People With Type 'O' Blood Are Protected From Most Severe Forms Of Malaria Infection

In a list of the world's most deadly infectious diseases, malaria is ranked third, behind tuberculosis and HIV, when it comes to annual casualties around the world. While scientists have known for some time that people with blood type O are protected from the most severe (and deadly) forms of malaria, they have never understood the reasons why. Now, Scandinavian researchers explain how a protein secreted by malarial parasites makes its way to the surface of blood cells, where it acts like glue, and blocks blood flow (and ultimately leads to death). However, this protein o­nly weakly bonds with type O blood cells, the researchers say, while it strongly bonds to type A.

Blood type O conveys protection against malaria because RIFIN, a protein secreted by parasites,  bonds weakly with type O blood cells while strongly linking to type A.Photo courtesy of Shutterstock.

"The new knowledge is important in order to develop new treatments for severe malaria," Dr. Mats Wahlgren, a professor in microbiology and cell biology at Sweden's Karolinska Institutet, toldMedical Dailyin an email, clarifying that to treat or cure patients it is necessary "to understand the mechanisms that bring about severe disease." Importantly, having demonstrated the ways type O blood protects against severe malaria, this explains why the blood type is so common in areas where malaria is common. "In Nigeria, for instance, more than half of the population belongs to blood group O, which protects against malaria," Wahlgren stated in a press release.

A Special Protein

Ninety percent of all malaria deaths occur in Africa. Nearly 600,000 deaths occurred in 2013, according to the World Health Organization, the result of about 198 million cases of malaria. The disease is caused by different kinds of parasites, which are spread to people through infected mosquitoes, which bite between dusk and dawn. Pretty much all cases of severe, sometimes fatal, malaria result from the Plasmodium falciparum species of parasite. What happens in the worst cases of malaria is infected red blood cells stick to capillaries and other small vessels in an infected person's circulatory system, blocking blood flow and causing oxygen deficiency and tissue damage. This leads to coma, brain damage, and in some cases death.

So what's going o­n there? The team of Karolinska Institutet scientists who have been studying the RIFIN protein say this parasitic secretion is key to why o­nly some blood types are vulnerable to the most severe forms of malaria. Using data from various experiments o­n cell cultures and animals, they demonstrate how the Plasmodium falciparum parasite secretes RIFIN. This special protein makes its way to the surface of an infected person's blood cells, where it becomes sticky and begins its damage. However, while RIFIN bonds strongly with type A blood cells, it o­nly weakly links to type O. While simple, this explanation o­nly became possible after the researchers had isolated the correct o­ne of many existing variants of the protein.

"The RIFINs have not be known to have a role in development of severe malaria previously," Wahlgren toldMedical Daily.Now, though, he believes these proteins can be used as "targets when screening for new drugs."

Generally, the news of malaria is all good, even if a new issue of mosquitoes becoming resistant to insecticide-treated nets has emerged. However, in Africa, the prevalence of this disease has been sloping downward since 2000. Though the population in high transmission areas has increased by 43 percent, WHO estimates infections fell from 173 million in 2000 to 128 million in 2013 - a reduction of 26 percent.

"I started to work with malaria of the simple reason that is a disease of the poor and there was a lack of knowledge, there was a lot to be done," Wahlgren told Medical Daily. Apparently, the work of Wahlgren and other scientists in the field has been beneficial.

Malaria: people with blood group A more vulnerable to severe disease

A protein produced by some strains of the malaria parasite can cause red blood cells, especially in blood group A individuals, to form clumps, thereby increasing the severity of disease, according to research just published. When certain strains of Plasmodium falciparum, the single-celled parasite that is responsible for the most dangerous forms of malaria, get into red blood cells, those cells start sticking to other red blood cells as well as to walls of blood vessels. The resulting obstruction to blood flow can damage tissues and lead to severe malaria that is life-threatening.

Previous research had implicated the 'P. falciparumerythrocyte membrane protein 1' (PfEMP1) in red blood cells forming clumps. (Such clumps are called 'rosettes'). o­nce the parasite infects red blood cells, this protein that it produces appears o­n the outer surface of those cells. The protein then latches o­n to receptor molecules found o­n other red blood cells, creating rosettes. However, when PfEMP1 was removed from red blood cell surfaces using enzymes, rosette-formation was reduced o­nly in those of blood group O but not blood group A. This indicated that PfEMP1 may not be the o­nly molecule involved in rosette formation, noted a Scandinavian team of scientists in a Nature Medicine paper.

With a series of experiments, the team showed that another protein could have a hand too, principally affecting individuals of blood group A. The RIFINs too are secreted by the parasite and then get to the surface of red blood cells. There are 150 rif genes that carry the genetic information for RIFINs. o­ne P. falciparum parasite examined by the team carried 85 such genes, but with just o­ne of those genes being responsible for much of the RIFINs it produced. The RIFINs were thought to act as decoys, making it difficult for the human immune system to detect and destroy parasite-infected red blood cells, commented G. Padmanabhan of the Indian Institute of Science in Bangalore, who has studied the malaria parasite over many decades but was not involved in the research that led to the Nature Medicine paper. "For the first time another role has been found for the rif gene family," he told this correspondent.

Suchi Goel of Karolinska Institutet at Stockholm in Sweden and colleagues introduced a rif gene into Chinese hamster ovary cells. Those cells, with the RIFIN protein o­n their surface, "bound large numbers of group A RBCs [red blood cells]," the scientists noted in their paper. The rosette formation with group O RBCs was "less pronounced." Moreover, when molecular tags that marked RBCs as belonging to group A were removed, their binding to cells bearing RIFIN were similar to those of group O. o­nly RIFINs of sub-group A, which accounts for about 70 per cent of these proteins, led to rosettes being formed. The protection offered by blood group O could "explain why the blood type is so common in the areas where malaria is common," said Mats Wahlgren, the study's principal investigator, in a press release.

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