Plasmodium, commonly known as malaria parasites, may be described as a genus of intracellular parasitic protozoa. They are obligate parasites of insects (such as mosquitoes) and vertebrates and thus referred to as digenetic parasites.
They require two different hosts in order to complete their life cycle. In vertebrates, they multiply within liver cells and red cells where they not only obtain nourishment, but also damage the cells (thus causing diseases).
Plasmodium species capable of causing malaria include:
* The word "malaria" comes from two Italian words; "mal" meaning bad, and "aria" which means air.
* A mosquito infected by the parasite is not affected (nor does it die from malaria). This is because mosquitoes, unlike vertebrates, do not have red blood cells in which the parasite develops and thrive.
* Recently, researchers discovered that infecting female Anopheles stephensi caused significant reduction in the number of plasmodium in the midgut and salivary glands of the mosquito. This may, therefore, prove to be one of the best approaches of controlling the malaria parasite.
· Kingdom: Protista - The kingdom protista (protoctista) consists of various single-celled eukaryotes that can be found in both terrestrial and aquatic environments.
· Sub-kingdom: Protozoa - Sub-kingdom that consists of both free-living and parasitic single-celled organisms.
· Family: Plasmodiidae - This is a family of apicomplexan parasites
· Genus - plasmodium
· Species - vivax, malariae, falciparum, ovale
As compared to the other species, P. falciparum is the most virulent species in man. It's responsible for severe malaria (malignant malaria) which is characterized by irregular paroxysms and high fever and may cause death if not treated. The morphological characteristics of the parasite vary depending on the diagnostic form/stage.
The ring form of P. falciparum is found inside the red cells. It has a ring-shape, thus the name, and consists of a nucleus, cytoplasm as well as a central vacuole. Measuring about a fifth the diameter of erythrocytes, the ring forms have also been shown to be very thin and thus delicate.
* The ring form of the parasite also contains very few chromatic: 1 or 2.
Trophozoites - are small and may range between 1.25 and 1.5um in size. They also have a thin cytoplasm and may have a signet ring shape (particularly for the early trophozoites). In addition, they are vacuolated and contain a single nucleus.
Schizonts - Measuring between 4.5 to 5 um in diameter, schizonts occupy about two-thirds of a red cell. They are characterized by 2 or 4 merozoites (and may mature to contain as many as 30 merozoites) as well as pigments that appear dark upon staining. Schizonts of P. falciparum are also small and immobile representing the dividing form of the parasite.
* A merozoite refers to the amoeboid trophozoite that is produced by the dividing form of the parasite (Schizonts).
Gametocytes - are the sexual forms of the parasite and are characterized by a crescent shape (banana-shape). Being the sexual forms, there are both male and female forms of the parasite that are about one and a half the size of a normal red cell.
* Gametocytes are infectious to mosquitoes.
Sporozoites - are infective to humans and are characterized by a thick pellicle, a mitochondrion, a single nucleus as well as a sickle-shape that is often portrayed in books. They measure between 10 and 15 um in length and are capable of locomotion (made possible by peripheral fibers).
* The pellicle of sporozoites consist of double-membrane as well as an additional layer consisting of subpellicular microtubules.
Rings - Have a signet ring shape, P. vivax is characterized by a large cytoplasm that contains a large chromatin. As they develop, they start to become more amoeboid in shape. The ring form of the parasite is about a third the diameter of red cells.
Trophozoites - The trophozoites of P. vivax are characterized by a few dots of large chromatin, amoeboid cytoplasm as well as fine pigments (hematin) that are yellowish-brown in color.
Gametocytes - Unlike the trophozoites, P. vivax gametocytes are round and oval in shape and thus have a more defined shape. They are characterized by high amounts of brown pigments that scatter inside infected red cells.
Schizonts - The schizonts of P. vivax are characterized by 12 to 24 merozoites and are large enough to fill the entire cell (red cell). They are also characterized by a yellowish-brown pigment that can be seen under the microscope following staining.
