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  • Exposure to anopheline mosquitoes in a malaria-endemic area.

  • Intermittent attacks of chills, fever, and sweating.

  • Headache, myalgia, vomiting, splenomegaly; anemia, thrombocytopenia.

  • Intraerythrocytic parasites identified in thick or thin blood smears or positive rapid diagnostic tests.

  • Falciparum malaria complications: cerebral malaria, severe anemia, hypotension, pulmonary edema, acute kidney injury, hypoglycemia, acidosis, and hemolysis.


Malaria is the most important parasitic disease of humans, causing hundreds of millions of illnesses and hundreds of thousands of deaths each year. The disease is endemic in most of the tropics, including much of South and Central America, Africa, the Middle East, the Indian subcontinent, Southeast Asia, and Oceania. Transmission, morbidity, and mortality are greatest in Africa, where most deaths from malaria are in young children. Malaria is also common in travelers from nonendemic areas to the tropics. Although the disease remains a major problem, impressive advances have been made in many regions. A 2016 study estimated a 57% decrease in the malaria death rate and 37% decrease in the annual number of malaria deaths in the past 15 years. However, after marked gains, morbidity and mortality appear to have leveled, with WHO estimates showing modest annual increases in incidence, but decreases in deaths (228 million cases and 405,000 deaths estimated in 2018); other estimates suggest greater morbidity and mortality.

Four species of the genus Plasmodium classically cause human malaria (eFigure 35–8). Plasmodium falciparum is responsible for nearly all severe disease, since it uniquely infects erythrocytes of all ages and mediates the sequestration of infected erythrocytes in small blood vessels, thereby evading clearance by the spleen. P falciparum is endemic in most malarious areas and is by far the predominant species in Africa. Plasmodium vivax is about as common as P falciparum outside of Africa. P vivax uncommonly causes severe disease, although this outcome may be more common than previously appreciated. Plasmodium ovale and Plasmodium malariae are much less common causes of disease, and generally do not cause severe illness. Plasmodium knowlesi, a parasite of macaque monkeys, causes illnesses in humans, including some severe disease, in Southeast Asia.

eFigure 35–8.

Morphologic characteristics of developmental stages of malarial parasites in the red blood cell. Note cytoplasmic Schüffner dots and enlarged host cells in Plasmodium vivax and Plasmodium ovale infections; the band-shaped trophozoite often seen in Plasmodium malariae infection; and the small, often multiply infected rings and the banana-shaped gametocytes in Plasmodium falciparum infections. Rings and gametocytes are typically seen in peripheral blood smears from patients with P falciparum infections. (Reproduced with permission from Goldsmith R, Heyneman D: Tropical Medicine and Parasitology. McGraw-Hill, 1989. © The McGraw-Hill Companies, Inc.)

Malaria is transmitted by the bite of infected female anopheline mosquitoes. During feeding, mosquitoes inject sporozoites (eFigure 35–9), which circulate to the liver, and rapidly infect hepatocytes, causing ...

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