Plasmodium ovale
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''Plasmodium ovale'' is a species of
parasitic 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 ha ...
protozoon that causes tertian
malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. ...
in humans. It is one of several species of ''
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 ve ...
'' parasites that infect humans, including ''
Plasmodium falciparum ''Plasmodium falciparum'' is a unicellular protozoan parasite of humans, and the deadliest species of ''Plasmodium'' that causes malaria in humans. The parasite is transmitted through the bite of a female '' Anopheles'' mosquito and causes the ...
'' and ''
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 ...
'' which are responsible for most cases of malaria in the world. ''P. ovale'' is rare compared to these two parasites, and substantially less dangerous than ''P. falciparum''. ''P. ovale'' has recently been shown by genetic methods to consist of what is considered to be two species (despite having been given subspecies names), namely '' P. ovale curtisi'' and '' P. ovale wallikeri''.


History

This species was first described in 1914 by
Stephens Stephens is a surname. It is a patronymic and is recorded in England from 1086. Notable people with the surname include: *Alexander H. Stephens (1812–1883), Vice President of the Confederate States of America *Alison Stephens (1970–2010), Brit ...
in a blood sample taken in the autumn of 1913 from a patient in the sanitarium of Pachmari in central India and sent by Major W. H. Kenrick to Stephens (who was working in
Liverpool Liverpool is a City status in the United Kingdom, city and metropolitan borough in Merseyside, England. With a population of in 2019, it is the List of English districts by population, 10th largest English district by population and its E ...
).


Epidemiology

''P. ovale'' is primarily concentrated in
sub-Saharan Africa Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the List of sov ...
and islands in the western Pacific. However ''P. ovale'' has also been reported in the
Philippines The Philippines (; fil, Pilipinas, links=no), officially the Republic of the Philippines ( fil, Republika ng Pilipinas, links=no), * bik, Republika kan Filipinas * ceb, Republika sa Pilipinas * cbk, República de Filipinas * hil, Republ ...
, eastern
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, and
Papua New Guinea Papua New Guinea (abbreviated PNG; , ; tpi, Papua Niugini; ho, Papua Niu Gini), officially the Independent State of Papua New Guinea ( tpi, Independen Stet bilong Papua Niugini; ho, Independen Stet bilong Papua Niu Gini), is a country i ...
, as well as in
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,
Cambodia Cambodia (; also Kampuchea ; km, កម្ពុជា, UNGEGN: ), officially the Kingdom of Cambodia, is a country located in the southern portion of the Indochinese Peninsula in Southeast Asia, spanning an area of , bordered by Thailand ...
,
India India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the List of countries and dependencies by area, seventh-largest country by area, the List of countries and dependencies by population, second-most populous ...
, Myanmar,
Thailand Thailand ( ), historically known as Siam () and officially the Kingdom of Thailand, is a country in Southeast Asia, located at the centre of the Indochinese Peninsula, spanning , with a population of almost 70 million. The country is b ...
and
Vietnam Vietnam or Viet Nam ( vi, Việt Nam, ), officially the Socialist Republic of Vietnam,., group="n" is a country in Southeast Asia, at the eastern edge of mainland Southeast Asia, with an area of and population of 96 million, making ...
In several studies, the reported prevalence of ''P. ovale'' was low relative to other malaria parasites, with fewer than 5% of malaria cases being associated with ''P. ovale'' infection. Higher prevalences of ''P. ovale'' are possible under certain conditions, as at least one study in Cameroon found the prevalence of ''P. ovale'' infection to be greater than 10%. It has been estimated that there are about 15 million cases of infection each year with this parasite. While similar to ''P. vivax'', ''P. ovale'' is able to infect individuals who are negative for the
Duffy Duffy may refer to: People *Duffy (surname), people with the surname Duffy or Duffey * Duffy (nickname) *Duffy (singer) (born 1984), Welsh singer, born Aimee Ann Duffy Places *Duffy, Australian Capital Territory, a suburb of Canberra * Duffy, Ohi ...
blood group, which is the case for many residents of sub-Saharan Africa. This has been said to explain the greater prevalence of ''P. ovale'' (versus ''P. vivax'') in most of Africa. However, low-parasitaemia or subpatent ''P. vivax'' cases might be more prevalent in Africa than has been thought.


Clinical features

In humans, symptoms generally appear 12 to 20 days after the parasite has entered the blood. In the blood, the parasite's replication cycle lasts approximately 49 hours, causing tertian fever which spikes approximately every 49 hours as newly replicated parasites erupt out of red blood cells. Mean maximum parasite levels have been found to be 6,944/microl for sporozoite-induced infections and 7,310/microl for trophozoite-induced infections. In some cases, relapse may occur up to 4 years after infection.


