Worldwide geographic distribution of malaria
Malaria, caused by the protozoan parasite Plasmodium falciparum, is transmitted to humans by the bite of the female anopheles mosquito. The sickle hemoglobin gene causes abnormal sickled red blood cells (RBCs) in humans, which confer a survival advantage against malaria compared to people without any sickle hemoglobin genes. As a result, sickle cell anemia is prevalent in areas of endemic malaria in Africa and other tropical regions. Details of this phenomenon are outlined here.
P. falciparum
P. falciparum takes many forms and lives the sexual part of its life cycle in the mosquito and the asexual part in the human host. In brief, P. falciparum sporozoites enter human blood from mosquito saliva and travel to the liver, taking up residence and transforming into schizonts. The schizonts reproduce and produce merozoites, which erupt from the liver cells and are released back into the blood, where they infect RBCs. The merozoites feed on hemoglobin and reproduce, forming merozoites and trophozoites. The RBCs eventually erupt, releasing merozoites back into the blood to infect more RBCs, and releasing trophozoites, which transform into gametes. A bite of the female anopheles mosquito picks up P. falciparum gametes, and the parasite reproduces sexually in the mosquito. P. falciparum is transmitted into humans via the bite of the female anopheles mosquito, continuing the life cycle.
Defenses
The human body has developed a variety of defenses against P. falciparum, one of which is the sickle hemoglobin gene and resulting sickled RBCs. The precise mechanism by which sickled RBCs kill P. falciparum is not fully understood, but two theories exist based upon the fact that P. falciparum infection normally reduces the oxygen levels in sickled RBCs. One hypothesis is that the reduced oxygen levels, coupled with the sickling of RBCs, causes the sickled cells to become more abnormally shaped or to sickle even more, and to be removed from the bloodstream. Another theory is that the low oxygen level P. falciparum creates in sickled RBCs actually harms the parasite, whereas this does not occur in normal RBCs.
Sickle Hemoglobin Genetics
A person who inherits two copies of the sickle hemoglobin gene, one from each parent, develops sickle cell anemia, in which all the RBCs have an abnormal sickled shape. These sickled RBCs clump together and cause pain, infections and organ damage. In contrast to sickle cell anemia, a person who inherits only one sickle hemoglobin gene is said to have the sickle cell trait and can pass the gene to offspring, but generally will not develop sickle cell anemia. The person will have fewer sickled RBCs than seen in sickle cell anemia, and the RBCs that are sickled will not be sickled to the degree seen in sickle cell anemia. Sickle cell trait usually has no significant effects.
Evolutionary Results
Of course, the mechanism by which sickled RBCs kill P. falciparum occurs in people with sickle cell trait as well as sickle cell anemia. People with sickle cell trait do not experience the detrimental effects of sickle cell anemia but clearly have a survival advantage over individuals without any sickle hemoglobin genes. Along with this advantage comes a necessary evil, due to genetics. Two copies of the sickle hemoglobin gene increase the chances of surviving malaria but will also cause sickle cell anemia, with its detrimental and life-threatening effects. In this way, the survival advantage of sickle cell trait has caused sickle cell disease to be prevalent in areas of endemic malaria in Africa and other tropical regions.
Tags: sickle cell, cell anemia, sickle cell anemia, sickle hemoglobin, sickled RBCs, cell trait