**4. Conclusions**

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

Despite the global awareness with the promulgation of malaria eradication goals,

This review confirms that the malaria parasite has co-evolved with its human host, each struggling for survival. The resulting stigmas appear as polymorphisms of the human genome. This process resulted in a symbiotic association, conferring to the host a relative protection against parasitic infection on one hand and allowing the parasite a greater longevity and proliferation due to host acquired resistance on other hand About polymorphisms of the proteins of red blood cells conferring an innate relative resistance to malaria, it is established that with an effect size >80%, the HbS variant confers the strongest protective effect against severe malaria, while the α- thalassemia confers a protective effect of about 40% in homozygotes [70, 71]. Other genes such as G6PD deficiency have also been shown to be present at high frequencies in endemic malaria populations [9, 10, 22, 142]. However, taking into account the limited mapping specific gene variants of early studies, recent studies have shown that the significant effects of known candidate genes would explain only a small fraction of the heritability of malaria [10, 22, 63, 143, 144]. This indicates that the genetic architecture of susceptibility to malaria is much more complex and that "missing heritability" could be explained by polygenetic or epigenetic effects or by gene–gene and gene–environment interactions [10, 145].

The MalariaGEN consortium has greatly contributed to understanding the correlation between the pathogenesis of malaria and polymorphisms in human RBC. A better understanding of how changes in RBC physiology affects malaria path-

ogenesis may uncover new strategies to combat the disease. Understanding the

despite the colossal efforts deployed in many forms: international and bilateral cooperation, foundations and humanitarian agencies, philanthropic works. Malaria remains a crucial public health concern within the world in general and in tropical countries in particular. According to the latest Global Malaria Report, there were 228 million cases of malaria in 2018, of which there were 405,000 deaths. Almost all of the morbidity and associated lethality, respectively 93% and 94%, occur in Africa (WMR, 2019) more than 50% of the disease burden of malaria is borne by only 6 countries namely: Nigeria (25%), the Democratic Republic of Congo (12%), Uganda (5%) and Côte d'Ivoire, Mozambique and Niger (4% each). With 67% of malariarelated deaths, children under 5 remain the most vulnerable group [2]. These health consequences of malaria bring with them very important economic and social tragedies. In some cases, the resulting disruption of family structures has consequences for the family itself and for the whole community over several generations [141]. The incidence of malaria is inversely proportional to the level of development of the affected societies. The global distribution of gross domestic product per capita shows a strong correlation between malaria and poverty. Malaria generates direct costs (medical care) and indirect costs (loss of productivity linked to disabilities and deaths due to malaria) [141]. The relief of all this sharp and stifled pain requires strengthening malaria prevention programs and promoting multidisciplinary research on effective and safe antimalarial drugs and vaccines.

services in order to reduce the burden of heamoglobinopathies.

**2.5 Global burden of the Malaria**

*Human Blood Group Systems and Haemoglobinopathies*

**3. Discussion**

**22**

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

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 genetic approaches into health systems.

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 potential would be particularly valuable and necessary.

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 to redefine or readjust malaria control strategies.

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* produces morbidity.

Vaccines are unquestionably the most cost-effective way for malaria control. The new generation of vaccine delivery systems is increasingly moving towards coadministration of certain immunostimulants and the use of more than one antigen in the same system. In any event, the best vaccine should be effective, safe, low cost, available, and easy to administer.

manifestations of malaria in subjects with sickle cell trait, gene therapy is a new approach to healing patients with hemoglobinopathies, which must be popularized. In this sense, clinical trials are underway with promising results. However, there are still frontiers to explore that could improve this approach: the stoichiometry between transgenic hemoglobin and endogenous hemoglobin in relation to the different genetic mutations of globins; the supply of donor cells, such as the use of induced pluripotent stem cells (iPSC); and the use of safer gene insertion methods

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

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

The overall prospects for malaria elimination are clear, encouraging and the potential opportunities are endless. Technological discoveries and advances are happening at an incredibly fast pace. The context of discovery and use of new technologies makes the eradication of malaria within the reach of the test tube. However, regardless of the time it will take, we must increase our efforts; intensify networking, with the financial support and strong political will of our leaders, especially in Africa where the problem of malaria is the most important.

We would like to acknowledge all authors whose articles were cited in this

BEC wrote the manuscript. SBS read and approved the final manuscript and

Bougouma Edith Christiane, Email: eddy.cnrfp@gmail.com/e.bougouma@gras.

bf. Sirima Bienvenu Sodiomon, Email: s.sirima@gras.bf/gras@fasonet.bf

The authors received no specific funding for this work.

The authors declare no competing financial interests.

There is no ethical approval for this article.

The authors have declared no conflict of interest.

agree to be accountable for all aspects of the work.

to prevent oncogenesis.

**Acknowledgements**

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**25**

chapter.
