Malaria Classification and external resources
Plasmodium falciparum ring-forms and gametocytes in human blood. A gametocyte is a Eukaryotic Germ cell that divides by Mitosis into other gametocytes or by Meiosis into Gametids during
ICD-10	B50.
ICD-9	084
OMIM	248310
DiseasesDB	7728
MedlinePlus	000621
eMedicine	med/1385  emerg/305 ped/1357
MeSH	C03.752.250.552

Malaria is a vector-borne infectious disease caused by protozoan parasites. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The International Statistical Classification of Diseases and Related Health Problems 10th Revision ( ICD -10) is a coding of diseases and signs symptoms abnormal findings A00-A79 - Bacterial infections and other intestinal infectious diseases and STDs (A00-A09 Intestinal Infectious diseases ( The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Mendelian Inheritance in Man project is a Database that catalogues all the known Diseases with a genetic component, and—when possible—links them The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. MedlinePlus, with the MedlinePlus Medical Encyclopedia, is a website network containing Health information from the world's largest medical Library eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books In Epidemiology, a vector is an Organism that does not cause Disease itself but which transmits Infection by conveying Pathogens from An infectious disease is a clinically evident Disease resulting from the presence of Pathogenic microbial agents including Pathogenic viruses Pathogenic Protozoa (in Greek πρῶτον proton "first" and ζῷα zoia "animals" are unicellular Eukaryotes (singular Parasitism is a type of symbiotic relationship between Organisms of different Species. It is widespread in tropical and subtropical regions, including parts of the Americas, Asia, and Africa. The Tropics are centered on the Equator and limited in Latitude by the Tropic of Cancer in the northern hemisphere at approximately 23°26' (23 The Americas are the lands of the Western hemisphere or New World, consisting of the Continents of North America and South America Each year, there are approximately 515 million cases of malaria, killing between one and three million people, the majority of whom are young children in Sub-Saharan Africa. Sub-Saharan Africa is a geographical term used to describe the area of the African continent which lies south of the Sahara, or those African countries ^[1] Malaria is commonly associated with poverty, but is also a cause of poverty and a major hindrance to economic development. Economic development is the development of economic wealth of countries or regions for the well-being of their inhabitants

Malaria is one of the most common infectious diseases and an enormous public health problem. Public health is "the science and art of preventing disease prolonging life and promoting health through the organised efforts and informed choices of society organisations The disease is caused by protozoan parasites of the genus Plasmodium. Protozoa (in Greek πρῶτον proton "first" and ζῷα zoia "animals" are unicellular Eukaryotes (singular Parasitism is a type of symbiotic relationship between Organisms of different Species. A genus (plural genera from Γένος Latin genus "descent family type gender" is a low-level Taxonomic A plasmodium is also the macroscopic form of the Protist known as a Slime mould. Only four types of the plasmodium parasite can infect humans; the most serious forms of the disease are caused by Plasmodium falciparum and Plasmodium vivax, but other related species (Plasmodium ovale, Plasmodium malariae) can also affect humans. Plasmodium falciparum is a Protozoan Parasite, one of the species of Plasmodium that cause Malaria in humans Plasmodium vivax is a Protozoal Parasite and a human Pathogen. Plasmodium ovale is a species of parasitic Protozoa that causes tertian Malaria in humans Plasmodium malariae is a parasitic Protozoa that causes Malaria in humans and animals This group of human-pathogenic Plasmodium species is usually referred to as malaria parasites.

Malaria parasites are transmitted by female Anopheles mosquitoes. Anopheles is a Genus of Mosquito ( Culicidae) There are approximately 400 Anopheles species of which 30-40 transmit five different Mosquitoes are insects in the family Culicidae. They have a pair of scaled wings a pair of Halteres, a slender body and long legs The parasites multiply within red blood cells, causing symptoms that include symptoms of anemia (light headedness, shortness of breath, tachycardia etc. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative ), as well as other general symptoms such as fever, chills, nausea, flu-like illness, and in severe cases, coma and death. Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris Rigor is a shaking occurring during a high Fever. It occurs because cytokines and Prostaglandins are released as part of an Immune Nausea ( Latin: Nausea, Greek:, " Sea-sickness " also called wamble) is the sensation of unease and discomfort In Medicine, a coma (from the Greek koma, meaning deep sleep is a profound state of Unconsciousness. Malaria transmission can be reduced by preventing mosquito bites with mosquito nets and insect repellents, or by mosquito control measures such as spraying insecticides inside houses and draining standing water where mosquitoes lay their eggs. A mosquito net offers Protection against Mosquitos flies, and other Insects and thus against diseases such as Malaria. An insect repellent is a substance applied to skin clothing or other surfaces which discourages Insects (and Arthropods in general from landing or climbing on that An insecticide is a Pesticide used against Insects in all developmental forms

Although some are under development, no vaccine is currently available for malaria; preventative drugs must be taken continuously to reduce the risk of infection. A vaccine is a biological preparation which is used to establish or improve immunity to a particular disease These prophylactic drug treatments are often too expensive for most people living in endemic areas. Prophylaxis ( Greek "προφυλάσσω" to guard or prevent beforehand) is any medical or Public health procedure whose purpose In Epidemiology, an Infection is said to be endemic (from Greek en- in or within + demos people in a Population when Most adults from endemic areas have a degree of long-term recurrent infection and also of partial resistance; the resistance reduces with time and such adults may become susceptible to severe malaria if they have spent a significant amount of time in non-endemic areas. They are strongly recommended to take full precautions if they return to an endemic area. Malaria infections are treated through the use of antimalarial drugs, such as quinine or artemisinin derivatives, although drug resistance is increasingly common. Antimalarial drugs are designed to prevent or cure Malaria. Some antimalarial agents particularly Chloroquine and Hydroxychloroquine, are also used Quinine (ˈkwaɪnaɪn kwɪˈniːn ˈkwiːniːn is a natural white Crystalline Alkaloid having Antipyretic (fever-reducing antimalarial, Artemisinin (ɑrtɨˈmɪsɨnɨn is a drug used to treat multi-drug resistant strains of falciparum Malaria. Drug resistance is the reduction in effectiveness of a drug in curing a disease or improving a patient's symptoms

History

Further information: History of malaria

Charles Louis Alphonse Laveran

Malaria has infected humans for over 50,000 years, and may have been a human pathogen for the entire history of our species. The history of malaria began before Human history, as this ancient disease appears to have evolved before humans appeared on Earth. A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious ^[2] Indeed, close relatives of the human malaria parasites remain common in chimpanzees, our closest relatives. ^[3] References to the unique periodic fevers of malaria are found throughout recorded history, beginning in 2700 BC in China. ^[4] The term malaria originates from Medieval Italian: mala aria — "bad air"; and the disease was formerly called ague or marsh fever due to its association with swamps. Italian ( or lingua italiana) is a Romance language spoken by about 63 million people as a First language, primarily in Italy. The miasmatic theory of disease held that Diseases such as Cholera or the Black Death were caused by a miasma (Greek language "pollution"

Scientific studies on malaria made their first significant advance in 1880, when a French army doctor working in the military hospital of Constantine Algeria named Charles Louis Alphonse Laveran observed parasites for the first time, inside the red blood cells of people suffering from malaria. Constantine ( Latin: Cōnstantīnus, Greek:) is a given name and surname derived from the Latin word constans, meaning constant or Algeria ( ar [[Arabic]] الجزائر, Al Jaza'ir ælʤæˈzæːʔir Amazigh: ⴷⵥⴰⵢⴻⵔ Dzayer) officially the People's Charles Louis Alphonse Laveran ( June 18, 1845 &ndash May 18, 1922) was a French Physician. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood He therefore proposed that malaria was caused by this protozoan, the first time protozoa were identified as causing disease. Protozoa (in Greek πρῶτον proton "first" and ζῷα zoia "animals" are unicellular Eukaryotes (singular ^[5] For this and later discoveries, he was awarded the 1907 Nobel Prize for Physiology or Medicine. The Nobel Prize in Physiology or Medicine (Nobelpriset i fysiologi eller medicin is awarded once a year by the Swedish Karolinska Institute. The protozoan was called Plasmodium by the Italian scientists Ettore Marchiafava and Angelo Celli. Ettore Marchiafava ( 1847 Rome - 1935 Rome) was an Italian Physician and Zoologist who worked on Malaria Ettore Marchiafava Angelo Celli (1857, Cagli – 1914, Rome) was an Italian Physician and zoologist who studied Malaria. ^[6] A year later, Carlos Finlay, a Cuban doctor treating patients with yellow fever in Havana, first suggested that mosquitoes were transmitting disease to and from humans. Carlos Juan Finlay (born Juan Carlos Finlay y Barrés on December 3 1833, Puerto Principe Cuba &ndash August 20 1915 Yellow fever (also called yellow jack, black vomit or sometimes American Plague) is an acute viral disease Havana ( IPA: aˈβana officially Ciudad de La Habana, is the Capital city, major port and leading However, it was Britain's Sir Ronald Ross working in the Presidency General Hospital in Calcutta who finally proved in 1898 that malaria is transmitted by mosquitoes. Sir Ronald Ross KCB, ( 13 May 1857 – 16 September 1932) was an Indian Physician. The Institute of Post-Graduate Medical Education and Research and Seth Sukhlal Karnani Memorial Hospital is a tertiary referral government hospital for the state of West Bengal He did this by showing that certain mosquito species transmit malaria to birds and isolating malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. ^[7] For this work Ross received the 1902 Nobel Prize in Medicine. After resigning from the Indian Medical Service, Ross worked at the newly-established Liverpool School of Tropical Medicine and directed malaria-control efforts in Egypt, Panama, Greece and Mauritius. The Liverpool School of Tropical Medicine (LSTM England, was founded on 12 November 1898, by a donation from Sir Alfred Lewis Jones, a This article is about the country of Egypt For a topic outline on this subject see List of basic Egypt topics. Panama, officially the Republic of Panama (República de Panamá) is the southernmost country of Central America. Greece (Ελλάδα transliterated: Elláda, historically, Ellás,) officially the Hellenic Republic (Ελληνική Δημοκρατία Mauritius (pronounced məˈrɪʃəs L’île Maurice /il mɔ'ʁis/ Mauritian Creole: Maurice) officially the Republic of Mauritius, République ^[8] The findings of Finlay and Ross were later confirmed by a medical board headed by Walter Reed in 1900, and its recommendations implemented by William C. Gorgas in the health measures undertaken during construction of the Panama Canal. Major Walter Reed, MD, ( September 13 1851 - November 23 1902) was a U Major General William Crawford Gorgas KCMG ( October 3, 1854, in Mobile Alabama -- July 3, 1920, in London One of the greatest challenges facing the builders of the Panama Canal was dealing with the Tropical diseases rife in the area The Panama Canal is a man-made Canal in Panama which joins the This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against this disease.

