Plasmodium falciparum
Blood smear of Plasmodium falciparum
Scientific classification
Kingdom: Protista Phylum: Apicomplexa Class: Aconoidasida Order: Haemosporida Family: Plasmodiidae Genus: Plasmodium Species: P. falciparum
Binomial name
Plasmodium falciparum Welch, 1897

Plasmodium falciparum is a protozoan parasite, one of the species of Plasmodium that cause malaria in humans. It is transmitted by Anopheles mosquitoes. P. falciparum is the most dangerous of these infections as P. falciparum malaria has the highest rates of complications and mortality. In addition it accounts for 80% of all human malarial infections and 90% of the deaths. It is more prevalent in sub-Saharan Africa than in other regions of the world. Image File history File links Plasmodium_falciparum_01. ... For other uses, see Scientific classification (disambiguation). ... Typical phyla Rhodophyta (red algae) Chromista Heterokontophyta (heterokonts) Haptophyta Cryptophyta (cryptomonads) Alveolates Pyrrhophyta (dinoflagellates) Apicomplexa Ciliophora (ciliates) Excavates Euglenozoa Percolozoa Metamonada Rhizaria Radiolaria Foraminifera Cercozoa Amoebozoa Choanozoa Many others; classification varies The Kingdom Protista or Protoctista is one of the commonly recognized biological kingdoms, including all the eukaryotes except for... Classes & Subclasses Aconoidasida Haemosporasina Piroplasmasina Blastocystea Conoidasida Coccidiasina Gregarinasina The Apicomplexa are a large group of protozoa, characterized by the presence of a unique organelle called an apical complex. ... Orders Haemosporida Piroplasmida The Aconoidasida are a class of Apicomplexan parasites. ... The Haemosporida are an order of the class Aconoidasida and include the protozoa responsible for the disease malaria. ... The Plasmodiidae are a family of apicomplexan parasites, including the type genus Plasmodium, which is responsible for malaria. ... Species Plasmodium achiotense Plasmodium achromaticum Plasmodium acuminatum Plasmodium adunyinkai Plasmodium aegyptensis Plasmodium aeuminatum Plasmodium agamae Plasmodium anasum Plasmodium anomaluri Plasmodium arachniformis Plasmodium ashfordi Plasmodium atheruri Plasmodium aurulentum Plasmodium australis Plasmodium attenuatum Plasmodium azurophilum Plasmodium balli Plasmodium bambusicolai Plasmodium basilisci Plasmodium beebei Plasmodium beltrani Plasmodium berghei Plasmodium bertii Plasmodium bigueti Plasmodium... This article does not cite any references or sources. ... William Henry Welch (April 8, 1850 - April 30, 1934) was an American physician and medical school administrator. ... 1897 (MDCCCXCVII) was a common year starting on Friday (see link for calendar). ... Leishmania donovani, (a species of protozoan) in a bone marrow cell Protozoa (in Greek proto = first and zoa = animals) are one-celled eukaryotes (that is, unicellular microbes whose cells have membrane-bound nuclei) that commonly show characteristics usually associated with animals, mobility and heterotrophy. ... A parasite is an organism that spends a significant portion of its life in or on the living tissue of a host organism and which causes harm to the host without immediately killing it. ... Species Plasmodium achiotense Plasmodium achromaticum Plasmodium acuminatum Plasmodium adunyinkai Plasmodium aegyptensis Plasmodium aeuminatum Plasmodium agamae Plasmodium anasum Plasmodium anomaluri Plasmodium arachniformis Plasmodium ashfordi Plasmodium atheruri Plasmodium aurulentum Plasmodium australis Plasmodium attenuatum Plasmodium azurophilum Plasmodium balli Plasmodium bambusicolai Plasmodium basilisci Plasmodium beebei Plasmodium beltrani Plasmodium berghei Plasmodium bertii Plasmodium bigueti Plasmodium... Malaria is a vector-borne infectious disease caused by protozoan parasites. ... Some Species Anopheles atroparvus Anopheles barberi Anopheles beklemishevi Anopheles coustani Anopheles crypticus Anopheles culicifacies Anopheles earlei Anopheles farauti Anopheles fluviatilis Anopheles forattinii Anopheles funestus Anopheles gambiae Anopheles grabhamii Anopheles hailarensis Anopheles halophylus Anopheles hyrcanus Anopheles introlatus Anopheles kosiensis Anopheles latens Anopheles maculipennis Anopheles minimus Anopheles moucheti Anopheles nili Anopheles ovengensis... For other uses, see Mosquito (disambiguation). ...

