Antigenic Variation and the Genetics and Epigenetics of the PfEMP1 Erythrocyte Surface Antigens in Plasmodium falciparum Malaria.

How immunity to malaria develops remains one of the great unresolved issues in bio-medicine and resolution of its various paradoxes is likely to be the key to developing effective malaria vaccines. The basic epidemiological observations are; under conditions of intense natural transmission, humans do become immune to P. falciparum malaria, but this is a slow process requiring multiple disease episodes which many, particularly young children, do not survive. Adult survivors are immune to the symptoms of malaria, and unless pregnant, can control the growth of most or all new inoculations. Sterile immunity is not achieved and chronic parasitization of apparently healthy adults is the norm. In this article, we analyse the best understood malaria "antigenic variation" system, that based on Plasmodium falciparum's PfEMP1-type cytoadhesion antigens, and critically review recent literature on the function and control of this multi-gene family of parasite variable surface antigens.