Plasmodium - WikiHQ

Plasmodium is a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects. The life cycles of Plasmodium species involve development in a blood-feeding insect host which then injects parasites into a vertebrate host during a blood meal. Parasites grow within a vertebrate body tissue (often the liver) before entering the bloodstream to infect red blood cells. The ensuing destruction of host red blood cells can result in malaria. During this infection, some parasites are picked up by a blood-feeding insect (mosquitoes in majority cases), continuing the life cycle.

Plasmodium is a member of the phylum Apicomplexa, a large group of parasitic eukaryotes. Within Apicomplexa, Plasmodium is in the order Haemosporida and family Plasmodiidae. Over 200 species of Plasmodium have been described, many of which have been subdivided into 14 subgenera based on parasite morphology and host range. Evolutionary relationships among different Plasmodium species do not always follow taxonomic boundaries; some species that are morphologically similar or infect the same host turn out to be distantly related.

Species of Plasmodium are distributed globally wherever suitable hosts are found. Insect hosts are most frequently mosquitoes of the genera Culex and Anopheles. Vertebrate hosts include reptiles, birds, and mammals. Plasmodium parasites were first identified in the late 19th century by Charles Laveran. Over the course of the 20th century, many other species were discovered in various hosts and classified, including five species that regularly infect humans: P. vivax, P. falciparum, P. malariae, P. ovale, and P. knowlesi. P. falciparum is by far the most lethal in humans, resulting in hundreds of thousands of deaths per year. A number of drugs have been developed to treat Plasmodium infection; however, the parasites have evolved resistance to each drug developed.

Although the parasite can also infect people via blood transfusion, this is very rare, and Plasmodium cannot be spread from person to person. Some subspecies of Plasmodium are obligate intracellular parasites.

Description

thumb|Plasmodium is a [[eukaryote but with unusual features.]]

The genus Plasmodium consists of all eukaryotes in the phylum Apicomplexa that both undergo the asexual replication process of merogony inside host red blood cells and produce the crystalline pigment hemozoin as a byproduct of digesting host hemoglobin. Attached to the nucleus is the endoplasmic reticulum (ER), which functions similarly to the ER in other eukaryotes. Proteins are trafficked from the ER to the Golgi apparatus which generally consists of a single membrane-bound compartment in Apicomplexans. From here, proteins are trafficked to various cellular compartments or to the cell surface. Adjacent to the rhoptries are smaller structures termed micronemes that contain parasite proteins required for motility as well as recognizing and attaching to host cells. Spread throughout the parasite are secretory vesicles called dense granules that contain parasite proteins involved in modifying the membrane that separates the parasite from the host, termed the parasitophorous vacuole. Like in other eukaryotes, the Plasmodium mitochondrion is capable of generating energy in the form of ATP via the citric acid cycle; however, this function is only required for parasite survival in the insect host, and is not needed for growth in red blood cells. The apicoplast is involved in the synthesis of various metabolic precursors, including fatty acids, isoprenoids, iron-sulphur clusters, and components of the heme biosynthesis pathway.

Life cycle

thumb|right|Life cycle of a species that infects humans

right|thumb|Ring forms of Plasmodium inside human red blood cells ([[Giemsa stain)]]

The life cycle of Plasmodium involves several distinct stages in the insect and vertebrate hosts. Parasites are generally introduced into a vertebrate host by the bite of an insect host (generally a mosquito, with the exception of some Plasmodium species of reptiles). Parasites first infect the liver or other tissue, where they undergo a single large round of replication before exiting the host cell to infect erythrocytes. At this point, some species of Plasmodium of primates can form a long-lived dormant stage called a hypnozoite, which can remain in the liver for more than a year. However, for most Plasmodium species, the parasites in infected liver cells are only what are called merozoites. After emerging from the liver, they enter red blood cells, as explained above. They then go through continuous cycles of erythrocyte infection, while a small percentage of parasites differentiate into a sexual stage called a gametocyte which is picked up by an insect host taking a blood meal. In some hosts, invasion of erythrocytes by Plasmodium species can result in disease, called malaria. This can sometimes be severe, rapidly followed by death of the host (e.g. P. falciparum in humans). In other hosts, Plasmodium infection can apparently be asymptomatic.

thumb|upright|[[Sporozoites, one of several different forms of the parasite, from a mosquito]]

Within the red blood cells, the merozoites grow first to a ring-shaped form and then to a larger form called a trophozoite. Trophozoites then mature to schizonts which divide several times to produce new merozoites. The infected red blood cell eventually bursts, allowing the new merozoites to travel within the bloodstream to infect new red blood cells. Most merozoites continue this replicative cycle, however some merozoites upon infecting red blood cells differentiate into male or female sexual forms called gametocytes. These gametocytes circulate in the blood until they are taken up when a mosquito feeds on the infected vertebrate host, taking up blood which includes the gametocytes. Within Apicomplexa, Plasmodium is within the order Haemosporida, a group that includes all apicomplexans that live within blood cells. Based on the presence of the pigment hemozoin and the method of asexual reproduction, the order is further split into four families, of which Plasmodium is in the family Plasmodiidae. These species have been categorized on the basis of their morphology and host range into 14 subgenera:

