''Leucocytozoon '' (or ''Leukocytozoon'') is a

genus Genus ( plural genera ) is a taxonomic rank used in the biological classification of living and fossil organisms as well as viruses. In the hierarchy of biological classification, genus comes above species and below family. In binomial nom ...

of parasitic

alveolates The alveolates (meaning "pitted like a honeycomb") are a group of protists, considered a major clade and superphylum within Eukarya. They are currently grouped with the stramenopiles and Rhizaria among the protists with tubulocristate mitochond ...

belonging to the phylum

Apicomplexa The Apicomplexa (also called Apicomplexia) are a large phylum of parasitic alveolates. Most of them possess a unique form of organelle that comprises a type of non-photosynthetic plastid called an apicoplast, and an apical complex structure. Th ...

(which also includes the malaria parasites). The species of this genus use either blackflies ('' Simulium'' species) or a

biting midge Ceratopogonidae is a family of flies commonly known as no-see-ums, or biting midges, generally in length. The family includes more than 5,000 species, distributed worldwide, apart from the Antarctic and the Arctic. Ceratopogonidae are holomet ...

as their definitive host and birds as their intermediate host. There are over 100 species in this genus. Over 100 species of birds have been recorded as hosts to these parasites.

Life cycle

Parasites in the genus ''Leucocytozoon'' have a life cycle that involves both a bird host, and a

black fly A black fly or blackfly (sometimes called a buffalo gnat, turkey gnat, or white socks) is any member of the family Simuliidae of the Culicomorpha infraorder. It is related to the Ceratopogonidae, Chironomidae, and Thaumaleidae. Over 2,200 spec ...

(with the exception of ''Leucocytozoon caulleryi'' which cycles between a bird host and a

). Parasites enter the bird host in a form called a

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 ...

through the bite of the blood-sucking black fly. The sporozoites invade host cells in the liver where they undergo asexual replication, forming numerous daughter cells called merozoites within 4–5 days. The duration of this stage depends in part upon the species. In some species this stage may occur in the endothelial cells instead of the liver. The newly released merozoites infect either

erythrocyte 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, leukocytes, macrophages or endothelial cells. Those infecting the macrophages or endothelial cells develop into megaloschizonts. The megaloschizonts divide into primary cytomeres, which in turn multiply into smaller cytomeres, which mature into schizonts, which in turn divide into merozoites. In erythrocytes or leukocytes, merozoites develop into gametocytes. The gametocytes are taken up by a blood-sucking fly as it bites the bird host. Gametocytes then mature in the insect

midgut The midgut is the portion of the embryo from which most of the intestines develop. After it bends around the superior mesenteric artery, it is called the "midgut loop". It comprises the portion of the alimentary canal from the end of the foregut a ...

into macrogametocytes (female) with red-staining nuclei and microgametocytes (male) with pale-staining diffuse nuclei: these fuse to form an ookinete. The male gametocytes normally give rise to eight microgametes. The ookinete penetrates an intestinal cell of the fly and matures into an oocyst. After several days the oocyst produces ~100 sporozoites that leave and migrate to the salivary glands of the fly.

Description

The nuclei of the schizonts is enclosed in a trilaminar membrane with peripherally arranged chromatin. The schizonts also contain numerous cytomers also with trilaminar membranes and containing multiple ribosomes. Repeated invagination of the cytomeres gives rise to the merozoites which also have a trilaminar membrane. The merozoites have rhoptries,

microneme Micronemes are secretory organelles, possessed by parasitic apicomplexans. Micronemes are located on the apical third of the protozoan body. They are surrounded by a typical unit membrane. On electron microscopy they have an electron-dense matrix ...

s and three apical rings. The mitochondrion contains vesicular cristae. There may be one or two paranuclear bodies in some species. Their function is unknown. Two gametocyte forms are recognised: an elongated (sail-like) form and a compact spherical form. These are usually 12–14 micrometres long. The large gametocytes tend to grossly distort the infected cells and make cell identification difficult. A pseudopigment known as volutin may be present.

