Sickle Cell and Malaria

Red blood cells in human beings that carry oxygen, are in the shape of turgid biconcave discs. However, when a person suffers from sickle cell disease, the cells become sickle shaped, which reduces their oxygen carrying capacity. This causes severe anemia, strokes and lung problems. Physiologically, the HBB gene contributes to the formation of a protein called beta hemoglobin. The mutated gene results in the formation of Hb S (S stands for sickle), an abnormal type of hemoglobin, causing the red blood cells to become sickle shaped. If an individual inherits mutated genes from both the parents he will develop the sickle cell disease. In such cases, the individual is said to be homozygous for the mutated gene. These individuals die early in life. However, a single copy of the mutated gene will result in sickle cell trait, in which only some of the red blood cells of the individual will be sickle shaped. Such individuals who are the 'carriers' of these mutated gene are referred to as the heterozygotes.

Sickle Cell and Malaria
An interesting pattern of incidence of sickle cell has been observed in Africa, where malaria is a prevalent disease. The relation between sickle cell and anemia gains further ground on the fact, that there is a greater incidence of sickle cell in the African lowland populations, where malaria is severe and widespread than among their highland counterparts. It is believed that sickle cell provides resistance, to individuals living in malaria - endemic regions, against the malarial parasite. The various explanations given for the association between sickle cell trait and malaria are as follows:

• Malaria is caused by the plasmodium parasite that completes a part of its life cycle in the red blood cells of human beings. It enters the human bloodstream when a female Anopheles mosquito, carrying the parasite, bites a healthy individual. It has been observed that the red blood cells of individuals with sickle cell trait, break down when infected with the malarial parasite. Since the parasite needs to complete a part of its life cycle inside the red blood cells, destruction of the cells does not allow the disease to get established in the individual.
• The malarial parasite thrives on hemoglobin in order to grow. The mutated Hb S leads to the polymerization of hemoglobin that does not allow the malarial parasite to ingest hemoglobin. Hence, the malarial parasite is not able to complete its life cycle and cause disease in the individual.
• The red blood cells of people with sickle cell trait, tend to sickle under very low oxygen tension. The malarial parasite reduces the oxygen tension in the blood cells that they infect, because they use up the oxygen carried by the hemoglobin for their own metabolism. This sickles the red blood cells that is destroyed by the phagocytes.
• In case of low oxygen concentration, the potassium in the red blood cells leak out of the cells that contain the abnormal hemoglobin. The parasite needs high levels of potassium to develop and due to its leakage the parasite fails to grow in a blood cell, that have the abnormal hemoglobin.
• The increased levels of resistance in individuals with sickle cell trait to malaria has been explained on the basis of increased immunity by Dr. Tom Williams of the Kenya Medical Research Institute. According to him, individuals in malaria endemic regions get the malarial parasite introduced in to their bloodstream a couple of times during their childhood. However, the mutant gene does not allow the 'carrier' to get infected. Due to this association with the parasite the carriers develop immunity against malaria.

More research is required to get a conclusive explanation for the association of sickle cell, in areas with high incidence of malaria. However, this association is a remarkable example of heterozygous advantage in which the carriers of a recessive allele have higher chances of survival than those homozygous for the mutated gene.