- Researchers have found that people with a rare blood group called Dantu are protected from malaria.
- Dantu is a type of blood group which is very rare and mostly found in East Africa. In 2017, scientists found that Dantu provides some degree of protection against severe malaria.
- Results of a study published in the journal Nature last week show that people with one copy of the Dantu gene had 40 percent protection against malaria while those with two copies had 70 percent protection.
- Red blood cells in people with Dantu blood have a higher surface tension that prevents them to a certain degree from being invaded by Plasmodium falciparum – malaria parasite, says the study.
- Scientists at KEMRI-Wellcome Trust Research Programme in Kenya, the Wellcome Sanger Institute, the University of Cambridge collected red blood cells from 42 children in Kilifi, Kenya who had either zero, one, or two copies of the rare Dantu gene.
- The researchers then observed the ability of the parasites to invade the cells in the laboratory, using multiple tools including time-lapse video microscopy to identify the specific step at which invasion was impaired.
- The Dantu blood group has a novel ‘chimeric’ protein that is expressed on the surface of red blood cells and alters the balance of other surface proteins.
- Analysis of the characteristics of the red blood cell samples indicated that the Dantu variant created cells with a higher surface tension – like a drum with a tighter skin says a press release from Wellcome Sanger Institute.
- At a certain tension, malaria parasites were no longer able to enter the cell, halting their lifecycle and preventing their ability to multiply in the blood, says the press release.
- “The explanation for how Dantu protects against malaria is potentially very important. The red cell membrane only needs to be slightly more tense than usual to block malaria parasites from entering,” said Dr. Viola Introini, of the University of Cambridge.
- Malaria parasites utilize a specific ‘lock-and-key’ mechanism to infiltrate human red blood cells. When we set out to explain how the Dantu variant protects against these parasites, we expected to find subtle changes in the way this molecular mechanism works, but the answer turned out to be much more fundamental, said Dr. Silvia Kariuki, of the KEMRI-Wellcome Trust Research Programme, Kenya.
- “The Dantu variant actually slightly increases the tension of the red blood cell surface. It’s like the parasite still has the key to the lock, but the door is too heavy for it to open.”, said Kariuki.
Malaria remains a major global health problem causing an estimated 435,000 deaths per year, with 61 percent occurring in children under five years of age. P. falciparum is responsible for the deadliest form of malaria and is particularly prevalent in Africa, accounting for 99.7 percent of African malaria cases and 93 percent of global malaria deaths in 2017.
Researchers suggest one of the most significant implications of the study stems from the fact that the surface tension of human red blood cells varies naturally, generally increasing during their approximately 90-day lifespan.
This means a proportion of all of our red blood cells are naturally resistant to infection by malaria parasites, and it may be possible to develop drugs that take advantage of this process.
Because the surface tension of human red blood cells increases as they age, it may be possible to design drugs that imitate this natural process to prevent malaria infection or reduce its severity.
There is currently no evidence that the Dantu variant is accompanied by other health complications. But humans evolve alongside diseases and develop genetic resistance like sickle cell trait, which confers 80 percent resistance to malaria, but can cause serious illness in those with two copies of the gene.
“Malaria is still an incredibly destructive disease, but evolutionary adaptations like the sickle cell trait and the Dantu variant may partially explain why the mortality rate is much lower than the rate of infection. We’ve been fighting malaria parasites for as long as we’ve been human, so there may be other adaptations and mechanisms yet to be discovered” said Dr. Alejandro Marin-Menendez, of the Wellcome Sanger Institute.
“Developing a drug that emulates this increased tension could be a simple but effective way to prevent or treat malaria. This would depend on the increase in cell tension not having unintended consequences, of course. But evidence from the natural protection already seen in Dantu people, who don’t seem to suffer negative side effects, is promising,” said Dr. Introini.References:https://www.nature.com/articles/s41586-020-2726-6https://www.sanger.ac.uk/news_item/how-dantu-blood-group-protects-against-malaria-and-how-all-humans-could-benefit/