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Malaria (Italian bad air; formerly called ague in English) is a tropical disease which causes about half a billion infections and 2 million deaths annually, mainly in tropical countries and especially in sub-Saharan Africa.

The symptoms are fever, shivering, pain in the joints, vomiting, and convulsions; especially in young children, the disease can lead to coma and death if untreated. Malaria is caused by the protozoan parasite Plasmodium (mainly P.falciparum and P.vivax, but also more rarely P.ovale and P.malariae), one of the Apicomplexa, which travels in the Anopheles mosquito and, after the mosquito bites the host, infects hepatic cells in the liver and then circulating red blood cells.

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Mechanism of the disease

Infected female Anopheles mosquitos carry Plasmodium sporozoites[?] in their salivary glands. If they bite a person, which they usually do starting at dusk and during the night, the sporozoites enter the person's liver cells, multiply and turn into merozoites[?] which then enter red blood cells. Here they feed on hemoglobin and multiply further and periodically break out of the cells, causing chills and fever and infecting new red blood cells.

Within liver and blood cells, the parasite is relatively protected from attack by the body's immune system. However, circulating infected blood cells are killed in the spleen. To avoid this fate, the parasite produces certain proteins and induces infected blood cells to express them at their cell surface, causing the blood cells to stick to the walls of blood vessels. These surface proteins are highly variable and cannot serve as a reliable target for the immune system.

Some merozoites turn into male and female gametocytes[?]. If a mosquito bites the infected person and picks up gametocytes with the blood, fertilization 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 mosquitos, and malaria in pregnant women is an important cause of still births and infant mortality.

Treatment and prevention

If diagnosed early, malaria can be treated, but prevention is always much better, and substances that inhibit the parasite are widely used by visitors to the tropics. Since the 17th century quinine has been the prophylactic of choice for malaria. The development of quinacrine[?], chloroquine[?], and primaquine[?] in the 20th century reduced the reliance on quinine.

Certain strains of Plasmodium have recently developed resistance to some of those drugs, thus complicating the treatment. In west Africa, where the local strains of malaria are particularly virulent, Larium[?] is now the recommended prophylactic, despite causing psychological problems in some vulnerable people. It seems inevitable that resistance to this will also occur.

In addition to the antimalarial drugs, the use of mosquito repellants such as DEET[?], and mosquito nets and screens can reduce the chance of malaria, as well as the discomfort of insect bites.

Extracts from the plant Artemesia[?], containg substances unrelated to the quinine derivatives, offer some future promise.

How do these drugs work?

Vaccines for malaria are under development, but no effective vaccine existed as of 2001. In 2002, the complete genome of the most deadly variant, Plasmodium falciparum, was sequenced. It consists of 25 million base pairs on 14 chromosomes, forming about 5,600 genes. It is hoped that the sequence can provide targets for new drugs or vaccines. The known anti-malaria medications can be taken preventively, which is recommended for travellers to affected regions.

Efforts to eradicate malaria by attacking mosquitos have been successful in some areas. Malaria was once common in the United States and southern Europe, but the draining of wetland breeding grounds and better sanitation eliminated it from affluent regions.

Malaria was eliminated from the northern parts of the USA in the early twentieth century, and the use of the pesticide DDT during the 1950s eliminated it from the south.

Since most of the deaths today occur in poor rural areas of Africa without health care, the distribution to children of mosquito nets impregnated with insect repellants has been suggested as the most cost-effective prevention method.

Sickle cell anemia and other genetic effects

Carriers of the sickle cell anemia gene are protected against malaria because of their particular hemoglobin mutation; this explains why sickle cell anemia is particularly common among people of African origin. There is a theory that another hemoglobin mutation, which causes the genetic disease thalassemia[?], may also give its carriers an enhanced immunity to malaria.

It is thought that humans have been afflicted by malaria for about 8,000 years, and several human genes responsible for blood cell proteins and the immune system have been shaped by the struggle against the parasite.

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