Leishmania donovani: Difference between revisions
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It is estimated that visceral leishmaniasis (VL) affects more than 100 million people worldwide, with 500,000 new cases and |
It is estimated that visceral leishmaniasis (VL) affects more than 100 million people worldwide, with 500,000 new cases and |
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more than 50,000 deaths each year.<ref name=desj/><ref>{{cite journal|last=Desjeux|first=P|title=The increase in risk factors for leishmaniasis worldwide.|journal=Transactions of the Royal Society of Tropical Medicine and Hygiene|date=2001 May-Jun|year=2001|volume=95|issue=3|pages=239-43|pmid=11490989}}</ref> Although ''L. donovani'' is only the second-most prevalent ''Leishmania'' causing VL, it is the most dangerous form and directly fatal to humans. It is responsible for tens of thousands of mortality among Africans in eastern and southern parts of Sudan. During the epidemic of 1984–1994 death toll was as high as 70% in the [[Sudanese people|Sudanese]] population.<ref>{{cite journal|last=Seaman|first=J|coauthors=Mercer, AJ; Sondorp, E|title=The epidemic of visceral leishmaniasis in western Upper Nile, southern Sudan: course and impact from 1984 to 1994.|journal=International Journal of Epidemiology|year=1996|volume=25|issue=4|pages=862-71|pmid=8921468}}</ref> Moreover due to emergence of [[drug resistance]] the prevalence is not subsiding, and in fact has spread to central Europe. For example during the the late 1990s hundreds of cases were reported in [[Switzerland]]. |
more than 50,000 deaths each year.<ref name=desj/><ref>{{cite journal|last=Desjeux|first=P|title=The increase in risk factors for leishmaniasis worldwide.|journal=Transactions of the Royal Society of Tropical Medicine and Hygiene|date=2001 May-Jun|year=2001|volume=95|issue=3|pages=239-43|pmid=11490989}}</ref> Although ''L. donovani'' is only the second-most prevalent ''Leishmania'' causing VL, it is the most dangerous form and directly fatal to humans. It is responsible for tens of thousands of mortality among Africans in eastern and southern parts of Sudan. During the epidemic of 1984–1994 death toll was as high as 70% in the [[Sudanese people|Sudanese]] population.<ref>{{cite journal|last=Seaman|first=J|coauthors=Mercer, AJ; Sondorp, E|title=The epidemic of visceral leishmaniasis in western Upper Nile, southern Sudan: course and impact from 1984 to 1994.|journal=International Journal of Epidemiology|year=1996|volume=25|issue=4|pages=862-71|pmid=8921468}}</ref> Moreover due to emergence of [[drug resistance]] the prevalence is not subsiding, and in fact has spread to central Europe. For example during the the late 1990s hundreds of cases were reported in [[Switzerland]].<ref name=max>{{cite web|title=Cure for Fatal Tropical Disease - Oral Treatment of Leishmaniasis|url=http://www3.mpibpc.mpg.de/groups/eibl/pressrelease/leish_e.html|publisher=Max Planck Institute for Biophysical Chemistry|accessdate=25 January 2014|date=18 February 2000}}</ref> |
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==Pathogenicity== |
==Pathogenicity== |
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''L. donovani'' is the causative agent of visceral leishmaniasis, traditionally known as ''kala-azar'' ("black fever", particularly in India), because of its characteristic symptoms. The disease is a highly lethal if not treated properly. [[Incubation period]] generally ranges from 3 to 6 months, and in some cases may be over a year. Clinical symptoms include [[pyrexia]] (recurring high fever which may be continuous or remittent), enlargement of spleen and liver, and heavy [[melanism|skin pigmentation]] which darkens the physical appearance (the reason for naming "black fever"). Skin becomes coarse and hard. In African infections [[wart]]y eruptions are common. In a fully developed stage, the patient show [[emaciation]] and [[anaemia]]. Where medical facilities are poor, mortality can be as high as 75–95% within 2 years of epidemics. The disease is often accompanied by complications with [[dysentery]], [[tuberculosis]], [[septicaemia]] and even [[HIV]] infection.<ref name=chat/><ref>{{cite journal|last=Okwor|first=I|coauthors=Uzonna, JE|title=The immunology of Leishmania/HIV co-infection.|journal=Immunologic Research|date=2013 May|year=2013|volume=56|issue=1|pages=163-71|pmid=23504228|doi= 10.1007/s12026-013-8389-8}}</ref><ref>{{cite journal|last=Olivier|first=M|coauthors=Badaró, R; Medrano, FJ; Moreno, J|title=The pathogenesis of Leishmania/HIV co-infection: cellular and immunological mechanisms.|journal=Annals of tropical medicine and parasitology|year=2003|volume=97|issue=Suppl 1|pages=79-98|pmid=14678636}}</ref> |