Evolution

It has been suggested that this genus arose after the two others genera ''Plasmodium'' and ''Haemoproteus'', the latter originating from the late Oligocene or early

Eocene The Eocene ( ) Epoch is a geological epoch that lasted from about 56 to 33.9 million years ago (mya). It is the second epoch of the Paleogene Period in the modern Cenozoic Era. The name ''Eocene'' comes from the Ancient Greek (''ēṓs'', " ...

at about the same time as

Piciformes Nine families of largely arboreal birds make up the order Piciformes , the best-known of them being the Picidae, which includes the woodpeckers and close relatives. The Piciformes contain about 71 living genera with a little over 450 species, of ...

and

Coraciiformes The Coraciiformes are a group of usually colourful birds including the kingfishers, the bee-eaters, the rollers, the motmots, and the todies. They generally have syndactyly, with three forward-pointing toes (and toes 3 & 4 fused at their base) ...

Taxonomy

The genus is divided into two subgenera—''Akiba'' and ''Leucocytozoon''—based on the vector species. The only known member of the subgenus ''Akiba'' is ''Leucocytozoon (Akiba) caulleryi'' which uses members of the genus ''

Culicoides ''Culicoides'' is a genus of biting midges in the family Ceratopogonidae. There are over 1000 species in the genus,Connelly, C. RBiting midges: ''Culicoides'' spp.Featured Creatures, Entomology and Nematology Department, University of Florida IF ...

'' as its vectors. The remaining species in the genus use members of the genus '' Simulium'' as their vectors. In 1977, Greiner and Kocan in an extensive examination of species in the order ''

Falconiformes The order Falconiformes () is represented by the extant family Falconidae (falcons and caracaras) and a handful of enigmatic Paleogene species. Traditionally, the other bird of prey families Cathartidae (New World vultures and condors), Sagitt ...

'' declared that the only valid species infecting this order was ''L. toddi''. ''L. dubreuili'' is considered to be restricted to the family ''

Turdidae The thrushes are a passerine bird family, Turdidae, with a worldwide distribution. The family was once much larger before biologists reclassified the former subfamily Saxicolinae, which includes the chats and European robins, as Old World fl ...

''; ''L. fringillinarum'' is considered to be restricted to several passiform families; and ''L. majoris'' is considered restricted to the family ''

Paridae The tits, chickadees, and titmice constitute the Paridae, a large family of small passerine birds which occur mainly in the Northern Hemisphere and Africa. Most were formerly classified in the genus ''Parus''. Members of this family are common ...

''. ''L. ziemanni'' infects owls.

Diagnostic criteria

Form gamonts in white blood cells and/or erythrocytes. Gametocytes cause marked enlargement and distortion of the infected cell producing a football-like appearance. No

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 ...

occurs in either leucocytes or erythrocytes. Merogony occurs in the parenchyma of liver, heart, kidney, or other organs.

Meront 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 may form large bodies divided into cytomeres. Hemozoin deposits (pigment) are not formed—a useful distinguishing feature for ''Leucocytozoon'' from '' Haemoproteus'' and '' Plasmodium''. Oocysts develop rapidly in 3–5 days. The oocysts are small and nonexpanding, reaching 13 micrometres in diameter and typically have less than 100 short, thick sporozoites. The vectors are '' Simulium'' or ''

'' species. The vertebrate hosts are birds. Type species: ''Leucocytozoon ziemanni''

Pathology

The typical pathology of infection with these parasites includes anaemia and enlargement of the

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 ...

and

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

. Gross lesions also include pulmonary congestion and pericardial effusion. Megaloschizonts appear as grey-white nodules found in the

heart The heart is a muscular organ in most animals. This organ pumps blood through the blood vessels of the circulatory system. The pumped blood carries oxygen and nutrients to the body, while carrying metabolic waste such as carbon dioxide to t ...