Diagnosis

The microscopic appearance of ''P. ovale'' is very similar to that of ''P. vivax'' and if there are only a small number of parasites seen, it may be impossible to distinguish the two species on morphological grounds alone. There is no difference between the medical treatment of ''P. ovale'' and ''P. vivax'', and therefore some laboratory diagnoses report "''P. vivax/ovale''", which is perfectly acceptable as treatment for the two is very similar.
Schüffner's dots Schüffner's dots refers to a hematological finding that is associated with malaria, exclusively found in infections caused by ''Plasmodium ovale'' or ''Plasmodium vivax''. ''Plasmodium vivax'' induces morphologic alterations in infected host ery ...
are seen on the surface of the parasitised
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 "hol ...
, but these are larger and darker than in ''P. vivax'' and are sometimes called James' dots or James' stippling. About twenty percent of the parasitised cells are oval in shape (hence the species name) and some of the oval cells also have fimbriated edges (the so-called "comet cell"). The mature schizonts of ''P. ovale'' never have more than twelve nuclei within them and this is the only reliable way of distinguishing between the two species. '' P. vivax'' and ''P. ovale'' that have been sitting in
EDTA Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes ev ...
for more than half an hour before the blood film is made will look very similar in appearance to '' P. malariae'', which is an important reason to warn the laboratory immediately when the blood sample is drawn so they can process the sample as soon as it arrives. Molecular tests (tests that detect DNA in blood) must take into account the fact that there are two ''P. ovale sensu lato'' taxa. Tests designed for one will not necessarily detect the other.


Treatment

Standard treatment is concurrent treatment with
chloroquine Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...
and
primaquine Primaquine is a medication used to treat and prevent malaria and to treat ''Pneumocystis'' pneumonia. Specifically it is used for malaria due to ''Plasmodium vivax'' and '' Plasmodium ovale'' along with other medications and for prevention if oth ...
. The combination atovaquone-proguanil may be used in those patients who are unable to take
chloroquine Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...
for whatever reason. An overdose on
Chloroquine Chloroquine is a medication primarily used to prevent and treat malaria in areas where malaria remains sensitive to its effects. Certain types of malaria, resistant strains, and complicated cases typically require different or additional medi ...
can be very dangerous and can result in death.


Phylogenetics

Among the species infecting the great apes, '' Plasmodium schwetzi'' morphologically appears to be the closest relation to ''P.ovale''. this had not been confirmed by DNA studies. The original species has been shown to be two morphologically identical forms – ''
Plasmodium ovale curtisi ''Plasmodium ovale curtisi'' is a subspecies of parasite, parasitic protozoa that causes tertian malaria in humans. The subspecies was described in 2010 when it was established that the two subspecies of ''Plasmodium ovale,'' while morphologicall ...
'' and ''
Plasmodium ovale wallikeri ''Plasmodium ovale wallikeri'' is a subspecies of parasitic protozoa that causes tertian malaria in humans. The subspecies was described in 2010 when it was established that the two subspecies of ''Plasmodium ovale,'' while morphologically identi ...
'' – which can be differentiated only by genetic means. Both species have been identified in
Ghana Ghana (; tw, Gaana, ee, Gana), officially the Republic of Ghana, is a country in West Africa. It abuts the Gulf of Guinea and the Atlantic Ocean to the south, sharing borders with Ivory Coast in the west, Burkina Faso in the north, and Tog ...
,
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,
Nigeria Nigeria ( ), , ig, Naìjíríyà, yo, Nàìjíríà, pcm, Naijá , ff, Naajeeriya, kcg, Naijeriya officially the Federal Republic of Nigeria, is a country in West Africa. It is situated between the Sahel to the north and the Gulf o ...
,
São Tomé São Tomé is the capital and largest city of the Central African island country of São Tomé and Príncipe. Its name is Portuguese for " Saint Thomas". Founded in the 15th century, it is one of Africa's oldest colonial cities. History Álvar ...
,
Sierra Leone Sierra Leone,)]. officially the Republic of Sierra Leone, is a country on the southwest coast of West Africa. It is bordered by Liberia to the southeast and Guinea surrounds the northern half of the nation. Covering a total area of , Sierr ...
and
Uganda }), is a landlocked country in East Africa. The country is bordered to the east by Kenya, to the north by South Sudan, to the west by the Democratic Republic of the Congo, to the south-west by Rwanda, and to the south by Tanzania. The ...
. The separation of the lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. A second analysis suggests that these species separated (95% confidence interval 0.5 – 7.7 Mya). A third worked sequenced the whole genome of both species, confirmed the differences and dated the split at around million years. Although dating is always difficult, the authors date that split to be 5 times older than the ''P. falciparum'' and ''P. reichenowi'' split. These species appear to be more closely related to '' Plasmodium malariae'' than to ''
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 ...
''. The two species appear to differ biologically, with ''P. ovale wallikeri'' having a shorter latency period than ''P. ovale curtisi''.