The first effective treatment for malaria was the bark of cinchona tree, which contains quinine. Cinchona is a Genus of about 25 Species in the family Rubiaceae, native to tropical South America. Quinine (ˈkwaɪnaɪn kwɪˈniːn ˈkwiːniːn is a natural white Crystalline Alkaloid having Antipyretic (fever-reducing antimalarial, This tree grows on the slopes of the Andes, mainly in Peru. The Andes form the world's longest exposed Mountain range. They lie as a continuous chain of highland along the western coast of South America. Peru (Perú Piruw Piruw officially the Republic of Peru ( reˈpuβlika del peˈɾu is a country in western South America. This natural product was used by the inhabitants of Peru to control malaria, and the Jesuits introduced this practice to Europe during the 1640s where it was rapidly accepted. Peru (Perú Piruw Piruw officially the Republic of Peru ( reˈpuβlika del peˈɾu is a country in western South America. The Society of Jesus ( Latin: Societas Iesu, SJ and SI or SJ, SI) is a Catholic religious order ^[9] However, it was not until 1820 that the active ingredient quinine was extracted from the bark, isolated and named by the French chemists Pierre Joseph Pelletier and Joseph Bienaimé Caventou. Year 1820 ( MDCCCXX) was a Leap year starting on Saturday (link will display the full calendar of the Gregorian calendar (or a Leap year Pierre-Joseph Pelletier ( 22 March 1788 &ndash 19 July 1842) was a French Chemist who did notable research work on vegetable ^[10]

In the early twentieth century, before antibiotics, patients with syphilis were intentionally infected with malaria to create a fever, following the work of Julius Wagner-Jauregg. In modern usage an antibiotic is a Chemotherapeutic agent with activity against Microorganisms such as Bacteria, fungi or Protozoa Syphilis is a Sexually transmitted disease caused by the spirochetal Bacterium Treponema pallidum pallidum. Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris Julius Wagner-Jauregg, ( March 7, 1857 Wels, Upper Austria – September 27, 1940 Vienna) was an Austrian physician By accurately controlling the fever with quinine, the effects of both syphilis and malaria could be minimized. Quinine (ˈkwaɪnaɪn kwɪˈniːn ˈkwiːniːn is a natural white Crystalline Alkaloid having Antipyretic (fever-reducing antimalarial, Although some patients died from malaria, this was preferable to the almost-certain death from syphilis. ^[11]

Although the blood stage and mosquito stages of the malaria life cycle were identified in the 19th and early 20th centuries, it was not until the 1980s that the latent liver form of the parasite was observed. The 19th century of the Common Era began on January 1, 1801 and ended on December 31, 1900, according to the Gregorian calendar The twentieth century of the Common Era began on ^[12][13] The discovery of this latent form of the parasite finally explained why people could appear to be cured of malaria but still relapse years after the parasite had disappeared from their bloodstreams.

Distribution and impact

Further information: Diseases of poverty, Tropical disease

Areas of the world where malaria is endemic in the 21st Century (coloured blue). Diseases of Poverty are Diseases that are more Prevalent among "the poor" than among wealthier people Tropical diseases are diseases that are prevalent in or unique to tropical and subtropical regions In Epidemiology, an Infection is said to be endemic (from Greek en- in or within + demos people in a Population when ^[14]

Malaria causes about 400–900 million cases of fever and approximately one to three million deaths annually^[15][16] — this represents at least one death every 30 seconds. The vast majority of cases occur in children under the age of 5 years;^[17] pregnant women are also especially vulnerable. Despite efforts to reduce transmission and increase treatment, there has been little change in which areas are at risk of this disease since 1992. ^[18] Indeed, if the prevalence of malaria stays on its present upwards course, the death rate could double in the next twenty years. ^[15] Precise statistics are unknown because many cases occur in rural areas where people do not have access to hospitals or the means to afford health care. Consequently, the majority of cases are undocumented. ^[15]

Although co-infection with HIV and malaria does cause increased mortality, this is less of a problem than with HIV/tuberculosis co-infection, due to the two diseases usually attacking different age-ranges, with malaria being most common in the young and active tuberculosis most common in the old. Tuberculosis (abbreviated as TB for tubercle bacillus or T u' b' erculosis Bacillus --> is a common ^[19] Although HIV/malaria co-infection produces less severe symptoms than the interaction between HIV and TB, HIV and malaria do contribute to each other's spread. This effect comes from malaria increasing viral load and HIV infection increasing a person's susceptibility to malaria infection. Viral load is a measure of the severity of a viral infection and can be calculated by estimating the amount of virus in an involved body fluid ^[20]

Malaria is presently endemic in a broad band around the equator, in areas of the Americas, many parts of Asia, and much of Africa; however, it is in sub-Saharan Africa where 85– 90% of malaria fatalities occur. The Americas are the lands of the Western hemisphere or New World, consisting of the Continents of North America and South America ^[21] The geographic distribution of malaria within large regions is complex, and malarial and malaria-free areas are often found close to each other. ^[22] In drier areas, outbreaks of malaria can be predicted with reasonable accuracy by mapping rainfall. ^[23] Malaria is more common in rural areas than in cities; this is in contrast to dengue fever where urban areas present the greater risk. ^[24] For example, the cities of Vietnam, Laos and Cambodia are essentially malaria-free, but the disease is present in many rural regions. Vietnam (ˌviːɛtˈnɑːm Việt Nam) officially Laos (ˈlɑːoʊs or /ˈlaʊs/ officially the Lao People's Democratic Republic, is a Landlocked country in Southeast Asia, bordered by Burma The Kingdom of Cambodia ( formerly known as Kampuchea (, transliterated: Preăh Réachéanachâkr Kâmpŭchea) is a country in South East ^[25] By contrast, in Africa malaria is present in both rural and urban areas, though the risk is lower in the larger cities. ^[26] The global endemic levels of malaria have not been mapped since the 1960s. In Epidemiology, an Infection is said to be endemic (from Greek en- in or within + demos people in a Population when However, the Wellcome Trust, UK, has funded the Malaria Atlas Project^[27] to rectify this, providing a more contemporary and robust means with which to assess current and future malaria disease burden. The Wellcome Trust was established in 1936 as an independent charity funding research to improve human and animal health The Malaria Atlas Project, abbreviated as MAP, is a non-profit project funded for five years by the Wellcome Trust, UK Disease burden is the impact of a health problem in an area measured by financial cost mortality morbidity or other indicators

Socio-economic effects

Malaria is not just a disease commonly associated with poverty, but is also a cause of poverty and a major hindrance to economic development. Economic development is the development of economic wealth of countries or regions for the well-being of their inhabitants The disease has been associated with major negative economic effects on regions where it is widespread. A comparison of average per capita GDP in 1995, adjusted to give parity of purchasing power, between malarious and non-malarious countries demonstrates a fivefold difference ($1,526 USD versus $8,268 USD). Moreover, in countries where malaria is common, average per capita GDP has risen (between 1965 and 1990) only 0. 4% per year, compared to 2. 4% per year in other countries. ^[28] However, correlation does not demonstrate causation, and the prevalence is at least partly because these regions do not have the financial capacities to prevent malaria. In its entirety, the economic impact of malaria has been estimated to cost Africa $12 billion USD every year. The economic impact includes costs of health care, working days lost due to sickness, days lost in education, decreased productivity due to brain damage from cerebral malaria, and loss of investment and tourism. ^[17] In some countries with a heavy malaria burden, the disease may account for as much as 40% of public health expenditure, 30-50% of inpatient admissions, and up to 50% of outpatient visits. ^[29]

Symptoms

Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia (caused by hemolysis), hemoglobinuria, and convulsions. Fever (also known as pyrexia, from the Greek pyretos meaning fire or a febrile response, from the Latin word Febris Arthralgia (from Greek arthro-, joint + -algos, pain literally means joint pain; it is a symptom of injury infection illnesses -- in particular Vomiting (also called throwing up, emesis) is the forceful expulsion of the contents of one's Stomach through the Mouth and sometimes the Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative Hemolysis (or haemolysis)—from the Greek Hemo-, Greek meaning blood - Lysis, meaning to break open—is the breaking In Medicine, hemoglobinuria is a condition in which the Oxygen transport Protein Hemoglobin is found in abnormally high concentrations in the An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting There may be the feeling of tingling in the skin, particularly with malaria caused by P. falciparum. The classical symptom of malaria is cyclical occurrence of sudden coldness followed by rigor and then fever and sweating lasting four to six hours, occurring every two days in P. Rigour or rigor (see spelling differences) has a number of meanings in relation to intellectual life and discourse vivax and P. ovale infections, while every three for P. malariae. ^[30] P. falciparum can have recurrent fever every 36-48 hours or a less pronounced and almost continuous fever. For reasons that are poorly understood, but which may be related to high intracranial pressure, children with malaria frequently exhibit abnormal posturing, a sign indicating severe brain damage. Intracranial pressure, ( ICP) is the pressure exerted by the Cranium on the Brain tissue Cerebrospinal fluid (CSF and the brain's circulating Abnormal posturing is an involuntary Flexion or extension of the arms and legs indicating severe Brain injury. ^[31] Malaria has been found to cause cognitive impairments, especially in children. It causes widespread anemia during a period of rapid brain development and also direct brain damage. Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative This neurologic damage results from cerebral malaria to which children are more vulnerable. ^[32]

