**1. Introduction**

Despite health better care and new strategies of disease control of, mortality remains high in many countries and worldwide [1]. Malaria is the biggest cause of childhood mortality in Africa.

In 2018, malaria was the cause of about 405 000 deaths, More than 90% of these deaths occurred in sub-Saharan Africa [2].

Malaria parasites enter red blood cells during key stages of their life cycle so that there is no surprise that a change of red blood structures or make-up could affect malaria infection. Some changes of red blood cells make more resistant to malaria infection whereas others create the potential for a harmful reaction to certain antimalarial drugs [3].

*Falciparum* malaria has had a profound effect on human evolution, evidenced by the high frequencies of malaria protective mutations observed in populations from historically malarious regions. This big pressure has resulted in the selection of many genetic variants that confer protection against severe malaria and reducing death due to malaria in some populations [4–6].


**Gene** 

**5**

**(chromosome)**

 **Mutation**

**Change**

S (HbS)

 Glu6Val

2–5

β-Globin

Component

hemoglobin

againstuncomplicated

severe malaria.

Reduced

parasitaemia

 malaria and

 of

HbS alleles protect

GAG/GTG

 **Number**

**Protein Function**

 **Reported Genetic** 

**with Malaria**

**Associations**

**Mechanistic**

**Proposed protective mechanism**

Enhanced antibody binding and

subsequent

RBCs [88]. Increased

ring-parasitised

100].

Impairment

invasion and growth under conditions of

low oxygen tension [31, 43].

Enhanced removal of

HbAS red blood cell [31, 44].

Reduced infected red blood cells because of reduced expression of PfEMP1 [33, 41].

Improved acquisition of

immunity [33, 46, 48].

Selective sickling of infected sickle trait

erythrocytes

clearance by the spleen [49].

Reduced erythrocyte

phagocytosis,

growth under oxygen stress in venous

micro vessels. [49].

Enhancement

immunity [41].

Increased clearance of sickled infected

RBCs by the spleen Acquired host

immunity and increased

ring-parasitised

Reduced Impaired trafficking of parasite proteins

to RBC surface [49]. And Inhibition of

 variant RBCs [44].

cytoadherence

 and rosetting

phagocytosis

 of

 of innate and acquired

 and inhibited parasite

 invasion, early

 leading to enhanced

malaria-specific

pathogenicity

 of *P. falciparum*

parasite-infected

*Inherited Disorders of Hemoglobin and* Plasmodium falciparum *Malaria*

 of *P. falciparum* red cell

Africa

 0.2

*DOI: http://dx.doi.org/10.5772/intechopen.93807*

 variant RBCs [80, 96,

phagocytosis

 of

 clearance of infected variant

 **hypotheses**

**Distribution**

 **High** **Frequency**

