CHAPTER ONE:
INTRODUCTION
Plasmodium. malaria is a major cause of morbidity and mortality throughout human history. As a result, malaria has exerted extraordinary evolutionary pressure on the human genome and appears to have selected for multiple genetic polymorphisms that provide protection against severe disease. The best characterized humanAN EXPANDED ANALYSIS OF PHARMACOGENETICS DETERMINANTS OF EFAVIRENZ RESPONSE THAT INCLUDES 3′-UTR SINGLE NUCLEOTIDE POLYMORPHISMS AMONG BLACK SOUTH AFRICAN HIV/AIDS PATIENTS associated with malaria is sickle haemoglobin (HbS). The high prevalence of HbS in sub-Saharan Africa and some other tropical areas is almost certainly due to the protection against, malaria afforded to heterozygotes (Mackinnon et al., 2005: Pielet al., 2010). The protective effect of sickle cell trait on malaria was first described over 60 years ago. Sickle haemoglobin (HbS) is a structural variant of normal adult haemoglobin. Adult haemoglobin (HbAA) is made up of two alpha and two beta globin chains. HbS is the result of a single point mutation (GluVa.l) on the sixth codon of the beta globin gene7. Homozygotes Cor haemoglobin S (HbSS) with two affected beta chains develop sickle cell disease, in which there are occluded blood vessels, Vaso-occlusion affects many organs and tissues, and results in high morbidity and mortality. Heteroxygotes for sickle haemoglobin (HbAS) have sickle cell ‘trait and are generally asymptomatic , About 50 years ago, it was noticed that the incidence of sickle cell trait with HbAS erythrocytes was higher in regions where malaria was prevalent than elsewhere. That observation has been repeatedly confirmed over the years and it is now widely accepted that sickle cell trait confers partial protection against severe malaria partial (Aidooet al., 2002). In epidemiological sense, the protection provided by sickle cell trait against death from malaria somehow compensates for the health devastation inflicted by sickle cell disease”. Unfortunately, individuals with sickle cell anemia (HbSS) are not protected from malaria, perhaps because of their pre-existing poor health (Luzzatto, and Pinching 1990).