The genus Plasmodium is a member of the order Haemosporidia. It is the largest genus within this order and currently consists of over 250 species. They cause malaria in many different vertebrates.

The species in this genus are entirely parasitic with part of their life cycle spent in a vertebrate host and another in an invertebrate host - usually a mosquito. Vertebrates infected by members of this genus include mammals, birds and reptiles.

Host range among the mammalian orders is non uniform. At least 29 species infect non human primates; rodents outside the tropical parts of Africa are rarely affected; a few species are known to infect bats, porcupines and squirrels; carnivores, insectivores and marsupials are not known to act as hosts.

The listing of host species among the reptiles has rarely been attempted. Ayala in 1978 listed 156 published accounts on 54 valid species and subspecies between 1909 and 1975. The regional breakdown was Africa: 30 reports on 9 species; Australia, Asia and Oceania: 12 reports on 6 species and 2 subspecies; Americas: 116 reports on 37 species.

Diagnostic criteria of the order Haemosporida Currently there are ~550 species recognised in this order organised into 17 genera.

The diagnostic criteria of this family are:

macrogametes and microgamonts develop independently syzygy is absent microgametocyte produces 8 flagellated microgametes zygote is motile (known as an ookinete) conoid present in ookinete stage only sporozoites naked in oocyst (that is without a sporocyst) heteroxenous: merogony and gamogony occur in vertebrate host and fertilization and sporogony in definitive host (a blood sucking insect) hemozoin pigment produced in some genera (including Plasmodium)

Diagnostic criteria of the genus Plasmodium Merogony occurs both in erythrocytes and other tissues Merozoites, schizonts or gametocytes can be seen within erythrocytes and may displace the host nucleus Merozoites have a "signet-ring" appearance due to a large vacuole that forces the parasite's nucleus to one pole Schizonts are round to oval inclusions that contain the deeply staining merozoites Forms gamonts in erythrocytes Gametocytes are 'halter-shaped' similar to Haemoproteus but the pigment granules are more confined Hemozoin is present Vectors are either mosquitoes or sandflies (Lutzomyia). Vertebrate hosts include mammals, birds and reptiles

Note Mammalian erythrocytes do not possess a nucleus. Although it has been suggested that the nucleus was lost in the erythrocytes better to enable them to traverse capillaries evidence for this is lacking. It appears that this loss along with the mitochondria that the erythrocytes also lose may protect the erythrocytes against oxidative stress.

Subgenera The full taxonomic name of a species includes the subgenus but this is often omitted in practice. The full name indicates some features of the morphology and type of host species. Sixteen subgenera are currently recognised.

The avian species were discovered soon after the description of P. falciparum and a variety of generic names were created. These were subsequently placed into the genus Plasmodium although some workers continued to use the genera Laverinia and Proteosoma for P. falciparum and the avian species respectively.

The 5th and 6th Congresses of Malaria held at Istanbul (1953) and Lisbon (1958) respectively recommended the creation and use of subgenera in this genus. Laverinia was applied to the species infecting humans and Haemamoeba to those infecting lizards and birds. This proposal was not universally accepted. Bray in 1955 proposed a definition for the subgenus Plasmodium and a second for the subgenus Laverinia in 1958. Garnham described a third subgenus - Vinckeia - in 1964.

In 1963 Corradetti, Garnham and Laird proposed a new classification of the avian malaria parasites. They created four sub-genera - Giovannolaia, Haemamoeba, Huffia and Novyella - based on the size of the schizonts, the gametocyte forms and the type of exo-erythrocytic schizogony.

Additional subgenera have been created since.

The currently recognised subgenera are listed below.

Asiamoeba Telford 1988 Bennettinia Valkiūnas 1997Valkiunas G. (1997). Bird Haemosporidia. Institute of Ecology, Vilnius Carinamoeba Garnham 1966 Giovannolaia Corradetti, Garnham & Laird 1963 Haemamoeba Grassi & Feletti 1890 Huffia Garnham & Laird 1963 Lacertamoeba Telford 1988 Laverania Bray 1958 Novyella Corradetti, Garnham & Laird 1963 Nyssorhynchus Poinar 2005 Ophidiella Garnham 1966 Papernaia Landau et al 2010 Paraplasmodium Telford 1988 Plasmodium Bray 1963 emend. Garnham 1964 Sauramoeba Garnham 1966 Vinckeia Garnham 1964

Classification criteria for subgenera The current classification scheme was developed prior to the widespread use of DNA sequence based taxonomy and is based on host and morphological criteria. Plasmodium has since been shown to be paraphytic with the genera Haemoproteus and Hepatocystis (vide infra). Revision of this genus will be undertaken once sufficient DNA sequence material is available.

This forthcoming reclassification project is not unique to this genus as DNA based taxonomy is revising many traditional groupings of protozoa.

The bird infecting taxa can be separated into two groups on the basis of the gametocytes: species with round gametocytes (Bennettinia, Haemamoeba) and species with elongated gametocytes (Giovanniola, Huffia and Novyella). The monophyly of the Bennettinia, Haemamoeba and Huffia subgenera was subsequently confirmed by molecular studies. The other two genera were found to be paraphytic. The genera were then revised and a new subgenus - Papernaia - was created.

