Malaria is a serious disease that is estimated by the WHO to infect 200 million people a year, 600,000 of whom, primarily children under five, fatally. Malaria, which is most endemic in sub-Saharan Africa, is caused by different kinds of parasites from the plasmodium family, and effectively all cases of severe or fatal malaria come from the species known as Plasmodium falciparum.

Red blood cells get sticky

In severe cases of the disease, the infected red blood cells adhere excessively in the microvasculature and block the blood flow, causing oxygen deficiency and tissue damage that can lead to coma, brain damage and, eventually death. Scientists have therefore been keen to learn more about how this species of parasite makes the infected red blood cells so sticky.

It has long been known that people with blood type O are protected against severe malaria, while those with other types, such as A, often fall into a coma and die. Unpacking the mechanisms behind this has been one of the main goals of malaria research.

A team of scientists led from Karolinska Institutet in Sweden have now identified a new and important piece of the puzzle by describing the key part played by the RIFIN protein. Using data from different kinds of experiment on cell cultures and animals, they show how the Plasmodium falciparum parasite secretes RIFIN, and how the protein makes its way to the surface of the blood cell, where it acts like glue. The team also demonstrates how it bonds strongly with the surface of type A blood cells, but only weakly to type O.

Principal investigator Mats Wahlgren, a Professor at Karolinska Institutet’s Department of Microbiology, Tumour and Cell Biology, describes the finding as “conceptually simple”. However, since RIFIN is found in many different variants, it has taken the research team a lot of time to isolate exactly which variant is responsible for this mechanism.

“Our study ties together previous findings”, said Professor Wahlgren. “We can explain the mechanism behind the protection that blood group O provides against severe malaria, which can, in turn, explain why the blood type is so common in the areas where malaria is common. In Nigeria, for instance, more than half of the population belongs to blood group O, which protects against malaria.”

Researchers from Stockholm University

The researchers from Stockholm University who participated in the project with malaria proteins are Patricia Lara, Nasim Moradi, Karin Öjemalm, Gunnar von Heijne and IngMarie Nilsson.

IngMarie Nilsson
IngMarie Nilsson

“It has been a fantastic partnership with Mats Wahlgren at Karolinska Institutet and we are very excited for the publication in Nature Medicine. Our cooperation has been going on for several years and only recently have we, together with Mats Wahlgren received a grant from SSF to continue work on malaria and its proteins few years”, says IngMarie Nilsson.

The study was financed by grants from the Swedish Foundation for Strategic Research, the EU, the Swedish Research Council, the Torsten and Ragnar Söderberg Foundation, the Royal Swedish Academy of Sciences, and Karolinska Institutet. Researchers from Karolinska Institutet, Stockholm University, Lund University, and the national research facility SciLifeLab in Sweden, and the University of Copenhagen in Denmark and University of Helsinki in Finland have been involved in the study.