{{infobox disease | name	Malaria | ICD10 | ICD9 | Image Plasmodium.jpg | Caption Ring-forms and gametocytes of Plasmodium falciparum in human blood. | DiseasesDB 7728 | MedlinePlus 000621 | OMIM 248310 | eMedicineSubj med | eMedicineTopic 1385 | eMedicine_mult | MeshName Malaria | MeshNumber C03.752.250.552 | }}

Malaria is a mosquito-borne infectious disease of humans caused by eukaryotic protists of the genus Plasmodium. It is widespread in tropical and subtropical regions, including much of Sub-Saharan Africa, Asia and the Americas. Malaria is prevalent in these regions because of the significant amounts of rainfall and consistent high temperatures; warm, consistent temperatures and high humidity, along with stagnant waters in which their larvae mature, provide mosquitoes with the environment needed for continuous breeding. The cause of the disease is a protozoan, discovered in 1880 by Charles Louis Alphonse Laveran; while he was working in the military hospital in Constantine, Algeria, he observed the parasites in a blood smear taken from a patient who had just died of malaria. The disease results from the multiplication of malaria parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases progressing to coma, and death.

Four species of Plasmodium can infect and be transmitted by humans. Severe disease is largely caused by Plasmodium falciparum. Malaria caused by Plasmodium vivax, Plasmodium ovale and Plasmodium malariae is generally a milder disease that is rarely fatal. A fifth species, Plasmodium knowlesi, is a zoonosis that causes malaria in macaques but can also infect humans.

Malaria transmission can be reduced by preventing mosquito bites by distribution of inexpensive 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. Although many are under development, the challenge of producing a widely available vaccine that provides a high level of protection for a sustained period is still to be met. Two drugs are also available to prevent malaria in travellers to malaria-endemic countries (prophylaxis).

A variety of antimalarial medications are available. In the last 5 years, treatment of P. falciparum infections in endemic countries has been transformed by the use of combinations of drugs containing an artemisinin derivative. Severe malaria is treated with intravenous or intramuscular quinine or, increasingly, the artemisinin derivative artesunate which is superior to quinine in both children and adults. Resistance has developed to several antimalarial drugs, most notably chloroquine.

Each year, there are more than 225 million cases of malaria, killing around 781,000 people each year according to the World Health Organisation's 2010 World Malaria Report, 2.23% of deaths worldwide. The majority of deaths are of young children in sub-Saharan Africa. Ninety percent of malaria-related deaths occur in sub-Saharan Africa. Malaria is commonly associated with poverty, and can indeed be a cause of poverty and a major hindrance to economic development.

Signs and symptoms

Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia (caused by hemolysis), hemoglobinuria, retinal damage, and convulsions. The classic 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. vivax and P. ovale infections, while every three days for P. malariae. 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 that may be related to high intracranial pressure, children with malaria frequently exhibit abnormal posturing, a sign indicating severe brain damage. 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. This neurologic damage results from cerebral malaria to which children are more vulnerable. Cerebral malaria is associated with retinal whitening, which may be a useful clinical sign in distinguishing malaria from other causes of fever.

Severe malaria is almost exclusively caused by P. falciparum infection, and usually arises 6–14 days after infection. Consequences of severe malaria include coma and death if untreated—young children and pregnant women are especially vulnerable. Splenomegaly (enlarged spleen), severe headache, cerebral ischemia, hepatomegaly (enlarged liver), hypoglycemia, and hemoglobinuria with renal failure may occur. Renal failure is a feature of blackwater fever, where hemoglobin from lysed red blood cells leaks into the urine. Severe malaria can progress extremely rapidly and cause death within hours or days. In the most severe cases of the disease, fatality rates can exceed 20%, even with intensive care and treatment. 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. Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.

Cause

Malaria parasites are members of the genus Plasmodium (phylum Apicomplexa). In humans malaria is caused by P. falciparum, P. malariae, P. ovale, P. vivax and P. knowlesi. P. falciparum is the most common cause of infection, and is also responsible for about 90% of the deaths from malaria. Parasitic Plasmodium species also infect birds, reptiles, monkeys, chimpanzees and rodents. There have been documented human infections with several simian species of malaria, namely P. knowlesi, P. inui, P. cynomolgi, P. simiovale, P. brazilianum, P. schwetzi and P. simium; however, with the exception of P. knowlesi, these are mostly of limited public health importance.

Malaria parasites contain apicoplasts, an organelle usually found in plants, complete with their own functioning genomes. These apicoplast are thought to have originated through the endosymbiosis of algae and play a crucial role in various aspects of parasite metabolism e.g. fatty acid bio-synthesis. To date, 466 proteins have been found to be produced by apicoplasts and these are now being looked at as possible targets for novel anti-malarial drugs.

Life cycle

The parasite's secondary (intermediate) hosts are humans and other vertebrates. Female mosquitoes of the Anopheles genus are primary hosts and transmission vectors. 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. 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's gut. This produces an ookinete that penetrates the gut lining and produces an oocyst in the gut wall. 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. This type of transmission is occasionally referred to as anterior station transfer. The sporozoites are injected into the skin, alongside saliva, when the mosquito takes a subsequent blood meal.

Only female mosquitoes feed on blood while male mosquitoes feed on plant nectar, thus males do not transmit the disease. The females of the Anopheles genus of mosquito prefer to feed at night. 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.

Recurrent malaria

Malaria recurs after treatment for three reasons. Recrudescence occurs when parasites are not cleared by treatment, whereas reinfection indicates complete clearance with new infection established from a separate infective mosquito bite; both can occur with any malaria parasite species. Relapse is specific to P. vivax and P. ovale and involves re-emergence of blood-stage parasites from latent parasites (hypnozoites) 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. Approximately one in five of P. vivax malaria cases in temperate areas involve overwintering by hypnozoites (i.e., relapses begin the year after the mosquito bite).

Pathogenesis

Malaria develops via two phases: an exoerythrocytic and an erythrocytic phase. The exoerythrocytic phase involves infection of the hepatic system, or liver, whereas the erythrocytic phase involves infection of the erythrocytes, or red blood cells. 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. Within minutes of being introduced into the human host, the sporozoites infect hepatocytes, multiplying asexually and asymptomatically for a period of 8–30 days. 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. The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.

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.

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. However, circulating infected blood cells are destroyed in the spleen. 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. This "stickiness" is the main factor giving rise to hemorrhagic complications of malaria. High endothelial venules (the smallest branches of the circulatory system) can be blocked by the attachment of masses of these infected red blood cells. 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.

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 effectively limitless versions within parasite populations. 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. Since the gametocytes are formed in the blood of the vertebrate host, the vertebrate host is the definitive host of the disease. 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. New sporozoites develop and travel to the mosquito's salivary gland, completing the cycle. Pregnant women are especially attractive to the mosquitoes, and malaria in pregnant women is an important cause of stillbirths, infant mortality and low birth weight, particularly in P. falciparum infection, but also in other species infection, such as P. vivax.

Genetic resistance

Malaria is thought to have been the greatest selective pressure on the human genome in recent history. This is due to the high levels of mortality and morbidity caused by malaria, especially the P. falciparum species. A number of diseases may provide some resistance to it including sickle cell disease, thalassaemias, glucose-6-phosphate dehydrogenase, Duffy antigens, and possibly others.

Diagnosis

The mainstay of malaria diagnosis has been the microscopic examination of blood. Although blood is the sample most frequently used to make a diagnosis, both saliva and urine have been investigated as alternative, less invasive specimens.

