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Malaria is among the leading infectious causes of morbidity and mortality in children worldwide. Each year, there are more than 200 million clinical cases, causing an estimated 438,000 deaths in 2015, most in sub-Saharan African children under the age of 5 years. Increasing drug resistance, climatic changes, population shifts, economic changes, abandonment of malaria control programs, and insecticide resistance all contributed to a resurgence of malaria in the developing world from the 1970s to the 2000s. Recent World Health Organization (WHO), governmental, and nonprofit foundation support for effective preventative measures—such as insecticide-treated bednets, indoor residual spraying, and the implementation of artemisinin combination therapy as first-line treatment for malaria in many sub-Saharan African countries—has significantly reduced malaria incidence and deaths in many countries.

Diagnostic and treatment approaches differ significantly in malaria-endemic countries as compared to countries like the United States, where almost all malaria is imported. Occasional cases of local transmission have been reported in the United States since elimination of malaria in the United States in 1951, and transfusion-associated malaria also occurs rarely.

Malaria can be a life-threatening illness. Delay in seeking treatment, misdiagnosis, or both are often seen in individuals who die from malaria in the United States. Any febrile child who has been in a malaria-endemic area in the preceding year should be assessed for malaria, and it is critical to obtain an appropriate travel history in children with unexplained febrile illness.


Plasmodium species can infect many different animals, but most are host-specific. Plasmodium falciparum infects all ages of red blood cells, so it generally causes a much higher level of parasitemia than the other Plasmodium species. Plasmodium vivax and Plasmodium ovale preferentially infect reticulocytes and tend to cause a lower level of parasitemia than does P falciparum. Plasmodium malariae preferentially infects senescent red cells and causes the lowest level parasitemia of the human Plasmodium species, but this low-level parasitemia can occasionally persist for decades. It is not clear at this point if Plasmodium knowlesi preferentially infects a subset of red cells, but it multiplies rapidly and can cause very high levels of parasitemia. Morphologically, it can be confused with P malariae on microscopic examination.

Understanding the malaria parasite life cycle is crucial to understanding malarial infection and disease. The malaria life cycle is summarized in Figure 347-1. Sporozoites are inoculated into the bloodstream by the Anopheles mosquito and migrate within minutes to the liver, where they invade hepatic parenchymal cells. Here, the sporozoites undergo asexual multiplication (hepatic schizogony), forming schizonts that rupture the hepatic cells and release merozoites into the bloodstream. Very few hepatic cells are invaded by sporozoites, but multiplication within the hepatic cell produces thousands of merozoites from each sporozoite-infected hepatic cell. The process of liver schizogony lasts from 7 to 10 days for P falciparum, P ovale, and P vivax and 10 to 14 ...

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