Species with mammalian hosts Laverania

Species in this subgenus infect higher primates (including man) and have characteristic sickle shaped female gametocytes.

The type species is Plasmodium falciparum.

Plasmodium

Species infecting higher primates other than those in the subgenus Laverania are placed in the subgenus Plasmodium.

The type species is Plasmodium malariae.

Vinckeia

Parasites infecting other mammals including lower primates (lemurs and others) are classified in the subgenus Vinckeia.

The type species is Plasmodium bubalis.

Species with avian hosts Bennettinia

Schizonts contain scant cytoplasm, are often round, do not exceed the size of the host nucleus and stick to it. Gametocytes, while varying in shape tend to be round or oval, do not exceed the size of the nucleus and stick to it.

The type species is Plasmodium juxtanucleare.

Giovannolaia

Schizonts contain plentiful cytoplasm, are larger than the host cell nucleus and frequently displace it. They are found only in mature erythrocytes. Gametocytes are elongated. Exoerythrocytic schizogony occurs in the mononuclear phagocyte system.

The type species is Plasmodium circumflexum.

Haemamoeba

Mature schizonts are larger than the host cell nucleus and commonly displace it. Gametocytes are large, round, oval or irregular in shape and are substantially larger than the host nucleus.

The type species is Plasmodium relictum.

Huffia

Mature schizonts, while varying in shape and size, contain plentiful cytoplasm and are commonly found in immature erythryocytes. Gametocytes are elongated.

The type species is Plasmodium elongatum.

Novyella

Mature schizonts are either smaller than or only slightly larger than the host nucleus. They contain scanty cytoplasm. Gametocytes are elongated. Sexual stages in this subgenus resemble those of Haemoproteus. A white/blue globule is present in the cytoplasm. Exoerythrocytic schizogony occurs in the mononuclear phagocyte system

The type species is Plasmodium vaughani.

Papernaia

The gametocytes are elongated. The schizonts apically or lateroapically placed and are rounded or irregularly shaped. The host nucleus may be tilted.

The type species is Plasmodium polare

Species with reptilian hosts Although over 3200 species of lizard have been identified as hosts to Plasmodium species, only 29 species of snakes have been. All snake infecting species are placed into the subgenus Ophidiella.

Asiamoeba

The schizonts and gametocytes are greatly disparate in size (4 to 15 times).

Carinamoeba

The schizonts are small and give rise to 8 or fewer merozoites. The gametocytes like the schizonts are small.

The type species is Plasmodium minasense.

Lacertamoeba

The schizonts are medium-sized and undergo 3 to 5 nuclear divisions. The gametocytes are medium-sized

Paraplasmodium

The schizonts are of medium size. Exoerythrocytic schizonts may be produced in both fixed and wandering host cells. The gametocytes are large. One species in this sub-genus is capable of merogony in a vector of the genus Lutzomyia.

Sauramoeba

Large schizonts giving rise to 12 or more merozoites. The gametocytes like the schizonts are large. The asexual stages tend to disappear from the lymphocytes once the gametocytes appear in the lymphocytes.

The type species is Plasmodium agamae.

Ophidiella

The species in this subgenus infect only snakes.

The type species is Plasmodium weyoni.

Species with unknown hosts One species has been identified from Dominican amber - Plasmodium dominicum. The vertebrate host of this species is unknown but it seems likely that it may have been a bird.

Nyssorhynchus

The type species is Plasmodium dominicum.

Phylogenetics Although the evolution of this genus has been studied by a number of authors, details are still being elucidated. A brief summary of the pattern that has emerged is as follows:

The most basal split in the genus is between the reptile/bird species and the mammalian species. The bird/reptile clade appears to be related to the genera Haemoproteus, Leukocytozoon and Polychromophilus. The genus Hepatocystis appears to have evolved from with the mammalian species clade. Within the mammalian species the subgenus Laverinia appears to be basal with the subgenus Plasmodium and the rodent species being sister clades. Hepatocystis appears to have diverged after the separation of the rodent species. The species infecting lemurs may belong in the subgenus Plasmodium instead of their current placement within the subgenus Vinckeia.

Within the subgenus Plasmodium, P. vivax groups with an Asian clade which appears to be rooted in Africa. P. malaria and P. ovale both belong to an African clade and are more closely related to each other than to P. vivax. Within the subgenus Laverinia P. falciparum and P. reichenowi form a clade while the other four known species form a second clade.

There are a number of additional species in these taxa that await full description so changes to the branching order are likely. However the overall arrangement outlined above seems to be supported by a number of studies by different authors and is unlikely to change. Given the recently recognised paraphytic nature of several of the taxa above, the introduction of new genera and possibly families in the near future seems highly likely.

Relations with other Haemosporidian genera

While most phylogenetic trees have tended to agree that Plasmodium has descended from Leukocytozoon or Haemoproteus like species a Bayesian phylogenetic reconstruction suggests that Plasmodium may be the ancestral genus that has given rise to Haemoproteus and other genera. Further study in this area is required.