Areas that cannot afford 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 when clinical predictors (rectal temperature, nailbed pallor, and splenomegaly) were used as treatment indications, rather than using only a history of subjective fevers, a correct diagnosis increased from 2% to 41% of cases, and unnecessary treatment for malaria was significantly decreased.

Blood films

! Species	! Appearance	! Periodicity	! Liver persistent
Plasmodium vivax		tertian	yes
Plasmodium ovale		tertian	yes
Plasmodium falciparum		tertian	no
Plasmodium malariae		quartan	no

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. 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.

From the thick film, an experienced microscopist can detect parasite levels (or parasitemia) as few as 5 parasites/µL blood. Diagnosis of species 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.

One important thing to note is that P. malariae and P. knowlesi (which is the most common cause of malaria in South-east Asia) look very similar under the microscope. However, P. knowlesi parasitemia increases very fast and causes more severe disease than P. malariae, so it is important to identify and treat infections quickly. Therefore modern methods such as PCR (see "Molecular methods" below) or monoclonal antibody panels that can distinguish between the two should be used in this part of the world.

Antigen tests

For areas where microscopy is not available, or where laboratory staff are not experienced at malaria diagnosis, there are commercial antigen detection tests that require only a drop of blood. 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 the results are read visually as the presence or absence of colored stripes on the dipstick, so they are suitable for use in the field. The threshold of detection by these rapid diagnostic tests is in the range of 100 parasites/µl of blood (commercial kits can range from about 0.002% to 0.1% parasitemia) compared to 5 by thick film microscopy. One disadvantage is that dipstick tests are qualitative but not quantitative – they can determine if parasites are present in the blood, but not how many.

The first rapid diagnostic tests were using P. falciparum glutamate dehydrogenase as antigen. PGluDH was soon replaced by P.falciparum lactate dehydrogenase, a 33 kDa oxidoreductase [EC 1.1.1.27]. 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. Depending on which monoclonal antibodies are used, this type of assay can distinguish between all five different species of human malaria parasites, because of antigenic differences between their pLDH isoenzymes.

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) are being developed with the hope of being able to deploy them in endemic areas.

PCR (and other molecular methods) 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 parasitemia in the field.

Prevention

Methods used in order 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 much of the Middle East. However, unless the parasite is eliminated from the whole world, it could become re-established if conditions revert to a combination that favours the parasite's reproduction. Many countries are seeing an increasing number of imported malaria cases owing to extensive travel and migration.

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. The economist Jeffrey Sachs estimates that malaria can be controlled for US$3 billion in aid per year.

A 2008 study that examined international financing of malaria control found large regional variations in the levels of average annual per capita funding ranging from US$0.01 in Myanmar to US$147 in Suriname. The study found 34 countries where the funding was less than US$1 per capita, including 16 countries where annual malaria support was less than US$0.5. The 16 countries included 710 million people or 50% of the global population exposed to the risks of malaria transmission, including seven of the poorest countries in Africa (Côte d'Ivoire, Republic of the Congo, Chad, Mali, Democratic Republic of the Congo, Somalia, and Guinea) and two of the most densely populated stable endemic countries in the world (Indonesia and India).

Brazil, Eritrea, India, and Vietnam, unlike many other developing nations, have successfully reduced the malaria burden. Common success factors have 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.

Medications

Several drugs, most of which are also used for treatment of malaria, can be taken preventively. Chloroquine may be used where the parasite is still sensitive. However due to resistance one of three medications: mefloquine (Lariam), doxycycline (available generically), and the combination of atovaquone and proguanil hydrochloride (Malarone) is frequently needed. Doxycycline and the atovaquone and proguanil combination are the best tolerated with mefloquine associated with higher rates of neurological and psychiatric symptoms.

The prophylactic effect does not begin immediately upon starting 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). 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.

Quinine was used historically, however the development of more effective alternatives such as quinacrine, chloroquine, and primaquine in the 20th century reduced its use. Today, quinine is not generally used for prophylaxis. The use of prophylactic drugs where malaria-bearing mosquitoes are present may encourage the development of partial immunity.

Vector control

Efforts to eradicate malaria by eliminating mosquitoes have been successful in some areas. Malaria was once common in the United States and southern Europe, but vector control programs, in conjunction with the monitoring and treatment of infected humans, eliminated it from those regions. In some areas, the draining of wetland breeding grounds and better sanitation were adequate. Malaria was eliminated from most parts of the USA in the early 20th century by such methods, and the use of the pesticide DDT and other means eliminated it from the remaining pockets in the South by 1951 (see National Malaria Eradication Program). In 2002, there were 1,059 cases of malaria reported in the US, including eight deaths, but in only five of those cases was the disease contracted in the United States.

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. These methods have seen little application in Africa for more than half a century.

Sterile insect technique is emerging as a potential mosquito control method. Progress towards transgenic, or genetically modified, insects suggest that wild mosquito populations could be made malaria-resistant. Researchers at Imperial College London created the world's first transgenic malaria mosquito, with the first plasmodium-resistant species announced by a team at Case Western Reserve University in Ohio in 2002. Successful replacement of current populations with a new genetically modified population, relies upon a drive mechanism, such as transposable elements to allow for non-Mendelian inheritance of the gene of interest. However, this approach contains many difficulties and success is a distant prospect.

Indoor residual spraying

Indoor residual spraying (IRS) is the practice of spraying insecticides on the interior walls of homes in malaria affected 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 pesticide used for IRS was DDT. Although it was initially used exclusively to combat malaria, its use quickly spread to 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. The DDT resistance shown by Anopheles mosquitoes can be compared to antibiotic resistance shown by bacteria. The overuse of anti-bacterial soaps and antibiotics led to antibiotic resistance in bacteria, similar to how overspraying of DDT on crops led to DDT resistance in Anopheles mosquitoes. 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. Since the use of DDT has been limited or banned for agricultural use for some time, DDT may now be more effective as a method of disease-control.

Although 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.

The World Health Organization (WHO) currently advises the use of 12 different insecticides in IRS operations, including DDT as well as alternative insecticides (such as the pyrethroids permethrin and deltamethrin). 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. However, because of its legacy, many developed countries previously discouraged DDT use even in small quantities.

One problem with all forms of Indoor Residual Spraying is insecticide resistance via evolution of mosquitos. According to a study published on Mosquito Behavior and Vector Control, mosquito species that are affected by IRS are endophilic species (species that tend to rest and live indoors), and due to the irritation caused by spraying, their evolutionary descendants are trending towards becoming exophilic (species that tend to rest and live out of doors), meaning that they are not as affected—if affected at all—by the IRS, rendering it somewhat useless as a defense mechanism.

Mosquito nets and bedclothes

Mosquito nets help keep mosquitoes away from people and greatly reduce the infection and transmission of malaria. The nets are not a perfect barrier and 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 (ITNs) are estimated to be twice as effective as untreated nets and offer greater than 70% protection compared with no net. Although ITNs are proven to be very effective against malaria, less than 2% of children in urban areas in Sub-Saharan Africa are protected by ITNs. 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.

Vaccination

Immunity (or, more accurately, tolerance) does occur naturally, but only in response to repeated infection with multiple strains of malaria. Vaccines for malaria are under development, with no completely effective vaccine yet available. 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. 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 1,000 bites from infected yet irradiated mosquitoes.

Other methods

Education in recognizing the symptoms of malaria has reduced the number of cases in some areas of the developing world by as much as 20%. Recognizing 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 e.g. 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 are large centers 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. 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.

An example of the importance of computer modeling 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. The malaria parasites do not affect animal species and therefore eradication of the disease from the human population would be expected to be effective.

Other interventions for the control of malaria include mass drug administrations and intermittent preventive therapy.