Subgenus Asiamoeba (Telford, 1988) – reptiles
Subgenus Bennettinia (Valkiunas, 1997) – birds
Subgenus Carinamoeba (Garnham, 1966) – reptiles
Subgenus Giovannolaia (Corradetti, et al. 1963) – birds
Subgenus Haemamoeba (Corradetti, et al. 1963) – birds
Subgenus Huffia (Corradetti, et al. 1963) – birds
Subgenus Lacertamoeba (Telford, 1988) – reptiles
Subgenus Laverania (Bray, 1958) – great apes, humans
Subgenus Novyella (Corradetti, et al. 1963) – birds
Subgenus Ophidiella (Telford, 1988) – reptiles
Subgenus Paraplasmodium (Telford, 1988) – reptiles
Subgenus Plasmodium (Bray, 1955) – monkeys and apes
Subgenus Sauramoeba (Garnham, 1966) – reptiles
Subgenus Vinckeia (Garnham, 1964) – mammals inc. primates

Species infecting monkeys and apes with the exceptions of P. falciparum and P. reichenowi (which together make up the subgenus Laverania) are classified in the subgenus Plasmodium. Parasites infecting other mammals including some primates (lemurs and others) are classified in the subgenus Vinckeia. The five subgenera Bennettinia, Giovannolaia, Haemamoeba, Huffia, and Novyella contain the known avian malarial species. The remaining subgenera: Asiamoeba, Carinamoeba, Lacertamoeba, Ophidiella, Paraplasmodium, and Sauramoeba contain the diverse groups of parasites found to infect reptiles. Many Plasmodium species that are morphologically similar or infect the same hosts turn out to be only distantly related. In the 1990s, several studies sought to evaluate evolutionary relationships of Plasmodium species by comparing ribosomal RNA and a surface protein gene from various species, finding the human parasite P. falciparum to be more closely related to avian parasites than to other parasites of primates.

Estimates for when different Plasmodium lineages diverged have differed broadly. Estimates for the diversification of the order Haemosporida range from around 16.2 million to 100 million years ago.]]

Plasmodium parasites have been described in a broad array of vertebrate hosts including reptiles, birds, and mammals.

Humans are primarily infected by five species of Plasmodium, with the overwhelming majority of severe disease and death caused by Plasmodium falciparum. Some species that infect humans can also infect other primates, and zoonoses of certain species (e.g. P. knowlesi) from other primates to humans are common. Many other mammals also carry Plasmodium species, such as a variety of rodents, ungulates, and bats. Again, some species of Plasmodium can cause severe disease in some of these hosts, while many appear not to.

Over 150 species of Plasmodium infect a broad variety of birds. In general each species of Plasmodium infects one to a few species of birds. Plasmodium parasites that infect birds tend to persist in a given host for years or for the life time of the host, although in some cases Plasmodium infections can result in severe illness and rapid death. Unlike with Plasmodium species infecting mammals, those infecting birds are distributed across the globe. Again, parasites can result either in severe disease or be apparently asymptomatic depending on the parasite and the host. Resistance to quinine spurred the development of a broad array of antimalarial medications through the 20th century including chloroquine, proguanil, atovaquone, sulfadoxine/pyrimethamine, mefloquine, and artemisinin. In general, antimalarial drugs target the life stages of Plasmodium parasites that reside within vertebrate red blood cells, as these are the stages that tend to cause disease. However, drugs targeting other stages of the parasite life cycle are under development in order to prevent infection in travelers and to prevent transmission of sexual stages to insect hosts.

File:Saving_Lives_with_SMS_for_Life.jpg|A clinic for treating human malaria in Tanzania

File:Anolis carolinensis.jpg|Over 3000 species of lizard, including the Carolina anole (Anolis carolinensis), carry some 90 kinds of malaria.

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Insects

thumb|The mosquito [[Anopheles stephensi is among the blood-feeding insects that can be infected by a species of Plasmodium.]]

In addition to a vertebrate host, all Plasmodium species also infect a bloodsucking insect host, generally a mosquito (although some reptile-infecting parasites are transmitted by sandflies). Mosquitoes of the genera Culex, Anopheles, Culiseta, Mansonia and Aedes act as insect hosts for various Plasmodium species. The best studied of these are the Anopheles mosquitoes which host the Plasmodium parasites of human malaria, as well as Culex mosquitoes which host the Plasmodium species that cause malaria in birds. Only female mosquitoes are infected with Plasmodium, since only they feed on the blood of vertebrate hosts. Different species affect their insect hosts differently. Sometimes, insects infected with Plasmodium have reduced lifespan and reduced ability to produce offspring. Further, some species of Plasmodium appear to cause insects to prefer to bite infected vertebrate hosts over non-infected hosts.

History

Charles Louis Alphonse Laveran first described parasites in the blood of malaria patients in 1880. He named the parasite Oscillaria malariae.