Sickle cell trait is an inherited blood disorder in which a person has one abnormal allele of the hemoglobin beta gene (heterozygous) but does not display the severe symptoms of sickle cell disease, that occur in a person who has two copies of that allele (homozygous) (Ajayi, 2005). A normal haemoglobin is (Hbs) which turns normal, red blood cells into abnormally sickle shape.
Person inherits two copies of the gene that produces beta-globin chain a protein needed to produce normal hemoglobin while a sickle cell trait inherits one normal gene and one abnormal gene encoding hemoglobins (Hbs) (Alcais, et al, 2009).
Sickle cell gene mutation arose spontaneously in different geographic areas as suggested by restriction endonuclease analysis. In people with heterozygous for Hbs (carriers of sickling haemoglobin) the polymerization problems are minor, because the normal allele is able to produce over 50% of the haemoglobin. (Frodsham and Hill 2004).
Sickle cell trait provides a survival advantage over people with normal hemoglobin in regions where malaria parasite is endemic. It presents a high degree of resistance to malaria parasite (Aidoo, et al, 2002). The trait is known to cause significantly fewer deaths due to malaria, especially when plasmodium falciparum is the causative agent. Because of the unique survival advantage, people with the trait increase in number as more people infected with malaria and having the normal hemoglobin tend to succumb to the complications (Shear, et al, 1993).
Although the precise mechanism for this phenomenon is not known, but several factors are believed to be responsible, which includes infected erythrocytes tend. To have lower oxygen tension, because it is significantly reduced by the parasite and this causes sickling of that particular erythrocyte, signaling the phagocytes to get rid of the cell and hence the parasite within, sickle trait erythrocytes produce higher levels of the superoxide anion and hydrogen complicated malaria peroxide than the normal erythrocytes both are toxic to malaria parasites.
Since the sickling of parasite infected cells is higher, these selectively get removed by the reticulo-endothelial system thus sparing the normal erythrocytes. And also excessive vacoule formation occurs in those parasites infecting sickle cells. (Friedman, 2009). The sickle cell trait was found to be 50% protective against mild clinical malarial 75% protective.
All those factors are important because recent observations made suggested that the mechanism might involve an immune component, for instance, a study conducted in Gambia, it was found out that the immune recognition of plasmodium falciparum infected red blood cells was enhanced in HbAs children and up-regulation of malaria specific cell-mediated immune responses has also been observed in HbAs individuals in sudan (McAuley, et al, 2010).
Parasitization of red bloods cells in individuals with sickle cell trait (heterozygotes) has a selective advantage in some environments. Sickle cell homozygotes are at a strong selective disadvantage while protection against malaria favours the heterozygotes, it will be expected that high frequencies of the Hbs gene will be found only in populations living in regions where malaria transmission is intense (Gong, et al, 2012). Frequencies of sickle-cell heterozygotes are 20-40% in malarious areas, whereas they were very low or zero in the highlands of Kenya, Uganda, and Tanzania (Allison, 2009).
The mechanisms by which erythrocytes containing abnormal hemoglobins, or G-6-P-D deficient are partially protected against plasmodium falciparum infectious are not fully understood, although there has been no shortage of suggestions. During the peripheral blood stage of replication malaria parasites have a high rate of oxygen consumption and ingest large amounts of hemoglobin (Vaidya and Mather, 2009). It is likely that Hbs in endocytic vesicles is deoxygenated, polymerizes and is poorly digested. In red cells containing abnormal hemoglobins, oxygen radicals are produced and malaria parasites induce additional oxidative stress (Elliott, et al, 2008).
This can result in changes in red cell membranes including translocation of phosphatidylserine to their surface followed by macrophage recognition and ingestion (Foller, et al, 2009). This mechanism occur earlier in abnormal than in normal red cells, thereby restricting multiplication in the former binding of parasitized sickle cells to endothelial cells is significantly decreased because of an altered display of plasmodium falciparum erythrocyte membrane protein-I (Cholera, et al, 2008).
Stimulation of adaptive immunity will occur in the sense that it comprises pattern recognition receptors such as Toll-like receptors, which induce the production of interferons and other cytokines increasing resistance of cells such as monocytes to infections.
The protective effect of sickle cell trait does not apply to people with sickle cell disease, because they are uniquely vulnerable to malaria, since the most common cause of painful crises in malarial countries is infection with malaria. It is therefore been recommended that people with sickle cell disease living in malarial endemic countries should receive anti-malarial chemoprophylaxis for life because they are vulnerable to malaria infection than people with sickle cell trait (Oniyangi and Omari 2006).
To balance the polymorphism that occur in fitness of different genotypes. Anthony Allison estimated that the fitness of the As heterozygote would have to be 1.26 times than that of the normal homozygote. In Gambia it was estimated that As heterozygotes have 90% protection against P. falciparum associated severe anemia and cerebral malaria. Where as luo population of Kenya it was estimated that As heterozygtotes have 60% protection against severe malarial anemia. (Aidoo, et al’ 2002). These differences reflect the intensity of transmission of P. falciparum malaria from locality to locality and season to season, therefore the fitness calculations are varies.
In many African populations the AS frequency is about 20% and a fitness superiority over those with normal hemoglobin of the order of 10% is sufficient to produce a stable polymorphism.
It is diagnosed by using electrophoresis, Isoelectric focusing or high performance liquid chromatography (HPLC) and the result shows that HbAs are 55% of HbA and 45% of Hbs. Hemoglobin, reticulocyte count, and all laboratory tests are normal with sickle cell trait.