Ring form - Of P. ovale is characterized by one or two large chromatin dots as well as a sturdy/thick cytoplasm. As they mature, the Schuffner's dots may develop.
Trophozoites - Like in the ring forms, the cytoplasm of trophozoites is sturdy with a few chromatin dots. They are also irregular, while some may appear to be more compact.
Gametocytes - The gametocytes have a well defined shape (round or oval) and are large enough to fill the red cells. They are characterized by a brown pigment that tends to be more coarse when compared to that of P. vivax.
Schizonts - With 6 to 14 merozoites, the schizonts of P. ovale are characterized by a mass of dark-brown pigment that is surrounded by large nuclei.
Apart from human beings, Plasmodium species also infect the following vertebrates:
As mentioned earlier, members of the genus plasmodium are digenetic. As such, they complete their life cycle in two hosts. This cycle consists of both sexual and asexual cycles that occur in the vector/mosquito and vertebrate respectively.
Given that all malaria parasites are digenetic, the life cycle of P. falciparum will be used to describe the general life cycle of plasmodium in this section.
According to research studies, the survival and development of plasmodium through all the life cycle processes made possible by well over 5,000 genes and associated proteins.
With the parasite going through various processes of reproduction and development in different hosts, these genes make it possible to complete these cycles, but also evade various responses of the host that may otherwise destroy them.
In the life cycle of plasmodium falciparum, a mosquito acts as the definitive host. As such, it supports the adult form of the parasite that is capable of sexual reproduction. Before the parasite is transmitted from the insect to the human host, gametocyte forms in the mosquito fuse in the gut of the organism to form the zygote.
Through molecular and cellular changes, the zygotes develop into ookinetes that are capable of active movement. This allows the parasite into the midgut of the mosquito from where it can later migrate to the salivary gland of the mosquito.
In the midgut, the oocysts go through further division and develop producing numerous sporozoites that contain a single set of chromosomes (haploid). In a period of between 8 and 15 days, the oocyst breaks open to release the sporozoites which allow them to migrate and invade the salivary glands of the insect.
When the infected mosquito starts feeding, using its proboscis to suck blood from a person, the sporozoites are injected into the skin thus causing an infection.
* According to research studies, mosquitoes that are infected with the parasite feed at a higher rate compared to uninfected ones. Moreover, they have been shown to have a higher survival rate.
* Following a mosquito bite, between 10 and several hundreds of sporozoites are injected into the bloodstream (through the skin) of the secondary host (man).
As compared to the mosquito, man is the secondary or intermediate host. As such, they are hosts to immature forms of the parasites that do not reproduce sexually. Once they are deposited into the skin, some of the sporozoites make it into the lymphatic system while others migrate and reach the blood vessels.
For the sporozoites that enter the bloodstream, this allows them to be transported to the liver. In some animals, they may first invade the spleen, macrophages or endothelial cells. In the liver, they invade the cells (hepatocytes) and proliferate to produce merozoites.
This is described as the pre-erythrocytic phase. Within the hepatocytes, the sporozoites have been shown to proliferate and grow in the parasitophorous vacuoles producing schizonts that may contain well over 30,000 merozoites. For Plasmodium falciparum, this phase may last between 5 and 6 days and is enhanced by the parasites' protein known as circumsporozoite protein.
* Before the merozoites are released into the bloodstream, they are enclosed within merosomes (vesicles) that protect them from some cells of the immune system particularly the Kupffer cells.
* In the bloodstream, sporozoites have been shown to use a type of movement referred to as stick-and-slip by using special proteins and actin-myosin motor. Using this movement, they continuously move towards the liver and process that may take several hours.
From the hepatocytes, merozoites are transported to the lungs (in the lung capillaries) from where they are released into the bloodstream. Using receptor-ligand interactions, merozoites released from the liver attach and invade red cells. This invasion has been shown to take less than a minute, which helps prevent the parasite from being exposed to immune cells.
