Many of the studies that examined the association between the sickle cell trait and malaria stemmed from the question, “Why is the sickle cell trait maintained in such high frequency when the homozygous mutations (two genes with Sickle mutation) result in death?” One possible explanation was that the heterozygous trait (only one sickle gene) must be advantageous under certain conditions such as malaria.
The first associations between sickle cell anemia and protection from malaria were made in the early years of this decade. E.A. Beets, a British medical officer stationed in Northern Rhodesia (now Zimbabwe), observed the malaria parasite less frequently in the blood films of persons with sickle cell trait. A study done by Alison in 1956 concluded that people with sickle cell trait developed malaria less frequently and less severely than those without the trait. This was the beginning of a long-standing controversy between the sickle cell trait and the protection from malaria mainly because several experimenters were unable to reproduce the data highlighted in Alison’s study.
Today it is accepted that the sickle cell trait offers some protection against malaria especially during early childhood. A very recent study on this can be found here. Several mechanisms are proposed and debated on, including selective sickling of cells infected with parasites more effectively being removed, inhibition of parasite growth due to the lower pH and reduced levels of potassium in sickled red cells, and increased endothelial adherence of parasitized red cells.