Life cycle

''P. ovale'' is introduced into the human host by the bite of an infected mosquito, in a motile form called a sporozoite. The sporozoites are carried by the blood to the liver, where they replicate asexually by
merogony 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 ...
into non-motile merozoites. Several hundred merozoites are produced and released into the bloodstream where they infect
erythrocytes 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 ...
. Inside the erythrocyte, the parasite's replication cycle takes approximately 49 hours, after which the erythrocyte ruptures and between 8 and 20 merozoites are released to infect other erythrocytes. Some of these merozoites will instead form
gametocytes 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 T ...
which remain in the blood and are ingested by a mosquito. When gametocytes are ingested by a mosquito, the gametocytes enter the mosquito gut where
fertilisation Fertilisation or fertilization (see spelling differences), also known as generative fertilisation, syngamy and impregnation, is the fusion of gametes to give rise to a new individual organism or offspring and initiate its development. Pro ...
occurs forming 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 ...
known as an
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 is ...
. The ookinete moves to the outer wall of the mosquito midgut where it develops over the course of several weeks. This developing stage is called an oocyst. After the oocyst develops, it ruptures releasing several hundred sporozoites. The sporozoites are carried by the mosquito's circulation to the mosquito salivary glands. When the mosquito feeds again, the sporozoites enter through the salivary duct and are injected into a new host, starting the life cycle again. There are situations where some of the sporozoites hypothetically do not immediately start to grow and divide after entering the hepatocyte, but remain in a dormant,
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 verteb ...
stage for weeks or months. However, unlike the ''P. vivax'' situation, hypnozoites have yet to actually be seen in the life cycle of ''P. ovale''. The duration of latency is variable from one (assumed in the case of ''P. ovale'') hypnozoite to another and the factors that will eventually trigger growth are not known; this could explain how a single infection can be responsible for a series of waves of parasitaemia or "relapses".


Hosts

While humans appear to be the natural mammalian host of ''P. ovale'', chimpanzees and ''
Saimiri Squirrel monkeys are New World monkeys of the genus ''Saimiri''. ''Saimiri'' is the only genus in the subfamily Saimirinae. The name of the genus is of Tupi origin (''sai-mirím'' or ''çai-mbirín'', with ''sai'' meaning 'monkey' and ''mirím'' ...
'' monkeys have also been experimentally infected. ''
Anopheles gambiae The ''Anopheles gambiae'' complex consists of at least seven morphologically indistinguishable species of mosquitoes in the genus ''Anopheles''. The complex was recognised in the 1960s and includes the most important vectors of malaria in sub- ...
'' and ''
Anopheles funestus ''Anopheles funestus'' is a species of mosquito in the Culicidae family. This species was first described in 1900 by Giles. The female is attracted to houses where it seeks out humans in order to feed on their blood, mostly during the night. Th ...
'' are likely the natural mosquito hosts of ''P. ovale''. Experimentally, several other mosquito species have been shown to be capable of transmitting ''P. ovale'' to humans, including: *''
Anopheles albimanus ''Anopheles albimanus'' is a species of mosquito in the order Diptera. It is found in coastal Central and South America, the Caribbean, and Mexico. It is a generalist species and capable of wide dispersion. ''A. albimanus'' is a common malaria ...
'' *''
Anopheles atroparvus ''Anopheles atroparvus'' is a European species of mosquito, which was first identified in 1927. It is one of the most abundant palearctic Anopheles species belonging to the family Culicidae, commonly called mosquitoes. Although research interest ...
'' *''
Anopheles dirus ''Anopheles dirus'' is a vector of malaria in Asian forested zones. Taxonomy It is often seen as a species complex including at least sevenDash AP, Adak, T., Raghavendra, K., Singh, OP. (2007) The biology and control of malaria vectors in Ind ...
'' *'' Anopheles farauti'' *''
Anopheles freeborni ''Anopheles freeborni'', commonly known as the western malaria mosquito, is a species of mosquito in the family Culicidae. It is typically found in the western United States and Canada. Adults are brown to black, with yellow-brown hairs and g ...
'' *'' Anopheles maculatus'' *''
Anopheles quadrimaculatus ''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'', whi ...
'' *''
Anopheles stephensi ''Anopheles stephensi'' is a primary mosquito vector of malaria in urban India and is included in the same subgenus as '' Anopheles gambiae'', the primary malaria vector in Africa. ''A. gambiae'' consists of a complex of morphologically identica ...
'' *''
Anopheles subpictus ''Anopheles (Cellia) subpictus'' is a species complex of four species (A, B, C and D) of mosquito belonging to the genus ''Anopheles''. Subgenus classification The genus ''Anopheles'' has been subdivided into seven subgenera – ''Anopheles'', ...
''


Genomes

The full genomes of the two ''P. ovale'' species can be seen o
geneDB.org – ''P. ovali curtisi''
tp://ftp.sanger.ac.uk/pub/project/pathogens/Plasmodium/ovale/PovaleWallikeri/CR01/ ''P. ovale wallikeri'' an
plasmoDB.org
published 2017.


See also

* List of parasites (human)


References


External links


Malaria
– TDR: For research on diseases of poverty {{Taxonbar, from=Q134445
ovale Ovale is a village and gram panchayat in India, situated in Mawal taluka of Pune district in the state of Maharashtra. It encompasses an area of . Administration The village is administrated by a sarpanch, an elected representative who leads ...