Leishmania

Abstract

Leishmania are vector‐borne parasitic protozoa that cause the human tropical disease leishmaniasis. Over 30 species have been described, with 11 of these being important pathogens. The disease has three main forms: cutaneous, mucocutaneous and visceral leishmaniasis. The parasites undergo a complex developmental cycle in their phlebotomine sand fly vectors leading to the differentiation of infectious metacyclic promastigote forms, and are transmitted by bite. Many species are zoonotic, being maintained in domestic or wild animal reservoir hosts, and the others are anthroponotic and transmitted from human to human. In their mammalian hosts they live as intracellular amastigote forms inside macrophages. There are relatively few drugs available to treat leishmaniasis, and control of the sand fly vectors or reservoir hosts is difficult. The best long‐term solution to the public health challenge of leishmaniasis will be vaccines, and progress is being made, but an effective vaccine for human usage has not been developed yet.

Key Concepts

  • Leishmania are intracellular parasites that live in the phagolysosomes of macrophages, a unique location for a eukaryotic pathogen.
  • The different forms of leishmaniasis result from infection of differently located populations of macrophages and the human response to infection.
  • Leishmaniasis is a chronic infection that can be treated, but limited drugs are available and no prophylactic vaccine is yet available for human use.
  • There are many species of Leishmania but all share a common set of molecular, biochemical and cell biological features along with species‐specific properties.
  • There are more sand fly vectors than Leishmania species, but they exist in specific pairs, each parasite being transmitted by one or more particular species of sand fly.

Keywords: parasitic protozoa; phlebotomine sand fly; tropical medicine; anthroponotic; zoonotic; promastigote; amastigote; Viannia; Sauroleishmania

Figure 1. The geographical distribution of leishmaniasis. The distribution of individual Leishmania species and the diseases they cause is given in Table. Some 350 million people in over 100 countries are at risk of infection. The main areas are indicated, but within these transmission varies from sporadic to intense, and may be continuous, seasonal or epidemic in nature. Risk of transmission is localised, with each individual focus of transmission separated from others by geographical or ecological barriers.
Figure 2. Phylogeny of Leishmania. Analysis of 21 species of Leishmania is shown, including the 11 species described in Table. In addition to these are shown: L. turanica and L. gerbilli, two nonpathogenic species closely related to L. major, and both in subgenus Leishmania (A); four species in the subgenus Sauroleishmania (B), L. adleri, L. gymnodactyli, L. hoogstraali and L. tarentolae, none of which are pathogenic to humans; two additional species in subgenus Viannia (C), L. naiffi and L. lainsoni both human pathogens; and two members of the L. enriettii species complex, L. enriettii (nonpathogen) and L. martiniquensis (pathogen). Crithidia fasciculata was used as the outgroup.
Figure 3. The life cycle of Leishmania. The parasites alternate between a female sand fly and mammalian host. In addition to humans, the medically important species can also be transmitted to a variety of animal reservoir hosts (for details see Table). In most endemic regions it is these reservoir hosts that are responsible for long‐term maintenance of the parasite life cycle. This is because human infections, although serious for the individual, are not easily acquired by sand flies and, therefore, represent a dead end for the parasite in such cases. However, important exceptions are L. donovani and L. tropica, where sand flies can acquire infection from human hosts. The progress of human infection is quite variable, but follows two general patterns: a skin lesion developing into cutaneous leishmaniasis or absence of a skin lesion followed by development of visceral leishmaniasis. Parasites are acquired by female sand flies during blood feeding, and initially multiply in the blood meal within the abdominal midgut of the sand fly. Two patterns of development are seen: in members of the subgenus Leishmania the infection spreads directly to the anterior midgut; in members of the subgenus Viannia there is a phase in the hindgut first. In both cases the parasites accumulate at the stomodeal valve, which separates the midgut from the foregut. From this position they can be transmitted when the sand fly inserts her proboscis to take another blood meal.
Figure 4. Developmental forms of Leishmania. Each cell contains a central nucleus (n) and kinetoplast (k) in the single mitochondrion (mt). The flagellum (f) arises from the flagellar pocket (fp). Amastigote forms are intracellular, nonmotile and found in the mammalian host. Promastigote forms are extracellular, motile and found in the sand fly host.
Figure 5. The leishmaniasis spectrum: the range of potential events and outcomes following inoculation of a human host by Leishmania parasites. Individual Leishmania species have different potentials: letters by arrows indicate parasites with potential to cause cutaneous (C), mucocutaneous (MC) or visceral (V) disease (Table). The final outcomes are boxed in blue. ‘Subclinical infection’ is where the parasite is present but there are no overt signs of disease; ‘metastasis’ indicates spread from the initial site of inoculation to other locations and ‘intractable lesions’ are persistent lesions that do not respond to treatment and do not resolve naturally. Only the most common outcomes are shown. For example, chemotherapy could be used to treat all infections, but is commonly applied only to visceral disease.
close