Once the parasite is attached to a red cell, the cell membrane of the red cell is deformed to form a junction that allows the parasite to penetrate into the cell using a number of specialized protein structures. In the cell, the parasite, which starts taking a ring-like shape, creates a vacuole (parasitophorous vacuole) that separates it from the intracellular environment of the red cell.
In the red cells, hemoglobin in the primary source of nutrition. Following the breakdown of this molecule, amino acids are used for biosynthesis. This allows the parasite to continue proliferating and thus increasing in numbers. As a result, some red cells have been shown to also increase in size as the parasite continues to multiply inside.
The parasite continues dividing within the cell and goes through several stages that produce the trophozoites and ultimately the schizonts. As they increase in numbers, this causes the cell to burst thus releasing new merozoites that infect other red cells.
* As the parasites continue dividing (asexual reproduction) and increasing in numbers, some of the parasites develop into gametocyte forms. Unlike the asexual forms, the male and female gametocytes do not invade the cells (red cells).
They are also non-pathogenic and infect mosquitoes when the insect feeds on infected individuals. In the mosquito, the primary/definite host, the gametocytes fuse and continue the sexual phase of reproduction allowing the cycle to continue.
· Relatively high number of sporozoites - Studies have shown that tens to several hundreds of sporozoites are introduced into the skin during mosquito feeding. This allows some of the parasites to survive even when some are ingested by phagocytes.
· Plasmodium have a complex life cycle - Through various processes, a number of threats can affect this cycle. However, a number of adaptations have been shown to contribute to the processes thus allowing the parasite to thrive.
· Switching the expression of some proteins on and off - In 2007, researchers discovered that by switching the expression of some proteins on and off, P. falciparum are successfully able to enter the red cells of the intermediate host. According to the researchers, this action allows the parasite to adapt to the new environment (within the red cells) without negatively affecting the parasite.
· Changes in the surface proteins and metabolic pathways - The changes of surface proteins of the parasites, as well as their metabolic pathways, have been shown to protect the parasites from immune cells in the host. In some cases, this has also been shown to contribute to drug resistance.
· Sexual and asexual phases - Plasmodium species depend on two hosts to complete their life cycle. This is an important and beneficial adaptation that allows the parasites to survive within the host.
Whereas insects such as mosquito provide the right environment for sexual reproduction, the red cells of vertebrates provide the conducive environment for stages of asexual reproduction. This allows for a successful life cycle of the parasite.
· Motility - Using proteins known as TRAP (thrombospondin-related anonymous protein) and an actin-myosin motor, sporozoites in the bloodstream in the intermediate host are able to migrate and reach the hepatocytes where they undergo further development.
· Enter the red cells within a short period of time - Merozoites from hepatocytes contain surface proteins that allow them to attach and ultimately enter the red cells. However, these proteins also make it possible for phagocytes to identify and ingest them.
To avoid this, parasites use special structures produced by apical secretory organelles to penetrate the cell within a few seconds and avoid being ingested. Once in the cell, they also form a protective vacuole that separates them from the cell cytoplasm.
· Prevent immature rapture/bursting of red cells - As the parasite multiplies and increases in number within the red cells, the cells expand in size, which can cause them to burst. This can negatively affect further development of the parasites.
To prevent this, studies have shown there to be increased ingestion, digestion and detoxification rates of the hemoglobin in order to maintain osmotic stability. This prevents the cell from bursting even as the parasites increase in number allowing them to continue developing sufficiently.
Return to iPhone Microscope - looking at Malaria as an example
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Martin, K. Rono eta l. (2017). Adaptation of Plasmodium falciparum to its transmission environment. Nature, Ecology, and Evolution.
William E. Collins and Geoffrey M. Jeffery. (2007). Plasmodium malariae: Parasite and Disease. American Society for Microbiology. All Rights Reserved.
William E. Collins and Geoffrey M. Jeffery. (2005). Plasmodium ovale: Parasite and Disease. American Society for Microbiology.