TABLE OF CONTENTS
Title page – – – – – – – – i
Certification – – – – – – – – ii
Dedication – – – – – – – – iii
Acknowledgments – – – – – – iv
Table of contents – – – – – – – v
CHAPTER ONE: INTRODUCTION – – – 1
CHAPTER TWO: CAUSES OF MALARIA – – 6
2.1 Plasmodium – – – – – – – 6
2.2 Life cycle of the malaria parasite – – – 9
2.3 Signs and symptoms of malaria – – – – 11
2.4 Prevention and treatment – – – – – 12
CHAPTER THREE: THE SICKLE CELL TRAIT
AND MALARIA – – – – – – – 15
3.1 The red blood cells – – – – – – 15
3.1.1 Structure and functions of the red blood cells – – 16
3.1.2 Life span of normal red blood cells – – – 18
3.2 The sickle cell trait – – – – – – 19
3.2.1 Homozygotes – – – – – – 19
3.2.2 Homozygotes (carriers) – – – – – 20
3.3 Effect of the malaria parasite on the sickle cell trait – 21
3.3.1 Effect on homozygotes – – – – – – 22
3.3.2 Effect on heterozygotes (carriers) – – – 23
CHAPTER FOUR: SUMMARY AND CONCLUSION 23
4.1 Summary – – – – – – – 23
4.2 Conclusion – – – – – – – 24
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 human genetic polymorphism 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). The specific mechanisms of protection were examined in many studies, group of them are in vivo and others affect parasite in vitro and apply this theory as occurs in vivo. Possible causes of protection done in the world which are; Red cells of patients of sickle cell trait, when infected with the parasite, deform, most probably because the parasite reduces the oxygen tension within the erythrocytes to very low levels as it carries out its metabolism. Deformed sickle trait red cell when passes through splenic sinusoids sequestered out by the phagocytes . Similar result was also obtained by (Kodjoet al., 2004). where in vitro experiment showed increased phagocytosis of ring parasitised HBCs in HbAS individual by mononuciearphogocytic system of spleen where as trophozoite – parasitized normal RBC and RBC in MbAA were phagocytosed at equal pace. They concluded that ring parasitized RBC in sickle cell trait patients was predominantly complement mediated and very similar to phagocytosis of senescent or damaged normal RBCs. It was also concluded that the phagocytosis of ring parasitized red cells by monocytes have advantages in various ways. First, it reduces parasite growth and density. Then, phagocytosed ring of parasitized red cells is digested rapidly by monocytes. The process is repeated without loss of function, whereas more mature form of parasite actively phagocytosecl and severely affect the function of monocyte. In another study by Roth et al , in vitro experiment showed that sickle trait red cells infected with malaria sickled much more readily than uninfected cells under low oxygen tension. Since sickle cells are removed from the circulation and destroyed in ,the reticulo-endothelial system, it reduces the parasite burden in people with sickle trait. These people are more likely to survive acute malarial infections. It was further highlighted in another study, by Friedman16, this study showed that malaria parasites could be killed directly in sickle red cells. When parasites are cultured in sickle trait red cells and incubated at low oxygen tension, they do not survive. Ultra structural studies showed extensive I vacuole formation in parasites in sickle trait red cells when incubated at low oxygen tension and this suggests that there is some metabolic damage to the parasites. Other investigations show that there is oxygen radical formation in sickle trait erythrocytes arid it retards growth and even kills parasites. There is more production of super oxides (O2-) and hydrogen peroxide (H2O2) in sickle trait red cell than the normal erythrocyte. There is formation of membrane associated hemin in homozygous hemoglobin S red cell which can oxidize membrane lipids and protein. However sickle trait red cell produce little hemin. But. infected sickle trait red cells owing to formation of sickle polymer due to low oxygen tension and due to parasite metabolism produce enough hemin to damage the parasites. Immune system also plays an important role in attack of Maternal antibodies passed to fetus provide protection from malaria for first few months of life. There after toddler’s immune system provides protection. Many epidemiological studies conducted in endemic areas showed that antibody titer of are lower in children in sickle cell trait than in normal children. It is speculated low level of titer might reflect a low parasite burden in children with sickle trait due to clearance of infected red cell. In contrast children suffering with sickle cell disease have high fatality rate when infected with malarial parasites.