Severe malaria is almost exclusively caused by P. falciparum infection and usually arises 6-14 days after infection. ^[33] Consequences of severe malaria include coma and death if untreated—young children and pregnant women are especially vulnerable. In Medicine, a coma (from the Greek koma, meaning deep sleep is a profound state of Unconsciousness. Splenomegaly (enlarged spleen), severe headache, cerebral ischemia, hepatomegaly (enlarged liver), hypoglycemia, and hemoglobinuria with renal failure may occur. Splenomegaly is an enlargement of the Spleen, which usually lies in the left upper quadrant (LUQ of the Human abdomen. A headache ( cephalalgia in medical terminology is a condition of pain in the Head; sometimes Neck or upper back pain may also be interpreted In Medicine, ischemia ( Greek ισχαιμία, isch- is restriction hema or haema is Blood) is a restriction Hepatomegaly is the condition of having an enlarged Liver. It is a nonspecific medical sign having many causes which can broadly be broken down into Infection Hypoglycemia or hypoglycaemia is the medical term for a pathologic state produced by a lower than normal level of Glucose ( sugar) in the blood Renal failure or kidney Renal failure may cause blackwater fever, where hemoglobin from lysed red blood cells leaks into the urine. Blackwater fever is a complication of Malaria characterized by intravascular Haemolysis, haemoglobinuria and Kidney failure. Severe malaria can progress extremely rapidly and cause death within hours or days. ^[33] In the most severe cases of the disease fatality rates can exceed 20%, even with intensive care and treatment. ^[34] In endemic areas, treatment is often less satisfactory and the overall fatality rate for all cases of malaria can be as high as one in ten. ^[35] Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria. ^[36]

Chronic malaria is seen in both P. vivax and P. ovale, but not in P. falciparum. Here, the disease can relapse months or years after exposure, due to the presence of latent parasites in the liver. Describing a case of malaria as cured by observing the disappearance of parasites from the bloodstream can therefore be deceptive. The longest incubation period reported for a P. vivax infection is 30 years. ^[33] Approximately one in five of P. vivax malaria cases in temperate areas involve overwintering by hypnozoites (i. To overwinter is to pass through or wait out the Winter season or to pass through that period of the year when “winter” conditions (cold or Sub-zero temperatures e. , relapses begin the year after the mosquito bite). ^[37]

Causes

A Plasmodium sporozoite traverses the cytoplasm of a mosquito midgut epithelial cell in this false-color electron micrograph. A micrograph, microphotograph or photomicrograph is a Photograph or similar image taken through a Microscope or similar device to show

Malaria parasites

Malaria is caused by protozoan parasites of the genus Plasmodium (phylum Apicomplexa). Protozoa (in Greek πρῶτον proton "first" and ζῷα zoia "animals" are unicellular Eukaryotes (singular Parasitism is a type of symbiotic relationship between Organisms of different Species. A plasmodium is also the macroscopic form of the Protist known as a Slime mould. In humans malaria is caused by P. falciparum, P. malariae, P. ovale, P. vivax and P. Plasmodium falciparum is a Protozoan Parasite, one of the species of Plasmodium that cause Malaria in humans Plasmodium malariae is a parasitic Protozoa that causes Malaria in humans and animals Plasmodium ovale is a species of parasitic Protozoa that causes tertian Malaria in humans Plasmodium vivax is a Protozoal Parasite and a human Pathogen. knowlesi. P. falciparum is the most common cause of infection and is responsible for about 80% of all malaria cases, and is also responsible for about 90% of the deaths from malaria. ^[38] Parasitic Plasmodium species also infect birds, reptiles, monkeys, chimpanzees and rodents. ^[39] There have been documented human infections with several simian species of malaria, namely P. knowlesi, P. Plasmodium knowlesi is a Primate Malaria parasite commonly found in Southeast Asia. inui, P. cynomolgi,^[40] P. simiovale, P. brazilianum, P. schwetzi and P. simium; however, with the exception of P. knowlesi, these are mostly of limited public health importance. Although avian malaria can kill chickens and turkeys, this disease does not cause serious economic losses to poultry farmers. Avian malaria is a Parasitic disease affecting Birds Etiology Avian malaria is most notably caused by Plasmodium relictum ^[41] However, since being accidentally introduced by humans it has decimated the endemic birds of Hawaii, which evolved in its absence and lack any resistance to it. This article is one of a series providing information about endemism among birds in the World's various zoogeographic zones ^[42]

Mosquito vectors and the Plasmodium life cycle

The parasite's primary (definitive) hosts and transmission vectors are female mosquitoes of the Anopheles genus. In Epidemiology, a vector is an Organism that does not cause Disease itself but which transmits Infection by conveying Pathogens from Mosquitoes are insects in the family Culicidae. They have a pair of scaled wings a pair of Halteres, a slender body and long legs Anopheles is a Genus of Mosquito ( Culicidae) There are approximately 400 Anopheles species of which 30-40 transmit five different Young mosquitoes first ingest the malaria parasite by feeding on an infected human carrier and the infected Anopheles mosquitoes carry Plasmodium sporozoites in their salivary glands. Anopheles is a Genus of Mosquito ( Culicidae) There are approximately 400 Anopheles species of which 30-40 transmit five different In the life-cycle of Apicomplexan protozoa sporozoites ( sporos, seed + zoon, animal are cells that infect new hosts The salivary glands in mammals are exocrine glands that produce saliva A mosquito becomes infected when it takes a blood meal from an infected human. Once ingested, the parasite gametocytes taken up in the blood will further differentiate into male or female gametes and then fuse in the mosquito gut. A gametocyte is a Eukaryotic Germ cell that divides by Mitosis into other gametocytes or by Meiosis into Gametids during A gamete (from Ancient Greek γαμέτης; translated gamete = wife gametes = husband is a cell that fuses with another gamete This produces an ookinete that penetrates the gut lining and produces an oocyst in the gut wall. An ookinete (G oon, egg + kinetos, motile is a Zygote of Protozoans such as the Malaria organism An oocyst is the spore phase of certain Protists such as Cryptosporidium and Toxoplasma. When the oocyst ruptures, it releases sporozoites that migrate through the mosquito's body to the salivary glands, where they are then ready to infect a new human host. In the life-cycle of Apicomplexan protozoa sporozoites ( sporos, seed + zoon, animal are cells that infect new hosts This type of transmission is occasionally referred to as anterior station transfer. ^[43] The sporozoites are injected into the skin, alongside saliva, when the mosquito takes a subsequent blood meal.

Only female mosquitoes feed on blood, thus males do not transmit the disease. The females of the Anopheles genus of mosquito prefer to feed at night. Anopheles is a Genus of Mosquito ( Culicidae) There are approximately 400 Anopheles species of which 30-40 transmit five different They usually start searching for a meal at dusk, and will continue throughout the night until taking a meal. Malaria parasites can also be transmitted by blood transfusions, although this is rare. Blood transfusion is the process of transferring Blood or blood-based products from one person into the Circulatory system of another ^[44]

Pathogenesis

The life cycle of malaria parasites in the human body. A mosquito infects a pregnant woman, first in the liver and then in the bloodstream. First, sporozoites enter the bloodstream, and migrate to the liver. They infect liver cells (hepatocytes), where they multiply into merozoites, rupture the liver cells, and escape back into the bloodstream. Then, the merozoites infect red blood cells (erythrocytes), where they develop into ring forms, then trophozoites (a feeding stage), then multinucleated schizonts (a reproduction stage), then merozoites again. The merozoites rupture the blood cells and return to the bloodstream to infect more blood cells. Only the ring forms circulate in the bloodstream; the other red blood cells stick (adhere) to the walls (endothelium) of small blood vessels (venules), preventing the infected red blood cells from traveling to the spleen and being destroyed.

Malaria in humans develops via two phases: an exoerythrocytic (hepatic) and an erythrocytic phase. When an infected mosquito pierces a person's skin to take a blood meal, sporozoites in the mosquito's saliva enter the bloodstream and migrate to the liver. In the life-cycle of Apicomplexan protozoa sporozoites ( sporos, seed + zoon, animal are cells that infect new hosts The liver is a vital organ in the human body and is present in Vertebrates and some other animals Within 30 minutes of being introduced into the human host, they infect hepatocytes, multiplying asexually and asymptomatically for a period of 6–15 days. Hepatocytes make up 70-80% of the Cytoplasmic mass of the Liver. Once in the liver these organisms differentiate to yield thousands of merozoites which, following rupture of their host cells, escape into the blood and infect red blood cells, thus beginning the erythrocytic stage of the life cycle. A merozoite (G meros, part a series + zoon, animal is a Daughter cell of a Protozoan Parasite. Red blood cells are the most common type of Blood cell and the Vertebrate body's principal means of delivering Oxygen to the body tissues via the Blood ^[45] The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell. ^[46]

Within the red blood cells the parasites multiply further, again asexually, periodically breaking out of their hosts to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells.

Some P. vivax and P. ovale sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead produce hypnozoites that remain dormant for periods ranging from several months (6–12 months is typical) to as long as three years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in these two species of malaria. ^[47]

The parasite is relatively protected from attack by the body's immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor However, circulating infected blood cells are destroyed in the spleen. The spleen is an organ found in all Vertebrate animals In humans the spleen is located in the abdomen of the body where it functions in the destruction of redundant Red To avoid this fate, the P. falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thereby sequestering the parasite from passage through the general circulation and the spleen. Proteins are large Organic compounds made of Amino acids arranged in a linear chain and joined together by Peptide bonds between the Carboxyl ^[48] This "stickiness" is the main factor giving rise to hemorrhagic complications of malaria. Bleeding, technically known as hemorrhaging / haemorrhaging (see American and British spelling differences) is the loss of Blood from High endothelial venules (the smallest branches of the circulatory system) can be blocked by the attachment of masses of these infected red blood cells. High endothelial venules (HEV are specialized Post-capillary venous swellings characterized by Simple cuboidal cells as opposed to Simple squamous The blockage of these vessels causes symptoms such as in placental and cerebral malaria. In cerebral malaria the sequestrated red blood cells can breach the blood brain barrier possibly leading to coma. The blood-brain barrier (BBB is a metabolic or cellular structure in the Central nervous system (CNS that restricts the passage of various chemical substances and microscopic ^[49]

Although the red blood cell surface adhesive proteins (called PfEMP1, for Plasmodium falciparum erythrocyte membrane protein 1) are exposed to the immune system they do not serve as good immune targets because of their extreme diversity; there are at least 60 variations of the protein within a single parasite and perhaps limitless versions within parasite populations. ^[48] Like a thief changing disguises or a spy with multiple passports, the parasite switches between a broad repertoire of PfEMP1 surface proteins, thus staying one step ahead of the pursuing immune system.