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''L. donovani'' is the causative agent of visceral leishmaniasis, traditionally known as ''kala-azar'' ("black fever"), because of its characteristic symptoms. The disease is a highly lethal if not treated properly. |
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==Evolution== |
==Evolution== |
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*[https://www.msu.edu/course/zol/316/lspptissue.htm Brief account] |
*[https://www.msu.edu/course/zol/316/lspptissue.htm Brief account] |
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*[http://homepages.uel.ac.uk/D.P.Humber/akhter/trans.htm Transmission of visceral leishmaniasis] |
*[http://homepages.uel.ac.uk/D.P.Humber/akhter/trans.htm Transmission of visceral leishmaniasis] |
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*[https://www.stanford.edu/class/humbio103/ParaSites2006/Leishmaniasis/visceral.htm Visceral leishmaniasis at Stanford] |
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{{Protozoal diseases}} |
{{Protozoal diseases}} |
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Revision as of 03:35, 25 January 2014
| Leishmania donovani | |
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| Leishmania donovani in bone marrow cell | |
| Scientific classification | |
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| Species: | Leishmania donovani
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| Leishmania donovani | |
Leishmania donovani is a species of intracellular parasitic protozoan belonging to the genus Leishmania, a group of haemoflagellate kinetoplastids that cause the disease leishmaniasis. It is a human blood parasite responsible for visceral leishmaniasis or kala-azar, the most severe form of leishmaniasis. It infects the mononuclear phagocyte system including spleen, liver and bone marrow. Infection is transmitted by species of sandfly belonging to the genus Phlebotomus in Old World and Lutzomyia in New World. Threfore the parasite is prevalent throughout tropical and temperate regions including Africa (mostly in Sudan), China, India, Nepal, southern Europe, Russia and South America.[1][2][3] It is responsible thousands of deaths every year in 88 countries, with 350 million people at constant risk of infection and 0.5 million new cases in a year.[4]
L. donovani require two diiferent hosts to complete its life cycle, humans as the definitive host and sandflies as the intermediate host. In some parts of the world other mammals, especially canines, act as reservoir hosts. In human cell they exist as small, spherical and unflagellated amastigote form; while they are elongated with flagellum as promastigote form in sandflies. Unlike other parasitic protists they are unable to directly penetrate the host cell, and are dependent upon phagocytosis.[5][6] The whole genome sequence of L. donovani obtained from southeastern Nepal was published in 2011.[7]
Structure
Leishmania donovani is a unicellular eukaryote having well-defined nucleus and other cell organelles including kinetoplast and flagellum. Depending on its host it exists in two structural variants, as follows:[8][9]
- Amastigote form found in the mononuclear phagocyte and circulatory systems of humans. It is an intracellular and non-motile form, being devoid of external flagellum. 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.
- Promastigote form found in the alimentary tract of sandfly. 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 kinetoplast and basal body.
Infection and life cycle
Leishmania donovani is a digenetic parasite passing its life cycle in two different hosts.
