The malaria parasite: change and conquer.

A parasitic relationship resembles a biological arms race. Over evolutionary time, an infected host puts up a new defense to stave off a parasite, only to have that parasite evade the defense and sharpen its skills for circumventing the host's next defensive strategy. And so on, and so on, in a biochemical escalation process that usually ends with the parasite attaining the upper hand.

This change-and-conquer strategy has made it particularly difficult for scientists to develop vaccines against parasites, including the most dangerous malaria organism, Plasmodium falciparum (SN: 5/4/91, p.276). Now, researchers led by David J. Roberts of John Radcliffe Hospital in Headington, England, have figured out part of the protein shell game that keeps the malaria parasite in business. A better understanding of this process could lead to new approaches for treating and preventing the deadly disease.

Once the malaria parasite infects a host's red blood cells, it makes proteins that help the infected cells stick to the inner walls of blood vessels. In the June 25 NATURE, Roberts' group reports that P. falciparum can mutate these proteins at a rate of 2 percent each generation. This rapid mutation rate helps the organism evade the immune system and avoid traveling to the spleen, where a red blood cell carrying it could be destroyed, the researchers conclude.

P. falciparum has a complex life cycle. Infected mosquitoes inject the parasite's first stage, the sporozoite, into a host while drawings a blood meal. Sporozoites find their way to the host's liver, where each can divide into thousands of merozoites. After roughly a week, an army of merozoites leaves the liver to take up residence in the host's red blood cells. Later, the red cells explode, some releasing more merozoites and others releasing gametocytes, the parasite's sex cells. This causes the fever and chills characteristic of malaria. When another mosquito bites the host, ingesting gametocytes and merozoites, the sex cells combine to form new sporozoites -- and the cycle begins anew.

Previous studies have shown that merozoites place proteins on the surfaces of the red cells they infect and that the proteins bind to so-called cell adhesion molecules on other cells (SN: 6/13/92, p.392). This makes the infected red cells stick to uninfected red cells and to the walls of tiny veins, preventing infected cells from being swept into the spleen. The spleen would normally filter out such bulging, parasite-packed cells.

In the new study, Roberts and his colleagues grew one type of P.falciparum merozoite in red blood cells maintained in culture dishes. They found that these merozoites divided to form a group of new merozoites that could stick to 10 different cell adhesion molecules.

The researchers conclude that this variation has two functions: It allows the parasite to stay one step ahead of a host's ability to make antibodies that could attack the merozoite proteins, and it ensures that the merozoite-infected red cells won't run out of cells to stick to in order to avoid the spleen.

The process "is really quite amazing," says Russell J. Howard, who studies malaria at the DNAX Research Institute of Molecular and Cellular Biology in Palo Alto, Calif. He adds that it might help explain cerebral malaria, which can cause coma and death.

In cerebral malaria, Howard speculates, P. falciparum merozoites might make proteins that stick only to cell adhesion molecules on the cells of blood vessels that serve the brain. This could gum up the specialized blood-brain barrier and block the movement of oxygen and nutrients into the brain -- simultaneously strangling and starving that essential organ.