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PRESS RELEASE: How Dantu blood group protects against malaria

PRESS RELEASE                                                                                     Embargoed: 16 September 2020: 1800hrs

HOW DANTU BLOOD GROUP PROTECTS AGAINST MALARIA – AND HOW ALL HUMANS COULD BENEFIT

The secret of how the Dantu genetic blood variant helps to protect against malaria has been revealed for the first time by scientists at the KEMRI-Wellcome Trust Research Programme, in Kilifi in collaboration with colleagues at the Wellcome Sanger Institute and the University of Cambridge in the UK. The findings were published today (16 September) in the world-leading scientific journal Nature,

Malaria remains a major global health problem, causing an estimated 435,000 deaths per year. Over 90% of the deaths occur in Africa mainly among children under five years of age.

Researchers have long known that genetic mutations of the red cell, such as sickle cell, protect against malaria. In 2017, researchers discovered that a mutation which results in the rare Dantu blood group provides a significant degree of protection against severe malaria (40% protection among those with one copy of the mutated gene and 70% among those with two copies).  By contrast, the best malaria vaccines currently provide 35% protection. Though the mutation is rare elsewhere, up to 10% of Kilifi residents carry at least one copy of the Dantu gene.  This new study was aimed at explaining how the Dantu mutation protects against malaria.

The researchers collected red blood cell samples from 42 healthy children in Kilifi who had either normal red cells or had one or two copies of the Dantu gene. Because malaria parasites grow inside red cells, the researchers then looked at the ability of malaria parasites to penetrate the cells in the laboratory using multiple tools including time-lapse video microscopy, to identify the specific step at which invasion was impaired.

Analysis of the red blood cell samples indicated that cells of the Dantu variant had a stiffer cell membrane than normal cells. The increased stiffness prevented the malaria parasites from penetrating Dantu cells, thus, halting their lifecycle and preventing their ability to multiply in the blood and cause symptoms.

Dr Silvia Kariuki, of the KEMRI-Wellcome Trust Research Programme and a research fellow under the Initiative to Develop African Research Leaders (IDeAL), Kenya, remarked: “Malaria parasites utilise 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. The Dantu variant actually slightly increases the stiffness 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.”

These findings have significant implication in the wider battle against malaria. Because all human red blood cells grow stiffer as they age, it may be possible to design drugs that imitate this natural process to prevent malaria infection or reduce its severity.

Professor Tom Williams from the KEMRI-Wellcome Trust Research Programme, one of the joint senior authors of the study, said: “It has been great working on this collaborative project with some of the leading scientists in the world. Learning how Dantu protects against malaria has been really interesting. It seems to work by making the red cell membrane just a little bit stiffer than usual, something that stops malaria parasites from entering the cell to establish the infection in humans.  It might be possible to invent drugs that do the same thing that could potentially be used to prevent or treat malaria.”

Among the key UK researchers involved in this collaboration were Dr Viola Introini, Dr Alejandro, Marin-Martinez, Professor Julian Rayner and Professor Pietro Cicutta, whose expertise lies in human and malaria genetics. In highlighting the power of collaboration in research, Professor Sam Kinyanjui, the Director of the Initiative to Develop African Research Leaders, which partially funded the work, added: “This work demonstrates the synergy gained from the collaboration between African and UK researchers in carrying out cutting edge research to address local health challenges”.

ENDS