Research on the Impact Genetics on the Longevity of Malaria-Ill People

This part is focused on the impacts of genetics on the susceptibility of humans to Malaria, Response to drug treatment modified by genetics and Genetic basis for personal differences in response to drug dosage and clinical response. It will also include how some of the human genes are related to Malaria or responsible to stand against Malaria. The aim is to drag the attention to genetic variation of diseases and drug response while targeting the therapy to optimize the impacts of medicines to meet the need of Malaria.

The impact genetics on susceptibility to Plasmodium falciparum malaria has been drastically studied over recent years. It is now clear that malaria parasites have imposed strong selective forces on the human genome in endemic regions. Different genes have been identified that are associated with unique malaria-related phenotypes. Recent advances in human genome studies technologies such as genome-wide affiliation studies (GWAS) and excellent genotyping equipment have enabled the discovery of several genetic polymorphisms and biomarkers that warrant further study in host-parasite interactions. This evaluation describes and discusses human gene polymorphisms identified thus far which are associated with resistance to P. falciparum malaria. The discovery of genetic markers related to exceptional malaria phenotypes will assist elucidate the pathophysiology of malaria and enable improvement of interventions or cures. Diversity in human populations, as well as environmental effects, can affect the clinical heterogeneity of malaria, consequently warranting further investigations to grow new interventions, therapies and better control in opposition to malaria.

Several gene mutations causing inherited diseases or traits have been reported to influence malaria severity. Mutations in these genes have been linked to erythrocytes including hemoglobin (Hb) variants or related to proteins such as haptoglobin and Nitric Oxide metabolism. For example, the heterozygote HbAS (sickle cell trait) which protects against severe malaria is widespread in malaria-endemic regions as a result of natural selection over generations. It has also been shown that the rate-limiting enzyme haem oxygenase I (HO-1), responsible for the catabolism of free haem in the body, plays an important moderator role in malaria Epistatic interactions between genetic disorders of hemoglobin (HbAS, thalassemia, HbE, etc.) show evidence of heterozygote protection from malaria and protection against malaria by the sickle cell trait is removed if there is co-inheritance of alpha-thalassemia.

These studies emphasize the underlying complexity of the field and therefore stress the need for newer methods of genomic analysis. Although malaria resistance gene mutations have been well studied, genes associated with red cell disease severity deserve further scrutiny. Treatments for or curative interventions of malaria are barely protective against malaria over the long run (TED, 2018). As discussed later, malaria has developed a range of mechanisms such as to counter most, if not all, current anti-malaria drugs and controls. So far, Artemisinin-Based Combination Therapy (ACT) and, most recently, RTS, S/AS01 (RTS, S) are a curative intervention and (only) vaccine used to cure and protect against malaria, particularly among young children, respectively.

Medically, malaria parasites have developed anti-malaria drug mechanisms. This is shown not only in genomic makeup of malaria parasites in Africa (“Malaria Control Success in Africa at Risk,” 2019; Leffler et al., 2017) but also in a new – and only – vaccine for malaria, RTS, S or Mosquirix, piloted in African countries Malawi, Ghana, and Kenya (De Vrieze, 2019). Against much hype by the medical community, including WHO, Mosquirix has shown, so far, mixed results in Malawi involving only slight protection against malaria but also growing concerns of developing meningitis and lesser immunity for girls (De Vrieze). To complicate matters more, different malaria variants are shown in a growing body of research to resist pyrethroid insecticides, employed in bed nets, in many malaria-afflicted African countries (Ranson&Lissenden, 2016).

Further, pregnant women, one most vulnerable patient segment contracting malaria, are increasingly referred to in literature as good indicators to help monitor malaria, particularly for erythrocytes infected with P. falciparum which, accumulating in placenta, express surface protein VAR2CSA (Rogerson et al., 2018). In response, a range of anti-malaria interventions has been proposed, in addition to existing drugs and vaccines, including most notably next-generation sequencing (NGS) methodologies (Ghansah et al., 2019) by which “molecular detection of genetic mutations associated with resistance or reduced susceptibility to anti-malarial is a simple and powerful tool for early detection and monitoring of the prevalence of resistant parasites at population level” in Sub-Saharan Africa (SSA) (Ishengoma et al., 2019).

Developmentally, Africa is still plagued by a historical healthcare resource management challenge. Indeed, Africa has for long decades experienced dramatic fortunes to healthcare services informed by a broad range of reasons including, but not limited to, income inequalities, political corruption, inadequacy of public services and infrastructure, lack of healthcare awareness among local communities and, for malaria, a persistent state of healthcare coverage. In a cross-sectional study conducted on 201,704 children younger than 5 years, based on 103 surveys, and across 33 African countries, findings show that, despite notable progress in malaria program over 2003-2015 period, ACT interventions for children is “unacceptably low” due to differential healthcare access, poor service delivery and inadequate ACT administration (Bennett et al., 2017).

The case for lack of resources, medical and non-medical, provided to help eliminate malaria in Africa is made evident by adopting monotherapies increasingly shown to develop stronger resistance among a variety of malaria parasites (Tan, 2017). The case of development cannot be overemphasized in Africa. If anything, economic development in Africa is not only a means by which more prosperity is brought to larger populations. More critically, development helps save millions of lives lost only because of lack of adequate resources, often minimal, to provide access to adequate healthcare services for potential and existing malaria-afflicted individuals, communities and areas in Africa at large.

Ecologically, natural ecosystems and habitats are breeding grounds for malaria. Africa is a resource-rich continent whose full potential is yet to be put into more optimum uses. Moreover, Africa, a continent predicted to achieve rapid economic growth in the next few decades, is also home to the world's most important natural ecosystems and habitats. The acceleration of economic growth is, however, believed to bring about a range of negative direct and indirect consequences to local communities. Specifically, major construction projects, particularly dams, in SSA region are shown to “generally increase malaria by providing breeding habitats for prominent malaria vector species” in “unstable areas where transmission is limited by availability of water bodies for vector breeding” and, as such, require integrated vector control measures including reservoir management, coupled with conventional malaria control strategies to reduce malaria transmission risks around dams in Africa (Kibret et al., 2017).

Needless to say, economic development and environmental challenges are now on a collision course on a global scale. In Africa, risks of not balancing out requirements for development and essential disease controls, particularly for malaria, is apt not only to confound economic development plans but, more critically, to pose an immediate health hazards for large portions of African populations close to or around major dam construction projects.