Background

Malaria is caused by an infection with protozoa of the genus Plasmodium. The name malaria comes from the Italian mala aria, meaning bad air, comes from the linkage suggested by Lancisi (1717) of malaria with the poisonous vapours of swamps. The organism itself was first seen by Laveran on November 6th 1880 at a military hospital in Constantine, Algeria, when he discovered a microgametocyte exflagellating. Manson (1894) hypothesised that mosquitoes could transmit malaria - an association made considerably earlier in India, possibly as early as 2000BC^{[citation needed]}. This hypothesis was experimentally confirmed independently by Giovanni Battista Grassi and Ronald Ross in 1898. Grassi (1900) proposed an exerythrocytic stage in the life cycle and this was later confirmed by Short, Garnham, Covell and Shute (1948) who found Plasmodium vivax in the human liver. // Events January 4 — The Netherlands, Britain & France sign Triple Alliance February 26-March 6 What is now the northeastern United States was paralyzed by a series of blizzards that buried the region. ... Malaria is a vector-borne infectious disease caused by protozoan parasites. ... Laveran won a Nobel Prize in 1907 Charles Louis Alphonse Laveran (June 18, 1845 – May 18, 1922) (sometimes spelled Alfons or Alfonse) was a French physician. ... Year 1880 (MDCCCLXXX) was a leap year starting on Thursday (link will display the full calendar) of the Gregorian calendar (or a leap year starting on Tuesday of the 12-day slower Julian calendar). ... Position of Constantine in Algeria. ... Manson may refer to: Locations Manson, Iowa Manson, Indiana Manson, Washington People Marilyn Manson (Brian Warner), lead singer of the band of the same name Charles Manson, a convicted mass-murderer from the United States of America Shirley Manson, from the band Garbage Mahlon Dickerson Manson, a Union General during... Giovanni Battista Grassi (1854-1925) was an Italian zoologist, known for work demonstrating that mosquitos carry the malaria plasmodium in their digestive tract, on the embryological development of honey bees, on parasites, particularly the vine parasite phylloxera, migrations and metamorphosis in eels, and on termites. ... Ronald Ross Sir Ronald Ross (May 13, 1857 – September 16, 1932) was a Scottish physician. ... Year 1898 (MDCCCXCVIII) was a common year starting on Saturday (link will display the full calendar) of the Gregorian calendar (or a common year starting on Monday of the 12-day-slower Julian calendar). ... Ğ: For the film, see: 1900 (film). ... Year 1948 (MCMXLVIII) was a leap year starting on Thursday (link will display the 1948 calendar) of the Gregorian calendar. ... Binomial name Plasmodium vivax Grassi & Feletti 1890 The parasite Plasmodium vivax is the most frequent and widely distributed cause of benign, but recurring (tertian), malaria. ...

Malaria has been a scourge throughout history and has killed more people than all wars and other plagues combined^{[citation needed]}. It remains globally the most important parasitic disease of man and claims the lives of more children worldwide than any other infectious disease. Since 1900 the area of the world exposed to malaria has been halved but in this time two billion more are presently exposed. Morbidity as well as mortality is substantial. Infection rates in children in endemic areas are of the order of 50%: chronic infection has been shown to reduce school scores by up to 15%. Reduction in the incidence of malaria coincides with increased economic output. The term plague is usually define mnd as a pestilence, an epidemic disease causing a high rate of mortality. ... A parasitic disease is a disease caused or transmitted by a parasite. ... Äž: For the film, see: 1900 (film). ...

