MALARIA

a serious, acute and chronic relapsing infection in humans, characterized by periodic attacks of chills and fever, anemia, splenomegaly (enlargement of the spleen), and often fatal complications. Malaria also is found in apes, monkeys, rats, birds, and reptiles. It is caused by various species of protozoa (one-celled organisms) called sporozoans (subphylum Sporozoa) that belong to the genus Plasmodium. These parasites are transmitted to humans by the bite of various species of mosquitoes belonging to the genus Anopheles. Malaria is one of the most ancient infections known. It was noted in some of the West's earliest medical records in the 5th century BC, when Hippocrates differentiated malarial fevers into three types according to their time cycles. It is not known when malaria first made its appearance in the Americas, but it is highly probable that it was a post-Columbian importation; some rather severe epidemics were first noted in 1493. The association between swampy or marshy areas and the disease has long been recognized, but the roles of the mosquito and of the malarial parasite were not known until the beginning of the 20th century. In 1880 the French army surgeon Alphonse Laveran became the first person to describe the malarial parasite and to recognize it as the cause of malaria. In 189798 the British physician Sir Ronald Ross proved that bird malaria is transmitted by Culex mosquitoes, and he described the entire life cycle of that parasite in the mosquito. In 1898 the Italian investigators Amico Bignami, Giovanni Battista Grassi, and Giuseppe Bastianelli first infected humans with malaria by mosquitoes, described the full development of the parasite in humans, and noted that human malaria is transmitted only by anopheline mosquitoes. The disease can also be transmitted unnaturally by common use of the hypodermic needle, as among drug addicts, or occasionally by blood transfusion from infected donors. Malaria occurs throughout the tropical and subtropical regions of the world and is the most prevalent of all serious infectious diseases. In the late 20th century, annual cases worldwide were estimated at 250 million, with 2 million deaths resulting. Incomplete or faulty reports from Africa make even those rough estimates unreliable, however. Though malaria can occur in temperate regions, it is most common in the tropics and subtropics, where climatic conditions are favourable for the mosquitoes that transmit the disease throughout the year. In many parts of sub-Saharan Africa, entire human populations are infected more or less constantly. Malaria is also common in Central America, the northern half of South America, and in South and Southeast Asia. The disease also occurs in countries bordering on the Mediterranean, in the Middle East, and in East Asia. Anopheline mosquitoes are the only known vectors of malaria in humans, and about 60 different species perform this function throughout the world. These mosquitoes undergo an aquatic larval stage, pupate, and then hatch into flying adults. The females require a meal of blood to produce fertile eggs, and females of some species prefer human to animal blood. The female mosquito ingests the malarial parasite by biting a human already infected with the parasite. The malarial parasite has a complicated double life cycle, with a sexual reproductive cycle while it lives in the mosquito and an asexual reproductive cycle while in the human host. While in its asexual, free-swimming stage, when it is known as a sporozoite, the malarial parasite is injected into the human bloodstream by a mosquito, passing through the skin along with the latter's saliva. The sporozoite eventually enters a red blood cell of its human host, where it goes through ring-shaped and amoeba-like forms before fissioning (dividing) into smaller forms called merozoites. The red blood cell containing these merozoites then ruptures, releasing them into the bloodstream (and also causing the chills and fever that are typical symptoms of the disease). The merozoites can then infect other red blood cells, and their cycle of development is repeated. A small proportion of the merozoites, however, become gametocytes, or germ cells, and can go through a sexual reproductive cycle once back in a mosquito. After they have been ingested by a mosquito from an infected human host, the separate male and female gametocytes pair off while in the mosquito's stomach and unite to form a single-celled zygote, which grows to become an oocyst. This oocyst eventually divides, releasing a multitude of (asexual, free-swimming) sporozoites that migrate to the mosquito's head and salivary glands, where they are ready to pass into the human bloodstream during the mosquito's next bite. The entire (asexual) cycle is then repeated. A remarkable feature of the asexual cycle is that the parasites grow and divide synchronously, and the resulting mass fissions (into merozoites) produce the regularly recurring attacks, or paroxysms, that are typical of malaria. A malarial attack normally lasts 4 to 10 hours and consists successively of a stage of shaking and chills; a stage of fever, with the temperature reaching 105 F, and severe headache; and then a stage of profuse sweating during which the temperature drops back to normal. Between attacks, the temperature may be normal or below normal. In the early days of the infection, the attacks may occur every day, but they soon begin appearing at regular intervals of either 48 hours (called tertian malaria) or 72 hours (called quartan malaria). The first attack usually occurs from 8 to 25 days after a person has been bitten by an infected mosquito. Four species of Plasmodium are known to cause malaria in humans: P. falciparum, P. vivax, P. malariae, and P. ovale. The most common of these malarial types, accounting for about 50 percent of all cases, is falciparum (subtertian, or malignant tertian) malaria, which has the most severe symptoms and is the most frequently fatal; it accounts for as many as 95 percent of all deaths from malaria. Falciparum malaria requires higher temperatures for optimal development and is confined more closely to the tropical areas. In western Africa, for example, it exists almost to the exclusion of the other varieties. Once a person has recovered from falciparum malaria, however, relapses rarely if ever occur. Vivax (tertian) malaria accounts for about 40 percent of all cases and is widespread mainly because of its ability to withstand therapy and to recur frequently for a period of several years, though the initial acute phase lasts only two to three weeks. The two less common types of malaria are quartan malaria (caused by P. malariae), which is confined to the Mediterranean area, and ovale tertian malaria (caused by P. ovale), which is basically confined to an isolated area of eastern Africa. Infections with one or more species can occur simultaneously, however. Furthermore, a double brood of tertian parasites can segment on alternate days, giving a daily or quotidian fever. Besides attacks, persons with malaria commonly suffer from anemia (owing to the destruction of red blood cells by the parasites), enlargement of the spleen (the organ responsible for ridding the body of degenerate red blood cells), and general weakness and debility. In falciparum malaria, the parasitized blood cells tend to stick together, and some of the smaller blood vessels may be blocked as a result. Falciparum malaria may also cause other complications, such as blackwater fever (q.v.). Malaria can be reliably diagnosed upon finding the parasites in stained blood smears examined under a microscope. An effective treatment for malaria was known long before the cause of the disease was understood: the bark of the cinchona tree, whose most active principle, quinine, was used to alleviate malarial fevers from 1700 until World War II, when more effective, synthetic drugs were developed. Chief among these newer drugs are chloroquine, pamaquine, pyrimethamine, and amodiaquin, all of which can destroy the malarial parasites while they are living inside red blood cells. In their initial decades of use, chloroquine and related drugs could relieve symptoms of an attack that had already started, prevent attacks altogether, and even wipe out the plasmodial infection entirely. By the late 20th century, however, some vivax strains as well as most falciparum strains had become resistant to the drugs, which were thus rendered ineffective. As a result, the incidence of malaria began to increase after having steadily declined for decades. Both one's natural resistance, as occurs among those who are carriers of one gene for the sickle-cell trait, and one's acquired immunity through previous exposure will reduce susceptibility to malaria. The basic method of prevention is to eliminate the breeding places of Anopheles mosquitoes by draining and filling marshes, swamps, stagnant pools, and other large or small bodies of standing fresh water. DDT, dieldrin, and other, less toxic insecticides have proved potent in controlling mosquito populations in affected areas. Window screens and mosquito netting are widely used to secure interior spaces from the mosquitoes, which are mainly active at night.