**2.4 Global burden of the hemoglobin disorders**

To our knowledge, no studies have investigated the risk of severe malaria in

A case–control study in Liberia, have showed a low prevalence of β-thalassaemia in participants with uncomplicated malaria compare to community controls [72].

A other study that was done in Northern Liberia, found no differences, although

they did report lower parasite densities in those with β-thalassaemia [46].

*2.3.3 Deficiency Glucose-6-phosphate dehydrogenase (G6PD) and* P. falciparum

G6PD deficiency is a common X-linked recessive genetic disorder inherited from parents. Although, in most cases, G6PD-deficient individuals appear normal, it can lead to life-threatening anemia in severely G6PD-deficient individuals during oxidative stress-induced by the consumption of certain foodstuff (fava beans), legumes, and taking such as particular antimalarial (primaquine and pamaquine), sulfonamide, sulfamethoxazole, and other drugs and chemicals [123] and also probably infection with microorganisms [124]. Additionally, some authors show that G6PD deficiency increases the risk of severe neonatal hyperbilirubinemia, which can lead to lifetime disability with kernicterus if inadequately treated

However, there is a big beneficial effect of G6PD deficiency. Some studies have reported that G6PD deficiency provides resistance against malaria as the malaria parasite cannot complete its life cycle in compromised G6PD deficient RBC which have a decrease in life span or because of early phagocytosis of deficient RBC [126, 127]. Deficient G6PD enzyme activity has been shown to correlate with protection against severe malaria [43, 89]. Reduced parasite replication in G6PDdeficient erythrocytes is thought to be the mechanism of protection [128], but the

The geographical distribution of G6PD deficiency is consistent with evolutionary selection by malaria [130], and a hypothesis of positive selection [131–133]. The results of studies examining the risk of malaria for various G6PD-deficient genotypes are not consistent. Some authors [43, 134] found in Gambia and Kenya that the reduction in risk of severe malaria in male hemizygotes was 58% and that the reduction in risk for heterozygous females was 46%. Other hand, other authors found that in two populations in Mali, the reduction in risk of severe malaria in male hemizygotes was also 58%, but no reduction in risk in the female heterozygotes [93]. Some authors [27, 133] found no protective effect for either male hemizygotes or female heterozygotes. However, a protective effect has been reported on for females that were found to be G6PD deficient. This finding appears to be based on the incomplete correlation of genotype and phenotype for G6PD deficiency in female heterozygotes due to variable inactivation of the two X chro-

Several mechanisms have been proposed to explain the malaria protection

• Increased phagocytosis of ring-parasitized variant RBCs due to enhanced

parasite appears to counter this by manufacturing G6PD itself [129].

patients with β-thalassaemia.

• *P. falciparum* parasitaemia

*malaria*

[115, 125].

mosomes [127].

oxidative

**20**

offered by G6PD deficiency [45, 127].

• Uncomplicated *P. falciparum* malaria

*Human Blood Group Systems and Haemoglobinopathies*

Hemoglobinopathies are a group of IDH initially described in the subtropical regions, they are now spread all around the world. Their high frequency and clinical severity make them a global health burden mostly in Africa where there is a huge lack of resources. The measure of the yardstick of under-5 mortality has been used to assess the broad effect of hemoglobin disorders on health because most affected children can die in early childhood and most survivors can have a chronic disease. Some authors show that the disease may be cause of at least 3.4% of deaths in children aged under 5 years [135]. However, it is very difficult to estimate the burden especially as inherited disorders affect families and then communities. Worldwide, over 1% of couples are at risk for IDH most have at least one affected child. Most affected children could die in early childhood although there are now better health facilities and medical care.

Although the West African death rate in children aged under 5 years is 18.4%, This rate is 16.5% for children born to couples, not at risk for sickle-cell disorders, and 40% for children born to couples who are at risk [135]. Clearly, methods to assess the health burden of inherited disorders must include also a family perspective [135].

The burden of disease due to malaria across worldwide vary according to selected visible traits of major medical importance, including the alleles of genes encoding hemoglobin. There are several reasons for the extremely high frequency and uneven distribution of inherited hemoglobin disorders. Natural selection is by far the most important, because of the frequency of the heterozygote and the protection against malaria afforded to the homozygotes of thalassemia and HbC, followed by consanguineous marriages [9, 136]. The epidemiological transition whereby, owing to improvements of health care services, nutrition, and health positive social and behavioral factors, babies who would have probably died from the more severe hemoglobin disorders survive nowadays [39]. Then, the migration from areas of high frequency of SCD into regions like Europe and the United States are also cited.