References

Abdeladhim M, Kamhawi S and Valenzuela JG (2014) What's behind a sand fly bite? The profound effect of sand fly saliva on host hemostasis, inflammation and immunity. Infection, Genetics and Evolution 28: 691–703. DOI: 10.1016/j.meegid.2014.07.028.

Alvar J, Vélez ID, Bern C, et al. (2012) WHO leishmaniasis control team: leishmaniasis worldwide and global estimates of its incidence. PLoS One 7: e35671.

Ashford RW (2000) The leishmaniases as emerging and reemerging zoonoses. International Journal for Parasitology 30: 1269–1281.

Bates PA and Rogers ME (2004) New insights into the developmental biology and transmission mechanisms of Leishmania. Current Molecular Medicine 4: 601–609.

Bates PA and Ashford RW (2005) Leishmaniasis in the old world. In: Wakelin D, Cox FEG, Despommier D and Gillespie S (eds) Topley and Wilson's Microbiology and Microbial Infections, 10th edn, vol. 5, Parasitology, pp. 283–312. London: Edward Arnold.

Bates PA (2007) Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies. International Journal for Parasitology 37: 1097–1106.

Bates PA, Depaquit J, Galati EA, et al. (2015) Recent advances in phlebotomine sand fly research related to leishmaniasis control. Parasites and Vectors 8: 131. DOI: 10.1186/s13071-015-0712-x.

Boelaert M, Verdonck K, Menten J, et al. (2014) Rapid tests for the diagnosis of visceral leishmaniasis in patients with suspected disease. Cochrane Database Systematic Reviews 6: CD009135.

Bogdan C, Donhauser N, Doring R, et al. (2000) Fibroblasts as host cells in latent leishmaniosis. Journal of Experimental Medicine 191: 2121–2130.

Cantacessi C, Dantas‐Torres F, Nolan MJ and Otranto D (2015) The past, present, and future of Leishmania genomics and transcriptomics. Trends in Parasitology 31: 100–108.

Carlsen ED, Liang Y, Shelite TR, et al. (2015) Permissive and protective roles for neutrophils in leishmaniasis. Clinical and Experimental Immunology. DOI: 10.1111/cei.12674.

Cecílio P, Pérez‐Cabezas B, Santarém N, et al. (2014) Deception and manipulation: the arms of Leishmania, a successful parasite. Frontiers in Immunology 5: 480.

Croft SL and Olliaro P (2011) Leishmaniasis chemotherapy ‐ challenges and opportunities. Clinical Microbiology and Infection 17: 1478–1483.

Davies CR, Kaye P, Croft SL and Sundar S (2003) Leishmaniasis: new approaches to disease control. British Medical Journal 326: 377–382.

van Griensven J, Carrillo E, López‐Vélez R, Lynen L and Moreno J (2014) Leishmaniasis in immunosuppressed individuals. Clinical Microbiology and Infection 20: 286–299.

Hajduk S and Ochsenreiter T (2010) RNA editing in kinetoplastids. RNA Biology 7: 229–236.

von der Heyden S, Chao EE, Vickerman K and Cavalier‐Smith T (2004) Ribosomal RNA phylogeny of bodonid and diplonemid flagellates and the evolution of euglenozoa. Journal of Eukaryotic Microbiology 51: 402–416.

Jensen RE and Englund PT (2012) Network news: the replication of kinetoplast DNA. Annual Review of Microbiology 66: 473–491.

Kamhawi S (2006) Phlebotomine sand flies and Leishmania parasites: friends or foes? Trends in Parasitology 22: 439–445.

Kumar R and Engwerda C (2014) Vaccines to prevent leishmaniasis. Clinical and Translational Immunology 3: e13.

Kwakye‐Nuako G, Mosore MT, Duplessis C, et al. (2015) First isolation of a new species of Leishmania responsible for human cutaneous leishmaniasis in Ghana and classification in the Leishmania enriettii complex. International Journal for Parasitology. DOI: 10.1016/j.ijpara.2015.05.001.