, liver, lung or spleen. Microscopically there is ischemic necrosis and associated inflammation in the heart,

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

, spleen and liver due to occlusion of blood vessels by megaloschizonts in endothelial cells. Ruptured schizonts may induce granulomatous reactions in the surrounding tissues. Clinically the majority of birds affected with leucocytozoonosis exhibit no signs. Among those that do the signs include mild to severe signs of

anorexia Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gre ...

ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...

, weakness, anemia,

emaciation Emaciation is defined as the state of extreme thinness from absence of body fat and muscle wasting usually resulting from malnutrition. Characteristics In humans, the physical appearance of emaciation includes thinned limbs, pronounced and protrud ...

and difficulty breathing. The excess mortality due to ''Leucocytozoon'' in adult birds seems to occur as a result of debilitation and increased susceptibility to secondary infection.

Epidemiology

''L. simondi'' is suspected to be a major parasite of

Canada geese The Canada goose (''Branta canadensis''), or Canadian goose, is a large wild goose with a black head and neck, white cheeks, white under its chin, and a brown body. It is native to the arctic and temperate regions of North America, and it is o ...

in some areas, including the upper Midwestern

United States The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territori ...

and

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...

. ''L. smithi'' affects

turkey Turkey ( tr, Türkiye ), officially the Republic of Türkiye ( tr, Türkiye Cumhuriyeti, links=no ), is a transcontinental country located mainly on the Anatolian Peninsula in Western Asia, with a small portion on the Balkan Peninsula in ...

farms in the southeastern United States.

Host range

Bird hosts *''L. anatis''—ducks *''L. andrewsi''—chicken ('' Gallus gallus domesticus'') *''L. anseris''—geese *''L. artamidis''—wood-swallows ('' Artamidae'' species) *''L. atkinsoni''—common jery ('' Neomixis tenella'') *''L. balmorali''—shrikes ('' Laniidae'' species), bushshrikes ('' Malaconotidae'' species) *''L. bennetti''—hook-billed vanga ('' Vanga curvirostris'') *''L. berestneffi''—yellow-billed magpie ('' Pica nuttalia'') *''L. bishopi''—parrotbills (''

Paradoxornithidae The parrotbills are a family, Paradoxornithidae, of passerine birds that are primarily native to East and Southeast Asia (with a single species in western North America), though feral populations exist elsewhere. They are generally small, long-t ...

'' species) *''L. bonasae''—ruffed grouse ('' Bonasa umbellus''), spruce grouse ('' Canachites canadensis''), ptarmigan *''L. bouffardi''—weaver birds (''

Ploceidae Ploceidae is a family of small passerine birds, many of which are called weavers, weaverbirds, weaver finches and bishops. These names come from the nests of intricately woven vegetation created by birds in this family. In most recent classifica ...

'' species) *''L. brimonti''—bulbuls (''

Pycnonotus ''Pycnonotus'' is a genus of frugivorous passerine birds in the bulbul family Pycnonotidae. Taxonomy and systematics The genus ''Pycnonotus'' was introduced by the German zoologist Friedrich Boie in 1826 with the Cape bulbul as the type speci ...

'' species) *''L. caprimulgi''—nightjars ('' Caprimulgidae'' species) *''L. caulleryi'' Mathis and Leger 1909—chicken ('' Gallus gallus domesticus'') *''L. coracinae''—swifts ('' Apodidaeavian'' species), cuckoo-shrikes ('' Campephagidae'') *''L. danilewskyi''—owl ('' Strix occidentalis'') *''L. deswardti''—Sugarbirds ('' Promeropidae'' species) *''L. dubreuili''—American robin ('' Turdus migratorius'') *''L. dutoiti''—finches (''

Fringillidae The true finches are small to medium-sized passerine birds in the family Fringillidae. Finches have stout conical bills adapted for eating seeds and nuts and often have colourful plumage. They occupy a great range of habitats where they are usua ...

