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A 5-year-old American girl presents with a 1-week history of intermittent chills, fever, and sweats. She had returned home 2 weeks earlier after leaving the United States for the first time to spend 3 weeks with her grandparents in Nigeria. She received all standard childhood immunizations, but no additional treatment before travel, since her parents have returned to their native Nigeria frequently without medical consequences. Three days ago, the child was seen in an outpatient clinic and diagnosed with a viral syndrome. Examination reveals a lethargic child, with a temperature of 39.8°C (103.6°F) and splenomegaly. She has no skin rash or lymphadenopathy. Initial laboratory studies are remarkable for hematocrit 29.8%, platelets 45,000/mm3, creatinine 2.5 mg/dL (220 μmol/L), and mildly elevated bilirubin and transaminases. A blood smear shows ring forms of Plasmodium falciparum at 1.5% parasitemia. What treatment should be started?

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Malaria is the most important parasitic disease of humans and causes hundreds of millions of illnesses per year. Four species of plasmodium typically cause human malaria: Plasmodium falciparum, P vivax, P malariae, and P ovale. A fifth species, P knowlesi, is primarily a pathogen of monkeys, but has recently been recognized to cause illness, including severe disease, in humans in Asia. Although all of the latter species may cause significant illness, P falciparum is responsible for the majority of serious complications and deaths. Drug resistance is an important therapeutic problem, most notably with P falciparum.

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Parasite Life Cycle

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An anopheline mosquito inoculates plasmodium sporozoites to initiate human infection (Figure 52–1). Circulating sporozoites rapidly invade liver cells, and exoerythrocytic stage tissue schizonts mature in the liver. Merozoites are subsequently released from the liver and invade erythrocytes. Only erythrocytic parasites cause clinical illness. Repeated cycles of infection can lead to the infection of many erythrocytes and serious disease. Sexual stage gametocytes also develop in erythrocytes before being taken up by mosquitoes, where they develop into infective sporozoites.

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Figure 52–1
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Life cycle of malaria parasites. Only the asexual erythrocytic stage of infection causes clinical malaria. All effective antimalarial treatments are blood schizonticides that kill this stage. (Reproduced, with permission, from Baird JK: Effectiveness of antimalarial drugs. N Engl J M 2005;352:1565.)

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In P falciparum and P malariae infection, only one cycle of liver cell invasion and multiplication occurs, and liver infection ceases spontaneously in less than 4 weeks. Thus, treatment that eliminates erythrocytic parasites will cure these infections. In P vivax and P ovale infections, a dormant hepatic stage, the hypnozoite, is not eradicated by most drugs, and subsequent relapses can therefore occur after therapy directed against erythrocytic parasites. Eradication of both erythrocytic and hepatic parasites is required to cure these infections and usually requires two or more drugs.

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Drug Classification

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Several classes of antimalarial drugs are available (Table ...

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