Some merozoites turn into male and female gametocytes. A gametocyte is a Eukaryotic Germ cell that divides by Mitosis into other gametocytes or by Meiosis into Gametids during If a mosquito pierces the skin of an infected person, it potentially picks up gametocytes within the blood. Fertilization and sexual recombination of the parasite occurs in the mosquito's gut, thereby defining the mosquito as the definitive host of the disease. New sporozoites develop and travel to the mosquito's salivary gland, completing the cycle. Pregnant women are especially attractive to the mosquitoes,^[50] and malaria in pregnant women is an important cause of stillbirths, infant mortality and low birth weight,^[51] particularly in P. A stillbirth occurs when a Fetus which has died in the Uterus or during labor or delivery exits a Woman 's body falciparum infection, but also in other species infection, such as P. vivax. ^[52]

Evolutionary pressure of malaria on human genes

Further information: Evolution, Natural selection

Malaria is thought to have been the greatest selective pressure on the human genome in recent history. eVolution is the third Album by eLDee, it was due to be released in 2008 Natural selection is the process by which favorable Heritable traits become more common in successive Generations of a Population of In the context of Evolution, certain traits or Alleles of a Species may be subject to selection The human genome is the Genome of Homo sapiens, which is stored on 23 chromosome pairs ^[53] This is due to the high levels of mortality and morbidity caused by malaria, especially the P. falciparum species. Death is the termination of the biological functions that define living Organisms It refers both to a specific In Medicine, Epidemiology and Actuarial science, the term morbidity can refer to the state of poor health (from Latin Plasmodium falciparum is a Protozoan Parasite, one of the species of Plasmodium that cause Malaria in humans

Sickle-cell disease

Distribution of the sickle cell trait.

Distribution of malaria.

The best-studied influence of the malaria parasite upon the human genome is the blood disease, sickle-cell disease. Sickle-cell disease or sickle-cell anaemia (or anemia) is a Blood disorder characterized by Red blood cells that assume an abnormal rigid In sickle-cell disease, there is a mutation in the HBB gene, which encodes the beta globin subunit of haemoglobin. Hemoglobin ( also spelled haemoglobin and abbreviated Hb or Hgb) is the Iron -containing Oxygen -transport Metalloprotein The normal allele encodes a glutamate at position six of the beta globin protein, while the sickle-cell allele encodes a valine. Glutamic acid (abbreviated as Glu or E) is one of the 20 Alpha Amino acids It is not among the human Essential amino acids Its Valine (abbreviated as Val or V) is an α- Amino acid with the Chemical formula HO2CCH(NH2CH(CH32 This change from a hydrophilic to a hydrophobic amino acid encourages binding between haemoglobin molecules, with polymerization of haemoglobin deforming red blood cells into a "sickle" shape. Such deformed cells are cleared rapidly from the blood, mainly in the spleen, for destruction and recycling.

In the merozoite stage of its life cycle the malaria parasite lives inside red blood cells, and its metabolism changes the internal chemistry of the red blood cell. Infected cells normally survive until the parasite reproduces, but if the red cell contains a mixture of sickle and normal haemoglobin, it is likely to become deformed and be destroyed before the daughter parasites emerge. Thus, individuals heterozygous for the mutated allele, known as sickle-cell trait, may have a low and usually unimportant level of anaemia, but also have a greatly reduced chance of serious malaria infection. Zygosity refers to the genetic condition of a Zygote. In genetics zygosity describes the similarity or dissimilarity of DNA between Homologous Anemia ( AmE) or anæmia/anaemia ( BrE) (from the Ancient Greek grc-Latn anaîmia, meaning “without blood” is defined as a qualitative This is a classic example of heterozygote advantage. A heterozygote advantage ( heterozygous advantage) describes the case in which the heterozygote genotype has a higher relative fitness than either the

Individuals homozygous for the mutation have full sickle-cell disease and in traditional societies rarely live beyond adolescence. Zygosity refers to the genetic condition of a Zygote. In genetics zygosity describes the similarity or dissimilarity of DNA between Homologous However, in populations where malaria is endemic, the frequency of sickle-cell genes is around 10%. In Epidemiology, an Infection is said to be endemic (from Greek en- in or within + demos people in a Population when Allele frequency is a measure of the relative frequency of an Allele at a genetic place(locus in a Population. The existence of four haplotypes of sickle-type hemoglobin suggests that this mutation has emerged independently at least four times in malaria-endemic areas, further demonstrating its evolutionary advantage in such affected regions. The term haplotype is a contraction of the term " haploid Genotype. There are also other mutations of the HBB gene that produce haemoglobin molecules capable of conferring similar resistance to malaria infection. These mutations produce haemoglobin types HbE and HbC which are common in Southeast Asia and Western Africa, respectively. West Africa or Western Africa is the Westernmost Region of the African Continent.

Thalassaemias

Another well documented set of mutations found in the human genome associated with malaria are those involved in causing blood disorders known as thalassaemias. Thalassemia (from Greek θαλασσα thalassa sea + αίμα haima blood British spelling "thalassaemia" is an inherited Autosomal recessive Studies in Sardinia and Papua New Guinea have found that the gene frequency of β-thalassaemias is related to the level of malarial endemicity in a given population. Sardinia (sɑrˈdɪnɪə Sardegna Sardigna or Sardinnya is the second-largest island in the Mediterranean Sea (after Sicily) Papua New Guinea (or ˈpæpjuːə in Tok Pisin: Papua Niugini) officially the Independent State of Papua New Guinea, is a country in Oceania Allele frequency is a measure of the relative frequency of an Allele at a genetic place(locus in a Population. Thalassemia (from Greek θαλασσα thalassa sea + αίμα haima blood British spelling "thalassaemia" is an inherited Autosomal recessive A study on more than 500 children in Liberia found that those with β-thalassaemia had a 50% decreased chance of getting clinical malaria. Liberia, officially the Republic of Liberia, is a country on the west coast of Africa, bordered by Sierra Leone, Guinea, Côte d'Ivoire Similar studies have found links between gene frequency and malaria endemicity in the α+ form of α-thalassaemia. Presumably these genes have also been selected in the course of human evolution. Natural selection is the process by which favorable Heritable traits become more common in successive Generations of a Population of

Duffy antigens

The Duffy antigens are antigens expressed on red blood cells and other cells in the body acting as a chemokine receptor. The Duffy antigen is a protein located on the outside of Red blood cells and is named after the patient in which it was discovered An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response Chemokines are a family of small Cytokines, or Proteins secreted by cells Proteins are classified as chemokines according to shared structural characteristics The expression of Duffy antigens on blood cells is encoded by Fy genes (Fya, Fyb, Fyc etc. ). Plasmodium vivax malaria uses the Duffy antigen to enter blood cells. Plasmodium vivax is a Protozoal Parasite and a human Pathogen. However, it is possible to express no Duffy antigen on red blood cells (Fy-/Fy-). This genotype confers complete resistance to P. The genotype is the genetic constitution of a cell an organism or an individual (i vivax infection. The genotype is very rare in European, Asian and American populations, but is found in almost all of the indigenous population of West and Central Africa. ^[54] This is thought to be due to very high exposure to P. vivax in Africa in the last few thousand years.

G6PD

Glucose-6-phosphate dehydrogenase (G6PD) is an enzyme which normally protects from the effects of oxidative stress in red blood cells. Glucose-6-phosphate dehydrogenase ( G6PD) is a cytosolic Enzyme in the Pentose phosphate pathway (see image a Metabolic pathway that supplies Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Oxidative stress is caused by an imbalance between the production of reactive oxygen and a biological system's ability to readily detoxify the reactive intermediates or easily However, a genetic deficiency in this enzyme results in increased protection against severe malaria.

HLA and interleukin-4

HLA-B53 is associated with low risk of severe malaria. The human leukocyte antigen system ( HLA) is the name of the Major histocompatibility complex (MHC in humans This MHC class I molecule presents liver stage and sporozoite antigens to T-Cells. The major histocompatibility complex ( MHC) is a large genomic region or Gene family found in most Vertebrates It is the most gene-dense region The liver is a vital organ in the human body and is present in Vertebrates and some other animals In the life-cycle of Apicomplexan protozoa sporozoites ( sporos, seed + zoon, animal are cells that infect new hosts An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity. Interleukin-4, encoded by IL4, is produced by activated T cells and promotes proliferation and differentiation of antibody-producing B cells. A study of the Fulani of Burkina Faso, who have both fewer malaria attacks and higher levels of antimalarial antibodies than do neighboring ethnic groups, found that the IL4-524 T allele was associated with elevated antibody levels against malaria antigens, which raises the possibility that this might be a factor in increased resistance to malaria. ^[55]

Diagnosis

Further information: Blood film

Blood smear from a P. A Blood Film or Peripheral Blood Smear is a slide made from a drop of Blood, that allows the cells to be examined microscopically falciparum culture (K1 strain). Malaria culture is the method to grow Malaria Parasites continuously in an In vitro environment Several red blood cells have ring stages inside them. Close to the center there is a schizont and on the left a trophozoite.