While there are no effective vaccines for any of the six or more species that cause human malaria, drugs have been employed for centuries. In 1640, Huan del Vego first employed the tincture of the cinchona bark for treating malaria: the native Indians of Peru and Ecuador had been using it even earlier for treating fevers. Thompson (1650) introduced this "Jesuits' bark" to England: its first recorded use there was by Dr John Metford of Northampton in 1656. Morton (1696) presented the first detailed description of the clinical picture of malaria and of its treatment with cinchona. Gize (1816) studied the extraction of crystalline quinine from the cinchona bark and Pelletier and Caventou (1820) in France extracted pure quinine alkaloids which they named quinine and cinchonine. Events December 1 - Portugal regains its independence from Spain and João IV of Portugal becomes king. ... Species See text Cinchona L., is the name of a genus in Rubiaceae family, large evergreens that can grow over 10 metres tall. ... The Society of Jesus (Latin: Societas Iesu), commonly known as the Jesuits, is a Roman Catholic religious order. ... For other uses, see England (disambiguation). ... Northampton is a large market town and a local government district in the English East Midlands region. ... Morton is the name of several people, places, and things in the English language. ... The year 1696 had the earliest equinoxes and solstices for 400 years in the Gregorian calendar, because this year is a leap year and the Gregorian calendar would have behaved like the Julian calendar since March 1500 had it have been in use that long. ... Year 1816 (MDCCCXVI) was a leap year starting on Monday (link will display the full calendar) of the Gregorian calendar (or a leap year starting on Saturday of the 12-day slower Julian calendar). ... Quinine (IPA: ) is a natural white crystalline alkaloid having antipyretic (fever-reducing), antimalarial, analgesic (painkilling), and anti-inflammatory properties and a bitter taste. ... Pierre Joseph Pelletier, (1788-1842), was a chemist who did notable research work on vegetable alkaloids, and was the co-discoverer of quinine and strychnine. ... Joseph Bienaimé Caventou (1795–1877) was a French chemist. ... 1820 was a leap year starting on Saturday (see link for calendar). ... Quinine (IPA: ) is a natural white crystalline alkaloid having antipyretic (fever-reducing), antimalarial, analgesic (painkilling), and anti-inflammatory properties and a bitter taste. ... Chemical structure of ephedrine, a phenethylamine alkaloid An alkaloid is, strictly speaking, a naturally occurring amine produced by a plant,[1] but amines produced by animals and fungi are also called alkaloids. ...

Plasmodium Life Cycle

When an infected mosquito bites a human, sporozoites enter the human circulation. These go to and penetrate the liver cells, where they asexually reproduce, via the process of schizogony. This intracellular, asexually dividing form of the parasite is known as a schizont, and because this schizont is in liver cells and not RBCs, it is known as the exoerythrocytic schizont stage.

Aside: In Plasmodium vivax and Plasmodium ovale species, the development of the schizont is retarded, and a "resting" stage of the parasite, called the Hypnozoite, is formed. This is NOT the case in Plasmodium falciparum.

When the hepatocytes burst, exoerythrocytic schizonts release merozoites into the blood, which are capable of infecting erythrocytes. Inside the erythrocytes, the merozoites develop into ring-like trophozoites, which then form the erythrocytic schizonts.

Mature erythrocytic schizonts form merozoites again by breaking apart inside the erythrocytes. These merozoites are a transient intracellular form, either rapidly infecting new red blood cells to complete the erythrocytic cycle, or dying. In addition, when infection of new blood cells occurs, instead of forming trophozoites the parasites may grow into the immature gametocytes. These can be taken up in the bloodmeal of a mosquito, causing the parasite to go back to the intermediate host and completing the life cycle.

