Gene Drive Strategies to Combat Malaria

Introduction

Malaria is a mosquito-borne infectious disease, instigating one of the leading causes of death afflicting over millions of people worldwide. The disease is mainly orientated in subtropical regions around the world and Africa being the most prevalent country to the disease of malaria due to high level of transmission (Plewes et al., 2019). The current possible antimalarial drugs can only ease the symptoms of the disease. Moreover, there is no direct eradication of the disease, which is currently available. Therefore, research and development of gene drive strategies are essential to control the eradication and transmission of this disease (Plewes et al., 2019). The primary vector for malaria is the females Anopheles mosquito (sp. Anopheles gambiae, Anopheles arabiensis and Anopheles funestus) (Robert A, Holt et al., 2002; Staff et al., 1900). These mosquitos are anthropic organisms thus obtain their nourishment through blood meals. The life cycle of the mosquito is composed of four stages (Egg, Larvae, Pupa & Adult) and varies between 10 to 14 days (CDC, 2018).

Life cycle of the Anopheles mosquito

During the initial stage of the life cycle, the mosquito layover 200 egg and later develops into larvae, where the formation of abdomen, mouth brushes, thorax and later metamorphizes into pupae. The larvae also mostly feed on algae and bacteria and are located on the temporary bodies of water. The pupa is stage, which is heavily dependent on the ambient temperature and the transition of the thorax merging into a cephalothorax, forming a curved structure (radical metamorphosis). When the cephalothorax separates, the adult mosquito arises. Then finally, the fully formed adult is comprised of a head (retrieve sensory information), abdomen (digestion & development of eggs) and thorax (locomotion).

When the adult female Anopheles mosquito is ingesting a blood meal during the reproductive period, it infects the offspring with the Plasmodium. Additionally, at the seven to fourteen day cycle, the high temperature and humidity accelerates the growth of the parasite (CDC, 2018; Robert A, Holt et al., 2002).

Plasmodium

Genus of unicellular parasite, Plasmodium is the primary disease organism for Malaria. Currently, five species of Plasmodium’s (sp. Plasmodium falciparum, Plasmodium ovale, Plasmodium vivax, Plasmodium malariae and Plasmodium Knowlesi) are known as pathogens. The eukaryotic nature of the parasite can infect both vertebrates (humans) and insects (mosquito), making Anopheles the principle vector for carrying the parasite.

The Plasmodium structure is composed of micronemes (secretory organelles), which aid in the secretion of infectious debris into the host (Clayton et al., 2014). It also helps in the survival of the organism by encompassing the specialised organelles such as mitochondria and the apicoplast, involved in the metabolism and generation of Adenosine triphosphate (ATP).

Life cycle of Plasmodium Life cycle of the Plasmodium is separated between two hosts. The Plasmodium’s developmental stage occurs inside the mosquito’s gut and salivary glands, when the female Anopheles mosquito ingests the parasite (gametocytes) during a blood meal (Gardner, M. J. et al., 2002). The fertilisation of the gametocytes results in the formation of a zygote, which further changes into an ookinete and then transforms into an oocyte. The oocyte ruptures and undergoes sporogony thus forming sporozoites. During the next blood meal, the sporozoites are transferred into the human host, where it undergoes asexual reproduction initiating the parasitic life cycle (Clayton et al., 2014; Dina Vlachou et al., 2006; Elena ALevashina, 2004; Florens et al., 2002).

The parasitic life cycle is divided into two stages: Exo-erythrocytic phase and erythrocytic phase. At the exo-erythrocytic stage, the sporozoites attack the hepatic parenchymal cells (in the liver) and develops into schizonts, ruptures the hepatic cell (causing cell death) and releases merozoites. Some merozoites become dormant in the liver and can reappear at a later stage and the others invade the RBCs (erythrocyte). In the erythrocytic cycle, merozoite forms trophozoite by the digestion of haemoglobin. This trophozoite later develops into schizonts and gets released into the blood stream. Some of the trophozoites undergo gametogonia and develops into gametocytes (male and female Plasmodium) and the cycle repeats itself when the gametocytes are ingested by Anopheles mosquitos. (CDC, 2018; Clayton et al., 2014; Dina Vlachou et al., 2006; Elena ALevashina, 2004; Florens et al., 2002; Staff et al., 1900)

Conclusion

Understanding both the biology of the Anopheles’ mosquito and Plasmodium can aid in prevention and control strategies, thus, increasing longevity and reducing the susceptibility of the parasite to the human host (Clayton et al., 2014).

References

• CDC, 2018. Center for Disease Control and Prevention. Malaria. URL https://www.cdc.gov/malaria/about/biology/index.html
• Clayton, A.M., Dong, Y., Dimopoulos, G., 2014. The Anopheles Innate Immune System in the Defense against Malaria Infection. Journal of Innate Immunity 6, 169–181. https://doi.org/10.1159/000353602
• Dina Vlachou, Timm Schlegelmilch, Ellen Runn, Antonio Mendes, Fotis C.Kafatos, 2006. The developmental migration of Plasmodium in mosquitoes. ELSEVIER 16, 384–391. https://doi.org/doi.org/10.1016/j.gde.2006.06.012
• Elena ALevashina, 2004. Immune responses in Anopheles gambiae. ELSEVIER 34, 673–678.
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• Gardner, M. J. et al., 2002. ‘Genome sequence of the human malaria parasite Plasmodium falciparum’,. Nature 419, 498–511.
• Plewes, K., Leopold, S.J., Kingston, H.W.F., Dondorp, A.M., 2019. Malaria. Infectious Disease Clinics of North America 33, 39–60. https://doi.org/10.1016/j.idc.2018.10.002
• Robert A, Holt et al., 2002. The Genome Sequence of the Malaria Mosquito Anopheles gamblae. Science 298, 129.
• Staff, I. of M., Oaks, S.C., Mitchell, V.S., 1900. Malaria: Obstacles and Opportunities. National Academies Press, Washington.