# Leishmania

Leishmania /liːʃˈmeɪniə, -ˈmæn-/ is a parasitic protozoan, a single-celled organism of the genus Leishmania that is responsible for the disease leishmaniasis. They are spread by sandflies of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. At least 93 sandfly species are proven or probable vectors worldwide. Their primary hosts are vertebrates. 'Leishmania' commonly infects hyraxes, canids, rodents, and humans.

## History

Members of an ancient genus of Leishmania-like parasites, Paleoleishmania, have been detected in fossilized sand flies dating back to the early Cretaceous period. The first written reference to the conspicuous symptoms of cutaneous leishmaniasis surfaced in the Paleotropics within oriental texts dating back to the 7th century BC (allegedly transcribed from sources several hundred years older, between 1500 and 2000 BC). Due to its broad and persistent prevalence throughout antiquity as a mysterious disease of diverse symptomatic outcomes, leishmaniasis has been dubbed with various names ranging from "white leprosy" to "black fever". Some of these names suggest links to negative cultural beliefs or mythology, which still feed into the social stigmatization of leishmaniasis today.
In India, both cutaneous and visceral leishmaniasis are caused by Leishmania donovani. The first records of cutaneous leishmaniasis in India were from British medical officers in the early 19th century. The disease was by then known as "oriental sore" or "Delhi boil"; while the visceral form was variously called "Burdwan [after the city Burdwan] fever", "kala azar" (black fever), or "Dumdum [a city in West Bengal] fever".
The causative parasite for the disease was identified in 1901 as a concurrent finding by William Boog Leishman and Charles Donovan. They independently visualised microscopic single-celled parasites (later called Leishman-Donovan bodies) living within the cells of infected human organs. The parasitic genus would later be classed as trypanosomatid protozoans under the phylogenetic designation, Leishmania donovani. Several species have since been classified and grouped under two major subgenera i.e. Leishmania Viannia (generally located in the Neotropics) or Leishmania Leishmania (generally located in the Paleotropics, with the major exception of the L. mexicana subgroup).

## Epidemiology

Leishmania currently affects 6 million people in 98 countries. About 0.9–1.6 million new cases occur each year, and 21 species are known to cause disease in humans: it is considered a zoonosis.

## Structure

Leishmania species are unicellular eukaryotes having a well-defined nucleus and other cell organelles including kinetoplasts and flagella. Depending on the stage of their life cycle, they exist in two structural variants, as:
* The amastigote form is found in the mononuclear phagocytes and circulatory systems of humans. It is an intracellular and nonmotile form, being devoid of external flagella. The short flagellum is embedded at the anterior end without projecting out. It is oval in shape, and measures 3–6 μm in length and 1–3 μm in breadth. The kinetoplast and basal body lie towards the anterior end.
* The promastigote form is found in the alimentary tract of sandflies. It is an extracellular and motile form. It is considerably larger and highly elongated, measuring 15-30 μm in length and 5 μm in width. It is spindle-shaped, tapering at both ends. A long flagellum (about the body length) is projected externally at the anterior end. The nucleus lies at the centre, and in front of it are the kinetoplast and the basal body.

## Evolution

The details of the evolution of this genus are debated, but Leishmania apparently evolved from an ancestral trypanosome lineage. The oldest lineage is that of the Bodonidae, followed by Trypanosoma brucei, the latter being confined to the African continent. Trypanosoma cruzi groups with trypanosomes from bats, South American mammals, and kangaroos suggest an origin in the Southern Hemisphere. These clades are only distantly related.
The remaining clades in this tree are Blastocrithidia, Herpetomonas, and Phytomonas. The four genera Leptomonas, Crithidia, Leishmania, and Endotrypanum form the terminal branches, suggesting a relatively recent origin. Several of these genera may be polyphyletic and may need further division.
The origins of genus Leishmania itself are unclear. One theory proposes an African origin, with migration to the Americas. Another proposes migration from the Americas to the Old World via the Bering Strait land bridge around 15 million years ago. A third theory proposes a Palearctic origin. Such migrations would entail subsequent migration of vector and reservoir or successive adaptations along the way. A more recent migration is that of L. infantum from Mediterranean countries to Latin America (known as L. chagasi), since European colonization of the New World, where the parasites picked up their current New World vectors in their respective ecosystems. This is the cause of the epidemics now evident. One recent New World epidemic concerns foxhounds in the USA.
Although it was suggested that Leishmania might have evolved in the Neotropics, this is probably true for species belonging to the subgenera Viannia and Endotrypanum. However, there is evidence that the primary evolution of the subgenera Leishmania and Sauroleishmania is the Old World. While the Mundinia species appear to be more universal in their evolution. One theory is that different lineages became isolated geographically during different periods and it is this that gave rise to this evolutionary mosaicism. But there is no doubt that the Leishmaniinae are a monophyletic group.
A large data set analysis suggests that Leishmania evolved 90 to 100 million years ago in Gondwana. The reptile infecting species originated in mammalian clades.
Sauroleishmania species were originally defined on the basis that they infected reptiles (lizards) rather than mammals. Based on molecular evidences, they have been moved to subgenus status within Leishmania. This subgenus probably evolved from a group that originally infected mammals.

## Taxonomy

53 species are recognised in this genus. The status of several of these is disputed, so the final number may differ. At least 20 species infect humans. To make things more complex, hybrids might be involved, as it has been reported in Brazil with a hybrid between Leishmania (V.) guyanensis and Leishmania (V.) shawi shawi.
The genus is presently divided into 4 subgenera: Leishmania, Sauroleishmania, Mundinia and Viannia. The division into the two subgenera (Leishmania and Viannia) was made by Lainson and Shaw in 1987 on the basis of their location within the insect gut. The species in the Viannia subgenus develop in the hind gut: L. (V.) braziliensis has been proposed as the type species for this subgenus. This division has been confirmed by all subsequent studies. Shaw, Camargo and Teixeira created the subgenus Mundinia while revising Leishmaniinae in 2016.
Endotrypanum is closely related to Leishmania. Some Endotypanum species are unique in that they infect the erythrocytes of their hosts (sloths). All species are confined to Central and South America. E. colombiensis infections have been found in man.
Sauroleishmania was originally described by Ranquein 1973 as a separate genus, but molecular studies suggest this is actually a subgenus rather than a separate genus.
The proposed division of the Leishmania into Euleishmania and Paraleishmania groups in 2000 emphasized the deep phylogenic distance between parasites, some of which had been named as Leishmania species. The Euleishmania included species currently placed in the subgenera Leishmania, Sauroleishmania, Mundinia and Viannia. The proposed Paraleishmania included species of Endotypanum, Leishmamnia-L. colomubensis, L. herreri, L. hertigiand L. deanei and L. equatorensis. In a recent revision these species were given different generic status.
Four subgenera of Leishmania are now recognised - Leishmania, Sauroleishmania, Viannia and Mundinia (the L. enriettii complex). The genus Endotrypanum and Porcisia belong to the Paraleishmania.
There are four Mundinia species - L. (Mundinia) enriettii, L. (Mundinia) martiniquensis, L. (Mundinia) macropodum, and L. (Mundinia) orientalis, which is found in Thailand.
L. archibaldi's specific status is unsettled but it is closely related to L. donovani.
L. herreri belongs to the genus Endotypanum rather than to Leishmania.
L. donovani and L. infantum are closely related.