Plasmodium Cynomolgi
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''Plasmodium cynomolgi'' is an apicomplexan
parasite Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson has ...
that infects mosquitoes and Asian
Old World monkey Old World monkey is the common English name for a family of primates known taxonomically as the Cercopithecidae (). Twenty-four genera and 138 species are recognized, making it the largest primate family. Old World monkey genera include baboons ...
s. In recent years, a number of natural infections of humans have also been documented. This species has been used as a model for human ''
Plasmodium vivax ''Plasmodium vivax'' is a protozoal parasite and a human pathogen. This parasite is the most frequent and widely distributed cause of recurring malaria. Although it is less virulent than ''Plasmodium falciparum'', the deadliest of the five huma ...
'' because ''Plasmodium cynomolgi'' shares the same life cycle and some important biological features with '' P. vivax''.


Life cycle

The life cycle of ''P. cynomolgi'' resembles that of other ''Plasmodium'' species, particularly the related human parasite ''
Plasmodium vivax ''Plasmodium vivax'' is a protozoal parasite and a human pathogen. This parasite is the most frequent and widely distributed cause of recurring malaria. Although it is less virulent than ''Plasmodium falciparum'', the deadliest of the five huma ...
''. Like other ''Plasmodium'' species, ''P. cynomolgi'' infects both an insect host and a
vertebrate Vertebrates () comprise all animal taxa within the subphylum Vertebrata () (chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with c ...
(generally
Old World monkey Old World monkey is the common English name for a family of primates known taxonomically as the Cercopithecidae (). Twenty-four genera and 138 species are recognized, making it the largest primate family. Old World monkey genera include baboons ...
s). The parasite is transmitted when the mosquito host takes a blood meal from the vertebrate host. During the feeding, motile parasites called
sporozoite Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism is ...
s are injected from the mosquito salivary gland into the host tissue. These sporozoites move into the bloodstream and infect cells in the host
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
, where they grow and divide over the course of approximately one week. At this point, the parasitized liver cells rupture, releasing thousands of parasite daughter cells, called
merozoite Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism is ...
s, which either move into the bloodstream to infect
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s, or remain in the liver to reinfect liver cells. Those that reinfect liver cells form a quiescent stage called a
hypnozoite ''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 verte ...
, which can remain dormant in the liver cell for months or years before reactivating. The merozoites that enter the bloodstream infect
red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
s, where they grow and replicate. After approximately 48 hours, the infected red blood cell bursts, allowing the daughter merozoites to infect new red blood cells. This cycle can continue indefinitely. Occasionally, after infection of a red blood cell, the parasite develops into one of two distinct sexual forms called male and female
gametocyte A gametocyte is a eukaryotic germ cell that divides by mitosis into other gametocytes or by meiosis into gametids during gametogenesis. Male gametocytes are called ''spermatocytes'', and female gametocytes are called ''oocytes''. Development ...
s (also micro and macrogametocytes respectively). If a mosquito takes a blood meal containing a gametocyte of each sex, the two sexual stages merge and form a
zygote A zygote (, ) is a eukaryotic cell formed by a fertilization event between two gametes. The zygote's genome is a combination of the DNA in each gamete, and contains all of the genetic information of a new individual organism. In multicell ...
. The zygote develops into a motile stage called the
ookinete Apicomplexans, a group of intracellular parasites, have life cycle stages that allow them to survive the wide variety of environments they are exposed to during their complex life cycle. Each stage in the life cycle of an apicomplexan organism i ...
which penetrates the wall of the mosquito gut and forms a stationary oocyst. The oocyst develops over about 11 days, then begins to release thousands of sporozoites into the mosquito's
hemolymph Hemolymph, or haemolymph, is a fluid, analogous to the blood in vertebrates, that circulates in the interior of the arthropod (invertebrate) body, remaining in direct contact with the animal's tissues. It is composed of a fluid plasma in which ...
. The sporozoites move through the hemolymph and infect the mosquito salivary glands, where they will again be injected into a mammalian host when the mosquito takes a blood meal.


Description

''P. cynomolgi'' closely resembles the human parasite ''P. vivax'' throughout its life cycle. Similar to ''P. vivax'', ''P. cynomolgi'' infection changes the red blood cell membrane structure, causing surface perturbations that appear as pink dots (called Schüffner's dots) when stained with
Giemsa Giemsa stain (), named after German chemist and bacteriologist Gustav Giemsa, is a nucleic acid stain used in cytogenetics and for the histopathological diagnosis of malaria and other parasites. Uses It is specific for the phosphate groups of ...
.


