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Key Clinical Updates in Malaria

Artemisinin resistance is mediated by any of a series of mutations in the Plasmodium falciparum kelch (K13) gene; of great concern, these same mutations and evidence for delayed clearance after treatment with artemisinins were reported in East Africa in 2021.

Balikagala B et al. N Engl J Med. [PMID: 34551228]


  • 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, AKI, 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, progress appears to have stalled, particularly in Africa, where about 95% of cases occur. The WHO estimated that 241 million cases of malaria occurred in 85 endemic countries in 2020. The WHO changed its methods of estimation of malaria deaths, leading to an increase of past estimates; there were 627,000 estimated deaths in 2020, an increase of 69,000 from 2019, with 47,000 of these excess deaths attributed to service disruptions from the COVID-19 pandemic.

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 RBC. 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 ...

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