*2.2.3 Glucose-6-phosphate dehydrogenase deficiency and* P. falciparum *malaria*

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a genetic disorder that results in impaired enzyme activity.

This X-linked genetic condition is characterized by reduced G6PD enzyme activity, which can remain asymptomatic. Red blood cells obtain reduced glutathione (GSH) solely from the G6PD/reduced nicotinamide adenine dinucleotide phosphate (NADH) pathway [7, 12, 30, 40, 41].

The deficiency makes red cells more susceptible to oxidative haemolysis, this disease that can cause jaundice in newborn babies and haemolytic anemia (when red blood cells break up) throughout life. This is, usually caused by an infection or exposure to certain foods or chemicals [41, 42]. One of the chemicals that can trigger severe symptoms in people with G6PD deficiency is Primaquine, the only drug currently available to clear the relapsing life stages of the *Plasmodium vivax* parasite from the liver.

G6PD and a number of other human genetic traits including sickle cell anemia and related haemoglobinopathies are predominantly found in populations living in malaria endemic countries and have been suggested to provide the host protection from severe forms of malaria [30, 43–45] and asymptomatic malaria [27].

G6PD deficiency can be common in populations with high levels of malaria infection, indeed the prevalence is even higher (8%) in malaria-endemic countries [8]. Malaria control programs need to know this to inform their policies on using Primaquine as a treatment and as a malaria control measure.

#### **2.3 Epidemiology of inherited hemoglobin disorders and** *P. falciparum* **malaria**

For a very long time, human beings have interacted with malaria parasites and thus the parasite has had largely time to adapt and evolve with the human host [40]. Immune processes and genetic traits have contributed to reducing the profligacy of

the malaria parasite and a wide range of genetic polymorphisms has been developed to modify the individual response to this disease. Gene mutations involved in susceptibility and resistance to *P. falciparum* malaria. It has been shown that the severity of several malaria infections (such as asymptomatic, CM and SMA) varies significantly between individuals and between populations [5]. Many of the protective variants identified thus far affect erythrocytes, where the malaria parasite spends a crucial stage of its life cycle. Several of the best studied mutations affect the globin genes encoding hemoglobin [46]. Haemoglobinopathies and G6PD deficiency are among the most common single-gene disorders, which affect RBC stability and integrity [47].

• Selective sickling of infected sickle trait erythrocytes leading to enhanced clearance by the spleen. Reduced erythrocyte invasion, early phagocytosis, and inhibited parasite growth under oxygen stress in venous micro vessels [65].

• oxygen-dependent polymerization of HbS is responsible for *P. falciparum*

A study with children (between the ages of 2 and 10 years) found that the protective effect of HbAS against malaria increased from 20% to 56%, which implies that it enhances or acts in synergy with the acquired immune response [54, 67]. The compromise between risks and benefits allows us to maintain the HbS polymorphism at allele frequencies of environ 10% in many parts of Africa, despite the lethal consequences for homozygotes, which provides the most striking known

Some case–control and prospective cohort studies [10, 33, 54, 68–71] indicate that HbAS is consistently associated with large reductions in the risk of severe malaria.

A comparative studies [33, 44, 71–73] and several prospective studies [5, 26, 37, 74] have shown the reduction of risk in malaria attributable to HbS. In fact, the HbAS genotype protects against uncomplicated *P. falciparum* malaria by about 30% [33, 71]. In addition, this has been further confirmed by some genome-wide associ-

Cross-sectional studies have reported conflicting data on the prevalence of *P. falciparum* parasitemia in asymptomatic HbAS children compared with HbAA

A lower prevalence of parasitaemia in HbAS children was reported in some studies, [6, 26, 75], when others studies found contrary results of similar prevalence

In these surveys, parasite densities were reported in HbAS children as lower [6, 62, 76, 79, 80] or similar [27, 78, 81, 82] to those in HbAA children. We can conclude that HbAS does not consistently protect from *P. falciparum* parasitaemia.

A recent meta-analysis concluded that homozygotes for βC (Hb CC) were strongly protected against severe malaria, and heterozygotes (HbAC) were mildly protected [10, 33]. It has also been found that both both heterozygotes and homozygotes of HbC are protected against severe malaria [26, 30, 31, 44, 83] but the protective effect appears to be substantially greater in homozygotes [44].

Although a cohort study in Mali reports an increase in the incidence of clinical

HbC genotypes are not fully elucidated [56], but several mechanisms have been proposed to explain the malaria protection offered by HbC [32], including abnormal

• Enhancement of innate and acquired immunity [53]

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

example of heterozygote advantage in human genetics [9].

growth inhibition [66]

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

• Severe *P. falciparum* malaria

ation studies [70, 71].

children.

**15**

• *P. falciparum* parasitaemia

• Uncomplicated *P. falciparum* malaria

[72, 76, 77] or of higher prevalence [78, 79].

malaria in AC individuals relative to AA [84].

*2.3.1.2 HbC and* P. falciparum *malaria*

More than 700 abnormal hemoglobin have been described worldwide and more than 200 million people worldwide have RBC enzyme abnormality [48].

These genetic mutations are major causes of morbidity and mortality around the world [49]. Sickle hemoglobin and G6PD deficiency are genetically independent, their loci is located on chromosome 11 for sickle and chromosome X for G6PD deficiency genes.

**Table 1** summarizes the Common Erythrocyte variant that affects malaria infection particularly *P. falciparum* malaria.