Treatment and drug resistance

Attempts to make synthetic antimalarials began in 1891. Atabrine was developed in 1928, was used widely throughout the Pacific in World War II but was deeply unpopular because of the yellowing of the skin it caused. In the late 1930s, the Germans developed chloroquine, which went into use in the North African campaigns. Mao Zedong encouraged Chinese scientists to find new antimalarials after seeing the casualties in the Vietnam War. Artemisinin was discovered in the 1970s based on a medicine described in China in the year 340. This new drug became known to Western scientists in the late 1980s and early 1990s and is now a standard treatment. In 1976 P. falciparum was successfully cultured in vitro for the first time which facilitated the development of new drugs substantially.^[1] Quinacrine (trade name: Atabrine) is a drug with a number of different medical applications. ... Chloroquine is a 4-aminoquinoline drug long used in the treatment or prevention of malaria. ... Mao redirects here. ... Artemisinin (IPA: ) is a drug used to treat multi-drug resistant strains of falciparum malaria. ... Malaria culture is the method to grow malaria parasites continuously in an in vitro environment. ...

Vaccination

Although an antimalarial vaccine is urgently needed, infected individuals never develop a sterilizing (complete) immunity, making the prospects for such a vaccine dim. The parasites live inside cells, where they are largely hidden from the immune response. Infection has a profound effect on the immune system including immune suppression. Dendritic cells suffer a maturation defect following interaction with infected erythrocytes and become unable to induce protective liver-stage immunity. Infected erythrocytes directly adhere to and activate peripheral blood B cells from nonimmune donors. The var gene products, a group of highly expressed surface antigens, bind the Fab and Fc fragments of human immunoglobulins in a fashion similar to protein A to Staphylococcus aureus and this may offer some protection to the parasite from the human immune system. Despite the poor prospects for a fully protective vaccine, it may be possible to develop a vaccine that would reduce the severity of malaria for children living in endemic areas. A scanning electron microscope image of a single neutrophil (yellow), engulfing anthrax bacteria (orange). ... Dendritic cells (DC) are immune cells and form part of the mammal immune system. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... Immunity is a medical term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. ... B cells are lymphocytes that play a large role in the humoral immune response (as opposed to the cell-mediated immune response). ... For the server security software, see Microsoft Forefront. ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Binomial name Rosenbach 1884 Staphylococcus aureus , literally Golden Cluster Seed and also known as golden staph, is the most common cause of staph infections. ...

Microscopic appearance

Blood smear from a P. falciparum culture (K1 strain). Several red blood cells have ring stages inside them. Close to the center there is a schizont and on the left a trophozoite.

Among medical professionals, the preferred method to diagnose malaria and determine which species of Plasmodium is causing the infection is by examination of a blood film microscopically in a laboratory. Each species has distinctive physical characteristics that are apparent under a microscope. In P. falciparum, only early trophozoites and gametocytes are seen in the peripheral blood. It is unusual to see mature trophozoites or schizonts in peripheral blood smears as these are usually sequestered in the tissues. The parasitised erythrocytes are not enlarged and it is common to see cells with more than one parasite within them (multiply parasitised erythrocytes). Occasionally, faint comma-shaped red dots are seen on the red cell surface called "Maurer's dots". The comma shaped dots can also appear as pear shaped blotches. Image File history File links Download high-resolution version (1159x745, 95 KB) I, the creator of this work, hereby release it into the public domain. ... Image File history File links Download high-resolution version (1159x745, 95 KB) I, the creator of this work, hereby release it into the public domain. ... Malaria culture is the method to grow malaria parasites continuously in an in vitro environment. ... Blood films, Giemsa stained A blood film or peripheral blood smear is a slide made from a drop of blood, that allows the cells to be examined. ... Robert Hookes microscope (1665) - an engineered device used to study living systems. ... This article does not cite its references or sources. ... A gametocyte is a eukaryotic germ cell that divides by mitosis into other gametocytes or by meiosis into gametes. ...