'' species) *''L. frascai''—rufous-headed ground-roller ('' Atelornis crossleyi'') *''L. fringillinarum''—finches (''

Fringilla coelebs The common chaffinch or simply the chaffinch (''Fringilla coelebs'') is a common and widespread small passerine bird in the finch family. The male is brightly coloured with a blue-grey cap and rust-red underparts. The female is more subdued in ...

''), dark-eyed Juncos (''

Junco hyemalis The dark-eyed junco (''Junco hyemalis'') is a species of junco, a group of small, grayish New World sparrows. This bird is common across much of temperate North America and in summer ranges far into the Arctic. It is a very variable species, much ...

''), white winged crossbills ('' Loxia leucoptera''), yellow wagtail ('' Motacilla flava''), house sparrow ('' Passer domesticus biblicus'') *''L. gentili''—house sparrow (''

Passer domesticus The house sparrow (''Passer domesticus'') is a bird of the sparrow family Passeridae, found in most parts of the world. It is a small bird that has a typical length of and a mass of . Females and young birds are coloured pale brown and grey, an ...

'') *''L. greineri''—common sunbird asity ('' Neodrepanis coruscans''), velvet asity ('' Philepitta castanea'') *''L. grusi''— sandhill crane ('' Antigone canadensis'') *''L. hamiltoni''—Bukharan great tit ('' Parus bokharensis'') *''L. lairdi''—blue vanga ('' Cyanolanius madagascarinus'') *''L. liothricis''—Old World babblers ('' Timaliidae'' species) *''L. lovati''—greater sage-grouse (''

Centrocercus urophasianus The greater sage-grouse (''Centrocercus urophasianus''), also known as the sagehen, is the largest grouse (a type of bird) in North America. Its range is sagebrush country in the western United States and southern Alberta and Saskatchewan, Canad ...

''), blue grouse ('' Dendragapus obscurus''), willow ptarmigan ('' Lagopus lagopus''), wild rock ptarmigan (''

Lagopus mutus The rock ptarmigan (''Lagopus muta'') is a medium-sized game bird in the grouse family. It is known simply as the ptarmigan in the UK. It is the official bird for the Canadian territory of Nunavut, where it is known as the ''aqiggiq'' (ᐊᕿ� ...

'') *''L. maccluri''—Thailand thrush (''

Zoothera marginata The dark-sided thrush (''Zoothera marginata'') is a species of bird in the thrush family Turdidae. It is also known as the lesser brown thrush, the long-billed ground-thrush, and the dark-sided ground-thrush. The species is monotypic (lacking sub ...

'') *''L. macleani'' Sambon 1908—chickens (''

Gallus gallus domesticus The chicken (''Gallus gallus domesticus'') is a domesticated junglefowl species, with attributes of wild species such as the grey and the Ceylon junglefowl that are originally from Southeastern Asia. Rooster or cock is a term for an adult ...

'') *''L. majoris''—yellow wagtails ('' Motacilla flava'') *''L. marchouxi''—Mauritian pink pigeon ('' Columba mayeri''), doves *''L. nectariniae''—sunbird ('' Nectarinia olivacea'') *''L. neavei''—guinea fowl *''L. pogoniuli''—tinker barbets ('' Pogoniulus atroflavus'', '' Pogoniulus subsulphureus'') *''L. pycnonoti''—bulbuls (''

Pycnonotidae The bulbuls are members of a family, Pycnonotidae, of medium-sized passerine songbirds, which also includes greenbuls, brownbuls, leafloves, and bristlebills. The family is distributed across most of Africa and into the Middle East, tropical ...

'' species) *''L. roubaudi''—estrildid finches (''

Estrildidae Estrildidae, or estrildid finches, is a family of small seed-eating passerine birds of the Old World tropics and Australasia. They comprise species commonly known as munias, mannikins, firefinches, parrotfinches and waxbills. Despite the word "fi ...

