Image: TOBY FAGAN
Malaria is one of the most ubiquitous diseases known--there are more than 125 different species of malaria that infect mammals, birds and reptiles, which indicates an early origin. It has probably afflicted humans throughout our evolutionary history, although the first historical reports of symptoms that match those of malaria date back to the ancient Egyptians (around 1550 B.C.) and the ancient Greeks (around 413 B.C.). These early descriptions noted the association between fevers and wet ground. In fact, the word "malaria" actually derives from the Italian for "bad air"-- the mal'aria associated with marshes and swamps.
A single-celled parasite known as a sporozoan causes malaria. This sporozoan belongs to the genus Plasmodium, and the four species that threaten humans are P. falciparum, P. malariae, P. vivax and P. ovale. Of these four, P. falciparum and P. vivax are the most common, and P. falciparum is by far the most dangerous.
Image: JIM GATHANY/CDC
Mosquitoes alone spread malaria in nature. (The disease can be transmitted unnaturally through shared needles or by blood transfusion from infected donors.) When a mosquito bites an infected individual, the sporozoan's male and female sexual stages, or gametocytes, are taken up in the blood meal. Fertilization ensues in the mosquito's gut, and an "ookinete" forms. The ookinete then bores through the mosquito's stomach wall, becoming an oocyst, which subsequently divides to produce about a thousand infective sporozoites. In P. falciparum this process takes five to seven days, after which the sporozoites are released. They then migrate to the insect's salivary glands. Because mosquitoes inject their saliva when they bite (it contains anticoagulants and local anesthetic substances that facilitate blood sucking), the malaria sporozoites will be passed along to the mosquito's next victim.
Once inside the bloodstream of the bitten individual, the sporozoites home in on the liver. Each sporozoite invades a separate liver cell, and in P. falciparum takes five to seven days to divide and produce thousands of "merozoites," each of which will infect a red blood cell (erythrocyte) when the liver cell bursts. After entering the erythrocyte, the merozoite breaks down the cell's hemoglobin, feeding off the amino acids. The growing parasite, or trophozoite, will eventually become a "shizont" when it begins to divide again to form new merozoites. This erythrocytic cycle takes a variable amount of time in different malaria species--48 hours in P. falciparum but 72 hours in P. malariae infections. (One rare, sneaky exception to this progression can occur in P. vivax or P. ovale infections: when the sporozoite invades the liver cell, it does not produce merozoites immediately but may linger for a year or more in the liver before activating. This stage is known as a hypnozoite and can cause a relapse of malaria many months after an apparent cure.)
Characteristic signs of malaria infection are fever and flu-like symptoms, including headaches and muscle or joint pain. These usually begin after an incubation period of 10 to 14 days after the infective bite, during which the malaria parasite first inhabits the liver and then quietly multiplies in the blood. Classically, the fever is intermittent, recurring every few days, corresponding to the erythrocytic cycle. Each time the infected cells burst, liberating new merozoites, toxic metabolites and malarial antigens are also released. The body's immune system responds with a fever. In P. falciparum infections, fevers would occur on days 1, 3 and 5, whereas in P. malariae, fevers would occur on days 1, 4 and 7, and so forth. It is important, however, to remember two points. First, malarial fevers, especially in P. falciparum infections, do not always show cyclic temperature changes. Second, P. falciparum malaria can kill within 48 hours of the first signs, so it is essential that medical help is sought if one develops such symptoms after a visit to a region where malaria is a problem.
Alphonse Laveran, a French army doctor, described the malarial parasite--and proposed that it caused malaria--in 1880. But the final piece of the puzzle was put into place by a British physician, Sir Ronald Ross, who was working in India in 1897 when he observed the development of oocysts in mosquitoes that had been fed on infected individuals. Ross's description of the complete life cycle of the malarial parasite won him the Nobel Prize for Medicine in 1902.