Parasitology. Alan Gunn

out of glucose to metabolise. The glycosomes are the site of glucose metabolism, and therefore, like the kinetoplast DNA, they are a potential target for antiparasitic drug design.

      Many species within the Kinetoplastida are only parasitic in insects. For example, members of the genus Leptomonas live in the gut of various insects including blood‐feeding reduviid bugs (Kaufer et al. 2017). Because they have only a single host, these species are referred to as monoxenous although there are rare case reports of human infections in patients who are HIV+ve. There are also accounts of Leptomonas co‐infections with visceral leishmaniasis and post kala‐azar dermal leishmaniasis caused by Leishmania donovani (Thakur et al. 2020).

Many of the Kinetoplastida alternate between an invertebrate host such as a blood‐feeding insect or leech, and a vertebrate host with development occurring in both. Parasites that have more than one type of host are called heteroxenous. Heteroxenous Kinetoplastida species often express two or more morphological forms with one form present in the invertebrate and the other in the vertebrate (Table 4.2). Some members of the Kinetoplastida exhibit sexual reproduction, or something similar (Berry et al. 2019; Gibson and Peacock 2019), but it is uncertain whether it is a widespread phenomenon in the group.

4.2.1 Genus Leishmania

Members of the genus Leishmania exhibit two distinct morphologies: the amastigote form that occurs in the vertebrate host, and the promastigote form that occurs in the invertebrate vector. The vertebrate hosts are mostly mammals, whilst the invertebrates are various species of sandflies. Those species parasitic in reptiles belong to the subgenus Sauroleishmania and do not cause zoonotic infections. Perhaps counter‐intuitively, molecular evidence indicates that the Leishmania evolved in the Neotropical regions during the Mesozoic era as parasites of mammals and those species parasitizing reptiles, the Sauroleishmania, subsequently evolved from them (Noyes et al. 2000).

Table 4.2 Morphological forms of Kinetoplastida parasitic in humans and domestic animals.

Morphological form	Description	Example
Amastigote	Kinetoplast and kinetosome above the nucleus, flagellum short and confined in pocket. Cell shape globular	Leishmania donovani inside vertebrate macrophage Trypanosoma cruzi in human spleen, liver, muscle, and other cell types
Promastigote	Kinetoplast and kinetosome at anterior end of cell, flagellum free, and long. Cell shape elongate	Leishmania donovani in sandfly gut
Epimastigote	Kinetoplast and kinetosome close and anterior to the nucleus. There is a short undulating membrane before the flagellum emerges at the anterior of the cell. Cell shape elongate	Trypanosoma cruzi in triatomid gut
Trypomastigote	Kinetoplast and kinetosome at posterior end of cell. Flagellum forms an undulating membrane that runs the length of the cell and may continue free when it reaches the anterior end. Cell shape elongate	Trypansoma cruzi in human bloodstream

      Trypanosomes that are parasitic insects exhibit other morphological forms, such as choanomastigote, opisthomastigote, and paramastigote.

Table 4.3 Taxonomic divisions within the genus Leishmania.

Genus	Subgenus	Disease	Example
Leishmania	Leishmania	Visceral	Leishmania donovani phenetic complex Leishmania infantum phenetic complex
		Old World cutaneous	Leishmania major phenetic complex Leishmania tropica phenetic complex
		New World cutaneous	Leishmania mexicana phenetic complex
	Viannia	New World	Leishmania braziliensis phenetic complex
	Sauroleishmania	Lizard leishmaniasis	Leishmania tarentolae

The taxonomy of the genus Leishmania is complex, and it is extremely difficult or impossible to distinguish many of them from their morphology using a light microscope. Lainson and Shaw (1987) comprehensively reviewed the genus and molecular and phylogenetic studies have largely supported their proposals for how it should be divided (Table 4.3). However, agreement concerning the status of several species is far from complete, and there remain uncertainties about many aspects of the evolution of the Leishmania – see Schönian et al. (2018) for further details. Lainson and Shaw (1987) identified two subgenera: Leishmania and Viannia. In the subgenus Leishmania, the parasites begin their development in the sandfly vector’s midgut and then move forward to the pharynx. The sandfly then injects the parasites into the vertebrate host when she feeds. By contrast, in the subgenus Viannia the parasites begin development in the vector’s hindgut and then move forward to the pharynx.

      Those species within the subgenus Viannia (e.g., Leishmania braziliensis, Leishmania peruviana, Leishmania guyanensis, Leishmania panamensis) are restricted to South America and are primarily responsible for cutaneous disease. Species belonging to the subgenus Leishmania (e.g., Leishmania donovani, Leishmania major, Leishmania infantum, Leishmania tropica, Leishmania mexicana) have representatives in both the New World and the Old World and include agents of both visceral and cutaneous disease. Because of the difficulties associated with identifying the parasites and the diversity of the pathologies they cause, there is a tendency to refer to Leishmania phenetic complexes. That is, a species exhibits various phenotypes that may or may not relate to underlying genotypic differences. In addition, some species hybridize, and this can affect their subsequent transmission and pathology. For example, hybrids between L. infantum and L. major have greater transmission potential (Volf et al. 2007).

Present day members of the genus Leishmania are responsible for a great deal of morbidity and mortality in us and some cause serious disease in domestic and wild animals. There is even a suggestion that ancestral versions of Leishmania (with help from some other parasites) killed off the dinosaurs (Poinar and Poinar 2008). However, this theory has not gained a lot of support and most scientists continue to blame a meteorite. In humans, leishmaniasis exists as a complex of diseases caused by various species of Leishmania. While it is convenient to group those species of Leishmania, which invade organs as ‘visceral’ and those which affect the outer body surface as ‘cutaneous’, the distinctions are far from clear. For example, L. donovani is normally associated with the development of visceral leishmaniasis, but it can become cutaneous – as in the development of post kala‐azar dermal leishmaniasis (see later). Similarly, L. tropica usually causes cutaneous leishmaniasis but can infect the viscera. Some 12 million people are infected with