Red blood cell infected with P.vivaxThe countries where malaria is known to occur are shown in red. Source: CDC.
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Malaria

Malaria (Italian: "bad air"; formerly called ague or marsh fever in English) is an infectious disease which in humans causes about 350-500 million infections and approximately 1.3 million deaths annually, mainly in the tropics. Sub-Saharan Africa accounts for 85% of these fatalities. more...

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Malaria is caused by the protozoan parasites of the genus Plasmodium (one of the Apicomplexa), and the transmission vector for human malarial parasite is the female Anopheles mosquito. The P. falciparum variety of the parasite accounts for 80% of cases and 90% of deaths. Pregnant women and children under the age of five are most vulnerable to malaria.

For his discovery of the cause of malaria, French army doctor Charles Louis Alphonse Laveran was awarded the Nobel Prize for Physiology or Medicine in 1907. Britain's Sir Ronald Ross also received a Nobel prize (in 1902) for describing the life cycle of the malaria parasite as it develops in the bodies of its mosquito and human hosts.

Symptoms

Symptoms of malaria include fever, shivering, arthralgia (joint pain), vomiting, anemia, 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. Splenomegaly (enlarged spleen), intense headaches, cerebral ischemia and hemoglobinuria with renal failure may occur.

Mechanism of the disease

Infected female Anopheles mosquitoes carry Plasmodium sporozoites in their salivary glands. If they pierce a person's skin, which they usually do starting at dusk and continuing throughout 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 asexually. There they develop into merozoites which then enter red blood cells, where they multiply further, again asexually, periodically breaking out of the exploited red blood cells. The classical description of waves of fever coming every two or three days arises from simultaneous waves of merozoites breaking out of red blood cells during the same day. Development in the hepatic cell takes 6 to 15 days depending on the species. Some of the sporozoites in vivax and ovale malaria do not develop into merozoites immediately, but produce hypnozoites that remain dormant for several months (typically, from 6 to 12, but sometimes up to 3 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. About a half of the cases of vivax infection in temperate areas start after having overwintered, i.e. during the next year after the mosquito bite. The parasite is relatively protected from attack by the body's immune system because for most of its human life cycle it stays inside liver and blood cells. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the parasite produces certain surface proteins which infected blood cells present on their cell surface, causing the blood cells to stick to the walls of blood vessels. These surface proteins known as PfEMP1 are highly variable (there are at least 50 variations) and cannot serve as a reliable target for the immune systeme.

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Malaria's terrible toll
From Environment, 7/1/05

Despite recent efforts to combat malaria, the disease still kills one million people per year, most of them in Africa, according to a joint report by the World Health Organization (WHO) and the United Nations Children's Fund (UNICEF). The 2005 World Malaria Report, released in early May, found that since 2000, more countries have been introducing new medicines and more people have been receiving pesticide-treated mosquito nets, which could be a sign that the disease will decline. However, insufficient funding and problems with the supply of the new medications leave the battle's outcome in doubt in the near term.

Because some of the protozoans that cause malaria have developed resistance to established medicines like chloroquine, many countries are seeking a second-line medicine that is derived from a chemical, artemisinin, produced by a Chinese herb. However, according to BBC News, producing the drug takes a long time: six months to grow the herb and an additional three to five months to process it.

WHO announced a shortage of the artemisinin-derived drugs late last year. According to the recently released report, various agencies have come together to try to help alleviate the shortage by the end of this year. The main challenge--for everything from mosquito netting distribution to new medicines and other technology and support--has been funding: WHO and UNICEF estimate that US$3.2 billion will be needed each year to reach their goal of halving the incidence of malaria by 2010. This year, only $600 million has been made available for malaria control. However, according to a joint WHO and UNICEF press release in early May, the World Bank will commit between $500 million and $1 billion over the next five years. In mid-May, the Bill and Melinda Gates Foundation announced it would be contributing $250 million toward vaccine research, including research on a vaccine for malaria that will not need refrigeration.

--BBC News, 11 September 2004; Reuters, 3 May; WHO/UNICEF joint press release, 3 May; and Detroit Free Press, 24 May. (D.H.)

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