Severe malaria is commonly misdiagnosed in Africa, leading to a failure to treat other life-threatening illnesses. In malaria-endemic areas, parasitemia does not ensure a diagnosis of severe malaria because parasitemia can be incidental to other concurrent disease. Parasitemia is the quantitative content of Parasites in the Blood. Recent investigations suggest that malarial retinopathy is better (collective sensitivity of 95% and specificity of 90%) than any other clinical or laboratory feature in distinguishing malarial from non-malarial coma. Retinopathy is a general term that refers to some form of non-inflammatory damage to the Retina of the Eye. In Medicine, a coma (from the Greek koma, meaning deep sleep is a profound state of Unconsciousness. ^[56]

Symptomatic diagnosis

Areas that cannot afford even simple laboratory diagnostic tests often use only a history of subjective fever as the indication to treat for malaria. Using Giemsa-stained blood smears from children in Malawi, one study showed that unnecessary treatment for malaria was significantly decreased when clinical predictors (rectal temperature, nailbed pallor, and splenomegaly) were used as treatment indications, rather than the current national policy of using only a history of subjective fevers (sensitivity increased from 21% to 41%). ^[57]

Microscopic examination of blood films

The most economic, preferred, and reliable diagnosis of malaria is microscopic examination of blood films because each of the four major parasite species has distinguishing characteristics. A Blood Film or Peripheral Blood Smear is a slide made from a drop of Blood, that allows the cells to be examined microscopically Two sorts of blood film are traditionally used. Thin films are similar to usual blood films and allow species identification because the parasite's appearance is best preserved in this preparation. Thick films allow the microscopist to screen a larger volume of blood and are about eleven times more sensitive than the thin film, so picking up low levels of infection is easier on the thick film, but the appearance of the parasite is much more distorted and therefore distinguishing between the different species can be much more difficult. With the pros and cons of both thick and thin smears taken into consideration, it is imperative to utilize both smears while attempting to make a definitive diagnosis. ^[58]

From the thick film, an experienced microscopist can detect parasite levels (or parasitemia) down to as low as 0. Parasitemia is the quantitative content of Parasites in the Blood. 0000001% of red blood cells. Microscopic diagnosis can be difficult because the early trophozoites ("ring form") of all four species look identical and it is never possible to diagnose species on the basis of a single ring form; species identification is always based on several trophozoites. Please refer to the articles on each parasite for their microscopic appearances: P. falciparum, P. vivax, P. ovale, P. malariae. Plasmodium falciparum is a Protozoan Parasite, one of the species of Plasmodium that cause Malaria in humans Plasmodium vivax is a Protozoal Parasite and a human Pathogen. Plasmodium ovale is a species of parasitic Protozoa that causes tertian Malaria in humans Plasmodium malariae is a parasitic Protozoa that causes Malaria in humans and animals

Field tests

In areas where microscopy is not available, or where laboratory staff are not experienced at malaria diagnosis, there are antigen detection tests that require only a drop of blood. Malaria antigen detection tests are a group of commercially available tests that allow the rapid diagnosis of Malaria by people who are not otherwise skilled in traditional laboratory ^[59] Immunochromatographic tests (also called: Malaria Rapid Diagnostic Tests, Antigen-Capture Assay or "Dipsticks") have been developed, distributed and fieldtested. These tests use finger-stick or venous blood, the completed test takes a total of 15-20 minutes, and a laboratory is not needed. The threshold of detection by these rapid diagnostic tests is in the range of 100 parasites/µl of blood compared to 5 by thick film microscopy. The first rapid diagnostic tests were using P. falciparum glutamate dehydrogenase as antigen ^[60]. Glutamate dehydrogenase is an Enzyme, present in Mitochondria of Eukaryotes, as are some of the other enzymes required for Urea synthesis that PGluDH was soon replaced by P. falciparum lactate dehydrogenase, a 33 kDa oxidoreductase [EC 1. Lactate dehydrogenase ( LDH) is an Enzyme ( present in a wide variety of organisms including plants and animals 1. 1. 27]. It is the last enzyme of the glycolytic pathway, essential for ATP generation and one of the most abundant enzymes expressed by P. falciparum. PLDH does not persist in the blood but clears about the same time as the parasites following successful treatment. The lack of antigen persistence after treatment makes the pLDH test useful in predicting treatment failure. In this respect, pLDH is similar to pGluDH. The OptiMAL-IT assay can distinguish between P. falciparum and P. vivax because of antigenic differences between their pLDH isoenzymes. OptiMAL-IT will reliably detect falciparum down to 0. 01% parasitemia and non-falciparum down to 0. Parasitemia is the quantitative content of Parasites in the Blood. 1%. Paracheck-Pf will detect parasitemias down to 0. 002% but will not distinguish between falciparum and non-falciparum malaria. Parasite nucleic acids are detected using polymerase chain reaction. This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory. Moreover, levels of parasitemia are not necessarily correlative with the progression of disease, particularly when the parasite is able to adhere to blood vessel walls. Therefore more sensitive, low-tech diagnosis tools need to be developed in order to detect low levels of parasitaemia in the field. Areas that cannot afford even simple laboratory diagnostic tests often use only a history of subjective fever as the indication to treat for malaria. Using Giemsa-stained blood smears from children in Malawi, one study showed that unnecessary treatment for malaria was significantly decreased when clinical predictors (rectal temperature, nailbed pallor, and splenomegaly) were used as treatment indications, rather than the current national policy of using only a history of subjective fevers (sensitivity increased from 21% to 41%). ^[61]

Molecular methods

Molecular methods are available in some clinical laboratories and rapid real-time assays (for example, QT-NASBA based on the polymerase chain reaction)^[62] are being developed with the hope of being able to deploy them in endemic areas. In Molecular biology, real-time polymerase chain reaction, also called quantitative real time polymerase chain reaction (qPCR or kinetic polymerase chain reaction

Laboratory tests

OptiMAL-IT will reliably detect falciparum down to 0. 01% parasitemia and non-falciparum down to 0. Parasitemia is the quantitative content of Parasites in the Blood. 1%. Paracheck-Pf will detect parasitemias down to 0. 002% but will not distinguish between falciparum and non-falciparum malaria. Parasite nucleic acids are detected using polymerase chain reaction. This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory. Moreover, levels of parasitemia are not necessarily correlative with the progression of disease, particularly when the parasite is able to adhere to blood vessel walls. Therefore more sensitive, low-tech diagnosis tools need to be developed in order to detect low levels of parasitaemia in the field. ^[63]

Treatment

Active malaria infection with P. falciparum is a medical emergency requiring hospitalization. A medical emergency is an Injury or Illness that is acute and poses an immediate risk to a person's life or long term health A hospital is an institution for Health care providing treatment by specialised staff and equipment and often but not always providing for Infection with P. vivax, P. ovale or P. malariae can often be treated on an outpatient basis. Treatment of malaria involves supportive measures as well as specific antimalarial drugs. When properly treated, someone with malaria can expect a complete recovery. ^[64]

Antimalarial drugs

Further information: Antimalarial drugs

There are several families of drugs used to treat malaria. Antimalarial drugs are designed to prevent or cure Malaria. Some antimalarial agents particularly Chloroquine and Hydroxychloroquine, are also used Chloroquine is very cheap and, until recently, was very effective, which made it the antimalarial drug of choice for many years in most parts of the world. Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of Malaria. However, resistance of Plasmodium falciparum to chloroquine has spread recently from Asia to Africa, making the drug ineffective against the most dangerous Plasmodium strain in many affected regions of the world. In those areas where chloroquine is still effective it remains the first choice. Unfortunately, chloroquine-resistance is associated with reduced sensitivity to other drugs such as quinine and amodiaquine. Quinine (ˈkwaɪnaɪn kwɪˈniːn ˈkwiːniːn is a natural white Crystalline Alkaloid having Antipyretic (fever-reducing antimalarial, Amodiaquine (trade names Camoquin, Flavoquine) is a 4-aminoquinoline compound related to Chloroquine, used as an Antimalarial and Anti-inflammatory ^[65]

There are several other substances which are used for treatment and, partially, for prevention (prophylaxis). Many drugs may be used for both purposes; larger doses are used to treat cases of malaria. Their deployment depends mainly on the frequency of resistant parasites in the area where the drug is used. One drug currently being investigated for possible use as an anti-malarial, especially for treatment of drug-resistant strains, is the beta blocker propranolol. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Beta blockers (sometimes written as β-blocker) are a class of drugs used for various indications but particularly for the management of Cardiac arrhythmias Propranolol ( INN) is a non-selective Beta blocker mainly used in the treatment of Hypertension. Propranolol has been shown to block both Plasmodium's ability to enter red blood cell and establish an infection, as well as parasite replication. A December 2006 study by Northwestern University researchers suggested that propranolol may reduce the dosages required for existing drugs to be effective against P. falciparum by 5- to 10-fold, suggesting a role in combination therapies. ^[66]

Currently available anti-malarial drugs include:^[67]

• Artemether-lumefantrine (Therapy only, commercial names Coartem and Riamet)
• Artesunate-amodiaquine (Therapy only)
• Artesunate-mefloquine (Therapy only)
• Artesunate-Sulfadoxine/pyrimethamine (Therapy only)
• Atovaquone-proguanil, trade name Malarone (Therapy and prophylaxis)
• Quinine (Therapy only)
• Chloroquine (Therapy and prophylaxis; usefulness now reduced due to resistance)
• Cotrifazid (Therapy and prophylaxis)
• Doxycycline (Therapy and prophylaxis)
• Mefloquine, trade name Lariam (Therapy and prophylaxis)
• Primaquine (Therapy in P. Artemether ( INN) is an antimalarial for the treatment of multi-drug resistant strains of falciparum Malaria. Lumefantrine (or benflumetol) is an Antimalarial drug. The term "co-artemether" is sometimes used to describe the administration of lumefantrine Coartem is the commercial name of Artemether – Lumefantrine, a drug combination effective in treating Malaria, developed by the Ciba and Sandoz laboratories Artesunate ( INN) is part of the Artemisinin group of drugs that treat malaria Amodiaquine (trade names Camoquin, Flavoquine) is a 4-aminoquinoline compound related to Chloroquine, used as an Antimalarial and Anti-inflammatory Artesunate ( INN) is part of the Artemisinin group of drugs that treat malaria Mefloquine is an orally administered Antimalarial drug used as a Prophylaxis against and treatment for Malaria. Artesunate ( INN) is part of the Artemisinin group of drugs that treat malaria There are several sulfonamide-based groups of drugs The original antibacterial sulfonamides (sometimes called simply sulfa drugs are synthetic antimicrobial agents that contain the sulfonamide Pyrimethamine ( Daraprim) is a Medication used for Protozoal infections Atovaquone (alternative spelling atavaquone) is a chemical compound that belongs to the class of Naphthalenes Atovaquone is a hydroxy-14-naphthoquinone an analog Proguanil (proguanil hydrochloride is a Prophylactic Antimalarial drug, which works by stopping the malaria parasite Plasmodium falciparum Atovaquone (alternative spelling atavaquone) is a chemical compound that belongs to the class of Naphthalenes Atovaquone is a hydroxy-14-naphthoquinone an analog Quinine (ˈkwaɪnaɪn kwɪˈniːn ˈkwiːniːn is a natural white Crystalline Alkaloid having Antipyretic (fever-reducing antimalarial, Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of Malaria. Cotrifazid is a treatment and Prophylaxis for Malaria consisting of a multiple complex combination of Rifampicin, Isoniazid, Sulfamethoxazole Doxycycline ( INN) (ˌdɒksɪˈsaɪkliːn is a member of the Tetracycline antibiotics group and is commonly used to treat a variety of Infections Doxycycline Mefloquine is an orally administered Antimalarial drug used as a Prophylaxis against and treatment for Malaria. Primaquine (or primaquine phosphate) is a medication used in the treatment of Malaria and Pneumocystis pneumonia. vivax and P. ovale only; not for prophylaxis)
• Proguanil (Prophylaxis only)
• Sulfadoxine-pyrimethamine (Therapy; prophylaxis for semi-immune pregnant women in endemic countries as "Intermittent Preventive Treatment" - IPT)
• Hydroxychloroquine, trade name Plaquenil (Therapy and prophylaxis)

