Thursday, April 15, 2010

Duffy-negative humans at risk from Plasmodium vivax

There is a blood group called Duffy-negative that provides increased resistance to infection by Plasmodium vivax, the parasite that causes malaria. The Duffy antigen is a protein that can't displayed on the surface of blood cells, and people in the Duffy-negative blood group do not display the Duffy antigen. It has been known for many years that vivax enters blood cells by leveraging the Duffy antigen, and the absence of this Duffy antigen on the surface of blood cells makes it more difficult for the parasite to enter blood cells.

To understand this paper better, I looked up some statistics about malaria and they were very shocking. There are between 350-500 million cases of malaria per year, and one to three million people die per year from malarial infection. There is still not an effective vaccine for malaria, although the Gates Foundation is funding work in this area.

A recent paper in PNAS gives evidence that vivax may be evolving its way around the requirement for Duffy:

Plasmodium vivax clinical malaria is commonly observed in Duffy-negative Malagasy people

The striking sentence from their abstract is this:

"In Madagascar, P. vivax has broken through its dependence on the Duffy antigen for establishing human blood-stage infection and disease."

The authors investigated popluations of people in Madagascar without malarial symptoms, 72% of whom are in the Duffy-negative blood group. Using PCR and microscopy, the authors found that 8.8% of people Duffy-negative patients were infected with vivax. After isolating parasite samples from these people, polymorphic markers in the parasites were genotyped to see if this ability to infect Duffy-negative people was from a single clonal population. The markers suggested that the parasites infecting Duffy-negative people were from distinct genetic backgrounds, which is consistent with the idea that the ability to infect Duffy-negative humans has arisen multiple times in evolution.

While the authors don't know the molecular basis of infection for these parasites with novel infection mechanisms, that will certainly be the focus of new work. The paper is very interesting, and has very important implications for how we treat one of the most devastating diseases in the world.

Unfortunately, people must be subscribers to PNAS to read this article. Here's a link to a recent ScienceDaily news article summarizing the study:

Duffy-Negative Blood Types No Longer Protected from P. Vivax Malaria