Malaria is an infectious disease that is estimated to kill more than half a million people every year, mostly young children in Africa. It is spread by mosquitoes infected with Plasmodium parasites that attack red blood cells in the human body. Plasmodium falciparum, the species that is responsible for most of these deaths, causes malaria by entering red blood cells and releasing antigens that travel to the surface of the cells, where they change the adhesion properties.

P. falciparum is particularly dangerous because of its ability to vary the antigens displayed on the cell surface. This process, known as antigenic variation, helps to maintain infections for extended periods of time by allowing the antigens to stay one step ahead of the immune system (a process known as immune escape). The origins of antigenic variation lie in the fact that each P. falciparum genome has a repertoire of between 50 and 60 var genes that code for the variability of a major antigen that is responsible for immune escape in malaria. An antigen causes the production of antibodies. When antibodies bind to antigens, similar to the fit between a lock and key, this helps the immune system fight disease. 

In a paper published online Dec. 18, 2012 in the journal eLife, a team led by postdoctoral fellow Yael Artzy-Randrup describes the development of a new computational model of this highly diverse and complex system. The model simulates the dynamics of all the unique combinations of var genes in a population of hosts and shows that even with high rates of recombination, the parasite population self-organizes into a limited number of coexisting strains.

By investigating genetic variation at both antigenic sites and regions of the genome that do not code for antigens, Artzy-Randrup and her colleagues suggest that immune selection – the selection imposed on var repertoires by the buildup of specific immunity at the population level – plays a central role in structuring parasite diversity.

The new model should lead to a better understanding of the epidemiology of Plasmodium and other pathogens that work in similar ways, including those that cause sleeping sickness, Lyme disease and gastroenteritis. The model is also expected to help with global efforts to eliminate malaria and other diseases.

Artzy-Randrup’s co-authors include Mary Rorick, postdoctoral fellow and their mentor, Professor Mercedes Pascual.

eLife Research Journal

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