Furthering attempts to reduce transmission rates, a proposed alternative to mosquito nets is the mosquito laser, or photonic fence, which identifies female mosquitoes and shoots them using a medium-powered laser. The device is currently undergoing commercial development, although instructions for a DIY version of the photonic fence have also been published.

Another way of reducing the malaria transmitted to humans from mosquitoes has been developed by the University of Arizona. They have engineered a mosquito to become resistant to malaria. This was reported on the 16 July 2010 in the journal PLoS Pathogens. With the ultimate end being that the release of this GM mosquito into the environment, Gareth Lycett, a malaria researcher from Liverpool School of Tropical Medicine told the BBC that "It is another step on the journey towards potentially assisting malaria control through GM mosquito release."

Treatment

When properly treated, a patient with malaria can expect a complete recovery. The treatment of malaria depends on the severity of the disease; whether patients who can take oral drugs have to be admitted depends on the assessment and the experience of the clinician. Uncomplicated malaria is treated with oral drugs. The most effective strategy for P. falciparum infection recommended by WHO is the use of artemisinins in combination with other antimalarials artemisinin-combination therapy, ACT, in order to avoid the development of drug resistance against artemisinin-based therapies.

Severe malaria requires the parenteral administration of antimalarial drugs. Until recently the most used treatment for severe malaria was quinine but artesunate has been shown to be superior to quinine in both children and adults. Treatment of severe malaria also involves supportive measures.

Infection with P. vivax, P. ovale or P. malariae is usually treated on an outpatient basis. Treatment of P. vivax requires both treatment of blood stages (with chloroquine or ACT) as well as clearance of liver forms with primaquine.

It is advised to be cautious diagnosing and treating without the presence of a headache, as it is possible that the patient has dengue; not malaria.

Epidemiology

[[Image:Malaria world map - DALY - WHO2004.svg|thumb|Disability-adjusted life year for malaria per 100,000 inhabitants in 2004. ]] It is estimated that malaria causes 250 million cases of fever and approximately one million deaths annually. The vast majority of cases occur in children under 5 years old; 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. Indeed, if the prevalence of malaria stays on its present upwards course, the death rate could double in the next twenty years. 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. As a consequence, the majority of cases are undocumented.

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. 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.

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 geographic distribution of malaria within large regions is complex, and malaria-afflicted and malaria-free areas are often found close to each other. In drier areas, outbreaks of malaria can be predicted with reasonable accuracy by mapping rainfall. Malaria is more common in rural areas than in cities; this is in contrast to dengue fever where urban areas present the greater risk. For example, several cities in Vietnam, Laos and Cambodia are essentially malaria-free, but the disease is present in many rural regions. By contrast, in Africa malaria is present in both rural and urban areas, though the risk is lower in the larger cities. The global endemic levels of malaria have not been mapped since the 1960s. However, the Wellcome Trust, UK, has funded the Malaria Atlas Project to rectify this, providing a more contemporary and robust means with which to assess current and future malaria disease burden.

By 2010 countries with the highest death rate per 100,000 population are Cote d'Ivoire with (86.15), Angola (56.93) and Burkina Faso (50.66) - all in Africa.

History

Malaria has infected humans for over 50,000 years, and Plasmodium may have been a human pathogen for the entire history of the species. Close relatives of the human malaria parasites remain common in chimpanzees. Some new evidence suggests that the most virulent strain of human malaria may have originated in gorillas.

References to the unique periodic fevers of malaria are found throughout recorded history, beginning in 2700 BC in China. Malaria may have contributed to the decline of the Roman Empire, and was so pervasive in Rome that it was known as the "Roman fever". The term malaria originates from Medieval  — "bad air"; the disease was formerly called ague or marsh fever due to its association with swamps and marshland. Malaria was once common in most of Europe and North America, where it is no longer endemic, though imported cases do occur.

Malaria was the most important health hazard encountered by U.S. troops in the South Pacific during World War II, where about 500,000 men were infected. According to Joseph Patrick Byrne, "Sixty thousand American soldiers died of malaria during the African and South Pacific campaigns."

Prevention

An early effort at malaria prevention occurred in 1896, just before the mosquito malaria link was confirmed in India by a British physician, Ronald Ross. An 1896 Uxbridge malaria outbreak prompted health officer, Dr. Leonard White, to write a report to the Massachusetts State Board of Health, which led to study of mosquito-malaria links, and the first efforts for malaria prevention. Massachusetts State pathologist Theobald Smith, asked that White's son collect mosquito specimens for further analysis, and that citizens 1) add screens to windows, and 2) drain collections of water. Carlos Finlay was also engaged in mosquito related research, and mosquito borne disease theory, in the 1880s in Cuba, basing his work on the study of Yellow Fever.

Discovery of the parasite

Scientific studies on malaria made their first significant advance in 1880, when a French army doctor working in the military hospital of Constantine in Algeria named Charles Louis Alphonse Laveran observed parasites for the first time, inside the red blood cells of people suffering from malaria. He, therefore, proposed that malaria is caused by this organism, the first time a protist was identified as causing disease. For this and later discoveries, he was awarded the 1907 Nobel Prize for Physiology or Medicine. The malarial parasite was called Plasmodium by the Italian scientists Ettore Marchiafava and Angelo Celli.

Discovery of mosquito transmission

A year later, Carlos Finlay, a Cuban doctor treating patients with yellow fever in Havana, provided strong evidence that mosquitoes were transmitting disease to and from humans. This work followed earlier suggestions by Josiah C. Nott, and work by Sir Patrick Manson, The Father of Tropical Medicine, on the transmission of filariasis.

In April 1894, a Scottish physician Sir Ronald Ross visited Sir Patrick Manson at his house on Queen Anne Street, London. This visit was the start of four years of collaboration and fervent research which culminated in 1898 when Ross, who was working in the Presidency General Hospital in Calcutta, proved the complete life-cycle of the malaria parasite in mosquitoes; thus proving that the mosquito was the vector for malaria in humans. He did this by showing that certain mosquito species transmit malaria to birds. He isolated malaria parasites from the salivary glands of mosquitoes that had fed on infected birds. 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 findings of Finlay and Ross were later confirmed by a medical board headed by Walter Reed in 1900. Its recommendations were implemented by William C. Gorgas in the health measures undertaken during construction of the Panama Canal. This public-health work saved the lives of thousands of workers and helped develop the methods used in future public-health campaigns against the disease.

The liver stage

Shortt and Garnham discovered the pre-erythrocytic liver stage, first in the primate parasite P. cynomolgi and subsequently the human malarias P. vivax and P. falciparum. Further work confirmed the transformation of sporozoites from mosquitoes into liver forms, essentially completing documentation of the lifecycle.

In vitro culture

The first successful continuous in vitro malaria culture was established in 1976 by William Trager and James B. Jensen, which facilitated research into the molecular biology of the parasite and the development of new drugs.

History of treatment

The first effective treatment for malaria came from the bark of cinchona tree, which contains quinine. This tree grows on the slopes of the Andes, mainly in Peru. The indigenous peoples of Peru made a tincture of cinchona to control malaria. The Jesuits noted the efficacy of the practice and introduced the treatment to Europe during the 1640s, where it was rapidly accepted. 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. In the 20th century, chloroquine replaced quinine as treatment of both uncomplicated and severe falciparum malaria until resistance supervened. Artemisinins, discovered by Chinese scientists in the 1970s, are now recommended treatment for falciparum malaria, administered in combination with other antimalarials as well as in severe disease.