Currently, there are only limited data on the gene frequencies and the number of births of patients with common hemoglobin disorders, particularly in Africa. Micro mapping studies involving many different centers in these countries have recently found that there is remarkable diversity in the frequency of the hemoglobin disorders even over small geographical distances [137–139].

For the future more micro mapping data are then needed to provide an accurate picture global burden according selective factors distribution [60]. Hemoglobinopathies are so common that they provide a convenient model for working out a genetic approach to the control of chronic childhood diseases. At present, about 250 million people (4.5% of the world population) carry a potentially pathological haemoglobinopathy gene. Haemoglobinopathy control programs, based on WHO approaches and recommendations, have been established in different countries in all WHO Regions and have been successful in the management of the problem by reducing the burden of the Hemoglobin Disorders [108].

Nowadays effective prevention programs have been carried out successfully in many developed countries concerning medical care for hemoglobinopathies. The programs should be extended and followed to African regions where hemoglobin

disorders are frequency very high. Indeed this frequency accounts for more than 70% of total hemoglobinopathies in the world [140]. Reducing the incidence of IDH, better prevention against IDH should remain the major priority of health services in order to reduce the burden of heamoglobinopathies.

molecular basis of these polymorphisms may shed additional light on the variation in human susceptibility to malaria and offer insight into mechanisms of malaria pathogenesis likewise, a better understanding of red cell membrane structure and function will offer opportunities for the discovery of new and urgently needed

Hemoglobinopathies are among the most common monogenic diseases in populations. The complexity of their pathophysiological processes, the severity and diversity of their clinical manifestations reflect the relevance of their scientific interests. Genetic polymorphisms that affect the structure and production of the βor α-chains of hemoglobin are variously associated with protection from a range of clinical manifestations of *P. falciparum* infection. The degree of protection conferred by hemoglobinopathies, in general, is greatest against severe malaria, moderate against uncomplicated malaria, and probably absent against asymptomatic *P. falciparum* parasitaemia. Therefore, there is a positive relationship between the

However, people with hemoglobin disorders could be high-risk groups. Indeed subjects admitted with malaria are twice more likely to die than those admitted for other pathologies. The screening and genetic counseling for hemoglobin disorders should be an intrinsic part of health care in most countries. Health facility's services should be designed to provide a foundation for more comprehensive community genetics services because hemoglobin disorders are commonly a point of entry for

Although information about the precise world distribution and frequency of the inherited hemoglobin disorders is still limited, there is no doubt that they are going to pose an increasing burden on global health resources in the future. Increased knowledge of the biological basis of these diseases would offer significant advances in their therapeutic management and in the prevention of the occurrence of new cases. Indeed the high frequency of IDH because of natural selection associated due to consanguineous marriages in some countries could be reduced through public awareness campaigns. Improving health care conditions in general and those related to pathologies associated with IDH would enhance affected children's survival. Hemoglobin variants could shape the distribution of malaria parasites in human populations and their transmission potential. Therefore, the knowledge of our understanding of the interaction between hemoglobin variants and malaria parasites is still being incomplete even if it has improved these last years. Nonetheless, with the interest in malaria elimination, knowledge on how these prevalent genetic variants influence parasite distribution and probably cumulative host transmission

The malaria parasite has co-evolved with its human host in a struggle for their survival. The scars of this war on the human genome are polymorphisms conferring an innate resistance to malaria. Regarding relationships between malaria and human genetic alterations of RBC proteins, it appears that the MalariaGEN studies have clearly opened new doors to understand the malaria burden on human RBC polymorphisms and thus malaria pathogenesis. These new pieces of knowledge will help

In fact, despite the complexity of these interactions, hemoglobin variants in general and hemoglobinopathies, in particular, show a good model and natural experiment identifying cellular and molecular mechanisms by which *P. falciparum*

frequency of either βC or βS and malaria selection intensity favors.

therapeutic targets for the treatment of malaria.

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

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

genetic approaches into health systems.

potential would be particularly valuable and necessary.

to redefine or readjust malaria control strategies.

produces morbidity.

**23**

**4. Conclusions**
