A single letter in an individual’s DNA determines whether or not that person is likely to become infected with Plasmodium vivax, the world’s most common malaria parasite. New evidence suggests that the parasite may be evolving a way around this genetic hurdle to gain the ability to infect even more people.

Malaria already is one of the leading causes of death around the world, with 2.85 billion of the Earth’s 7 billion people at risk for the infection. It is a re-emerging problem in the United States where massive use of the now banned pesticide DDT after World War II eradicated the mosquito that carries the disease. Now, however, warming temperatures are helping malaria become reestablished in the American South.

If this new variant of the parasite gains a foothold on the continent of Africa, then millions of people once thought to be resistant to the bug “suddenly become susceptible to a new form of malaria,” said Peter Zimmerman at a news briefing at the AAAS Annual Meeting.

Malaria has a very complex life-cycle inside the human body. It invades red blood cells by grabbing on to Duffy protein receptors (named for the patient in which they were first identified) on the surface of those cells. It then pulls the blood cell down around itself like a cape, “to the point where the parasite is then inside the red cell, in a vacuole it has made for itself,” Zimmerman explained.

Most Africans are Duffy-negative—they lack the genetic letter that codes for the Duffy protein. They do not have that receptor protein on the surface of their red blood cells “and the parasite can’t get in,” continued the professor of global health at Case Western Reserve University School of Medicine.

So he was surprised to find that 10% of Duffy-negative persons were infected with Plasmodium vivax in a recent study on the island of Madagascar, off the east coast of Africa. “When we looked at people seeking treatment, 5% of those were negative,” he said. 

Casting the net wider, Zimmerman and colleagues discovered that the ratio of persons with and without the Duffy protein predicted the level of malaria infection in a local community. “When the number of each were essentially the same, that is where we saw the greatest prevalence of infection and disease in the Duffy-negative people.”

The greater the portion of those who were Duffy-positive, classically susceptible to malaria, the greater the likelihood that Duffy-negative people also would become infected. “In contrast, when the number of Duffy-negative people were in the majority, essentially the whole population experienced lower susceptibility to vivax malaria.” Zimmerman called it “a gene-based herd immunity.”

He hypothesized that the emergence of this resistance might be tied to the unique population history of Madagascar. The initial wave of humans came from southeast Asia and were Duffy-positive; Duffy-negative populations later migrated from Africa. Intermarriage created a combination of these genetic traits. It may be that the resulting gradient range of Duffy traits offered a more fertile opportunity for a resistant parasite to emerge.

Zimmerman said they have yet to figure out for sure how the parasite works in the absence of Duffy receptors, but they are looking at the question. Genomic and other studies have identified other surface proteins that it might use to bind elsewhere to red blood cells. “It just hasn’t been proven that those are necessary to enable infection of Duffy-negative people in natural populations.”

Complicating the task is the fact that malaria “does not like to be cultured in vitro.” This makes it difficult to study in the lab, he said.