Society and culture

Malaria is not just a disease commonly associated with poverty but also a cause of poverty and a major hindrance to economic development. Tropical regions are affected most; however, malaria’s furthest extent reaches into some temperate zones with extreme seasonal changes. The disease has been associated with major negative economic effects on regions where it is widespread. During the late 19th and early 20th centuries, it was a major factor in the slow economic development of the American southern states. A comparison of average per capita GDP in 1995, adjusted for parity of purchasing power, between countries with malaria and countries without malaria gives a fivefold difference ($1,526 USD versus $8,268 USD). 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.

Poverty is both cause and effect, however, since the poor do not have the financial capacities to prevent or treat the disease. 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. 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.

The demographic transition in Africa is slow and malaria may provide part of the answer. Total fertility rates were best explained by child mortality, as measured indirectly by infant mortality, in a 2007 study.

A study on the effect of malaria on IQ in a sample of Mexicans found that exposure during the birth year to malaria eradication was associated with increases in IQ. It also increased the probability of employment in a skilled occupation. The author suggests that this may be one explanation for the Flynn effect and that this may be an important explanation for the link between national malaria burden and economic development. A literature review of 44 papers states that cognitive abilities and school performance were shown to be impaired in sub-groups of patients (with either cerebral malaria or uncomplicated malaria) when compared with healthy controls. Studies comparing cognitive functions before and after treatment for acute malarial illness continued to show significantly impaired school performance and cognitive abilities even after recovery. Malaria prophylaxis was shown to improve cognitive function and school performance in clinical trials when compared to placebo groups. April 25 is World Malaria Day.

Counterfeit drugs

Sophisticated counterfeits have been found in several Asian countries such as Cambodia, China, Indonesia, Laos, Thailand, Vietnam and are an important cause of avoidable death in those countries. WHO said that studies indicate that up to 40% of artesunate based malaria medications are counterfeit, especially in the Greater Mekong region and have established a rapid alert system to enable information about counterfeit drugs to be rapidly reported to the relevant authorities in participating countries. 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.

War

Throughout history, the contraction of malaria (via natural outbreaks as well as via infliction of the disease as a biological warfare agent) has played a prominent role in the fortunes of government rulers, nation-states, military personnel, and military actions. "Malaria Site: History of Malaria During Wars" addresses the devastating impact of malaria in numerous well-known conflicts, beginning in June 323 B.C. That site's authors note: "Many great warriors succumbed to malaria after returning from the warfront and advance of armies into continents was prevented by malaria. In many conflicts, more troops were killed by malaria than in combat." The Centers for Disease Control ("CDC") traces the history of malaria and its impacts farther back, to 2700 BCE.

In 1910, Nobel Prize in Medicine-winner Ronald Ross (himself a malaria survivor), published a book titled The Prevention of Malaria that included the chapter: "The Prevention of Malaria in War." The chapter's author, Colonel C. H. Melville, Professor of Hygiene at Royal Army Medical College in London, addressed the prominent role that malaria has historically played during wars and advised: "A specially selected medical officer should be placed in charge of these operations with executive and disciplinary powers [...]."

Significant financial investments have been made to fund procure existing and create new anti-malarial agents. During World War I and World War II, the supplies of the natural anti-malaria drugs, cinchona bark and quinine, proved to be inadequate to supply military personnel and substantial funding was funnelled into research and development of other drugs and vaccines. American military organizations conducting such research initiatives include the Navy Medical Research Center, Walter Reed Army Institute of Research, and the U.S. Army Medical Research Institute of Infectious Diseases of the US Armed Forces.

Additionally, initiatives have been founded such as Malaria Control in War Areas (MCWA), established in 1942, and its successor, the Communicable Disease Center (now known as the Centers for Disease Control) established in 1946. According to the CDC, MCWA "was established to control malaria around military training bases in the southern United States and its territories, where malaria was still problematic" and, during these activities, to "train state and local health department officials in malaria control techniques and strategies." The CDC's Malaria Division continued that mission, successfully reducing malaria in the United States, after which the organization expanded its focus to include "prevention, surveillance, and technical support both domestically and internationally."

Eradication efforts

Several notable attempts are being made to eliminate the parasite from sections of the world, or to eradicate it worldwide. In 2006, the organization Malaria No More set a public goal of eliminating malaria from Africa by 2015, and the organization plans to dissolve if that goal is accomplished. Several malaria vaccines are in clinical trials, which are intended to provide protection for children in endemic areas and reduce the speed of transmission of the disease. The Global Fund to Fight AIDS, Tuberculosis and Malaria has distributed more than 160 million insecticide-treated nets intended to stop mosquito-born transmission of malaria. According to director Inder Singh, the U.S.-based Clinton Foundation has reduced the cost of drugs to treat malaria by 60%, and is working further reduce the spread of the disease. Other efforts, such as the Malaria Atlas Project focus on analyzing climate and weather information required to accurately predict the spread of malaria based on the availability of habitat of malaria-carrying parasites.

Research

With the onset of drug resistant Plasmodium parasites, new strategies are required to combat the widespread disease. One such approach lies in the introduction of synthetic pyridoxal-amino acid adducts, which are channelled into the parasite. Thus, trapped upon phosphorylation by plasmodial PdxK (pyridoxine/pyridoxal kinase), the proliferation of Plasmodium parasites is effectively hindered by a novel compound, PT3, a cyclic pyridoxyl-tryptophan methyl ester, without harming human cells.

References

Further reading

excerpt and text search excerpt and text search

External links

WHO site on malaria

Global Malaria action Plan

Malaria Atlas Project

Medicines for Malaria Venture (MMV)

World Malaria Report 2005

Doctors Without Borders/Médecins Sans Frontières – Malaria information pages

Medline Plus – Malaria

Who/TDR Malaria Database

Anti malaria and sustainable development

Worldwide Antimalarial Resistance Network (WWARN)

Category:Apicomplexa Category:Insect-borne diseases Category:Malaria Category:Medical emergencies Category:Protozoal diseases Category:Tropical diseases Category:Deaths from malaria Category:Millennium Development Goals

af:Malaria ar:ملاريا an:Malaria gn:Akanundu ro'y bn:ম্যালেরিয়া zh-min-nan:Ma-lá-lí-á be:Малярыя be-x-old:Малярыя bs:Malarija br:Malaria bg:Малария ca:Malària cs:Malárie cy:Malaria da:Malaria de:Malaria dv:މެލޭރިޔާ et:Malaaria el:Ελονοσία es:Malaria eo:Malario eu:Malaria fa:مالاریا fo:Malaria fr:Paludisme ga:Maláire gl:Malaria gu:મલેરિયા ko:말라리아 hi:मलेरिया hr:Malarija io:Malario id:Malaria ia:Malaria is:Malaría it:Malaria he:מלריה jv:Malaria kn:ಮಲೇರಿಯಾ ka:მალარია kk:Безгек ku:Lerzeta sw:Malaria ht:Malarya la:Malaria lv:Malārija lt:Maliarija ln:Malariyá hu:Malária mk:Маларија ml:മലമ്പനി mt:Malarja mr:मलेरिया arz:مالاريا ms:Malaria my:ငှက်ဖျားရောဂါ nl:Malaria ne:औलो new:अउल ja:マラリア no:Malaria nn:Malaria oc:Malària om:Malaria pnb:ملیریا ps:ملاريا pl:Malaria pt:Malária ro:Malarie qu:Chukchu rue:Маларія ru:Малярия sa:शीतज्वरः scn:Malaria si:මැලේරියාව simple:Malaria sk:Malária sl:Malarija so:Malaariyo sr:Маларија sh:Malarija su:Malaria fi:Malaria sv:Malaria tl:Malarya ta:மலேரியா te:మలేరియా th:มาลาเรีย tr:Sıtma uk:Малярія ur:ملیریا vi:Sốt rét fiu-vro:Malaaria war:Malaryá yi:מאלאריע yo:Màláríà bat-smg:Maliarėjė zh:疟疾

name	Nathan Myhrvold
birth date	August 03, 1959
birth place	Seattle, Washington
death date
workplaces	Intellectual Ventures, University of Cambridge, Microsoft Research
alma mater	Princeton University, UCLA
signature
spouse	}}

Nathan P. Myhrvold (born August 03, 1959 in Seattle, Washington), formerly Chief Technology Officer at Microsoft, is co-founder of Intellectual Ventures, and referred to by many as a patent troll. Myhrvold, usually with coinventors, holds 17 U.S. patents assigned to Microsoft and has applied for more than 500 patents. In addition, Myhrvold and coinventors hold 115 U.S. patents assigned mostly to The Invention Science Fund I, LLC.

