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Researchers Find Gene That Fights Severe Malaria in Children

Two children with malaria rest at the local hospital in the small village of Walikale, Congo (file photo)

Two children with malaria rest at the local hospital in the small village of Walikale, Congo (file photo)

Scientists have discovered a genetic variant in children that significantly reduces their risk of developing a life-threatening form of malaria.

Children with the unusual, or variant, gene have a 30 percent lower risk of developing cerebral malaria than those without the gene. Cerebral malaria is the most serious form of the parasitic illness that causes very high fever and coma, and leads rapidly to death in the 20 to 50 percent of people whose brains become infected.

The mosquito-borne illness affects almost 300 million people every year. But most of the one million deaths occur in children under the age of five.

Researchers at Germany’s Bernhard Nocht Institute for Tropical Medicine and Kumasi University in Ghana identified the protective gene in a study involving more than 6,000 children. Called FAS, the gene is responsible for a molecule involved in the programmed cell death of some white blood cells, which are immune system cells that attack and destroy microbes that invade the body.

Researchers think that children who develop a life-threatening form of malaria have a hyper-immune response to the parasite. But youngsters with the FAS variant have increased expression of the molecule, called CD95, which appears to promote a greater number of immune system cell suicides - thus a less intense and ultimately survivable immune reaction to malaria.

At least that’s the theory, according to Kathrin Schuldt, a biologist and co-author of the study. Schuldt says children who are vulnerable to cerebral malaria are constantly bitten by mosquitoes that carry the parasite.

“So the immune response is constantly on a very high level trying to eliminate the pathogen from the body. And so what we found with this naturally occurring variant, these children probably have a regulation in their immune response which down-regulates the immune response to a certain level and therefore is kind of protective,” Schuldt said.

Humans never develop full immunity against malaria, but they can gain a partial immunity to the parasite, which is why the disease is less severe in adults. But children can become quite sick because they have had less exposure to the disease.

Schuldt says her goal now is to figure out the underlying mechanism for the protective effect of the genetic variant. Then, Schuldt says, it may be possible to develop drugs to protect children from this fatal form of malaria.

An article on the protective malaria gene is published in the on-line journal PLoS Genetics.