Newly discovered gene mutation offers malaria defense like sickle cell


Researchers have discovered a gene mutation that protects people in Southeast Asia against malaria in much the same fashion that a sickle cell trait protects Africans from the disease.

But while the sickle cell protects against the frequently lethal form of the disease caused by the parasite Plasmodium falciparum, the newly discovered gene mutation protects against Plasmodium vivax, which is generally thought to be more benign.

Malaria causes an estimated 1 million deaths per year worldwide, and at least half the world’s population lives in areas at risk for the disease.

The sickle cell trait developed in Africa, where malaria is epidemic. People with one mutated gene have red blood cells that may occasionally assume a characteristic sickled shape under stress, generally with few or no severe effects.


People carrying two copies of the mutated gene, however, show much more severe sickling under similar conditions, and this can impede blood flow to organs, causing severe pain and organ deterioration.

The disease can be fatal. The trait has survived in the population, however, because carriers have a decreased vulnerability to P. falciparum malaria. They contract the disease, but symptoms are less severe.

The mechanism by which the trait provides protection is not yet clear, but it may involve changes in the membranes of red blood cells, which are attacked by the parasite.

A team of researchers led by geneticist Ivo Mueller of the Walter and Eliza Hall Institute in Parkville, Australia, and the Barcelona Center for International Health Research in Spain studied a genetic disorder called Southeast Asian Ovalocytosis or SAO, which causes red blood cells to become elliptical in shape or rod-shaped.

One copy of the gene produces mild disease, while two copies are generally lethal. Previous studies have shown that the carrier or trait form of the disorder, with one mutated gene, provides some protection against P. falciparum. Now Mueller and his colleagues have demonstrated that the mutation provides significant protection against P. vivax.

The team reported in the journal PLoS Medicine that they studied 1,975 children under the age of 15 in three independent epidemiological studies in Papua, New Guinea. About 10% to 15% of the population in that area carries the mutation.

The researchers found that infants with the SAO trait had a 46% reduction in clinical disease caused by P. vivax. Older children had a 52% to 55% decrease in risk. The researchers “saw a significant decrease in parasite numbers in infants and older children, which is linked to a decrease in risk of clinical disease,” Mueller said.

Researchers had previously believed that only P. falciparum was powerful enough to produce evolutionary pressure leading to protective mutations.

However, “our results suggest that P. vivax malaria, though until recently widely considered to be a ‘benign’ form of malaria, actually causes severe enough disease to provide evolutionary selection pressures in the Asia-Pacific,” Mueller said.


Mueller speculated that studying how the mutation protects against malaria could provide new insights into producing an effective vaccine against the disease, a goal that has long eluded researchers.