Plasmodium and the human genome

In the 50,000 years since Plasmodium first infected humans, the presence of the parasite in human populations has altered the human genome in a multitude of ways, as humans have been forced to develop resistance to the disease. Beet, a doctor working in Southern Rhodesia (now Zimbabwe) in 1948, first suggested that sickle-cell disease could offer some protection to malaria. This suggestion was reiterated by J. B. S. Haldane in 1949 who suggested that thalassaemia could provide similar protection. This hypothesis has since been confirmed and has been extended to hemoglobin C and hemoglobin E, abnormalities in ankyrin and spectrin (ovalocytosis , elliptocytosis), in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency, loss of the Gerbich antigen (glycophorin C) and the Duffy antigen on the erythrocytes, thalassemias and variations in the major histocompatibility complex classes 1 and 2 and CD32 and CD36. Southern Rhodesia was the name of the British colony situated immediately to the north of South Africa, known today as Zimbabwe. ... Year 1948 (MCMXLVIII) was a leap year starting on Thursday (link will display the 1948 calendar) of the Gregorian calendar. ... Sickle-cell disease is a group of genetic disorders caused by sickle hemoglobin (Hgb S or Hb S). ... John Burdon Sanderson Haldane (November 5, 1892 – December 1, 1964), who normally used J.B.S. as a first name, was a British geneticist and evolutionary biologist. ... Year 1949 (MCMXLIX) was a common year starting on Saturday (link will display the full calendar) of the Gregorian calendar. ... Hemoglobin C is a hemoglobinopathy, caused by an inherited abnormality of the beta globin gene. ... Ankyrin is a membrane protein that mediates the attachment of the erythrocyte membrane skeleton to the plasma membrane and interacts with CD44 and inositol triphosphate. ... Spectrin is a cytoskeletal protein that lines the intracellular side of the plasma membrane of many cell types in pentagonal or hexagonal arrangements, forming a scaffolding and playing an important role in maintenance of plasma membrane integrity and cytoskeletal structure (Huh et al. ... Hereditary ovalocytosis is an inherited condition in which your red blood cells, which are supposed to be round, instead have a slightly oval or elliptical shape. ... Hereditary elliptocytosis is a blood disorder in which a large proportion of the sufferers erythrocytes (i. ... Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive hereditary disease featuring nonimmune hemolytic anemia in response to a number of causes. ... Pyruvate Kinase Deficiency is an inherited autosomal recessive disorder which affects the survival of red blood cells, causing them to break down easily. ... Glycophorin C (GYPC; CD236/CD236R; glycoprotein beta; glycoconnectin; PAS-2) is an integral membrane protein of the erythrocyte and acts as the receptor for the Plasmodium falciparum protein PfEBP-2 (erythrocyte binding protein 2; baebl; EBA-140). ... Discovery In 1950 the Duffy antigen was discovered in a multiply transfused hemophiliac in whose serum contained the first example of anti-Fya. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... Thalassemia (British spelling, thalassaemia) is an inherited autosomal recessive blood disease. ... Protein images comparing the MHC I (1hsa) and MHC II (1dlh) molecules. ... The CD32 in action The AmigaCD32 was the worlds first 32bit CD_ROM based game console. ... CD36 is an integral membrane protein found on the surface of many cell types in vertebrate animals and is also known as FAT, SCARB3, GP88, glycoprotein IV (gpIV) and glycoprotein IIIb (gpIIIb). ...

In 1995 a consortium - the malaria genome project (MGP) - was set up to sequence the genome of P. falciparum. The genome of the parasite mitochondrion was reported in 1995, that of the plastid (apicoplast) in 1996, and the sequence of the first nuclear chromosome (Chromosome 2) in 1998. The sequence of chromosome 3 was reported in 1999 and the entire genome on 3rd October 2002. The ~24 megabase genome is extremely AT rich (~80%) and is organised into 14 chromosomes: just over 5300 genes were described. In biology the genome of an organism is the whole hereditary information of an organism that is encoded in the DNA (or, for some viruses, RNA). ... Electron micrograph of a mitochondrion showing its mitochondrial matrix and membranes In cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed organelle that is found in most eukaryotic cells. ... Plant cells with visible chloroplasts. ... Figure 1: A representation of a condensed eukaryotic chromosome, as seen during cell division. ...

