Pathogenesis of malaria
- Danny A Milner, Jr, MD
Danny A Milner, Jr, MD
- Associate Professor of Pathology
- Harvard Medical School
Understanding the pathogenesis of malaria requires investigation of mechanisms for parasite invasion and host defense. The parasite life cycle illustrates the interplay of parasite and host interactions (figure 1). Pathogenesis of P. 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 .
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 16 days in P. falciparum (and there is typically a longer liver phase in other species) and release thousands of merozoites into the bloodstream, where they invade red blood cells of various ages (the erythrocytic stage). The merozoites mature successively from ring forms to trophozoites to mature red cell 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 red cell proteins, primarily hemoglobin. As hemoglobin is digested, the breakdown products are toxic to the parasite and, thus, hemozoin (a polarizable crystal) is formed in the 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 . They also make the red cell membrane less deformable, resulting in hemolysis and accelerated splenic clearance, which ultimately 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 . (See "Anemia in malaria".)
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