Invasion of Red Blood Cells by Plasmodium Falciparum
Autoimmune diseases

Molecular Mechanism of Malaria Parasite Infection

Malaria is a life-threatening disease that is caused by Plasmodium parasites. It is transmitted to individuals through the bite of an infected female anopheles mosquito. Malaria is a tropical disease that is prevalent in Sub-Saharan African populations.

There are five species of plasmodium parasites, which affect humans. They are:

  • Plasmodium falciparum
  • Plasmodium vivax
  • Plasmodium malariae
  • Plasmodium ovale

Among the five species of plasmodium parasite, Plasmodium falciparum causes the most severe and life-threatening malaria, while Plasmodium vivax is the most widely distributed, representing 53% of malaria incidences.


Symptoms of Malaria

The signs and symptoms if malaria may include:

  • Fever
  • Headache
  • Chills
  • Vomiting and diarrhea
  • Nausea
  • Tiredness
  • Muscular pain


How Is Malaria Parasite Transmitted?

Malaria parasite can only be transmitted when an infective female anopheles mosquito bites and feeds on the blood of and person. At first, the female anopheles mosquito bites and feeds on the blood of an infective person, thereby taking along the blood plasmodium sporozoites. When the mosquito bites another individual, it injects the plasmodium sporozoites into the blood circulation, from it they move to the liver of the newly infected person.

When the sporozoites get to the liver cells they rapidly bind and invade the liver cells and undergo rapid multiplication. This leads to the release of infective merozoites which invade red blood cells and destroy them.


Life Cycle of Plasmodium Falciparum

The life cycle of malaria parasites involves two hosts which are the female anopheles mosquito and human hosts. In humans, the parasite grows and multiply in the liver cells and then in the red blood cells, where successive broods of parasites grow and destroy the cells, releasing the merozoites, which continue to the cycle by invading other red blood cells.


Stages of Life Cycle of Plasmodium Falciparum

As seen above, malaria parasite passes through several stages in its life cycle. We shall look at the major stages which are the human stages and the mosquito stages of the life cycle of plasmodium falciparum.


The human stage (Exo-erythrocytic schizogony)

In the liver, the sporozoites infect the liver cells and mature into Schizonts, which rupture and release the Merozoites. In plasmodium vivax, and plasmodium ovale a dormant stage called hypnozoites can persist in the liver, if untreated, and cause relapses by invading the bloodstream weeks or months later.


Human Blood Stage (Erythrocytic Schizogony)

In this stage, the merozoites released infect red blood cells and form a ring-stage, trophozoites. The trophozoites differentiate into sexual erythrocytic stage called gametocytes.

The blood stage parasites are responsible for the clinical manifestations of the disease.


Mosquito stage (Sporogonic cycle)

During blood meal, the female anopheles mosquito ingests the male and female gametocytes. The male gametocyte is called microgametocyte while the female gametocyte is called macrogametocyte.

In the mosquito’s stomach, the microgametes penetrate the macrogametes to form the zygotes. The zygotes then become motile and elongated, and are called Ookinetes. The ookinetes invade the mid gut of wall of the mosquito, where they develop into Oocysts. The Oocysts grow, rupture and release sporozoites. These then make their way to the mosquito’s salivary glands.

When the mosquito bites and feeds on another person’s blood, the sporozoites are inoculated, thereby repeating the life cycle of malaria.


Molecular Mechanism of Plasmodium Falciparum Erythrocyte Invasion

The entry of parasite into the erythrocytes is the key to establishing blood stage infection and thus, central to both acute and severe malaria. When the merozoites invades the red blood cells, it changes its orientation until its apical end containing specialized secretory organelles called micronemes, rhoptries and base granules is pointed at the erythrocyte.

The binding and invasion of erythrocytes are carried out by two proteins of the apical secretory organelles. These proteins are the reticulocyte-binding protein homologous (RHs) and erythrocyte-binding-like proteins (EBLs).

In EBLs, a dufy-binding-like (DBL) domain mediates specific binding to different host cell receptors, including glycophorins A, B, and C as well as duffy blood antigen. But in RHs, complement receptor 1 (CR1) and basigin are the receptors for PfRH4 and PfRH5 respectively.

Whereas RHs have early role in host sensing, EBLs play a direct role in junction formation. This suggests that RH sensing and subsequent interaction with a suitable host erythrocyte sends a signal to the merozoite that triggers the subsequent steps of invasion.


PfRH1 interaction with its receptor on erythrocyte surface initiates invasion of parasite.

The complex invasion process of merozoite erythrocyte invasion begins with the interaction of a relatively small amount of PfRH1 with its receptor on the erythrocyte surface. This interaction leads to a signaling cascade that leads to the release of intracellular Ca2+ stores, followed by triggering of microneme and rhoptry discharge and junction formation.

PfRH1 is located at the Rhoptry duct. Whereas its role in parasite invasion is known, its receptor on erythrocyte is unknown. PfRH1 is sialic acid-dependent and binds to its receptor in a protease sensitive manner.

EBA-175 binding and parasite invasion of red blood cells

EBA-175 is located on the microneme and is responsible for the binding and invasion of merozoites to erythrocytes. Unlike PfRH1, EBA-175 receptor is known; it binds to the glycophorin A (GpA). GpA is the major glycoprotein found on human erythrocytes and is heavily sialylated. It is a 131 amino acid transmembrane dimer. Each monomer spans the membrane once exposing its N terminus extracellularly. The EBA-175/GpA is the dorminant chymotrypsin-resistant invasion pathway.





Templeton, T. J., and Kaslow, D. C. (1997) Mol. Biochem. Parasitol. 84, 13–24

Collins, W. E., Miller, L. H., Glew, R. H., Contacos, P. G., Howard, W. A., and Wyler, D. J. (1973) J. Parasitol. 59, 855–858

Schmidt, L. H. (1978) Am. J. Trop. Med. Hyg. 27, 671–702

Collins, W. E., Galland, G. G., Sullivan, J. S., and Morris, C. L. (1994) Am. J. Trop. Med. Hyg. 51, 224–232

Pei X, Guo X, Coppel R, Mohandas N, An X. Plasmodium falciparum erythrocyte membrane protein 3 (PfEMP3) destabilizes erythrocyte membrane skeleton. J Biol Chem. 2007; 282:26754– 26758. [PubMed: 17626011]

Safeukui I, Correas JM, Brousse V, Hirt D, Deplaine G, Mule S, Lesurtel M, Goasguen N, Sauvanet A, Couvelard A, Kerneis S, Khun H, Vigan-Womas I, Ottone C, Molina TJ, Treluyer JM, Mercereau-Puijalon O, Milon G, David PH, Buffet PA. Retention of Plasmodium falciparum ring-infected erythrocytes in the slow, open microcirculation of the human spleen. Blood. 2008; 112:2520–2528. [PubMed: 18579796]

Camus, D. Hadley, T.J. A Plasmodium falciparum antigen that binds to host erythrocytes and merozoites. Science. 1985; 230: 553-556

Triglia, T., M. T. Duraisingh, R. T. Good, and A. F. Cowman. 2005. Reticulocyte-binding protein homologue 1 is required for sialic acid-dependent invasion into human erythrocytes by Plasmodium falciparumMol. Microbiol. 55:162-174.

Triglia, T., W. H. Tham, A. Hodder, and A. F. Cowman. 2009. Reticulocyte binding protein homologues are key adhesins during erythrocyte invasion by Plasmodium falciparumCell. Microbiol. 11:1671-1687.







Chidubem Olovo is a biochemist, researcher and a content writer.

Leave a Reply