'' species) *''L. sabrazesi'' Mathis and Léger 1910—chicken ('' Gallus gallus domesticus'') *''L. schoutedeni'' Rodhain, Pons, Vandenbranden and Bequaert 1913—chicken ('' Gallus gallus domesticus'') *''L. schufneri'' Prowazek 1912- chicken ('' Gallus gallus domesticus'') *''L. shaartusicum''—redstart ('' Phoenicurus phoenicurus'') *''L. simondii''—ring-necked ducks (''

Aythya collaris The ring-necked duck (''Aythya collaris'') is a diving duck from North America commonly found in freshwater ponds and lakes. The scientific name is derived from Greek , an unidentified seabird mentioned by authors including Hesychius and Arist ...

''), wood duck (''

Aix sponsa The wood duck or Carolina duck (''Aix sponsa'') is a species of perching duck found in North America. The drake wood duck is one of the most colorful North American waterfowl. Description The wood duck is a medium-sized perching duck. A typi ...

''), white Pekin duck ('' Anas bochas''), Mexican duck ('' Anas diazi''), mallard duck (''

Anas platyrhynchos The mallard () or wild duck (''Anas platyrhynchos'') is a dabbling duck that breeds throughout the temperate and subtropical Americas, Eurasia, and North Africa, and has been introduced to New Zealand, Australia, Peru, Brazil, Uruguay, Arge ...

''), black duck (''

Anas rubripes The American black duck (''Anas rubripes'') is a large dabbling duck in the family Anatidae. It was described by William Brewster in 1902. It is the heaviest species in the genus ''Anas'', weighing on average and measuring in length with an ...

''), geese (''

Branta canadensis The Canada goose (''Branta canadensis''), or Canadian goose, is a large wild goose with a black head and neck, white cheeks, white under its chin, and a brown body. It is native to the arctic and temperate regions of North America, and it is ...

''), Emperor Goose ('' Chen canagica''), mergansers ('' Mergus merganser''), trumpeter swans ('' Olor buccinator''), eider duck ('' Somateria mollissima'') *''L. smithi''—turkeys ('' Meleagris'' species) *''L. sturni''—starlings ('' Sturnidae'' species) *''L. tawaki''—penguins (''

Spheniscidae Penguins (order Sphenisciformes , family Spheniscidae ) are a group of aquatic flightless birds. They live almost exclusively in the Southern Hemisphere: only one species, the Galápagos penguin, is found north of the Equator. Highly adapte ...

'' species) *''L. timaliae''—Old World babblers ('' Timaliidae'' species) *''L. toddi''—Coopers hawk ('' Accipiter cooperii''), sharp-shinned hawks ('' Accipiter striatus''), Eurasian buzzard ('' Buteo buteo''), Red-shouldered hawks (''

Buteo lineatus The red-shouldered hawk (''Buteo lineatus'') is a medium-sized buteo. Its breeding range spans eastern North America and along the coast of California and northern to northeastern-central Mexico. It is a permanent resident throughout most of its ...

''), white-tailed sea eagle (''

Haliaeetus albicilla The white-tailed eagle (''Haliaeetus albicilla'') is a very large species of sea eagle widely distributed across temperate Eurasia. Like all eagles, it is a member of the family Accipitridae (or accipitrids) which includes other diurnal raptor ...

''), bald eagles ('' Haliaeetus leucocephalus''), Chimango Caracara ('' Milvago chimango''), grouse *''L. trachyphoni''—barbet ('' Trachyphonus purpureus'') *''L. ziemanni''—eagle owl (''

Bubo bubo The Eurasian eagle-owl (''Bubo bubo'') is a species of eagle-owl that resides in much of Eurasia. It is also called the Uhu and it is occasionally abbreviated to just the eagle-owl in Europe. It is one of the largest species of owl, and female ...

