heme derived from hemoglobin. Although the chemistry of this complex is becoming better understood (Goldie et al., 1990; Slater et al., 1991), its role in pathogenesis, drug action, or immunology remains undocumented.

Permeability Changes in Erythrocyte Membranes

Following parasite invasion, the intracellular metabolism of infected erythrocytes increases significantly. Nutrients must be brought in from outside, and waste products must be disposed of expeditiously. The cell membrane responds by increasing its capacity to transport a variety of substrates in and out of the erythrocyte, including essential amino acids, nucleosides, lactate, and fatty acids. The changes in membrane permeability allow a number of substrates, that otherwise would not be let in at all or would be let in to a limited degree, to enter the infected red blood cell. These substrates include hexitols, acidic and neutral amino acids, several small inorganic ions, and organic acids.

The appearance of new erythrocyte membrane transport pathways is the result of host cell “remodeling” by the intracellular malaria parasites. It is thought that in remodeling, proteins of parasite origin become associated with host membrane components, either by adhering to the inner aspects of the membrane or by inserting themselves directly into the membrane. The experimental data strongly support this hypothesis (Haldar et al., 1986; Ginsburg and Stein, 1987; Cabantchik, 1989, 1990; Ginsburg, 1990a; Tanabe, 1990a,b).

Other Parasite-Directed Changes in Erythrocyte-Membrane Structure

In P. falciparum, the trophozoite stage inserts new molecules into the host erythrocyte plasma membrane. These new membrane components are responsible for the sequestration of mature parasite stages in capillaries by the process of cytoadherence. Although among the human malaria parasites only P. falciparum exhibits cytoadherence, P. vivax also induces alterations in the infected erythrocyte membrane. Ultrastructure studies have shown that the membranes of erythrocytes infected with P. vivax contain caveolar structures that appear to be connected to vesicles (Atkinson and Aikawa, 1990; Barnwell, 1990). These caveolae-vesicle complexes appear to play a role in parasite interaction with the extracellular environment. They induce antibody production and are antigenically highly variable.

Nutrition and Metabolism

A malaria infection initiated by a single malaria parasite may produce as many as 10 billion new organisms. Nearly all the metabolic processes of



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