Looking for the exit: How do malaria parasites escape from red blood cells?

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Abstract
At the beginning of the 21st century malaria remains one of the world's most widespread and intractable diseases, parasites of the genus Plasmodium, especially P. falciparum, being responsible for many millions of deaths and much human misery. The malaria parasite Plasmodium is genetically sophisticated, with complex survival strategies that have consistently outmaneuvered attempts to control it with antimalarial drugs. The completion of the P. falciparum genome project will greatly help the development of new methods of counterattack, but to understand the data the project produces, a detailed understanding of the parasite's biology is essential. The research by Salmon and colleagues reported in the previous issue of PNAS (1) tackles a fundamental unsolved problem of Plasmodium biology, highly relevant to the development of novel antimalarials. In malaria infections, parasites injected by mosquitoes into the blood pass to the liver where they invade its main cell type, the hepatocyte. Within these, the parasites feed and grow, then multiply, each generating many hundreds of merozoites, minute, lemon-shaped infectious cells not much larger than a bacterium. These move into the bloodstream where each can invade a red blood cell (RBC), becoming entirely enclosed in this cell, and again feeding and multiplying, although this time to about 16 merozoites (in P. falciparum). These escape from the depleted RBC and invade new ones. After many cycles within RBCs, sexual forms (gametocytes) are produced, which when taken by a mosquito in a blood meal, break out of their enclosing RBCs as gametes, which fuse together and reinfect the insect. During RBC invasion, the merozoite induces a pit to form in the RBC surface and this closes over the parasite to form a minute bubble (the parasitophorous vacuole, PV) inside the RBC, where the parasite stays through successive stages—ring, trophozoite, and schizont—until its merozoite offspring mature and …