The development of drugs was facilitated when Plasmodium falciparum was successfully cultured. Proguanil (proguanil hydrochloride is a Prophylactic Antimalarial drug, which works by stopping the malaria parasite Plasmodium falciparum There are several sulfonamide-based groups of drugs The original antibacterial sulfonamides (sometimes called simply sulfa drugs are synthetic antimicrobial agents that contain the sulfonamide Pyrimethamine ( Daraprim) is a Medication used for Protozoal infections Hydroxychloroquine is an Antimalarial drug sold under the trade name Plaquenil, also used to reduce inflammation in the treatment of Rheumatoid arthritis Malaria culture is the method to grow Malaria Parasites continuously in an In vitro environment ^[68] This allowed in vitro testing of new drug candidates.

Extracts of the plant Artemisia annua, containing the compound artemisinin or semi-synthetic derivatives (a substance unrelated to quinine), offer over 90% efficacy rates, but their supply is not meeting demand. Artemisia annua, also known as Sweet Wormwood, Sweet Annie, Sweet Sagewort or Annual Wormwood ( is a common type of wormwood Artemisinin (ɑrtɨˈmɪsɨnɨn is a drug used to treat multi-drug resistant strains of falciparum Malaria. ^[69] One study in Rwanda showed that children with uncomplicated P. falciparum malaria demonstrated fewer clinical and parasitological failures on post-treatment day 28 when amodiaquine was combined with artesunate, rather than administered alone (OR = 0. Artesunate ( INN) is part of the Artemisinin group of drugs that treat malaria 34). However, increased resistance to amodiaquine during this study period was also noted. ^[70] Since 2001 the World Health Organization has recommended using artemisinin-based combination therapy (ACT) as first-line treatment for uncomplicated malaria in areas experiencing resistance to older medications. Artemisinin (ɑrtɨˈmɪsɨnɨn is a drug used to treat multi-drug resistant strains of falciparum Malaria. The most recent WHO treatment guidelines for malaria recommend four different ACTs. While numerous countries, including most African nations, have adopted the change in their official malaria treatment policies, cost remains a major barrier to ACT implementation. Because ACTs cost up to twenty times as much as older medications, they remain unaffordable in many malaria-endemic countries. The molecular target of artemisinin is controversial, although recent studies suggest that SERCA, a calcium pump in the endoplasmic reticulum may be associated with artemisinin resistance. SERCA stands for Sarco / Endoplasmic Reticulum Ca 2+- ATPase. The endoplasmic reticulum (Greek endo = "within" (prefix plásma = "formed entity" Latin reticulum = "little net" or ER, is an Organelle ^[71] Malaria parasites can develop resistance to artemisinin and resistance can be produced by mutation of SERCA. ^[72] However, other studies suggest the mitochondrion is the major target for artemisinin and its analogs. ^[73]

In February 2002, the journal Science and other press outlets^[74] announced progress on a new treatment for infected individuals. Science is the Academic journal of the American Association for the Advancement of Science and is considered one of the world's most prestigious Scientific A team of French and South African researchers had identified a new drug they were calling "G25". ^[75] It cured malaria in test primates by blocking the ability of the parasite to copy itself within the red blood cells of its victims. In 2005 the same team of researchers published their research on achieving an oral form, which they refer to as "TE3" or "te3". ^[76] As of early 2006, there is no information in the mainstream press as to when this family of drugs will become commercially available.

In 1996, Professor Geoff McFadden stumbled upon the work of British biologist Ian Wilson, who had discovered that the plasmodia responsible for causing malaria retained parts of chloroplasts,^[77] an organelle usually found in plants, complete with their own functioning genomes. This led Professor McFadden to the realisation that any number of herbicides may in fact be successful in the fight against malaria, and so he set about trialing large numbers of them, and enjoyed a 75% success rate.

These "apicoplasts" are thought to have originated through the endosymbiosis of algae^[78] and play a crucial role in fatty acid bio-synthesis in plasmodia. ^[79] To date, 466 proteins have been found to be produced by apicoplasts^[80] and these are now being looked at as possible targets for novel anti-malarial drugs.

Although effective anti-malarial drugs are on the market, the disease remains a threat to people living in endemic areas who have no proper and prompt access to effective drugs. Access to pharmacies and health facilities, as well as drug costs, are major obstacles. Médecins Sans Frontières estimates that the cost of treating a malaria-infected person in an endemic country was between US$0. Médecins Sans Frontières (pronounced) or Doctors Without Borders, is a secular humanitarian-aid Non-governmental organization best known The United States dollar ( sign: $; code: USD) is the unit of Currency of the United States; it has also been 25 and $2. 40 per dose in 2002. ^[81]

Counterfeit drugs

Sophisticated counterfeits have been found in Thailand, Vietnam, Cambodia^[82] and China,^[83] and are an important cause of avoidable death in these countries. A counterfeit drug or a counterfeit medicine is a Medication or pharmaceutical product which is produced and sold with the intent to deceptively represent its origin The Kingdom of Cambodia ( formerly known as Kampuchea (, transliterated: Preăh Réachéanachâkr Kâmpŭchea) is a country in South East ^[84] There is no reliable way for doctors or lay people to detect counterfeit drugs without help from a laboratory. Companies are attempting to combat the persistence of counterfeit drugs by using new technology to provide security from source to distribution.

Prevention and disease control

Anopheles albimanus mosquito feeding on a human arm. Anopheles is a Genus of Mosquito ( Culicidae) There are approximately 400 Anopheles species of which 30-40 transmit five different This mosquito is a vector of malaria and mosquito control is a very effective way of reducing the incidence of malaria.

Methods used to prevent the spread of disease, or to protect individuals in areas where malaria is endemic, include prophylactic drugs, mosquito eradication, and the prevention of mosquito bites. The continued existence of malaria in an area requires a combination of high human population density, high mosquito population density, and high rates of transmission from humans to mosquitoes and from mosquitoes to humans. If any of these is lowered sufficiently, the parasite will sooner or later disappear from that area, as happened in North America, Europe, and the Holy Land. The Holy Land ( Arabic: الأرض المقدسة al-Arḍ ul-Muqaddasah;Ancient Aramaic: ארעא קדישא Ar'a Qaddisha; Hebrew: ארץ_הקודש However, unless the parasite is eliminated from the whole world, it could become re-established if conditions revert to a combination that favors the parasite's reproduction. (See Anopheles. Anopheles is a Genus of Mosquito ( Culicidae) There are approximately 400 Anopheles species of which 30-40 transmit five different )

There is currently no vaccine that will prevent malaria, but this is an active field of research. Vaccination is the administration of Antigenic material (the Vaccine) to produce immunity to a disease

Many researchers argue that prevention of malaria may be more cost-effective than treatment of the disease in the long run, but the capital costs required are out of reach of many of the world's poorest people. Economic adviser Jeffrey Sachs estimates that malaria can be controlled for US$3 billion in aid per year. Jeffrey David Sachs (born November 5, 1954, in Detroit Michigan) is an American Economist and Director of the Earth Institute It has been argued that, in order to meet the Millennium Development Goals, money should be redirected from HIV/AIDS treatment to malaria prevention, which for the same amount of money would provide greater benefit to African economies. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome ^[85]

Brazil, Eritrea, India, and Vietnam have, unlike many other developing nations, successfully reduced the malaria burden. Common success factors included conducive country conditions, a targeted technical approach using a package of effective tools, data-driven decision-making, active leadership at all levels of government, involvement of communities, decentralized implementation and control of finances, skilled technical and managerial capacity at national and sub-national levels, hands-on technical and programmatic support from partner agencies, and sufficient and flexible financing. ^[86]

Vector control

Further information: Mosquito control

Before DDT, malaria was successfully eradicated or controlled also in several tropical areas by removing or poisoning the breeding grounds of the mosquitoes or the aquatic habitats of the larva stages, for example by filling or applying oil to places with standing water. The Mosquito Control EP is the first studio release by American Post-metal band Isis, released in 1998 by Escape Artist These methods have seen little application in Africa for more than half a century. ^[87]

Efforts to eradicate malaria by eliminating mosquitoes have been successful in some areas. Eradication is the reduction of an infectious disease's Prevalence in the global human population to zero Malaria was once common in the United States and southern Europe, but the draining of wetland breeding grounds and better sanitation, in conjunction with the monitoring and treatment of infected humans, eliminated it from affluent regions. The United States of America —commonly referred to as the In 2002, there were 1,059 cases of malaria reported in the US, including eight deaths. In five of those cases, the disease was contracted in the United States. Malaria was eliminated from the northern parts of the USA in the early twentieth century, and the use of the pesticide DDT eliminated it from the South by 1951. A pesticide is a substance or mixture of substances used to kill a pest. DDT (from its trivial name D ichloro- D iphenyl- T richloroethane is one of the best known synthetic Pesticides It is a chemical with a long In the 1950s and 1960s, there was a major public health effort to eradicate malaria worldwide by selectively targeting mosquitoes in areas where malaria was rampant. ^[88] However, these efforts have so far failed to eradicate malaria in many parts of the developing world - the problem is most prevalent in Africa.

