**2.5 Global burden of the Malaria**

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

## **3. Discussion**

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

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 therapeutic targets for the treatment of malaria.
