Malaria parasite circumvents natural defense
The Malaria Atlas Project estimates 2.5 billion people worldwide are at risk for P. vivax malaria.
P. vivax does not grow well in the laboratory, so to try to understand how the parasite lives and operates, the researchers gathered samples from malaria patients and focused on its genome.
They found a duplication of the Duffy binding protein in half of 189 P. vivax infection samples taken in Madagascar. Other researchers’ prior efforts to sequence the P. vivax genome missed the duplication but all indications are it’s a recent change, Serre said.
“The way we date duplications is to compare differences between the two parts: the more different they are, the older they are,” he explained. “They accumulate mutations. The two parts of this duplication have, among 8,000 base pairs, only one difference.”
Often a second copy of a gene enables an organism to outmaneuver a defense, Serre continued.
“Instead of making a supergene, a duplication is simpler for nature.”
The release notes that the researchers suspect the mutation is spreading from Madagascar through travelers. They found the duplication in less than 10 percent of samples from Cambodia and Sudan.
The new components found on the P. vivax genome are two proteins that closely resemble binding proteins used by related malaria parasites to enter immature and mature red blood cells. Both were present in samples from Cambodia, Brazil, Mauritania and North Korea.
The new proteins were absent in a 2008 sequencing of P. vivax, which is used as a reference genome, suggesting the developments are recent.
“Binding proteins and receptors are locks and keys,” Zimmerman said. “If the parasite has one key and there’s one lock, you may be able to block that. But if it has more keys and there are more locks, there are multiple ways in.”
The researchers say the duplication may be a cause of the growing infections among Duffy negative people, but it’s too early to tell.
Zimmerman, Serre, and colleagues aim to find the answer with the newly-funded research project.
They will begin by studying blood samples taken from 1,500 patients at each of two locations in Madagascar.
They and colleagues have great concern that a loss of resistance to P. vivax infection will now enable the parasite to travel the 250 miles across the Mozambique Channel to Africa.
There, falciparum malaria is wreaking havoc on a population that has for the most part lived P. vivax-free. In some regions of the continent, 100 percent of the population is Duffy negative.
The researchers will conduct similar studies on P. vivax carrying the new proteins, in samples taken from Asia, Africa and South America.
In addition to studying patients, they plan to study the mutated parasites in the lab.
Parasites that live a day or two could have enough time to invade new blood cells, but not many. Brian Grimberg, assistant professor of international health at the Case Western Reserve School of Medicine, is developing a scanning process that will enable the team to look through millions of red blood cells in a few minutes and spot newly infected cells. They will test the parasites in Duffy negative and Duffy positive red cells.
Zimmerman and Serre believe the work could help lead to a vaccine – that is the overall goal. The mechanisms P. vivax uses to attach and enter a cell could be targets.
— Read more in Danielle I. Stanisid et al., “Naturally Acquired Immune Responses to P. vivax Merozoite Surface Protein 3α and Merozoite Surface Protein 9 Are Associated with Reduced Risk of P. vivax Malaria in Young Papua New Guinean Children,” PLoS Neglected Tropical Disease (14 November 2013) (DOI: 10.1371/journal.pntd.0002498)