Early life and education

Myhrvold attended Mirman School, and began college at age 14. He studied mathematics, geophysics, and space physics at UCLA (BSc, Masters). He was awarded a Hertz Foundation Fellowship for graduate study and he chose to study at Princeton University, where he earned a master's degree in mathematical economics and completed a PhD in theoretical and mathematical physics by age 23. He also attended Santa Monica College. For one year, he held a postdoctoral fellowship at the University of Cambridge working under Stephen Hawking, studying cosmology, quantum field theory in curved space time and quantum theories of gravitation.

Career

Myhrvold left Cambridge to co-found a computer startup in Oakland, California. The company, Dynamical Systems Research Inc., sought to produce Mondrian, a clone of IBM's TopView multitasking environment for DOS. Microsoft purchased DSR in 1986.

Myhrvold worked at Microsoft for 13 years. At Microsoft he founded Microsoft Research in 1991.

After Microsoft, in 2000 Myhrvold co-founded Intellectual Ventures, a patent portfolio developer and broker in the areas of technology and energy, which has acquired over 30,000 patents and whose business practices have caused some controversy, being described by some as a patent troll company.

Hobbies and pursuits

Myhrvold is a prize-winning nature and wildlife photographer.

Science

He is also involved with paleontological research on expeditions with the Museum of the Rockies. His work has appeared in scientific journals including Science, Nature, Paleobiology (With Philip J. Currie), PLoS ONE and the Physical Review, as well as Fortune, Time, Scientific American, National Geographic Traveler and Slate. He and Peter Rinearson helped Bill Gates write The Road Ahead, a book about the future that reached No. 1 on the New York Times bestseller list in 1995 and 1996. Myhrvold has contributed $1 million to the nonprofit SETI Institute in Mountain View, CA, for the development of the Allen Telescope Array, planned to be the world's most powerful radio telescope.

After the Science Museum in London successfully built the computing section of Charles Babbage's Difference Engine #2 in 1991, Myhrvold funded the construction of the output section, which performs both printing and stereotyping of calculated results. He also commissioned the construction of a second complete Difference Engine #2 for himself, which has been on display at the Computer History Museum in Mountain View, California since May 10, 2008.

Cooking

In addition to his business and scientific interests, he is a master French chef who has finished first and second in the world championship of barbecue in Memphis, Tennessee. An early culinary learning experience took place when he was allowed to act as an observer and apprentice at Rover's, one of Seattle's leading restaurants, with Chef Thierry Rautureau. Myhrvold is the principal author of a book of culinary reference and instruction entitled Modernist Cuisine, released in March 2011, on the application of scientific research principles and new techniques and technology to cooking.

Advocacy

On December 20, 2009, Myhrvold appeared on CNN's Fareed Zakaria GPS and discussed his idea to eliminate global warming/climate change using geoengineering. It involves using hoses suspended 25 kilometers (15.5 miles) from the Earth into the atmosphere via helium balloons. The hoses would be placed near the North Pole and the South Pole and emit sulfur dioxide, which is known to scatter light. Myhrvold estimated that such a configuration could "easily dim the sun by one percent, and even do it in a way that wouldn't be visible."

Affiliations and awards

Myhrvold is also a member of the USA Science and Engineering Festival's Advisory Board

In 2010, he was named by Foreign Policy magazine to its list of top 100 global thinkers.

References

Further reading

Auletta, Ken, "The Highwaymen", Harvest Books, 1998. ISBN 0-15-600573-5 — cf Chapter 17: The Microsoft Provocateur: Nathan Myhrvold, Bill Gates Corporate Gadfly.

Edstrom, Jennifer and Eller, Marlin, "Barbarians Led by Bill Gates: Microsoft From The Inside: How The World's Richest Corporation Wields Its Power", Holt Paperbacks, 1999. ISBN 0-8050-5755-2

External links

Biography from Intellectual Ventures

Who's afraid of Nathan Myhrvold?, Fortune, July 10, 2006

In the Air: Who says big ideas are rare?, Malcolm Gladwell, The New Yorker, May 12, 2008

The intellectual venturer, by Michael Watts 21.January 2011 Wired UK

Microsoft’s Former CTO Takes On Modernist Cuisine, by Mark McClusky February 24, 2011 Wired.com

TED talk (embedded video): Nathan Myhrvold: A life of fascinations

Category:Academics of the University of Cambridge Category:University of California, Los Angeles alumni Category:Princeton University alumni Category:Microsoft employees Category:American chief executives Category:Chief technology officers Category:Geoengineers Category:Sustainability advocates Category:Living people Category:1959 births

de:Nathan Myhrvold no:Nathan Myhrvold

name	Tokio Hotel
background	group_or_band
origin	Magdeburg, Germany
years active	2001–present
genre	Alternative rock, electronic rock, pop rock, teen pop emo, pop punk (early)
label	Universal Music GermanyCherrytree, Interscope (US)
website	www.tokiohotel.com
current members	Bill KaulitzTom Kaulitz Georg ListingGustav Schäfer
past members	}}

Tokio Hotel is a pop rock band from Germany, founded in 2001 by singer Bill Kaulitz, guitarist Tom Kaulitz, drummer Gustav Schäfer and bassist Georg Listing. The quartet have scored four number one singles and have released three number one albums in their native country, selling nearly 5 million CDs and DVDs there. After recording an unreleased demo-CD under the name "Devilish" and having their contract with Sony BMG Germany terminated, the band released their first German-language album, Schrei, as Tokio Hotel on Universal Music Germany in 2005. Schrei sold more than half a million copies worldwide and spawned four top five singles in both Germany and Austria. In 2007, the band released their second German album Zimmer 483 and their first English album Scream which have combined album sales of over one million copies worldwide and helped win the band their first MTV Europe Music Award for Best InterAct. The former, Zimmer 483, spawned three top five singles in Germany while the latter, Scream, spawned two singles that reached the top twenty in new territories such as France, Portugal, Spain and Italy. In September 2008, they won in the US their first MTV Video Music Award (VMA) for Best New Artist. In October 2008, they won four awards including Best International Artist and Song of the year at Los Premios MTV Latinoamérica (MTV Video Music Awards Latin America) held in Mexico. Tokio Hotel became the first German band ever to win an award at the MTV VMAs and also at the MTV Latin America Awards. They also picked up the Headliner award at the MTV Europe Music Awards 2008 held in Liverpool on November 6, 2008 and the Award for Best Group on November 5, 2009 at the MTV Europe Music Award (EMA) held in Berlin. They won an Award for Best World Stage Performance on November 7, 2010 at the MTV Europe Music Awards in Madrid. In July 2011, they became the first German band to win an MTV Video Music Awards Japan (VMAJ).

