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[It. mala aria, bad air]
A febrile hemolytic disease caused by infection with protozoa of the genus Plasmodium. Worldwide malaria is responsible for about 3 million deaths a year. There are four species of malarial parasites: P. vivax, P. ovale, and P. malariae, which cause benign types of malaria; and the P. falciparum, which causes potentially malignant malaria. Each has its own geographic distribution, incubation period, symptoms, and treatment.
malarialmalarious (mă-ler′ē-ăl) (mă-ler′ē-ŭs), adj.

Malaria has been virtually eliminated from temperate climates, but it is widespread throughout the tropics and subtropics. It is most prevalent in Asia, Africa, and Latin America. As many as half a billion people may be infected with the disease worldwide; 300 to 500 million new infections occur annually. In the U.S., less than 1500 cases are diagnosed each year, usually in those who have just come from tropical or subtropical regions.

The malarial parasite is transmitted by the bite of an infected female Anopheles mosquito or, rarely, by transfusions or the sharing of needles during illicit drug use.

The life cycle of the parasite is complex. Once the parasitic sporozoite enters the bloodstream, it quickly invades organs such as the liver (the tissue phase of the infection). There, the organism matures as a schizont. After an incubation period ranging from about 10 to 30 days, malarial merozoites are released into the blood, where they invade red blood cells (the erythrocytic phase). Some dormant forms (hypnozoites) remain in the liver in P. vivax and P. ovale malaria, where they may serve as a reservoir for relapse. In the red blood cells, the organisms mature into ring forms and feeding forms (trophozoites). When the parasites break out of red cells to infect other cells in the circulation, they cause hemolysis and periodic symptoms (see below).

After several reproductive cycles, microgametocytes and macrogametocytes develop. Mosquitoes consume these when the parasites take their blood meal from infected humans. Further developmental stages occur within the mosquitoes, resulting in the production of the infectious sporozoites that are injected into human hosts when the mosquitoes feed again.

Initially, the symptoms are nonspecific and resemble those of a minor febrile illness with malaise, headache, fatigue, abdominal discomfort, and muscle aches, followed by fever and chills. The three stages of the malarial paroxysm are the defining characteristics of the illness. In the first (or chill) stage, patients complain of feeling cold and experience shaking chills that last from a few minutes to several hours. During the second (or hot) stage, minimal sweating occurs, although the temperature may rise to as high as 106°F (41°C). This stage lasts for several hours, and patients are at risk for febrile convulsions and hyperthermic brain damage. The patient also may exhibit tachycardia, hypotension, cough, headache, backache, nausea, abdominal pain, vomiting, diarrhea, and altered consciousness. The third (sweating) stage begins within 2 to 6 hr. In this period, the sweating is marked as the fever subsides and is followed by profound fatigue and by sleep. If untreated, malarial paroxysms caused by P. ovale or P. vivax will occur cyclically every 48 hr. If the infection is due to P. malariae, paroxysms will occur every 72 hr. Infections with P. falciparum may have a 48-hr cycle of paroxysms, but continuous fever is more characteristic. A severe form of falciparum malaria (cerebral malaria) is characterized by coma and, in spite of treatment, is associated with a 20% mortality rate in adults and 15% in children. About 10% of children who survive cerebral malaria have persistent neurological deficits. Residual deficits in adults who survive this form of malaria are unusual. Progressive, possibly severe anemia and enlargement of the spleen and liver are characteristic of all forms of malaria.

A rare but serious hematological complication of malaria is acute intravascular hemolytic anemia, associated with infection with P. falciparum. This condition is called blackwater fever because of the accompanying hemoglobinuria.

Malaria should be suspected in any febrile person who has returned in the last several months from an area where malaria is endemic. Giemsa-stained thick and thin blood films are examined to confirm the diagnosis (parasites may be seen in red blood cells).

In areas where malaria is endemic, pools of standing or stagnant water, in which mosquitoes breed, should be eliminated. People traveling to the tropics should wear protective clothing to which insect repellent has been applied. Protective screen netting impregnated with long-lasting insecticide should cover beds. People should apply DEET (N,N,-diethyl-3-methylbenzamide) or other effective insect repellents to exposed skin (but not hands or face) or to children's clothing, esp. between dusk and dawn, when mosquitoes feed most actively. Antimalarial vaccines may reduce the incidence of disease.

Chemoprophylaxis is begun 1 week before arriving in an area where malaria is endemic and is continued throughout the stay and for 4 weeks after leaving the area. Chemoprophylaxis is never perfectly effective; thus, malaria should always be considered when treating patients who have a febrile illness and who have traveled to an area where malaria is endemic even if they have taken prophylactic antimalarial drugs. The drug(s) advised for prophylaxis depend on the sensitivity of local parasites and whether infection is likely. Because of the changing sensitivity of the malarial parasites to drugs, it is not possible to be certain that a particular drug will be effective in all areas where malaria is endemic. The prophylactic drugs used for P. falciparum are usually effective in preventing infections with P. ovale and P. vivax. For nonimmune people traveling in areas where malaria is due to chloroquine-resistant P. falciparum and P. vivax, mefloquine, doxycycline, or atovaquone plus proguanil hydrochloride may be recommended. In areas where P. falciparum is chloroquine-sensitive, chloroquine is the drug of choice. Chloroquine may be used prophylactically during pregnancy.

The parasites that cause malaria constantly evolve, making drug treatment difficult. Patients and health care professionals are advised to contact the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, to obtain current recommendations (Phone: 800-311-3435; Web address: Effective nonantibiotic therapy for malaria sometimes includes exchange transfusion and iron chelation.

Health care providers in areas where malaria is endemic must work toward prompt detection and effective treatment of malaria. People traveling in areas where malaria is endemic and military personnel assigned to such areas must be made aware that missing even one dose of the prophylactic regimen increases the risk of contracting malaria. When an outbreak occurs among military personnel, it usually is found that only a small percentage of personnel have been taking the drug as prescribed in dosages sufficient to provide protection. Standard precautions are used in patient care; gloves are worn when handling blood or body fluids. Fluid balance should be closely monitored (hourly urine output) and urine checked for hematuria. The patient is also observed for signs of internal bleeding or electrolyte imbalance.

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