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Humanity has but three great enemies: Fever, famine, and war; of these by far the greatest, by far the most terrible, is fever.

William Osler, 1896

Malaria is a protozoan disease transmitted by the bite of infected female Anopheles mosquitoes. The most important of the parasitic diseases of humans, malaria is transmitted in 91 countries containing 3 billion people and causes ~1200 deaths each day. Mortality rates have decreased dramatically over the past 15 years as a result of highly effective control programs in several countries. Malaria was eliminated from the United States, Canada, Europe, and Russia >50 years ago, but its prevalence rose in many parts of the tropics between 1970 and 2000. In response to this rise, there has been substantial investment aimed at increasing access to accurate diagnosis, effective treatments, and insecticide-treated bed nets. This investment has resulted in a decline in the global burden of malaria, although in the past few years progress has stalled. An increasing number of countries are now targeting malaria elimination. This ambitious goal is threatened by increasing resistance to antimalarial drugs and insecticides.

Malaria remains today, as it has been for centuries, a heavy burden on tropical communities, a threat to nonendemic countries, and a danger to travelers.


Six species of the genus Plasmodium cause nearly all malarial infections in humans. These are P. falciparum, P. vivax, two morphologically identical sympatric species of P. ovale (curtisi and wallikeri), P. malariae, and—in Southeast Asia—the monkey malaria parasite P. knowlesi (Table 219-1). While almost all deaths are caused by falciparum malaria, P. knowlesi and occasionally P. vivax can also cause severe illness. Human infection begins when a female anopheline mosquito inoculates plasmodial sporozoites from its salivary glands during a blood meal (Fig. 219-1). These microscopic motile forms of the malaria parasite are carried rapidly via the bloodstream to the liver, where they invade hepatic parenchymal cells and begin a period of asexual reproduction. By this amplification process (known as intrahepatic or preerythrocytic schizogony), a single sporozoite may produce from 10,000 to >30,000 daughter merozoites. The swollen infected liver cells eventually burst, discharging motile merozoites into the bloodstream. These merozoites then invade red blood cells (RBCs) to become trophozoites and multiply six- to twentyfold every 48 h (P. knowlesi, 24 h; P. malariae, 72 h). When the parasites reach densities of ~50/μL of blood (~100 million parasites in the blood of an adult), the symptomatic stage of the infection begins. In P. vivax and P. ovale infections, a proportion of the intrahepatic forms do not divide immediately but remain inert for a period ranging from 2 weeks to ≥1 year. These dormant forms, or hypnozoites, are the cause of the relapses that characterize infection with these species.

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