History

Founding

Tokio Hotel by vocalist Bill Kaulitz and guitarist Tom Kaulitz, who are identical twin brothers, drummer Gustav Schäfer and bass-guitarist Georg Listing. The four met in 2001 after a live show in a Magdeburg-Club, where Listing and Schäfer, who knew each other from music school, watched from the audience while Bill and Tom Kaulitz played on the stage. Under the name Devilish, the band soon began playing in talent shows and small concerts. After Bill Kaulitz's participation in a children's Star Search in 2003 at age thirteen (which he lost in the quarter-final), he was discovered by music producer Peter Hoffmann. Devilish changed their name to Tokio Hotel: "Tokio", the German spelling of the Japanese city Tokyo, due to a love of the city, and "Hotel" due to their constant touring and living in hotels. In 2006, a third and fourth single, "Rette mich" ("Rescue Me") and "Der letzte Tag" ("The Final Day"), were released; both reached #1 as well. "Der letzte Tag" contained a B-side called "Wir schließen uns ein", which was also accompanied by a music video.

Zimmer 483

The first single off their second album Zimmer 483 (Room 483), called "Übers Ende der Welt" (later re-released in English under the name "Ready, Set, Go!"), was released on January 26, 2007 and quickly reached #1 in Germany and Austria, and #2 in France. Zimmer 483 was released in Germany on February 23, 2007, along with a deluxe edition of the album containing a DVD. The album's second single, "Spring nicht" ("Don't Jump") was released on April 7. The tour accompanying the release of the album, The Zimmer 483 Tour, was scheduled to start in March 2007, but was delayed by two weeks because the band members wished to have a different stage design. A third single, "An deiner Seite (Ich bin da)" ("By Your Side"), was released on November 16. The single contains the B-side "1000 Meere" ("1000 Oceans"), for which a music video was also produced. On April 28, 2008 Tokio Hotel released their single "Heilig" but no music video for the single was released, because of the tight schedule they had.

Scream

Tokio Hotel's first English language album, Scream, was released on June 4, 2007 throughout Europe. In Germany, the album was released as Room 483 in order to emphasize the continuity with their last German album Zimmer 483. Scream contains English versions of a selection of songs from their German-language albums Scream and Zimmer 483. "Monsoon", the English-language version of "Durch den Monsun", was the first single from the album. "Ready, Set, Go!" (the translation of "Übers Ende der Welt") was released as the album's second single and "Don't Jump" (the translation of "Spring nicht") as the third single. A video for "Scream", the English-language version of their 2005 hit "Schrei", was also recorded, and was released to the iTunes Store in early March 2008.

Tokio Hotel gave their first concert in the United Kingdom on June 19, 2007. "Ready, Set, Go!" was released in the UK as the band's first single on August 27, 2007. The song reached #77 in the UK Singles Chart.

Tokio Hotel won an MTV Europe Music Award for Best InterAct on November 1, 2007 and were also nominated for Best Band. They performed "Monsoon" at the event.

Tokio Hotel released their first US single, simply called "Tokio Hotel", in late 2007. The single contains the tracks "Scream" and "Ready, Set, Go!", and was available exclusively at Hot Topic stores. Their second US single, "Scream America", was released on December 11, 2007. The single contains the track "Scream" and a remix of "Ready, Set, Go!" by AFI's Jade Puget. In February 2008, the band toured North America for five dates starting in Canada and finishing up in New York. After appearing and performing live on MuchMusic, while touring in Canada, "Ready, Set, Go!" entered the MuchOnDemand Daily 10, a countdown of videos chosen by viewers. It remained there for over a week, then returned to the top of the MOD Daily 10 chart on April 8. "Scream" was released in Canada on March 25 and in the US on May. 6

1000 Hotels Tour

The "1000 Hotels" European Tour began on March 3, 2008 in Brussels and continued to locations including The Netherlands, Luxembourg, France, Spain, Portugal, Italy, and Scandinavia, and was scheduled to finish on April 9; during the concert in Marseille, France on March 14, Bill started to experience vocal problems. He let the audience sing more frequently than normal and instead of the original 21 songs that were on the set list, they only played 16 songs. Bill apologized, in German, for his bad singing and explained that he was sick. Two days later, the band canceled Lisbon, Portugal concert minutes before it was supposed to commence. The rest of the "1000 Hotels" Tour and a scheduled North American Tour were cancelled following an announcement in Bild by the band's manager that Bill Kaulitz had to undergo surgery to remove a cyst on his vocal cords.

Bill Kaulitz had been putting strain on his voice after playing 43 concerts in the 1000 Hotels tour without vacation. He had to undergo Larynx surgery on March 30 to remove a cyst that had formed on his vocal cords. The cyst was the result of a throat infection that went untreated. Following his surgery, Bill was unable to speak for twelve days, and had four weeks of vocal rehabilitation. If Bill had continued singing the rest of the tour, his voice would have eventually been permanently damaged. Tokio Hotel started performing again in May 2008 and after that they embarked on a 2nd part of their 1000 Hotels European Tour adding many Open Air concerts and wrapping up the tour on July 13 in Werchter, Belgium.

North American Tours and Humanoid

Tokio Hotel embarked on a second tour of North America in August 2008, which included a performance at the Bamboozled festival in New Jersey. The band's music video for "Ready Set Go!" was nominated for Best Pop Video at the 2008 MTV Video Music Awards, where they also won the award for Best New Artist. They returned to North America again in October 2008 for a month long tour of concerts and record store signings. In December 2008, a behind-the scenes DVD called Tokio Hotel TV – Caught on Camera was released. It contains footage from Tokio Hotel TV and backstage feature stories of the previous year on disc one entitled "History – The very best of Tokio Hotel TV!". A deluxe edition contains a second disc entitled "Future – The road to the new Album!" which features footage of the band on promotion tours and preparing for their third studio album.

In between the North American tours, the band returned to their record studio in Hamburg to record their third studio album, Humanoid, which, according to their producer David Jost, is currently set for release on October 2 in Germany & October 6, 2009 in the U.S. This is despite earlier statements predicting a March/April 2009 release or a May/June 2009 release. The album was recorded in both German and English with both versions were released simultaneously worldwide. Nevertheless, the video for the single was released on September 3.

On November 2, it was announced on Tom's Blog that the second English single would be "World Behind My Wall" and its German counterpart, "Lass uns laufen", would be the second German single. The music videos for both versions were released on December 14 and December 15.

On June 24, the live music video for their single, "Dark Side of the Sun" was released on the band website.

On July 20, 2010 they released their second live album Humanoid City Live from Milan, Italy On November 22, 2010, their new song "Hurricanes and Suns," premiered on the Greek radio station Mad Radio. It was included in the bonus track on all versions of "Tokio Hotel: Best Of," a compilation album of their most successful songs. As well as the single for the 'Best of' release. The album will also include "Mädchen aus dem All", the first song the band recorded in a studio.

On December 14, 2010 their 'Best of' was released. December 2 was the World Premiere of the video for "Hurricanes and Suns" on their Official Website. On April 28, 2011 they received the "Fan Army FTW" award at the MTV O Music Awards, the networks first online award show. A clip of Bill and Tom thanking their fans was played after the winner was announced.

