythrocytes, to continue a recurring process of invasion, growth, multiplication and release termed the asexual blood cycle. Some parasites leave this cycle to become sexual blood stages (d) (male and female gametocytes) which are taken up by a mosquito when it feeds (e). In the mosquito's gut (f) these transform into rounded female gametes and male gametes, the latter by a final rapid multiplication of nuclei and release of flagellated cells which go on to fertilise the female gametes. The resulting zygotes are transformed into elongated motile ookinetes which penetrates the gut wall and encyst (as oocysts) on its external surface. Here the parasites grow and multiply to each form large numbers of sporozoites which penetrate the cyst wall and enter the insect's blood cavity (haemocoel) where they move to the salivary glands. At the next blood meal these are injected with the mosquito's saliva into the skin where they enter the host's blood stream (a).
Figure 4. Asexual blood stages of P. falciparum. (a) High power light micrograph of a group of P. falciparum infected erythrocytes, from a blood film stained with Giemsa stain showing a double ring infection (left) and two schizonts (right). (b–e) Different stages of the parasite including (from left to right): (b) merozoite, (c) ring, (d) trophozoite and (e) schizont stages. Note the mass of brown pigment (haemozoin) in the more mature stages. (f, g) Transmission electron micrographs of sections through two blood stages, with colouring added to clarify the structure: erythrocyte – red; parasite cytoplasm – blue; parasite nucleus – purple; food vacuole – yellow; (f) trophozoite showing a large food vacuole containing dark crystals of haemozoin; note the irregular surface of the host erythrocyte. (g) Section through a mature schizont containing a cluster of merozoites ready for release; arrowheads indicate knobs. (h) Scannning electron micrograph of an infected erythrocyte showing surface irregularities and knobs. Scale bar for (a–e) as shown for (b) above, and scale bar for (f) to (h) as shown near (f–h) below. Micrographs (a–e) are unpublished images courtesy of Dr. Gabrielle Margos. Material in (f) and (g) prepared by John Hopkins.
Figure 5. Sequestration of P. falciparum infected erythrocytes in cerebral microvessels from a cerebral malaria post-mortem brain smear. The micrograph shows parallel blood vessels packed with numerous infected erythrocytes clogging the vessels; the parasites are dark because each contains malaria pigment. Interestingly, Plasmodium vivax was also present in this infection but did not sequester, providing evidence of the different behaviour of the two parasites. Courtesy of Manning et al. (2012).
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    ePath Wellcome Foundation Malaria website: http://malaria.wellcome.ac.uk/

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Medical Microbiology | Protozoa
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Article Title: Malaria
 
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Bannister, Lawrence H, and Sherman, Irwin W(Feb 2013) Malaria. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001927.pub2]