Sterile insect technique is emerging as a potential mosquito control method. Sterile insect technique is a method of Biological control, whereby millions of sterile Insects are released Progress towards transgenic, or genetically modified, insects suggest that wild mosquito populations could be made malaria-resistant. This article is about organisms which have been genetically modified Researchers at Imperial College London created the world's first transgenic malaria mosquito,^[89] with the first plasmodium-resistant species announced by a team at Case Western Reserve University in Ohio in 2002. Imperial College London (officially The Imperial College of Science Technology and Medicine as given in its Royal Charter It is one of only three universities to have reached Case Western Reserve University is a private research university located in Cleveland Ohio, United States, with some residence halls on the south end of campus Ohio ( is a Midwestern state of the United States. As part of the Great Lakes region, Ohio has long been a cultural and geographical crossroads ^[90] Successful replacement of existent populations with genetically modified populations, relies upon a drive mechanism, such as transposable elements to allow for non-Mendelian inheritance of the gene of interest. Transposons are sequences of DNA that can move around to different positions within the Genome of a single cell, a process called transposition

On December 21, 2007, a study published in PLoS Pathogens found that the hemolytic C-type lectin CEL-III from Cucumaria echinata, a sea cucumber found in the Bay of Bengal, impaired the development of the malaria parasite when produced by transgenic mosquitoes. Events 69 - The end of the Year of the four emperors: Following Galba, Otho and Vitellius, Vespasian Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. PLoS Pathogens is an open-access scientific journal published by the Public Library of Science. Lectins are sugar-binding Proteins which are highly specific for their sugar Moieties. Dendrochirotida are an order of Sea cucumber. Members of this type have branched tentacles and are Suspension feeders Examples are Thyonella and Cucumaria The sea cucumber (also known as trepang, bêche-de-mer, or ambiguously Sea slug) is an Echinoderm of the class Holothuroidea The Bay of Bengal is a bay that forms the northeastern part of the Indian Ocean. ^[91][92] This could potentially be used one day to control malaria by using genetically modified mosquitoes refractory to the parasites, although the authors of the study recognize that there are numerous scientific and ethical problems to be overcome before such a control strategy could be implemented.

Prophylactic drugs

Main article: Malaria prophylaxis

Several drugs, most of which are also used for treatment of malaria, can be taken preventively. Malaria prophylaxis is the prevention of Malaria. Malaria is thought to be one of the oldest infectious diseases evolving around 10000 years ago Generally, these drugs are taken daily or weekly, at a lower dose than would be used for treatment of a person who had actually contracted the disease. Use of prophylactic drugs is seldom practical for full-time residents of malaria-endemic areas, and their use is usually restricted to short-term visitors and travelers to malarial regions. This is due to the cost of purchasing the drugs, negative side effects from long-term use, and because some effective anti-malarial drugs are difficult to obtain outside of wealthy nations. In Medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as Chemotherapy or Surgery.

Quinine was used starting in the seventeenth century as a prophylactic against malaria. Quinine (ˈkwaɪnaɪn kwɪˈniːn ˈkwiːniːn is a natural white Crystalline Alkaloid having Antipyretic (fever-reducing antimalarial, As a means of recording the passage of Time, the 17th Century was that Century which lasted from 1601 - 1700 in the Gregorian calendar The development of more effective alternatives such as quinacrine, chloroquine, and primaquine in the twentieth century reduced the reliance on quinine. Quinacrine (trade name Atabrine) is a drug with a number of different medical applications being initially used in the 1930s as an Antimalarial drug Chloroquine is a 4-aminoquinoline drug used in the treatment or prevention of Malaria. Primaquine (or primaquine phosphate) is a medication used in the treatment of Malaria and Pneumocystis pneumonia. Today, quinine is still used to treat chloroquine resistant Plasmodium falciparum, as well as severe and cerebral stages of malaria, but is not generally used for prophylaxis. Plasmodium falciparum is a Protozoan Parasite, one of the species of Plasmodium that cause Malaria in humans Of interesting historical note is the observation by Samuel Hahnemann in the late 18th Century that over-dosing of quinine leads to a symptomatic state very similar to that of malaria itself. Christian Friedrich Samuel Hahnemann ( 10 April 1755 &ndash 2 July 1843) was a German Physician who created Homoeopathy The 18th century lasted from 1701 to 1800 in the Gregorian calendar, in accordance with the Anno Domini / Common Era numbering system This lead Hahnemann to develop the medical Law of Similars, and the subsequent medical system of Homeopathy. This article has been the subject of edit wars and has been placed on probation This article has been the subject of edit wars and has been placed on probation

Modern drugs used preventively include mefloquine (Lariam), doxycycline (available generically), and the combination of atovaquone and proguanil hydrochloride (Malarone). Mefloquine is an orally administered Antimalarial drug used as a Prophylaxis against and treatment for Malaria. Doxycycline ( INN) (ˌdɒksɪˈsaɪkliːn is a member of the Tetracycline antibiotics group and is commonly used to treat a variety of Infections Doxycycline Atovaquone (alternative spelling atavaquone) is a chemical compound that belongs to the class of Naphthalenes Atovaquone is a hydroxy-14-naphthoquinone an analog Proguanil (proguanil hydrochloride is a Prophylactic Antimalarial drug, which works by stopping the malaria parasite Plasmodium falciparum The choice of which drug to use depends on which drugs the parasites in the area are resistant to, as well as side-effects and other considerations. Drug resistance is the reduction in effectiveness of a drug in curing a disease or improving a patient's symptoms The prophylactic effect does not begin immediately upon starting taking the drugs, so people temporarily visiting malaria-endemic areas usually begin taking the drugs one to two weeks before arriving and must continue taking them for 4 weeks after leaving (with the exception of atovaquone proguanil that only needs be started 2 days prior and continued for 7 days afterwards).

Indoor residual spraying

Indoor residual spraying (IRS) is the practice of spraying insecticides on the interior walls of homes in malaria effected areas. After feeding, many mosquito species rest on a nearby surface while digesting the bloodmeal, so if the walls of dwellings have been coated with insecticides, the resting mosquitos will be killed before they can bite another victim, transferring the malaria parasite.

The first and historically the most poplar insecticide used for IRS is DDT. DDT (from its trivial name D ichloro- D iphenyl- T richloroethane is one of the best known synthetic Pesticides It is a chemical with a long While it was initially used to exclusively to combat malaria, its use quickly spread to agriculture. Agriculture refers to the production of goods through the growing of plants and fungi and the raising of domesticated Animals The study of agriculture In time, pest-control, rather than disease-control, came to dominate DDT use, and this large-scale agricultural use led to the evolution of resistant mosquitoes in many regions. eVolution is the third Album by eLDee, it was due to be released in 2008 During the 1960s, awareness of the negative consequences of its indiscriminate use increased ultimately leading to bans on agricultural applications of DDT in many countries in the 1970s.

Though DDT has never been banned for use in malaria control and there are several other insecticides suitable for IRS, some advocates have claimed that bans are responsible for tens of millions of deaths in tropical countries where DDT had once been effective in controlling malaria. Furthermore, most of the problems associated with DDT use stem specifically from its industrial-scale application in agriculture, rather than its use in public health. Public health is "the science and art of preventing disease prolonging life and promoting health through the organised efforts and informed choices of society organisations ^[93]

The World Health Organization (WHO) currently advises the use of 12 different insecticides in IRS operations. These include DDT and a series of alternative insecticides (such as the pyrethroids permethrin and deltamethrin) to both combat malaria in areas where mosquitoes are DDT-resistant, and to slow the evolution of resistance. Permethrin is a common synthetic chemical widely used as an Insecticide and Acaricide and as an Insect repellent. Deltamethrin is a Pyrethroid Ester Insecticide. Usage Deltamethrin products are among some of the most popular and widely used ^[94] This public health use of small amounts of DDT is permitted under the Stockholm Convention on Persistent Organic Pollutants (POPs), which prohibits the agricultural use of DDT. Stockholm Convention is an international legally binding agreement on persistent organic pollutants (POPs Persistent organic pollutants ( POP s are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic ^[95] However, because of its legacy, many developed countries discourage DDT use even in small quantities. ^[96]

Mosquito nets and bedclothes

Mosquito nets help keep mosquitoes away from people, and thus greatly reduce the infection and transmission of malaria. The nets are not a perfect barrier, so they are often treated with an insecticide designed to kill the mosquito before it has time to search for a way past the net. Insecticide-treated nets (ITN) are estimated to be twice as effective as untreated nets,^[85] and offer greater than 70% protection compared with no net. ^[97] Since the Anopheles mosquitoes feed at night, the preferred method is to hang a large "bed net" above the center of a bed such that it drapes down and covers the bed completely. Anopheles is a Genus of Mosquito ( Culicidae) There are approximately 400 Anopheles species of which 30-40 transmit five different

The distribution of mosquito nets impregnated with insecticide (often permethrin or deltamethrin) has been shown to be an extremely effective method of malaria prevention, and it is also one of the most cost-effective methods of prevention. Permethrin is a common synthetic chemical widely used as an Insecticide and Acaricide and as an Insect repellent. These nets can often be obtained for around US$2. The United States dollar ( sign: $; code: USD) is the unit of Currency of the United States; it has also been 50 - $3. 50 (2-3 euro) from the United Nations, the World Health Organization, and others. Please update other articles as well to avoid contradiction within Wikipedia e The United Nations ( UN) is an International organization whose stated aims are to facilitate cooperation in International law, International security

For maximum effectiveness, the nets should be re-impregnated with insecticide every six months. This process poses a significant logistical problem in rural areas. New technologies like Olyset or DawaPlus allow for production of long-lasting insecticidal mosquito nets (LLINs), which release insecticide for approximately 5 years,^[98] and cost about US$5. 50. ITNs have the advantage of protecting people sleeping under the net and simultaneously killing mosquitoes that contact the net. This has the effect of killing the most dangerous mosquitoes. Some protection is also provided to others, including people sleeping in the same room but not under the net.