Asian performances

Tokio Hotel performed their first concert in Asia (excluding their concert in Israel) at the Audi Showcase in Singapore, followed shortly by the TM Connects With Tokio Hotel event in Malaysia, promoting the sales of their album Humanoid. They concluded the series of mini-concerts with Taiwan. They returned to Malaysia a couple of months later to perform at MTV World Stage Live in Malaysia 2010. They performed in Tokyo on December 15, 2010, after their South American Tour concluded in Distrito Federal, Mexico on December 2, 2010. In February, 2011 Tokio Hotel travelled to Japan to complete a second promo tour. A number of TV appearances and media interviews took place between February 8 and February 11.

On June 24, 2011 Tokio Hotel performed in Japan at “The Next Premium Night Tokio Hotel in Tokyo". The event was presented by Audi A1 and 150 fans were chosen to win tickets to attend the show. The event was the bands first acoustic performance in Japan. On June 25, 2011 the band performed live at the MTV Video Music Aid Japan in Tokyo. The show, which was formerly called the Video Music Awards Japan, was used as a music benefit to raise money for the Japanese Red Cross in order to help those who were affected by the recent earthquake.

Modeling and commercials

On January 19, 2010, lead singer Bill Kaulitz teamed up with twins Dean and Dan Caten of DSquared to walk the runway at a fashion event in Milan. Kaulitz made two appearances, as he opened and closed DSquared's Menswear Autumn/Winter 2010 show to Tokio Hotel song "Screamin".

Car maker Audi hired the two frontmen to star in their new advertising campaign to attract the younger generation. They were featured in an episode of Tokio Hotel TV (on Tokio Hotel's website) and also in a commercial.

On August 4, 2010, Tom Kaulitz got his own Reebok shoe commercial. Reebok signed the 20-year-old Tokio Hotel guitarist and sneaker addict to model shoes for the company. "At home, I created a little room like a little storage room," he said of his sneakers. He also said that he gets 10 new pairs a week. That's 520 sneakers a year.

Band members

Bill Kaulitz

Bill Kaulitz was born on September 1, 1989, in Leipzig ten minutes after his identical twin brother, Tom.

Tom Kaulitz

Tom Kaulitz (born 1 September 1989 in Leipzig, German Democratic Republic) is a German guitarist singer, songwriter and model from Tokio Hotel. He is the twin brother of Bill Kaulitz, and Tom was born 10 minutes before Bill.

Early life

Tom Kaulitz was born 1 September 1989 in Leipzig. His parents, Simone and Jörg Kaulitz, separated when Kaulitz and his brother were seven years old.His mother began dating Gordon Trumper, and married him in August 2009. Tom's guitar playing and his brother's singing showed their natural aptitude for music, and gave an early indication of their possibility of fame. Trumper helped the twins to start their own band. He and Bill began writing music at the age of seven years old. Due to their great desire to create a band, his twin brother Bill entered and became renowned on the reality TV talent show "Star Search." They met Georg Listing (then 14) and Gustav Schäfer (then 13), in the audience of one of their shows. Listing and Schäfer were friends and after the show, having liked what they heard and saw, made an offer to join. The band was promptly re-named "Devilish" due to an article published at the time that referred to their "devilishly great"[citation needed] sound. This continued until 2005 when Jost arranged a meeting between the band and Universal Music Group's Interscope Records and Tokio Hotel was signed. They began working immediately, releasing their debut LP Schrei ("Scream") later that year. Their first single from the album Schrei was "Durch den Monsun" ("Through The Monsoon"), which reached #1 in Germany within a month of its release. He then continued his dream with 3 members of the group.

Stalking incident

More trouble came for Kaulitz when in late 2008/early 2009 several female stalkers pursued the band relentlessly, even following his twin brother Bill Kaulitz to his parents' home in Germany and attacked the twins' mother. The issue seemed to end after Tom allegedly hit one of the stalkers at a gas station in April 2009 and drove off. However, a recent article in Bild stated that the issue had resurfaced and that Tom Kaulitz may stand trial for assault. In late December 2009, the charges against Tom were lifted and he is pressing charges himself — against the girl he allegedly hit — on grounds of stalking.

Personal life

Tom Kaulitz and his identical twin brother, Bill, used to live in Hamburg but have recently moved to Los Angeles in response to an incident involving stalkers and a robbery. They have also stated that it is easier for them to work on their new album, as it is closer to their manager David Jost. They are currently living in Los Angeles but also have a second home in Hamburg. Tom and Bill, have modeled for a PETA.de photoshoot. He models for Reebok for sneakers and shoes. Tom is friends with Nicole Scherzinger. Tom prefers to listen to hip-hop music. His favorite rapper is Samy Deluxe. As of September 2007, Tom uses Gibson guitars and Mesa/Boogie Rectifier Heads with Mesa Boogie Rectifier 4x12 cabinets. Tom currently has his hair in cornrows, which he had done in early 2009. Tom had allegedly been dating Chantelle Paige after the stalker incident, but later it was said that they had been going out to better publicise Tom and his band, as well as Chantelle’s band, Flipsyde. In an interview with her, Chantelle had said : "I think Tom is quite nice, actually he is my dream boy. But my friends have warned me about him".

Georg Listing

Georg (Moritz Hagen) Listing was born on March 31, 1987. His hometown is Halle. He began playing bass when he was thirteen years old, He has said that his playing style was heavily influenced by Flea of Red Hot Chili Peppers, and other musical influences include Die Ärzte and Oasis.

Awards

Since the release of the "Durch den Monsun" single in 2005, Tokio Hotel have gone on to win 102 awards in various categories and countries.

;2005

! Category	!Award	! Date
Best Newcomer	Comet Awards (Germany)	October 6
Super Comet	Comet Awards (Germany)	October 6
Best Newcomer	Eins Live Krone	November 24
Best Pop National Act	Bambi Awards	December 1
Best Single	Golden Penguin (Austria)	...2005
Best Pop	Golden Penguin (Austria)	...2005
Rock Band 2005	Golden Penguin (Austria)	...2005

;2006

! Category	! Award	! Date
Album of the year	Golden Penguin (Austria)	February 8
Band of the year	Golden Penguin (Austria)	February 8
Song of the year – ‘Der Letzte Tag’	Golden Penguin (Austria)	February 8
Best Newcomer	Golden Penguin (Austria)	February 8
Ausverkaufte Tourhalle	Sold-out-Award of Königpilsener Arena	March 11
Best Newcomer		March 12
Best Newcomer	Steiger Awards	March 25
Pop National	Radio Regenbogen (Germany)	March 31
SuperBand Rock – Golden Otto	Bravo Otto	May 6
Music Award	Bild OSGAR	May 22
Best Newcomer International	Popcorn Awards (Hungary)	May 26
Best Newcomer	Bravo Otto (Hungary)	June 24
Best International Band	Bravo Otto (Hungary)	June 24
Best Newcomer Band	Popkomm Bavarian Music Lion	September 21
Best German Pop Band	Goldene Stimmgabel	September 24
Best Selling German Artist	World Music Awards	November 15
Best Pop National Act	Bambi Awards	November 30
Best Live Act	Eins Live Krone	December 7
Best Rock band	MTV France

;2007

! Category	! Award	! Date
Single of the Year – Durch Den Monsun	Golden Penguin
Best Selling German Act – Album Schrei	European Border Breakers Award	January 21
European Border Breakers Award	NRJ Awards	January 21
Rock Award	BZ-Kulturpreis	January 23
Best Video National	ECHO Awards (Germany)	March 25
SuperBand Rock – Golden otto	Bravo Otto	April 28
Best Video	Comet Awards (Germany)	May 3
Best Band	Comet Awards (Germany)	May 3
Supercomet	Comet Awards (Germany)	May 3
Best Band	Jabra Music	July 2007
Digital prize	Festivalbar (Italy)	September 7
Most Successful Group Rock International	Goldene Stimmgabel	September 22
Most Successful Popgroup International	Goldene Stimmgabel Awards	October 3
Best Album	TMF Awards (Belgium)	October 14
Best Video	TMF Awards (Belgium)	October 14
Best New Artist	TMF Awards (Belgium)	October 14
Best Pop	TMF Awards (Belgium)	October 14
Best International Act	MTV Europe Music Awards (Germany)	November 1
Best band of the Year	MTV Italy Nickelodeon Kids' Choice Award	December 1