''), great horned owls (''

Bubo virginianus The great horned owl (''Bubo virginianus''), also known as the tiger owl (originally derived from early naturalists' description as the "winged tiger" or "tiger of the air"), or the hoot owl, is a large owl native to the Americas. It is an extrem ...

''), snowy owls ('' Nyctea scandiaca''), spotted owls ('' Strix occidentalis'') *''L. zosteropis''—white-eyes (''

Zosteropidae The white-eyes are a family, Zosteropidae, of small passerine birds native to tropical, subtropical and temperate Sub-Saharan Africa, southern and eastern Asia, and Australasia. White-eyes inhabit most tropical islands in the Indian Ocean, the ...

'' species)

Vectors

*''L. bonasae''—'' Simulium aureum'', '' Simulium latipes'' *''L. caulleryi''—'' Culicoides arakawae'' *''L. lovati''—'' Prosimulium hirtipes'', '' Simulium japonicum'', '' Simulium uchidai'' *''L. simondi''—''

Cnephia ornithophilia ''Cnephia'' is a genus of 9 species of black flies. They are distributed in scattered locations across the Northern Hemisphere, from Ukraine to Eastern Siberia Siberia ( ; rus, Сибирь, r=Sibir', p=sʲɪˈbʲirʲ, a=Ru-Сибирь.ogg ...

'', '' Simulium rugglesi'' *''L. smithi''—'' Simulium nigritarse'' *''L. tawaki''—'' Austrosimulium ungulatum''

Notes

Like many protist species and genera this genus is subject to ongoing revision especially in the light of DNA based taxonomy. Described species may be subject to revision. *''L. anatis'' and ''L. anseris'' are considered to be synonyms of ''L. simondi''. *''L. andrewsi'' and ''L. schoutedeni'' are considered to be synonyms. *''L. bonasae'', ''L. jakamowi'' and ''L. mansoni'' are considered to be synonyms of ''L. lovati''. *''L. brimonti'' is considered to be a synonym of ''L. fringillinarum''. *''L. costai'' and ''L. numidae'' are considered to be synonyms of ''L. neavei''. *''L. francolini'', ''L. kerandeli'', ''L. martini'', ''L. mesnili'', ''L. sabrazesi'' and ''L. schuffneri'' are considered to be synonyms of ''L. macleani''. *The species ''L. galli'' is open to some doubt. *''L. molpastis'' is considered to be a synonym of ''L. brimonti'' *''L. monardi'' is considered to be a synonym of ''L. gentili'' *''L. toddi'' seems likely to be a cryptic species complex. *''L. turtur'' and its subspecies ''L. turtur orientalis'' are considered a synonym of ''L. marchouxi''

History

The first described observation of a ''Leucocytozoon'' parasite may have been by Vasily Danilewsky, who described certain parasites he observed in the blood of birds as "Leucocytozaire" in 1888 (as they appeared to infect

leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

). A more detailed description of parasites resembling ''Leucocytozoon'' was published in 1894 by N. Sakharoff from the blood of birds near

Tbilisi Tbilisi ( ; ka, თბილისი ), in some languages still known by its pre-1936 name Tiflis ( ), is the capital and the largest city of Georgia, lying on the banks of the Kura River with a population of approximately 1.5 million p ...

. Soon thereafter in 1898, Hans Ziemann described a ''Leucocytozoon'' parasite from the blood of the owl '' Athene noctua'', naming it ''Leukocytozoen danilewskyi'' in honor of Danilewsky. N. M. Berestneff was the first to use the current genus name ''Leucocytozoon'' while describing parasites he called ''Leucocytozoon danilewskyi'' from several common birds. The genus was subsequently formally defined in 1908 by Louis Sambon, and has remained largely unchanged since. In 1930 and 1931, Earl O'Roke and Louis V. Skidmore independently discovered black flies to be the vector of ''Leucocytozoon'' species.