Unfortunately, the cost of treating malaria is high relative to income, and the illness results in lost wages. Consequently, the financial burden means that the cost of a mosquito net is often unaffordable to people in developing countries, especially for those most at risk. Only 1 out of 20 people in Africa own a bed net. ^[85] Although shipped into Africa mainly from Europe as free development help, the nets quickly become expensive trade goods. They are mainly used for fishing, and by combining hundreds of donated mosquito nets, whole river sections can be completely shut off, catching even the smallest fish. ^[99]

A study among Afghan refugees in Pakistan found that treating top-sheets and chaddars (head coverings) with permethrin has similar effectiveness to using a treated net, but is much cheaper. Afghan refugees (known as Muhajir Afghans in South Asia) are people who fled Afghanistan after the Soviet invasion in 1979 and during the ^[100]

A new approach, announced in Science on June 10, 2005, uses spores of the fungus Beauveria bassiana, sprayed on walls and bed nets, to kill mosquitoes. Events 1190 - Third Crusade: Frederick I Barbarossa drowns in the Sally River while leading an army to Jerusalem A fungus (ˈfʌŋgəs is a eukaryotic Organism that is a member of the kingdom Fungi (ˈfʌndʒaɪ Beauveria bassiana is a Fungus that grows naturally in soils throughout the world and acts as a Parasite on various Insect species causing While some mosquitoes have developed resistance to chemicals, they have not been found to develop a resistance to fungal infections. ^[101]

Vaccination

Further information: Malaria vaccine

Vaccines for malaria are under development, with no completely effective vaccine yet available. Malaria vaccines are an area of intensive research however no effective vaccine has yet been introduced into clinical practice Vaccination is the administration of Antigenic material (the Vaccine) to produce immunity to a disease The first promising studies demonstrating the potential for a malaria vaccine were performed in 1967 by immunizing mice with live, radiation-attenuated sporozoites, providing protection to about 60% of the mice upon subsequent injection with normal, viable sporozoites. The attenuator plays an important regulatory role in prokaryotic cells because of the absence of the nucleus in Prokaryotic Organisms In the life-cycle of Apicomplexan protozoa sporozoites ( sporos, seed + zoon, animal are cells that infect new hosts ^[102] Since the 1970s, there has been a considerable effort to develop similar vaccination strategies within humans. It was determined that an individual can be protected from a P. falciparum infection if they receive over 1000 bites from infected, irradiated mosquitoes. ^[103]

It has been generally accepted that it is impractical to provide at-risk individuals with this vaccination strategy, but that has been recently challenged with work being done by Dr. Stephen Hoffman of Sanaria, one of the key researchers who originally sequenced the genome of Plasmodium falciparum. Plasmodium falciparum is a Protozoan Parasite, one of the species of Plasmodium that cause Malaria in humans His work most recently has revolved around solving the logistical problem of isolating and preparing the parasites equivalent to a 1000 irradiated mosquitoes for mass storage and inoculation of human beings. The company has recently received several multi-million dollar grants from the Bill & Melinda Gates Foundation and the U. The Bill & Melinda Gates Foundation (B&MGF is the largest transparently operated Private foundation in the world founded by Bill and Melinda S. government to begin early clinical studies in 2007 and 2008. ^[104] The Seattle Biomedical Research Institute (SBRI), funded by the Malaria Vaccine Initiative, assures potential volunteers that "the [2009] clinical trials won't be a life-threatening experience. While many volunteers [in Seattle] will actually contract malaria, the cloned strain used in the experiments can be quickly cured, and does not cause a recurring form of the disease. " "Some participants will get experimental drugs or vaccines, while others will get placebo. "^[105]

Instead, much work has been performed to try and understand the immunological processes that provide protection after immunization with irradiated sporozoites. An immune system is a collection of mechanisms within an Organism that protects against Disease by identifying and killing Pathogens and Tumor After the mouse vaccination study in 1967,^[102] it was hypothesized that the injected sporozoites themselves were being recognized by the immune system, which was in turn creating antibodies against the parasite. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily It was determined that the immune system was creating antibodies against the circumsporozoite protein (CSP) which coated the sporozoite. ^[106] Moreover, antibodies against CSP prevented the sporozoite from invading hepatocytes. ^[107] CSP was therefore chosen as the most promising protein on which to develop a vaccine against the malaria sporozoite. It is for these historical reasons that vaccines based on CSP are the most numerous of all malaria vaccines.

Presently, there is a huge variety of vaccine candidates on the table. Pre-erythrocytic vaccines (vaccines that target the parasite before it reaches the blood), in particular vaccines based on CSP, make up the largest group of research for the malaria vaccine. Other vaccine candidates include: those that seek to induce immunity to the blood stages of the infection; those that seek to avoid more severe pathologies of malaria by preventing adherence of the parasite to blood venules and placenta; and transmission-blocking vaccines that would stop the development of the parasite in the mosquito right after the mosquito has taken a bloodmeal from an infected person. A venule is a small Blood vessel that allows deoxygenated Blood to return from the Capillary beds to the larger blood vessels called Veins The placenta is an Ephemeral organ present in placental Vertebrates, such as Eutherial Mammals and Sharks during Gestation In Medicine, transmission is the passing of a Disease from an infected individual or group to a previously uninfected individual or group ^[108] It is hoped that the sequencing of the P. falciparum genome will provide targets for new drugs or vaccines. In classical genetics the genome of a Diploid Organism including Eukarya refers to a full set of chromosomes or genes in a Gamete, thereby ^[109]

The first vaccine developed that has undergone field trials, is the SPf66, developed by Manuel Elkin Patarroyo in 1987. Manuel Elkin Patarroyo (born November 13, 1947) is a Colombian Pathologist who developed the world's first synthetic Vaccine It presents a combination of antigens from the sporozoite (using CS repeats) and merozoite parasites. During phase I trials a 75% efficacy rate was demonstrated and the vaccine appeared to be well tolerated by subjects and immunogenic. The phase IIb and III trials were less promising, with the efficacy falling to between 38. 8% and 60. 2%. A trial was carried out in Tanzania in 1993 demonstrating the efficacy to be 31% after a years follow up, however the most recent (though controversial) study in the Gambia did not show any effect. Despite the relatively long trial periods and the number of studies carried out, it is still not known how the SPf66 vaccine confers immunity; it therefore remains an unlikely solution to malaria. The CSP was the next vaccine developed that initially appeared promising enough to undergo trials. It is also based on the circumsporoziote protein, but additionally has the recombinant (Asn-Ala-Pro15Asn-Val-Asp-Pro)2-Leu-Arg(R32LR) protein covalently bound to a purified Pseudomonas aeruginosa toxin (A9). Pseudomonas aeruginosa is a Gram-negative, aerobic, rod-shaped Bacterium with unipolar motility. However at an early stage a complete lack of protective immunity was demonstrated in those inoculated. The study group used in Kenya had an 82% incidence of parasitaemia whilst the control group only had an 89% incidence. The vaccine intended to cause an increased T-lymphocyte response in those exposed, this was also not observed.

The efficacy of Patarroyo's vaccine has been disputed with some US scientists concluding in The Lancet (1997) that "the vaccine was not effective and should be dropped" while the Colombian accused them of "arrogance" putting down their assertions to the fact that he came from a developing country. This article is about the journal For other uses of the term "lancet" see Lancet (disambiguation.

The RTS,S/AS02A vaccine is the candidate furthest along in vaccine trials. It is being developed by a partnership between the PATH Malaria Vaccine Initiative (a grantee of the Gates Foundation), the pharmaceutical company, GlaxoSmithKline, and the Walter Reed Army Institute of Research^[110] In the vaccine, a portion of CSP has been fused to the immunogenic "S antigen" of the hepatitis B virus; this recombinant protein is injected alongside the potent AS02A adjuvant. The Bill & Melinda Gates Foundation (B&MGF is the largest transparently operated Private foundation in the world founded by Bill and Melinda GlaxoSmithKline plc () is a United Kingdom -based pharmaceutical, biological and Healthcare Company. Immunogenicity is the ability of a particular substance which is called the Antigen, to provoke an Immune response. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response ^[108] In October 2004, the RTS,S/AS02A researchers announced results of a Phase IIb trial, indicating the vaccine reduced infection risk by approximately 30% and severity of infection by over 50%. In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices The study looked at over 2,000 Mozambican children. Mozambique, officially the Republic of Mozambique (Moçambique or República de Moçambique, ʁɛ'publikɐ d musɐ̃'bik is a country in southeastern Africa ^[111] More recent testing of the RTS,S/AS02A vaccine has focused on the safety and efficacy of administering it earlier in infancy: In October 2007, the researchers announced results of a phase I/IIb trial conducted on 214 Mozambican infants between the ages of 10 and 18 months in which the full three-dose course of the vaccine led to a 62% reduction of infection with no serious side-effects save some pain at the point of injection. In health care clinical trials are conducted to allow safety and Efficacy data to be collected for new drugs or devices ^[112] Further research will delay this vaccine from commercial release until around 2011. ^[113]

Other methods

Education in recognising the symptoms of malaria has reduced the number of cases in some areas of the developing world by as much as 20%. Recognising the disease in the early stages can also stop the disease from becoming a killer. Education can also inform people to cover over areas of stagnant, still water eg Water Tanks which are ideal breeding grounds for the parasite and mosquito thus, cutting down the risk of the transmission between people. This is most put in practice in urban areas where there is large centres of population in a confined space and transmission would be most likely in these areas.

The Malaria Control Project is currently using downtime computing power donated by individual volunteers around the world (see Volunteer computing and BOINC) to simulate models of the health effects and transmission dynamics in order to find the best method or combination of methods for malaria control. Malaria Control Project is an Application that makes use of Network computing for Stochastic modelling of the clinical Epidemiology and natural Volunteer computing is a type of Distributed computing in which computer owners donate their computing resources (such as processing power and storage to one or more "projects" The Berkeley Open Infrastructure for Network Computing ( BOINC) is a non-commercial Middleware system for volunteer and Grid computing. This modeling is extremely computer intensive due to the simulations of large human populations with a vast range of parameters related to biological and social factors that influence the spread of the disease. It is expected to take a few months using volunteered computing power compared to the 40 years it would have taken with the current resources available to the scientists who developed the program. ^[114]

An example of the importance of computer modelling in planning malaria eradication programs is shown in the paper by Águas and others. They showed that eradication of malaria is crucially dependent on finding and treating the large number of people in endemic areas with asymptomatic malaria, who act as a reservoir for infection. ^[115] The malaria parasites do not affect animal species and therefore eradication of the disease from the human population would be expected to be effective.

See also

• The Global Fund to Fight AIDS, Tuberculosis and Malaria

References

External links