The war against malaria just received a shot in the arm after new research should the potential a rare blood group could hold.
The study shows the blood group variant called Dantu protects against severe malaria, information that could boost therapies and vaccines. The research is by Kemri-Wellcome Trust in Kilifi, Wellcome Sanger Institute and the University of Cambridge in the UK.
Dantu only seems to occur commonly in East Africa.
In Kilifi, 10 per cent of the population has one copy of the Dantu gene, which confers up to 40 per cent protection against malaria, found the researchers. One per cent of the population has two copies, conferring up to 70 per cent protection. By contrast, the best malaria vaccines currently provide 35 per cent protection.
In 2017, researchers discovered that the rare blood variant provides some degree of protection against severe malaria. The new study, published last week in the journal Nature, intended to explain why.
Parasite has the key
The research team found that red blood cells in people with Dantu have a stiffer surface membrane that prevents them from being invaded by the world’s deadliest malaria parasite, Plasmodium falciparum.
Dr Silvia Kariuki, of Kemri-Wellcome Trust and a research fellow under the Initiative to Develop African Research Leaders Kenya, said malaria parasites use 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 Kariuki. “The Dantu variant actually slightly increases the stiffness of the red blood cell surface. It is like the parasite still has the key to the lock, but the door is too heavy for it to open.”
The researchers collected red blood cell samples from 42 healthy children in Kilifi who had one, two or zero copies of Dantu.
An analysis of the characteristics of the red blood cell samples indicated that the Dantu variant created stiffer cell membranes. “When it comes to the Dantu red blood cell, the parasite makes contact with the membrane and struggles. You can tell it is struggling to get in, but it does not. It gets exhausted and disappears,” said Dr Kariuki.
She added: “It was an exciting finding for us. At a certain stiffness, malaria parasites were no longer able to enter the cell, halting their lifecycle and preventing their ability to multiply in the blood,” she said.
The findings could be significant in the wider battle against malaria.
Because all human red blood cells grow stiffer as they age, the scientists believe it may be possible to design drugs that imitate this natural process to prevent malaria infection or reduce its severity. “It is a possibility that merits further research,” said Dr Kariuki.
“We are still a long way from producing a drug or vaccine based on the Dantu blood group. We are just now beginning to understand the biology of how this condition results in malaria protection. We plan to conduct more studies to fully understand the wider clinical implications of these stiffer red membranes,”she said.
The Dantu gene has also been detected in Tanzania and Malawi, though at a much lower frequency than in the Kilifi population.
“We have looked for it in other parts of Kenya, but not found any people with the Dantu blood group so far. As far as we know, it is only found in Kilifi, and not at all in the malaria-endemic populations in Western Kenya, for example,” she said.
Prof Tom Williams of Kenri-Wellcome Trust, one of the authors of the study, said: “It might be possible to invent drugs that do the same thing that could potentially be used to prevent or treat malaria,” he said.