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Annual cases: 300-500 million worldwide.

Deaths: at least one million, though some estimates put the figure as high as 2.7m. Aids is the only condition that leads to more deaths.

Pathogen: four species of the Plasmodium organism. One type, Plasmodium falciparum, acccounts for almost all fatal cases.

Symptoms: neck stiffness, convulsions, abnormal breathing, fever of up to 40C (104F).

Cost: US$12BN a year in Africa in lost GDP. Death and disability leads to loss of 45 million years of productive life each year.

Famous sufferers: Alexander the Great, Genghis Khan, Oliver Cromwell, Edward IV, Caravaggio and David Livingstone are amongst those thought to have died of malaria. Figures who contracted it and recovered include Horatio Nelson, Sir Arthur Conan Doyle, Mahatma Gandhi, Ernest Hemingway and John F. Kennedy.








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Malaria   

Malaria derives its named from the Italian for "bad air". In English, it was historically known as the ague.

Malaria is a tropical infectious disease which causes about half a billion infections and two million deaths annually, mainly in tropical countries and especially in sub-Saharan Africa.

Malaria is caused by the protozoan parasite Plasmodium (one of the so-called Apicomplexa). This discovery was made by a French army doctor, Charles Louis Alphonse Laveran; he was awarded the Nobel Prize for Physiology or Medicine in 1907.

The main culprits are Plasmodium falciparum and P. vivax, but P. ovale and P. malariae are also known to cause malaria. The vector for the malarial parasite is the Anopheles mosquito.

Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, and convulsions. There may be the feeling of tingling in the skin, particularly with malaria caused by P. falciparum. Complications of malaria include coma and death if untreated- young children are especially vulnerable.

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 body via the mosquito's saliva, migrate to the liver where they multiply within hepatic liver cells.

They then turn into merozoites which then enter red blood cells. There they multiply further, periodically breaking out of the red blood cells. The classical description of waves of fever coming every three or four days arises from simultaneous waves of merozoites breaking out of red blood cells during the same day.

The parasite is relatively protected from attack by the body's immune system because it stays inside liver and blood cells. However, circulating infected blood cells are killed in the spleen.

To avoid this fate, the parasite produces certain surface proteins which infected blood cells express on 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. The stickiness of the red blood cells are particularly pronounced in P. falciparum malaria and this is the main factor giving rise to hemorrhagic complications of malaria.

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. These anti-malarial medications can be taken preventively, which is recommended for travellers to affected regions.

Certain strains of Plasmodium have recently developed resistance to chloroquine which has been the first line of treatment in many countries, thus complicating the treatment. In west Africa, where the local strains of malaria are particularly virulent, Lariam 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 repellents 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 Artemisia (specifically Artemisia annua), containing the compound artemisinin, a substance unrelated to the quinine derivatives, offer some future promise.

Prospects of disease control

Several ameliorative drugs are available. Chloroquine costs 4p a day, but resistance runs at 90 per cent. Artemisinin is much more effective, but costs 10 to 20 times more.

Vaccines for malaria are under development, but no effective vaccine exists at this time. Several are in clinical trials; none are expected to be more than 50 per cent effective. It is hoped that the genome sequence of the most deadly agent of malaria, Plasmodium falciparum, which was completed in 2002, will provide targets for new drugs or vaccines. A genetically modified Anopheles mosquito that cannot transmit malaria has also been developed; these could be introduced to malarial swamps that have been sprayed to kill disease carriers.

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.

A major public health effort to eradicate malaria by selectively targeting mosquitos in areas where malaria was rampant was embarked upon in the 1950s and 1960s.

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. These nets can often be obtained for less than US$10 or 10 euros when purchased in bulk from the United Nations or other organizations. Mosquito nets for beds are proven to reduce child deaths by 20 per cent.

Some advocates believe that DDT spraying is even cheaper and more effective than nets, and charge that environmentalists have created perverse restrictions on DDT use that have multiplied African malaria deaths into the millions in countries where the disease had been all but eradicated.


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