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 . Plasmodium falciparum map is cited from Gething et al. and the P. vivax map is from Guerra et al. .

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. .



Anstee D (2010) The relationship between blood groups and disease. Blood 115: 4635–4643.

Anstey NM, Russell B, Yeo TW and Price RN (2009) The pathophysiology of vivax malaria. Trends in Parasitology 25: 220–227.

Aurrecoechea C, Brestelli J, Brunk BP et al. (2009) PlasmoDB: a functional genomic database for malaria parasites. Nucleic Acids Research 37: D539–D543.

Bagnaresi P, Nakabashi M, Thomas AP, Reiter RJ and Garcia CR (2012) The role of melatonin in parasite biology. Molecular and Biochemical Parasitology 181: 1–6.

Bannister L and Mitchell G (2003) The ins, outs and roundabouts of malaria. Trends in Parasitology 19: 209–213.

Beeson JG, Osier FHA and Engwerda CR (2008) Recent insights into humoral and cellular immune responses against malaria. Trends in Parasitology 24: 578–584.

Bruce‐Chwatt LJ and de Zulueta J (1980) The Rise and Fall of Malaria in Europe: A Historico‐Epidemiological Study. Oxford: Oxford University Press.

Carlton JM, Adams JH, Silva JC et al. (2008) Comparative genomics of the neglected human malaria parasite Plasmodium vivax. Nature 455: 757–763.

Checkley AM, Smith A, Smith V et al. (2012) Risk factors for mortality from imported falciparum malaria in the United Kingdom over 20 years: an observational study. British Medical Journal 344: e2116.

Chene A, Donati D, Orem J et al. (2009) Endemic Burkitt's lymphoma as a polymicrobial disease: new insights on the interaction between Plasmodium falciparum and Epstein–Barr virus. Seminars in Cancer Biology 19: 411–420.

Cox‐Singh J, Davis TME, Lee K‐S et al. (2008) Plasmodium knowlesi malaria in humans is widely distributed and potentially life‐threatening. Clinical Infectious Diseases 46: 165–171.

Day N (2008) Malaria. In: Eddleston M, Davidson R, Brent A and Wilkinson R (eds) Oxford Handbook of Tropical Medicine, 3rd edn, pp. 31–66. Oxford: Oxford University Press.

Dondorp A, Nosten F, Stepniewska K et al. (2005) Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 366: 717–725.

Dondorp AM, Nosten F, Yi P et al. (2009) Artemisinin resistance in Plasmodium falciparum malaria. New England Journal of Medicine 361: 455–467.

Doolan DL, Dobaño C and Baird JK (2009) Acquired immunity to malaria. Clinical Microbiology Reviews 22: 13–36.

Doumbo OK, Thera MA, Koné AK et al. (2009) High levels of Plasmodium falciparum rosetting in all clinical forms of severe malaria in African children. American Journal of Tropical Medicine and Hygiene 81: 987–993.

Driss A, Hibbert JM, Wilson NO et al. (2011) Genetic polymorphisms linked to susceptibility to malaria. Malaria Journal 10: 271e.

Ermert V, Fink A, Jones A and Morse A (2011) Development of a new version of the Liverpool malaria model. II. Calibration and validation for West Africa. Malaria Journal 10: 62.

Gardner MJ, Hall N, Fung E et al. (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 419: 498–511.

Gething PW, Patil AP, Smith DL et al. (2011) A new world malaria map: Plasmodium falciparum endemicity in 2010. Malaria Journal 10: e378.

Ghosh K (2007) Pathogenesis of anemia in malaria: a concise review. Parasitology Research 101: 1463–1469.

Grau GER and Craig AG (2012) Cerebral malaria pathogenesis: revisiting parasite and host contributions. Future Microbiology 7: 291–302.

Greenwood BM and Targett GA (2011) Malaria vaccines and the new malaria agenda. Clinical Microbiology of Infection 17: 1600–1607.

Guerra CA, Howes RE, Patil AP et al. (2010) The international limits and population at risk of Plasmodium vivax transmission in 2009. PLoS Neglected Tropical Diseases 4: e774.

Howes RE, Patil AP, Piel FB et al. (2011) The global distribution of the Duffy blood group. Nature Communications 2: e266.

Kelly‐Hope L and McKenzie FE (2009) The multiplicity of malaria transmission: a review of entomological inoculation rate measurements and methods across sub‐Saharan Africa. Malaria Journal 8: e19.

Krief S, Escalante AA, Pacheco MA et al. (2010) On the diversity of malaria parasites in African apes and the origin of Plasmodium falciparum from Bonobos. PLoS Pathogens 6: e1000765.

