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Clinical Summary

Malaria infects up to 300 million people annually with over 1 million deaths; it is the deadliest vector-borne disease in the world. This parasitic disease is transmitted by the night-biting female Anopheles mosquito and is caused by four protozoa of the genus Plasmodium (Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax), with P falciparum causing the most morbidity and mortality. It is most common in tropical areas, particularly sub-Saharan Africa and Southeast Asia, with specific species predominating in each area.

The parasites undergo a hepatic cycle before entering circulating red blood cells and replicating. Lysis of the cell then occurs, releasing toxic by-products and further parasites into the blood, thereby causing cyclical clinical manifestations. Symptoms include fever, rigors, headache, myalgias, and malaise. The classic cyclical fevers do not always occur. P falciparum infection can cause massive hemolysis due to overwhelming parasitemia. Parasitized erythrocytes lose flexibility, leading to microcirculatory obstruction, hypoxia of vital organs, and splenomegaly. Symptoms from P ovale and P vivax may be delayed for many months due to hepatic dormancy. Pregnancy is a risk factor for severe P falciparum infection and can result in maternal anemia, prematurity, and increased infant mortality.

Diagnosis is established by identification of the parasites on thick and thin smears. Rapid antigen kits are available in some regions. Bed nets, insecticides, and protective clothing are effective adjuncts for prevention. Chemoprophylaxis with an appropriate agent is highly recommended for travelers to endemic regions.

Management and Disposition

Treatment depends on geographic location, suspected species, and illness severity. Close adherence to CDC, WHO, or national guidelines is highly recommended for both prophylaxis and treatment. Oral treatment of uncomplicated malaria is feasible with one of several regimens. Quinidine is the only approved treatment for severe malaria in the United States, although artesunate is available on an emergency basis from the CDC when quinidine is not tolerated or available. Artemisinin combination therapy for severe disease is now available in many endemic countries, although IV quinine remains a common treatment. Patients in developing countries are often treated as outpatients. With rare exception, returning travelers with suspected malaria should be admitted for management and treatment. Admission is always warranted for patients with suspected or confirmed P falciparum, symptoms of cerebral malaria, children, pregnant women, or immunocompromised individuals.


  1. Malaria should be strongly considered in any patient exhibiting fever following recent travel to the tropics. It is the single most common cause of fever in this population.

  2. An emerging species, Plasmodium knowlesi, causes severe disease, but is currently limited in distribution to Southeast Asia.

  3. The average incubation period for P falciparum is about 13 days; average incubation periods are longer for the other species. Incubation periods for all species can be variable.

  4. Parasitemia fluctuates over time, with the highest incidence during episodes of fever. ...

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