Parasitic diseases have been a burden on human society since ancient times. Over the years, advancements in technology and medicine have provided ways to combat some of these ailments. However many parasitic diseases, like malaria, still have no cure or vaccine.
Malaria is an important parasitic player in human disease, causing more than one million deaths each year. While its impact in North America is minimal, it is an influential pathogenic agent in many parts of the world, particularly in areas close to the equator. This mosquito-transmitted disease successfully evades medical intervention due to a lack of an effective vaccine as well as its ability to develop drug resistance. Improved understanding of the pathogenesis of malaria, and how the body defends against the parasite, is critical for developing new drug targets. Fortunately, a study recently published in the New England Journal of Medicine has given scientists a new way of examining how malaria interacts with humans.
A team of researchers led by Dr. Kevin Kain, a professor in the Faculty of Medicine at the University of Toronto, set out to determine whether a pyruvate kinase enzyme deficiency, identified in mice as protective against malaria, would also protect humans against the disease. In addition, the team wanted to determine the molecular basis of the protective effects of a shortage of the enzyme.
Pyruvate kinase is a key component of energy production in red blood cells. Some individuals inherit a deficiency in this enzyme which can lead to a type of anemia, known as nonspherocytic hemolytic anemia. This is significant, as sickle cell anemia has also been shown to provide resistance against malaria.
The researchers drew blood samples from individuals with the deficiency and compared them with the normal red blood cells of control subjects. When the blood samples were exposed to the malaria parasite, the sample from the pyruvate kinase of deficient individuals showed a protective effect against the replication of malaria in red blood cells. Furthermore, the researchers found that the protection granted by the deficiency was two-fold. It hindered parasite replication by causing an inherent defect in the red blood cells and encouraged the immune system to eradicate infected blood cells.
“Understanding how [mutations occurring in our genome] make us more resistant to malaria can help us design innovative new strategies to prevent or treat severe malaria in places such as sub-Saharan Africa,” says Dr. Kain. “Our research shows that people who have an enzyme deficiency or those who carry the gene trait for this deficiency may be protected from severe and fatal malaria.”
The importance of these results suggests another mechanism by which humans may have evolved resistance to the malaria parasite in endemic regions. While a complete pyruvate kinase deficiency leads to poor overall health, a partial deficiency in this enzyme may offer some protection against malaria. This recently discovered role of kinase in malaria pathogenesis offers a novel mechanism by which humans have evolved self-preservation. The next step is to test whether there is an increase in mutant pyruvate kinase genes in regions where malaria is endemic. This could serve as a drug target, which has the potential to improve mortality statistics or, at the very least, lend itself to improving humanity’s knowledge base in the battle against malaria.