Ecology and distribution

''P. cynomolgi'' is found throughout Southeast Asia where it naturally infects a variety of macaque monkeys, including '' Macaca cyclopis'', ''
Macaca fascicularis The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque and referred to as the cynomolgus monkey in laboratories, is a cercopithecine primate native to Southeast Asia. A species of macaque, the crab-eating macaque ...
'', ''
Macaca mulatta The rhesus macaque (''Macaca mulatta''), colloquially rhesus monkey, is a species of Old World monkey. There are between six and nine recognised subspecies that are split between two groups, the Chinese-derived and the Indian-derived. Generally ...
'', '' Macaca nemestrina'', '' Macaca radiata'', '' Macaca sinica'', '' Trachypithecus cristatus'', and '' Semnopithecus entellus''. The effect of infection on primate hosts has primarily been studied in rhesus monkeys, where ''P. cynomolgi'' generally causes mild and self-limiting illness. Monkeys can suffer
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
and
thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients a ...
as well as occasional kidney inflammation, however all generally resolve without treatment. The exception to this is in pregnant monkeys, where ''P. cynomolgi'' infection can be severe, resulting in death of the mother and fetus without
antimalarial Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young ...
treatment. Infection of humans with ''P. cynomolgi'' was once thought to be exceedingly rare. However, documented cases of natural infection in humans have become more common in recent years, and initial misdiagnoses has led those researchers to theorize that other natural cases are being misidentified as ''P. vivax'' due to their morphological similarities''.'' Current evidence suggests that natural transmission is typically simian to human by a mosquito vector, but transmission of ''P. cynomolgi'' from human to human by a mosquito vector has also been shown in laboratory experiments. ''P. cynomolgi'' also infects a broad variety of ''
Anopheles ''Anopheles'' () is a genus of mosquito first described and named by J. W. Meigen in 1818. About 460 species are recognised; while over 100 can transmit human malaria, only 30–40 commonly transmit parasites of the genus ''Plasmodium'', which ...
'' mosquitoes; the effect of infection on these mosquitoes is not known.


Taxonomy and evolution

''P. cynomolgi'' is in the genus ''
Plasmodium ''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 ver ...
'', which contains all Apicomplexan parasites that undergo asexual reproduction through schizogony and digest red blood cell hemoglobin to produce the crystalline pigment
hemozoin Haemozoin is a disposal product formed from the digestion of blood by some blood-feeding parasites. These hematophagous organisms such as malaria parasites (''Plasmodium spp.''), ''Rhodnius'' and ''Schistosoma'' digest haemoglobin and release high ...
. Within ''Plasmodium'', ''P. cynomolgi'' is in the subgenus ''Plasmodium'', containing all species of ''Plasmodium'' that infect primates (except for some that infect the
Great Ape The Hominidae (), whose members are known as the great apes or hominids (), are a taxonomic family of primates that includes eight extant species in four genera: '' Pongo'' (the Bornean, Sumatran and Tapanuli orangutan); ''Gorilla'' (the ...
s, which are in the subgenus ''
Laverania ''Laverania'' is a subgenus of the parasite genus ''Plasmodium''. Infection with these species results in malaria. The subgenus was first described in 1958. The name was first proposed by Welch in 1897 as a genus name for the group now known as ...
''). Evolutionarily, ''P. cynomolgi'' is most closely related to the other ''Plasmodium'' species that infect monkeys, as well as ''P. vivax'' which infects humans. Evolutionary relationships among ''Plasmodium'' species have been inferred from
ribosomal RNA Ribosomal ribonucleic acid (rRNA) is a type of non-coding RNA which is the primary component of ribosomes, essential to all cells. rRNA is a ribozyme which carries out protein synthesis in ribosomes. Ribosomal RNA is transcribed from ribosom ...
sequencing, and are summarized in the cladogram below:


Research

''P. cynomolgi'' is the second-most studied malaria parasite of non-human primates after ''
Plasmodium knowlesi ''Plasmodium knowlesi'' is a parasite that causes malaria in humans and other primates. It is found throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Like other ''Plasmodium'' species, ''P. knowlesi'' has a li ...
'', primarily due to its similarity to the human parasite ''P. vivax''. In particular, ''P. cynomolgi'' is used as a model for
hypnozoite ''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 verte ...
biology as it (along with ''P. vivax'') is one of the few ''Plasmodium'' species known to have this lifecycle stage. ''P. cynomolgi'' can infect a variety of monkey species and can be transmitted by several common laboratory-grown mosquitoes. Due to this, ''P. cynomolgi'' has been used in research on a broad variety of malaria topics including hypnozoite biology, host immune responses to infection, and to test the efficacy of antimalarial drugs and vaccines.


History

''P. cynomolgi'' was first observed in 1905 in the blood of the
long-tailed macaque The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque and referred to as the cynomolgus monkey in laboratories, is a cercopithecine primate native to Southeast Asia. A species of macaque, the crab-eating macaque ...
.


References

{{Taxonbar, from=Q12505741 cynomolgi