;2008

! Category	! Award	! Date
Band of the Year 2007	Golden Penguin (Austria)	January
Best International Band	Rockbjörnen Award (Sweden)	January 24
Best Music National	Goldene Kamera (Germany)	February 6
Best Music Video	Echo Awards (Germany)	February 15
Best International Artist	Emma Gala Awards (Finland)	March 8
Best International Group	Disney Channel Kids Award (Italy)	March 28
Best Concert	Hitkrant (Netherlands)	May 2008
Best Mood Song – Monsoon	Hitkrant (Netherlands)	May 2008
Song that Satys in your Head – Monsoon	Hitkrant (Netherlands)	May 2008
Superband Rock – Silver Otto	Bravo Otto	May 3
Best Band	MTV TRL Awards (Italy)	May 17
Best Number 1 of the Year with Monsoon	MTV TRL Awards (Italy)	May 17
Best Band	Comet Awards (Germany)	May 23
Best Video – An Deiner Seite	Comet Awards (Germany)	May 23
Best Live Act	Comet Awards (Germany)	May 23
Super Comet	Comet Awards (Germany)	May 23
Best New Artist	MTV VMA Music Awards (USA)	September 7
Fan Choice Best Entrance	MTV VMA Music Awards (USA)	September 7
Best Male Artist International (Bill Kaulitz)	TMF Awards (Belgium)	October 11
Best Video International – Don't Jump	TMF Awards	MTV Europe Music Awards (Germany)	November 5
Best International Rock Band	Telehit Awards (Mexico)	November 12

;2010

! Category	!Award	! Date
Band of the Year	Golden Penguin (Austria)	January 29
Album of the Year	Golden Penguin (Austria)	January 29
Band of the Year	Bravoora Awards (Poland)	February 1
Best International Artist	Emma Gala Awards (Finland)	February 4
Walk of Fame	König-Pilsener Arena (Germany)	February 26
Best International Band	Radio Regenbogen Awards (Germany)	March 19
Favorite Music Star	Kids Choice Awards 2010 (Germany)	April 10
Best Live Act	Comet Awards (Germany)	May 21
Foreign Song of the Year - World Behind My Wall	Rockbjörnen Award (Sweden)	September 1
Concert of the Year	Rockbjörnen Award (Sweden)	September 1
Best World Stage Performance	MTV Europe Music Awards (Spain)	November 7
Best Band National	CMA Awards (Germany)	December 12
Best Single National - World Behind My Wall	CMA Awards (Germany)	December 12

;2011

! Category	!Award	! Date
Band of the Year	Bravoora Awards (Poland)	March
Star of the 20th Anniversary		March
Best Fan Army (Fan Army FTW)	MTV O Music Awards (USA)	April 28
Best Rock Video	MTV Video Music Awards Japan	July 2

References

External links

Official site

Official Youtube channel

Interscope records profile

Tokio Hotel on MTV

Category:German musical groups Category:German rock music groups Category:German pop music groups Category:German-language singers Category:English-language singers Category:People from Leipzig Category:Musical groups established in 2001 Category:Pop rock groups

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name	Oumou Sangaré
background	solo_singer
born	February 25, 1968
origin	Bamako, Mali
genre	Wassoulou music
occupation	Singer
website	http://www.oumousangare.co.uk
notable instruments	}}

Oumou Sangare (born February 25, 1968, in Bamako, Mali) is a Malian Wassoulou musician, sometimes referred to as "The Songbird of Wassoulou." Wassoulou is a historic region south of the Niger River, and the music there is descended from traditional hunting songs, and is accompanied by a calabash. Her mother was the singer Aminata Diakité.

She is an advocate for women's rights, opposing child marriage and polygamy.

Oumou Sangaré is also involved in the world of business, hotels, agriculture and the sale of cars: Oumou Sangaré has given her name to a Chinese automobile. She is the owner of the 30-room Hotel Wassoulou in Mali's capital, Bamako, a haven for musicians and her own regular performing space. "I helped build the hotel myself. I did it to show women that you can make your life better by working. And many more are working these days, forming co-operatives to make soap or clothes."

Although she also has been a goodwill ambassador for FAO she still says she does not want to be a politician: "While you're an artist, you're free to say what you think; when you're a politician, you follow instructions from higher up."

She is a cousin of an actor, Omar Sangare.

Early life

As a child, Oumou Sangaré sang in order to help her mother feed their family as her father had abandoned them. At the age of five, she was well known for her talents as a gifted singer. After making it to the finals of a contest for the nursery schools of Bamako, she performed in front of a crowd of 6,000 at the Omnisport Stadium. At 16, she went on tour with the percussion group Djoliba.

She then worked with Amadou Ba Guindo, a great maestro of Malian music with whom she recorded her first album Moussoulou ("Women"), which was very successful in Africa with more than 200,000 copies sold.

With the help of Ali Farka Touré, Oumou Sangaré signed with the English label World Circuit. At the age of 21, she was already a star.

Music

Oumou Sangaré is considered an ambassador of Wassoulou; her music has been inspired by the music and traditional dances of the region. She writes and composes her songs, which often include social criticism, especially concerning the place of women and their low position in society.

Since 1990, she has performed at some of the most important venues in the world: the Melbourne Opera, Roskilde festival, festival d'Essaouira, Opéra de la monnaie of Brussels.

Many of Sangaré's songs concern love and marriage, especially freedom of choice in marriage. Her 1989 album Moussoulou was an unprecedented West African hit. In 1995, she toured with Baaba Maal, Femi Kuti and Boukman Eksperyans. Other albums include Ko Sira (1993), Worotan (1996), and a 2-CD compilation Oumou (2004), all released on World Circuit Records. Oumou Sangaré supports the cause of women throughout the world. She was named an ambassador of the FAO in 2003 and won the UNESCO Prize in 2001 and a commander of the Arts and Letters of the Republic of France in 1998.

Sangaré is featured prominently in "Throw Down Your Heart," a documentary featuring world-renowned banjo player Bela Fleck, and his exploration of the relatively unknown relationship between his instrument and the musical traditions in Africa.

She contributed vocals to "Imagine" for the 2010 Herbie Hancock album, The Imagine Project along with Seal, P!nk, India.Arie, Jeff Beck, Konono N°1 and others.

Discography

Moussolou (1990)

Ko Sira (1993)

"Worotan" (1996), Nonesuch/Warner Music

Oumou (2003)

Seya (2009)

Prizes and awards

Music Prize of 2001 for UNESCO for her contribution to "the enrichment and the development of music as well as for the cause of peace, for the understanding among peoples and international cooperation".

On 16 October 2003, Oumou Sangaré was nominated Goodwill Ambassador of the Food and Agriculture Organization of the United Nations (FAO).

References

External links

Oumou Sangaré's official site

Oumou Sangaré on MySpace

Watch official Oumou Sangaré documentary film

Oumou Sangaré podcast and interview on flyglobalmusic.com

FAO Goodwill Ambassador website

Category:1968 births Category:Living people Category:Bambara-language singers Category:Malian musicians Category:World Circuit artists Category:People from Bamako

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