Lainson R and Shaw JJ (2005) New world leishmaniasis – the neotropical Leishmania species. In: Wakelin D, Cox FEG, Despommier D and Gillespie S (eds) Topley and Wilson's Microbiology and Microbial Infections, 10th edn, vol. 5, Parasitology, pp. 313–349. London: Edward Arnold.

Lukeš J, Skalický T, Týč J, Votýpka J and Yurchenko V (2014) Evolution of parasitism in kinetoplastid flagellates. Molecular and Biochemical Parasitology 195: 115–122.

McCall LI, Zhang WW and Matlashewski G (2013) Determinants for the development of visceral leishmaniasis disease. PLoS Pathogens 9: e1003053.

McConville MJ and Ferguson MAJ (1993) The structure, biosynthesis and function of glycosyl‐phosphatidylinositols in the parasitic protozoa and higher eukaryotes. Biochemical Journal 294: 305–324.

Moreira D, López‐García P and Vickerman K (2004) An updated view of kinetoplastid phylogeny using environmental sequences and a closer outgroup: proposal for a new classification of the class Kinetoplastea. International Journal of Systematic and Evolutionary Microbiology 54: 1861–1875.

Muller S, Liebau E, Walter RD and Krauth‐Siegel RL (2003) Thiol‐based redox metabolism of protozoan parasites. Trends in Parasitology 19: 320–327.

Noyes HA, Chance ML, Croan DG and Ellis JT (1998) Leishmania (Sauroleishmania): a comment on classification. Parasitology Today 14: 167.

Nylén S and Eidsmo L (2012) Tissue damage and immunity in cutaneous leishmaniasis. Parasite Immunology 34: 551–561.

Ready PD (2013) Biology of phlebotomine sand flies as vectors of disease agents. Annual Review of Entomology 58: 227–250.

Rogers ME, Chance ML and Bates PA (2002) The role of promastigote secretory gel in the origin and transmission of the infective stage of Leishmania mexicana by the sandfly Lutzomyia longipalpis. Parasitology 124: 495–508.

Rogers ME, Ilg T, Nikolaev AV, Ferguson MAJ and Bates PA (2004) Transmission of cutaneous leishmaniasis by sand flies is enhanced by regurgitation of fPPG. Nature 430: 463–467.

Rogers ME and Bates PA (2007) Leishmania manipulation of sand fly feeding behavior results in enhanced transmission. PLoS Pathogens 3: e91.

Roque AL and Jansen AM (2014) Wild and synanthropic reservoirs of Leishmania species in the Americas. International Journal for Parasitology: Parasites and Wildlife 3: 251–262.

Sacks D and Kamhawi S (2001) Molecular aspects of parasite–vector and vector–host interactions in leishmaniasis. Annual Review of Microbiology 55: 453–483.

Sakthianandeswaren A, Foote SJ and Handman E (2009) The role of host genetics in leishmaniasis. Trends in Parasitology 25: 383–391.

Stiles JK, Hicock PI, Shah PH and Meade JC (1999) Genomic organization, transcription, splicing and gene regulation in Leishmania. Annals of Tropical Medicine and Parasitology 93: 781–807.

Zilberstein D and Shapira M (1994) The role of pH and temperature in the development of Leishmania parasites. Annual Review of Microbiology 48: 449–470.

Further Reading

Adak S and Datta R (eds) (2015) Leishmania: Current Biology and Control. Poole, UK: Caister Academic Press.

Coombs GH and North M (eds) (1991) Biochemical Protozoology. London: Taylor & Francis.

Farrell JP (ed.) (2002) Leishmania (World Class Parasites 4). Boston, MA: Kluwer Academic Publishers.

Hide G, Mottram JC, Coombs GH and Holmes PH (eds) (1997) Trypanosomiasis and Leishmaniasis, Biology and Control. Wallingford, UK: CAB International.

Marr JJ, Nilsen TW and Komuniecki R (2003) Molecular Medical Parasitology. Boston, MA: Academic Press.

Molyneux DH and Ashford RW (1983) The Biology of Trypanosoma and Leishmania, Parasites of Man and Domestic Animals. London: Taylor & Francis.

Myler PJ and Fasel N (eds) (2008) Leishmania: After the Genome. Poole, UK: Caister Academic Press.

Peters W and Killick‐Kendrick R (eds) (1987) The Leishmaniases in Biology and Medicine. London: Academic Press.

Smith DF and Parsons M (eds) (1996) Molecular Biology of Parasitic Protozoa. Oxford: Oxford University Press.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Bates, Paul A(Nov 2015) Leishmania. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001968.pub3]