Evolution and Plasmodium falciparum

Surprisingly, malaria parasites harbor a plastid similar to plant chloroplasts, which they acquired by engulfing (or being invaded by) a eukaryotic alga, and retaining the algal plastid as a distinctive organelle encased within four membranes (see endosymbiotic theory). The apicomplexan plastid, or apicoplast, is an essential organelle, thought to be involved in the synthesis of lipids and several other compounds, and provides an attractive target for antimalarial drug development, particularly in light of the emergence of parasites resistant to chloroquine and other existing antimalarial agents. Chloroplasts are organelles found in plant cells and eukaryotic algae that conduct photosynthesis. ... Kingdoms Eukaryotes are organisms with complex cells, in which the genetic material is organized into membrane-bound nuclei. ... Schematic of typical animal cell, showing subcellular components. ... It has been suggested that Proto-mitochondrion be merged into this article or section. ... Classes & Subclasses Aconoidasida Haemosporasina Piroplasmasina Blastocystea Conoidasida Coccidiasina Gregarinasina The Apicomplexa are a large group of protozoa, characterized by the presence of a unique organelle called an apical complex. ... The Apicoplast is a relict, non-photosynthetic plastid found in the malaria parasite, Plasmodium falciparum. ...

The protist, Plasmodium falciparum, has evolved in more recent times. Most strains of malaria can be treated with chloroquine, however P. falciparum has developed resistance to this treatment. In addition the strain can be treated with a combination of quinine and tetracycline. There are strains of P. falciparum that have grown resistant to this treatment as well. Different strains of P. falciparum have grown resistant to different treatments. Often the resistance of the strain depends on where it was contracted. Many cases of malaria that come from parts of the Caribbean and west of the Panama Canal as well as the Middle East and Egypt can often be treated with chloroquin, since they have not yet developed resistance. Nearly all cases contracted in Africa, India, and southeast Asia have grown resistant to this medication and there have been cases in Thailand and Cambodia in which the strain has been resistant to nearly all treatments. Often the strain grows resistant to the treatment in areas where the use is not as tightly regulated.

Plasmodium falciparum is often used as an example for evolution. Since sickle-cell disease carriers are relatively resistant to malaria, and people from malaria-stricken countries are much more likely to have the sickle-cell trait, it is often given as an example to show how mutations are not inherently good or bad, but in different environments could have either negative or positive effects. Thus, if one lives in a malaria-stricken part of the world, natural selection gives a net advantage to having the sickle-cell trait. Other hemoglobin polymorphisms, such as thalassemias and hemoglobin C are also suspected to have arisen as a genetic means to reduce the burden of malaria. This article is about evolution in biology. ... Sickle-cell disease is a group of genetic disorders caused by sickle hemoglobin (Hgb S or Hb S). ... This article is about mutation in biology, for other meanings see: mutation (disambiguation). ...

References

ISSN, or International Standard Serial Number, is the unique eight-digit number applied to a periodical publication including electronic serials. ...

Sources and further reading

Overview

• Introductory
• Overview
• Malaria biology
• Life cycle cartoon

Spatial distribution

• Malaria Atlas Project

Blood slides

• Blood forms
• Blood forms
• Blood forms
• Blood forms
• Multiple blood forms
• Female gametocyte
• Female gametocyte
• ncbi.nlm.nih.gov

Case histories

• Case 1
• Case 2
• Case 3
• Case 4

Pathology due to Plasmodium falciparum

Brain

• Gross pathology
• Low power H & E stain
• High power H & E stain showing parasite adherence to the vessel walls

Spleen

• Gross pathology
• Low power H & E
• Smear preparation
• Smear preparation

Liver

• Low power H & E
• High power H & E

Kidney

• Low power H & E
• High power H & E
• High power H & E
• Membrane stain
• Membrane stain

Plasmodium falciparum genome data

• Gardner, M.J.; Hall, N.; Fung, E.; White, O.; Berriman, M.; Hyman, R.W.; Carlton, J.M.; Pain, A.; Nelson, K.E.; Bowman, S.; Others, (2002). "Genome sequence of the human malaria parasite Plasmodium falciparum". Nature 419: 498-511. doi:10.1038/nature01097. 

• PlasmoDB: The Plasmodium Genome Resource
• GeneDB Plasmodium falciparum
• Genome

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

Other

• Colombian scientists develop computacional tool to detect the plasmodium falciparum (in spanish)