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Pathogenesis of malaria

Danny A Milner, Jr, MD, MSc(Epi)
Section Editor
Johanna Daily, MD, MSc
Deputy Editor
Elinor L Baron, MD, DTMH


Understanding the pathogenesis of malaria requires investigation of mechanisms including parasite invasion, parasite biology, and host defense. The parasite life cycle illustrates the interplay of parasite and host interactions (figure 1). Pathogenesis of Plasmodium falciparum is the area of greatest study, since this species causes the most severe clinical disease (other species include P. ovale, P. vivax, P. malariae, and P. knowlesi). P. knowlesi malaria can also cause life-threatening illness [1], and, although rare, severe illness (including severe respiratory disease and anemia) and death due to P. vivax have been reported.

Issues related to the pathogenesis of malaria will be reviewed here. Issues related to epidemiology, clinical manifestations, diagnosis, and treatment are discussed in detail separately. (See related topics.)


Life cycle — Human malaria occurs by transmission of Plasmodium sporozoites via a bite from an infected anopheline mosquito (figure 1). The sporozoites travel from the salivary glands of the mosquito through the bloodstream of the host to the liver, where they invade hepatocytes. These cells divide many 1000-fold until mature tissue schizonts are formed, each containing thousands of daughter merozoites. This exoerythrocytic stage is asymptomatic.

The liver schizonts rupture after 6 to 30 days; 98 percent of patients experience liver schizogony by 90 days (there is typically a longer liver phase in species other than P. falciparum). This event releases thousands of merozoites into the bloodstream, where they invade red blood cells (the erythrocytic or asexual stage). P. falciparum may invade any red cell, while P. vivax and P. ovale prefer the younger, slightly larger reticulocytes. The merozoites mature successively from ring forms to trophozoites to mature schizonts (asexual forms) over 24 hours (P. knowlesi), 48 hours (P. vivax, P. ovale, P. falciparum), or 72 hours (P. malariae). Within red blood cells, the parasites digest hemoglobin. As hemoglobin is digested, the toxic metabolite hemozoin (a polarizable crystal) is formed and isolated in the parasite's food vacuole.

The intracellular parasites modify the erythrocyte in several ways. They derive energy from anaerobic glycolysis of glucose to lactic acid, which may contribute to clinical manifestations of hypoglycemia and lactic acidosis [2]. Parasites reduce red cell membrane deformability, resulting in hemolysis and accelerated splenic clearance, which may contribute to anemia. Alterations to uninfected red blood cells, such as the addition of P. falciparum glycosylphosphatidylinositol (GPI) to the membrane, may play a role in increased clearance of uninfected cells and contribute to anemia [3]. (See "Anemia in malaria".)

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Literature review current through: Oct 2017. | This topic last updated: Oct 30, 2017.
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