Malaria is a disease caused by the protist Plasmodium falciparum (CDC). The disease is transmitted from person-to-person via a known vector, the Anopheles mosquito (Olivier). The life cycle stages, sporozoite to merozoite, it has while inside the human host are known as well as the fact that no symptoms appear until the merozoite enters the bloodstream. Once it is present in the blood there are a variety of symptoms the disease can cause ranging from fever and chills to death (Olivier). Malaria is the fifth leading cause of death worldwide by infectious diseases, and can affect millions of people worldwide (CDC). For this reason the protist, Plasmodium, its life cycle, and how it interacts with the human cells it enters is greatly studied. The components being studied are the enzymes and surface proteins that Plasmodium secretes and the effects these proteins have on the human cells that they enter. It is a wonder how Plasmodium enters the host and evades the immune system, so scientists are attempting to understand exactly how the protist evades the immune system response. The survival of the parasite within the red blood cell is greatly studied since a red blood cell is essentially a transport cell, without any metabolic processes. These components of the malaria parasite are being studied in order to better understand the parasite and therefore treat the patients.
In order to identify the different enzymes and proteins that Plasmodium secretes and their effects on the host, it is necessary to study the different stages of the parasite while it inhabits the host. There have been specific studies conducted determining which proteins are necessary for movement between liver cells, before the parasite transforms from a sporozoite to a merozoite. The protist needs specific proteins such as, SPECT1 and SPECT2, in order to move from cell to cell (Olivier). If these proteins are not present the protest cannot enter the cells and will be immobilized in the skin, unable to cause infection. This mode of transportation is important in order to get to the liver, where the parasite will move between cells in order to form the infective form (Olivier). To traverse into the liver the parasite enters a vacuole that prevents plasma membrane rupture of the cells in the liver. Scientists believe that this is beneficial to the parasite, whereas migration through the liver via cell rupture entices the immune system response because it causes inflammation (Olivier). Through scientific study it has also been determined that the liver cells containing highly sulfated HSPG receptors instigate the protist causing it to develop into the infective stage, so these receptors located within the host stimulate the switch from non-infective stage to infection (Olivier).
Once inside the liver cell the sporozoites differentiate into merozoites and rapidly divide, but the immune system displays no real response. Specifically Plasmodium's circumsporozoite protein or CSP, ensures its survival while in the liver cells, by decreasing the expression of inflammatory genes preventing an immune response as well as increasing the parasite's rate of growth (Olivier). The vacuoles that the parasite is contained in, while in the merozoite form, allow for decreased detection by the immune system, since the parasite is enclosed in a vacuole consisting of similar material as the host cells it travelled through during infection. In experiment conducted on Plasmodium yoelii infected rodents parasitic vacuoles, merosomes, exited the liver cells without rupturing the cells (Olivier). This is another safeguard to protect the remaining parasites located in the liver from being identified by the immune system allowing the parasite to increase in number without detection.
After leaving the vacuole located within the liver, Plasmodium enters the erythrocytes of the host. Invasion of the erythrocytes occurs rather quickly, and only requires a few receptor-ligand interactions (Olivier). Once invasion of the erythrocytes occurs, the parasite will need to overcome the challenges posed by residing inside the erythrocyte. Living within the erythrocyte is difficult since there are limited biochemical pathways that occur, and it acts as a transporter cell, but for this reason the parasite can be used to study the how a parasite can thrive in a minimal nutrient environment (Olivier). In order to do this Plasmodium has a restricted diet of hemoglobin, which is found in plentiful amounts within erythrocytes. In order to get other nutrients the parasite forms a network inside the red blood cell called a tubovesicular network, which is used to transport items it needs to survive into and out of the cell, it helps the parasite receive proteins via the Plasmodium export system, which is a protein sequence made by cleavage of the N-acetylation site present in parasitic organisms (Olivier).
All these proteins and life cycle stages are tied together and produce the disease malaria, which can range in severity. Rodents are used to better understand the events behind severe malaria, specifically cerebral malaria (Olivier). These studies have demonstrated that the progression of cerebral malaria does not depend on the on the receptor, CD36, known to identify the other erythrocytes containing the parasite. There are many different factors that play into the development of the disease in mice such as, chemokine receptors, dendritic cells, and T cells (Olivier). Another important enzyme that displayed an effect on the ease of the mice developing cerebral malaria was heme oxigenase-1 or HO-1. Mice whose HO-1 was upregulated or induced displayed no signs of cerebral malaria or blood-brain barrier disruption, whereas the mice with less HO-1 were susceptible to the disease (Olivier). In addition to these studies CO, carbon monoxide, was introduced to the mice, and the results demonstrated that some inhaled CO also prevents penetration of the blood-brain barrier and inflammation of the neural tissues, and NO demonstrated similar effects. The molecules have the same effect because they share similar mechanisms when bound to heme, which affects red blood cells, the host cell of Plasmodium (Olivier).
All these studies are conducted in order to provide the scientific community with a better understanding of the parasite, which will in turn allow for better treatment and prevention of the microorganism. These studies are also important to diminish the widespread mortality rate in the millions, of children and the elderly in the Anopheles mosquito infested areas (Olivier). The studies conducted on the mice to determine how to decrease the incidence of cerebral malaria were interesting, and further studies regarding competitive inhibitors of heme should be conducted to determine the dosage techniques, or produce some other molecule similar to NO or CO that would prevent entry passage between the blood-brain barrier (Olivier). The vacuoles that the parasite encases itself in should be studied further, especially the factors that trigger the formation of the vacuoles. The proteins that the parasite has should be further studied in order to produce antibiotics targeting these proteins, specifically the SPECT proteins since they aid in entry of the body and without the SPECT proteins the parasite can be phagocytized in the skin (Olivier). The knowledge gained from all these studies seems like it will enable further understanding of the parasite, and hopefully will ultimately provide a solution to diminish the incidence and mortality rates of the disease.
Works Cited
“CDC – Malaria – About Malaria - Facts.” Centers for Disease Control and Prevention. Web. 22 Apr. 2010. <http://www.cdc.gov/malaria/about/facts.html>
Olivier, Silvie, Maria M. Mota, Kai Matuschewski, and Miguel Prudencio. “Interactions of the Malaria Parasite and Its Mammalian Host.” Current Opinion in Microbiology 11.4 (2008): 352-59. ScienceDirect. Web. 22 Apr. 2010.
