Malaria ranks among the major health and developmental challenges facing some of the poorest countries in the tropical and sub-tropical regions. As early as 2700 BCE, a disease marked by high fever and an enlarged spleen was noted in ancient Chinese documents. Believing the disease was transmitted through the air, the sixteenth-century Italians called the disorder mal'aria (bad or evil air). Plasmodium vivax stowed away with the English going to Jamestown, while P. falciparum rode along with slaves from Africa. In the United States, malaria flourished for centuries in the South and in port cities like Boston and New York. During the Civil War, armies on both sides stationed in the South sustained more than 1.2 million cases of malaria. The southern United States continued to be afflicted with millions of cases of malaria each year into the mid-1930s. The Public Health Service began an anti-malaria campaign in 1942, and by 1953, Plasmodium was considered to be tamed in the United States. Some authorities today, however, believe this public health campaign had less to do with malaria's retreat than did the country's increasing prosperity, which pushed millions of Americans out of the swampy hinterlands and into cities. In 1958 the World Health Organization (WHO) decided to wage a global campaign against malaria and sent workers into South American, African, and Asian villages to spray with DDT. But except for areas such as Egypt and southern Europe where the parasite was not firmly established, in the end the spraying only succeeded in making the mosquitos pesticide-resistant. By the 1960s, the WHO had scaled back its Global Eradication of Malaria Program to one of worldwide malaria control. Malaria threatens nearly 40 percent of the people in the world - 2.4 billion people - mostly in the tropics and subtropics. The disease is currently endemic in 90 to 100 countries. In 1990, 80 percent of cases were in Africa, with the remainder found in countries such as India, Brazil, Afghanistan, Sri-Lanka, Thailand, Indonesia, Vietnam, Cambodia, China, and others. Plasmodium falciparum is the predominant species, with over 120 million new cases and all the malaria deaths per year globally. P. falciparum is responsible for the alarming drug-resistant strains now emerging in the most endemic areas. About 1,200 cases of malaria are diagnosed in the United States each year. Most of these are "imported" by military personnel and travelers to, or immigrants from, countries where malaria is common. Malaria has occasionally been spread locally in the United States by infected mosquitoes stowed away on international airplanes, or, on rare occasions, by mosquitoes here that have bitten someone who was infected ("local transmission"). Despite mankind's longstanding struggle to control mosquito populations, the World Health Organization currently estimates that each year malaria causes 300 to 500 million infections and 1.5 to 3 million deaths each year. During the six-month Ebola outbreak in Zaire in 1995, about 250 people died; malaria kills over 5,000 Africans every day. The parasite seems to increase greatly one's susceptibility to other infections via generalized immunosuppression. A baby born to a pregnant woman infected with malaria will have a 40 percent greater chance of low birth weight, and congenital malaria may account for as many as half of all childhood deaths in Africa. For most people, symptoms begin 10 days to 4 weeks after an infective bite. Symptoms of malaria include high fever and flu-like illness with shaking chills, sweating, headache, muscle aches, tiredness, and sometimes nausea, vomiting, and diarrhea. The parasite alters human red blood cells, causing them to stick to the sides of blood vessels, eventually blocking capillaries to the brain and other organs. If not promptly treated, severe infection with P. falciparum may lead to unrousable coma, severe anemia, cerebral malaria, hypoglycemia, renal failure, acidosis, repeated convulsions, and death. Malaria is caused by infection with a protozoan parasite of the genus Plasmodium, four species of which infect human beings, the most common being P. vivax and most deadly P. falciparum. The Anopheles mosquito serves as Plasmodium's delivery system, or vector. Only female mosquitos are involved, since males don't take blood meals. Anopheles mosquitoes bite mainly during nighttime hours. The female Anopheles mosquito ingests the reproductive stage of the parasite when it feeds on someone who already has malaria. The parasites then incubate in the insect's midgut for a week or more, maturing until they reach an infective form, and are reintroduced into humans when the mosquito feeds again. A biting mosquito transfers about 10 percent of its parasite load into the victim's capillaries or the tissue around the blood vessels. The parasites make their way to the person's liver in less than 30 minutes of entering the bloodstream, and penetrate the liver cells (hepatocytes). During the period when the parasites are maturing further in the liver as little as eight days or as long as several months the infected person does not feel ill. Two kinds of malaria, P. vivax and P. ovale, can relapse, and some parasites can remain dormant in the liver from several months to years after a person is bitten. Once the parasites leave the liver and re-enter the bloodstream, they invade and multiply in the red blood cells, periodically bursting the cells. Their further development leads to the formation of gametocytes (the parasite's sexual stages), which are picked up and transmitted to others when another mosquito feeds on the infected person. In the absence of vaccines and effective drugs, malaria has been fought by spraying with insecticides such as DDT, coating marshes with paraffin (to block development of mosquito larvae), draining stagnant water, sleeping under bed nets, and preventing future occurrences of disease through drugs. New control strategies are badly needed: not only are mosquitos becoming more and more resistant to insecticides each year, but Plasmodium is shrugging off more and more once-effective drugs as well. Given the complexity of the malaria parasite's life cycle and the omnipresence of the Anopheles mosquito, a vaccine is probably our best chance for gaining control of malaria in a cost-effective manner. | 