Kwiatkowski DP (2005) How malaria has affected the human genome and what human genetics can teach us about malaria. American Journal of Human Genetics 77: 171–192.

Langhorne J, Ndungu FM, Sponaas AM and Marsh K (2008) Immunity to malaria: more questions than answers. Nature Immunology 9: 725–732.

Le Roch KG (2004) Global analysis of transcript and protein levels across the Plasmodium falciparum life cycle. Genome Research 14: 2308–2318.

Lindner SE, Miller JL and Kappe SHI (2012) Malaria parasite pre‐erythrocytic infection: preparation meets opportunity. Cellular Microbiology 14: 316–324.

Lopez C, Saravia C, Gomez A, Hoebeke J and Patarroyo MA (2010) Mechanisms of genetically‐based resistance to malaria. Gene 467: 1–12.

Malaria Atlas Project (2012):

Manning L, Rosanas‐Urgell A, Laman M et al. (2012) A histopathologic study of fatal paediatric cerebral malaria caused by mixed Plasmodium falciparum/Plasmodium vivax infections. Malaria Journal 11: 17e.

Martinsen ES, Perkins SL and Schall JJ (2008) A three‐genome phylogeny of malaria parasites (Plasmodium and closely related genera): Evolution of life‐history traits and host switches. Molecular Phylogenetics and Evolution 47: 261–273.

Pasternak ND and Dzikowski R (2009) PfEMP1: an antigen that plays a key role in the pathogenicity and immune evasion of the malaria parasite Plasmodium falciparum. International Journal of Biochemistry and Cell Biology 41: 1463–1466.

Pasvol G (2005) The treatment of complicated and severe malaria. British Medical Bulletin 75–76: 29–47

del Portillo HA, Ferrer M, Brugat T et al. (2012) The role of the spleen in malaria. Cellular Microbiology 14: 343–355.

bu‐Raddad LJ, Patnaik P and Kublin JG (2006) Dual infection with HIV and malaria fuels the spread of both diseases in sub‐Saharan Africa. Science 314: 1603–1606.

Rogerson SJ, Hviid L, Duffy PE, Leke RF and Taylor DW (2007) Malaria in pregnancy: pathogenesis and immunity. Lancet Infectious Diseases 7: 105–117.

Sherman IW (2011) Magic Bullets to Conquer Malaria. Washington, DC: ASM Press.

Sherman IW, Eda S and Winograd E (2003) Cytoadherence and sequestration in Plasmodium falciparum: defining the ties that bind. Microbes and Infection 5: 897–909.

Staines HM and Krishna S (2012) Treatment and Prevention of Malaria: Antimalarial Drug Chemistry, Action and Use (Milestones in Drug Therapy). Basel: Springer.

Stevenson MM and Riley EM (2004) Innate immunity to malaria. Nature Reviews Immunology 4: 169–180.

The RTS,S CTP (2012) A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants. New England Journal of Medicine 367: 2284–2295.

Tse MT (2010) Antimalarial drugs: a treasure trove of potential antimalarials. Nature Reviews Drug Discovery 9: 516–517.

White NJ (2004) Antimalarial drug resistance. Journal of Clinical Investigation 113: 1084–1092.

Wilson ML, Reller LB and Weinstein MP (2012) Malaria rapid diagnostic tests. Clinical Infectious Diseases 54: 1637–1641.

Winzeler EA (2008) Malaria research in the post‐genomic era. Nature 455: 751–756.

World Health Organization (2008) World Health Organization Global Malaria Control and Elimination: Report of a Technical Review, pp. 1–47. Geneva: WHO Press.

World Health Organization (2010) Guidelines for the Treatment of Malaria, 2nd edn, pp. 1–210. Geneva: WHO Press.

World Health Organization (2011) World Malaria Report 2011, pp. 1–248. Geneva: WHO Press.

Further Reading

Centres for Disease Control and Prevention (CDC) malaria website:

Dr. B.S. Kakkilaya's Malaria Site:

Malaria C (2007) Malaria – A Handbook for Health Professionals, pp. 1–220. New York: Macmillan.

Medicines for Malaria Venture website:‐us/malaria‐and‐medicines

Plasmodium vivax website:

Rocco F (2004) The Miraculous Fever‐Tree: Malaria, Medicine and the Cure that Changed the World. New York: Harper Collins.

Roll Back Malaria website:

Sherman IW (2005) Molecular Approaches to Malaria. Washington DC: ASM Press.

Webb LA Jr (2009) Humanity's Burden: A Global History of Malaria (Studies in Environment and History). Cambridge: Cambridge University Press.

Wellcome Foundation Malaria website:

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Bannister, Lawrence H, and Sherman, Irwin W(Feb 2013) Malaria. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001927.pub2]