Understanding The Link Between Two Illnesses: Malaria and Sickle Cell

Sickle cell disease is a relatively rare disease in the United States with only around 100,000 Americans having the disease, but among those with African ancestry, 1 in 365 people are expected to get the disease. The disease causes hemoglobin to be oddly shaped and causes difficulty in red blood cells carrying the hemoglobin to move through blood vessels and deliver oxygen to the bodies’ cells. Poor oxygen delivery can result in organ failure and death in those that have sickle cell disease. Why is a deadly disease so common among those with African ancestry? Anthony Allison, a South African medical doctor and molecular biologist, discovered that those that carried the sickle cell trait were more resistant to malaria than those without the trait.

Anthony Allison had grown up in the dry highlands of Kenya, but was aware of the malaria issue that plagued the lowlands on the eastern coast and the area around Lake Victoria. The Anopheles mosquitos that carried the parasite Plasmodium falciparum, which caused malaria in humans thrived in these warm and humid lowlands. He became interested in sickle cell disease after planning on conducting research on the blood types of African tribal peoples. Allison began testing for the sickle cell trait in Kenya and his research found that the frequency of the sickle cell trait was higher in people living in the warm and moist areas where malaria carrying mosquitos were most common. It became clear to Allison that there was a connection between sickle cell and malaria. He conducted further research collecting blood samples from around 5,000 children from different areas of East Africa. He found that children with the sickle cell trait had lower parasite counts than those without the sickle cell trait. The data confirmed his hypothesis that the sickle cell trait would be more common in areas where the risk of malaria was higher due to the commonality of malaria carrying mosquitos.

Allison’s research shows why 1 in 13 people with African ancestry carry the sickle cell trait. Malaria is most common in tropical regions, such as those that exist in large parts of the African continent. While possessing the sickle cell trait helps in resisting the potentially deadly effects of malaria, it is only effective if you are heterozygous for the sickle cell trait, meaning you have only one copy of the trait. If you are homozygous for the sickle cell trait, this leads to having sickle cell disease, which is a potentially deadly disease in which hemoglobin becomes crescent shaped and can have trouble traveling through blood vessels. This can result in poor oxygen delivery to cells throughout the body, which can be potentially deadly if essential organs do not receive adequate amounts of oxygen. If you are homozygous with no copies of the sickle cell trait, then you do not have any protection that the sickle cell trait provides against malaria infections. If each of your parents are heterozygous for the sickle cell trait, the offspring has a 50 percent chance of being heterozygous for the trait and their is a 25 percent chance each of either being homozygous with both copies or no copies of the sickle cell trait.

While it was understood that the sickle cell trait protects against malaria infections, the mechanism behind this effect was not understood. Early research suggested that the sickle cell hemoglobin was somehow preventing the Plasmodium falciparum from infecting red blood cells. It was unlikely to be the crescent shaped hemoglobin, since those that were only heterozygous carriers of the sickle cell trait did not exhibit the crescent shaped hemoglobin unless the blood was deprived of oxygen. In 2011, research from a team of Portugueses researchers may have solved the mystery. Instead of preventing the parasite from infecting red blood cells, the sickle cell hemoglobin made the host tolerant of the parasite. They were able to identify heme oxygenase-1 (HO-1), an enzyme that is expressed at a higher frequency in the presence of sickle hemoglobin, was producing carbon monoxide that was preventing the host from damage inflicted by malaria.

Evolution works to generate protective traits, but these traits may not be beneficial in all environments. The sickle cell trait is a prime example of this in that it can be a life-saver in areas where the risk of malaria infections is high, but can be deadly if two copies of the trait is inherited. The sickle cell trait is far less likely to be selected for in environments where the risk of malaria infection isn’t high. Certain traits that exist in high frequency, but are deleterious is likely to have some important function in a different environment that is more common in different parts of the world or conferred some advantage to our ancestors.