*Inherited Disorders of Hemoglobin and* Plasmodium falciparum *Malaria DOI: http://dx.doi.org/10.5772/intechopen.93807*

**Gene** 

**4**

**(chromosome)**

 **Mutation**

**Change**

G6PD (Xq28)

 Asn126Asp

1

 G6PD

 Enzyme That

G6PD deficiency protect against

severe malaria and

malaria

uncomplicated

parasitised variant RBCs due to

enhanced oxidative stress [94, 103].

Increased deficient erythrocyte

causes its protection against

parasitization

replication in

erythrocytes

Specific protection against malaria-

Mediterranean

0.8

area, South /

East Asia,

Pacific

0.03

induced anemia [94, 103].

Reduced cytoadherence

Immunological

species immunity between *P.vivax and*

*P.falciparum* [74].

Increased variant RBCs by monocytes and

enhanced antibody binding and

subsequent

RBCs [88, 89]. Reduced resetting. Increased micro-

erythrocyte

reduces the amount of Hb lost for given parasite density, thus protecting against

SMA [43, 82, 88, 90]. Enhanced removal of

red blood cells [96]. Reduced invasion

and growth of *P. falciparum*

[97, 98]. Reduced

reduced

cytoadherence

 or resetting [99].

parasite-infected

Africa

sub-Saharan

0.1

parasites

pathogenicity

 through

HBB

βthalassemia

Many

 Many

β-Globin

Component

hemoglobin

malaria

 of

Thalassemia

 protects against severe

(11p15.5)

(β-thal)

 count in

homozygotes

 clearance of infected variant

phagocytosis

 of infected

 priming through cross-

 or resetting [86, 87].

pathogenicity

 through reduced

 [94, 103].

G6PD-deficient

 and Reduced parasite

*Human Blood Group Systems and Haemoglobinopathies*

vulnerability

 of the G6PD

Africa

 2.5

> to oxidant stress

protects

against

oxidative tress

A376

Val68Met

1

G202A

HBA

α -

α + or α one

Many

α-Globin

Component

hemoglobin

malaria and severe malaria aneamia but appears to enhance mild malaria

episodes in some

environments

 of

Thalassemia

 protects against severe

(16p13.3)

thalassemia

gene

deleted

α 0 or - -

Many

> both genes

deleted

(α-thal)

 **Number**

**Protein Function**

 **Reported Genetic** 

**with Malaria**

**Associations**

**Mechanistic**

**Proposed protective mechanism**

Increased

phagocytosis

 of ring-

Africa

 0.4

 **hypotheses**

**Distribution**

 **High** **Frequency**


The high mortality and widespread impact of malaria have resulted in this disease being the strongest evolutionary selective force in recent human history,

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

The history of genetics and the study of malaria are much linked. Indeed Burden of disease due to malaria across much of the world has selected for a series of traits, including the alleles of genes encoding hemoglobin, red cell enzymes,

disorders of hemoglobin and glucose-6-phosphate dehydrogenase (G6PD)

Each year more than 7000000 babies born with either a congenital abnormality and/or a genetic disease, mainly (up to 90%) in low or middle-income countries [8]. About 25% of these births consist of five disorders, two of which, the inherited

In recent years there has been a major revival in scientific studies interest in the study of interactions between the inherited hemoglobin disorders and *P. falciparum* malaria, work that has been the subject of several extensive reviews [5, 9, 10].

This chapter focuses on IDH that are common enough to be of public health concern particularly those significantly associated with malaria as summarized in **Table 1**. By presenting the relationship between IDH and malaria susceptibility, making an overview of the current state of knowledge and the burden of IDH, this chapter outline some of the more important protective genetic variants that have been identified as far as summarized in the **Table 1**. The knowledge of our understanding of the interaction between hemoglobin variants and malaria could give point to

**2. Inherited disorders of hemoglobin (IDH) and** *Plasmodium falciparum*

Malaria is a severe infectious disease caused by parasites of the genus *Plasmodium*. *Plasmodium* is one of the longest-known parasites, which are transmitted to humans by a bite of an infected female mosquito of the species Anopheles.

Indeed, after inoculation into a human by a mosquito, the *P. falciparum* parasites enter the erythrocytic stage of their life cycle after a brief silent incubation in life (**Figure 2**). It is during this time that parasites sequentially invade and egress from their host RBCs and cause the signs and symptoms of malaria. Hemoglobin is the oxygen - carrying component and major protein of the RBC [11]. Indeed, the RBC is essential for the spread of malaria parasites, as summarized in **Figures 2** and **3**. Despite progress towards its control of malaria, it is still the most important parasitic disease and then, one of the world's worst health problems. In 2018, about 228 million cases of malaria occurred worldwide. Most of these cases (93%) occurred in African Africa region In the same year malaria was responsible for 405 000 deaths made up to 67% (272000) of children under 5 years recognized as the most vulnerable group [12]. However, early diagnosis and fast-acting treatment prevent unwanted outcomes. Until recently it was thought that only four species of malarial parasite (Plasmodium) especially *Plasmodium. falciparum (P. falciparum), Plasmodium.vivax (P.vivax), Plasmodium. malariae (P.malariae), and Plasmoduim. ovale (P.ovale)*, have humans as their natural hosts. But, it has been found that many cases of malaria that were previously diagnosed as being due to P. malariae infection are in fact due to a

fifth parasite, *Plasmodium. knowlesi (P. knowlesi)* mostly in Malaysia [13].

It has long been thought that *P. falciparum* was the only cause of severe malaria cases and deaths, until the equally destructive, if not worse, the role of *P. vivax* is

and genes that confer resistance to malaria [7].

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

deficiency, are monogenic diseases [8].

novel preventive and/or therapeutic approaches.

*(P. falciparum)* **malaria**

**7**

**2.1 Brief review of malaria infection**

and membrane proteins.

*Inherited Disorders of Hemoglobin and* Plasmodium falciparum *Malaria DOI: http://dx.doi.org/10.5772/intechopen.93807*

The high mortality and widespread impact of malaria have resulted in this disease being the strongest evolutionary selective force in recent human history, and genes that confer resistance to malaria [7].

The history of genetics and the study of malaria are much linked. Indeed Burden of disease due to malaria across much of the world has selected for a series of traits, including the alleles of genes encoding hemoglobin, red cell enzymes, and membrane proteins.

Each year more than 7000000 babies born with either a congenital abnormality and/or a genetic disease, mainly (up to 90%) in low or middle-income countries [8].

About 25% of these births consist of five disorders, two of which, the inherited disorders of hemoglobin and glucose-6-phosphate dehydrogenase (G6PD) deficiency, are monogenic diseases [8].

In recent years there has been a major revival in scientific studies interest in the study of interactions between the inherited hemoglobin disorders and *P. falciparum* malaria, work that has been the subject of several extensive reviews [5, 9, 10].

This chapter focuses on IDH that are common enough to be of public health concern particularly those significantly associated with malaria as summarized in **Table 1**.

By presenting the relationship between IDH and malaria susceptibility, making an overview of the current state of knowledge and the burden of IDH, this chapter outline some of the more important protective genetic variants that have been identified as far as summarized in the **Table 1**. The knowledge of our understanding of the interaction between hemoglobin variants and malaria could give point to novel preventive and/or therapeutic approaches.