Definitive host
In humans the metacyclic promastigotes are injected by sandfly through the skin during its blood meal. When sandfly bites using its proboscis it ejects the parasites that are stored inside the hollow tube. Some trypomastigotes may enter the blood stream directly where some are destroyed by macrophagic cytolysis. But many are also taken up through phagocytosis by mononuclear phagocytes in liver, spleen and bone marrow. Inside the cells they undergo spontaneous transformation into oval-shaped amastigotes. Then cell division occurs using binary fission. Multiplication continues until the host cell can no longer hold and ruptures. In a fully congested cell there can be as many as 50 to 200 amastigotes, which are released into tissue cavities. Each indivial amastigote is then capable of invading fresh cells. As a result the entire tissues is progressively infected and destroyed. A number of free amastigotes then enters the blood stream where many are phagocytosed by macrophages. These free and phagocytosed amastigotes in peripheral blood are then sucked up by blood-feeding sandfly.[10]
Intermediate host
L. donovani undergo further development only in the digestive tract of female sandfly. Hence only females are responsible for transmitting the infection. Once the amastigotes are ingested, they enter the midgut of the sandfly. Then they undergo structural modification into flagellated promastigotes, becoming larger and considerably elongated. They get attached to the gut epithelial lining where they multiply rapidly by binary fission. They migrate back towards the anterior part of the digestive system such as pharynx and buccal cavity. This process is known as anterior station development, which is unique in Leishmania. A heavy infection of pharynx can be observed within 6 to 9 days after initial blood meal. The promastigotes become infective only by this time, and the event is called the metacyclic stage.[10] The metacyclic trypomastigotes then enter the hollow proboscis completely blocking the food passage. Immediately biting a human, the parasites are released, which invariably results in infection. The stages of development in sandfly can be described as follows:[8]
- The amastigotes get coated with peritrophic matrix, which is composed of chitin and protein complex. This protects the prasites from the digestive enzymes of the host.
- The amastigotes travel as far as the abdominal midgut and first transform into a weakly motile "procyclic promastigotes" in the thoracic midgut within 1–3 days.
- The young promastigotes secrete a neuropeptide that stop peristalsis of the gut. This prevents the expulsion of promastigotes.
- During 4–7 days the peritrophic matrix is degraded by the activity of chitinases. This release the more actively motile "nectomonad promastigotes" which migrate anteriorly until they reach the opening of the thoraxic gut.
- Another transformation take place by which they turn into "leptomonad promastigotes". These are fully motile and capable of binary fission. Multiplication and migration towards thoraxic midgut cause congestion of the pharynx and buccal cavity. Here they secrete promastigote secretory gel (PSG) that contains high molecular weight filamentous proteophophoglycans.
- After 6–9 days the promastigote became metacyclic. Some are also transformed into non-replicating promastigotes, which also become metacyclic. The sandfly is able to regurgitate and eject the parasites from its proboscis with the help of PSG when it bites.
Reservoir host
Dogs are known to be susceptible to L. donovani infection.[11] Especially in the New World, infection is a zoonotic disease, involving different canine species, including domestic dog and the two fox species, Lycalopex vetulus and Cerdocyon thous. In the Mediterranean region domestic dogs and the three fox species Vulpes vulpes , V. Corsac and V. zerda are common reservoir hosts.[12][13] In Africa and Brazil, some marsupials and rodents are also reported to harbour L. donovani.[14]
Epidemiology
It is estimated that visceral leishmaniasis (VL) affects more than 100 million people worldwide, with 500,000 new cases and more than 50,000 deaths each year.[4][15] Although L. donovani is only the second-most prevalent Leishmania causing VL, it is the most dangerous form and directly fatal to humans. It is responsible for tens of thousands of mortality among Africans in eastern and southern parts of Sudan. During the epidemic of 1984–1994 death toll was as high as 70% in the Sudanese population.[16] Moreover due to emergence of drug resistance the prevalence is not subsiding, and in fact has spread to central Europe. For example during the the late 1990s hundreds of cases were reported in Switzerland.[17]
Pathogenicity
L. donovani is the causative agent of visceral leishmaniasis, traditionally known as kala-azar ("black fever", particularly in India), because of its characteristic symptoms. The disease is a highly lethal if not treated properly. Incubation period generally ranges from 3 to 6 months, and in some cases may be over a year. Clinical symptoms include pyrexia (recurring high fever which may be continuous or remittent), enlargement of spleen and liver, and heavy skin pigmentation which darkens the physical appearance (the reason for naming "black fever"). Skin becomes coarse and hard. In African infections warty eruptions are common. In a fully developed stage, the patient show emaciation and anaemia. Where medical facilities are poor, mortality can be as high as 75–95% within 2 years of epidemics. The disease is often accompanied by complications with dysentery, tuberculosis, septicaemia and even HIV infection.[10][18][19]
Evolution
L. donovani is now considered as a complex species as indicated by different pathological symptoms occurring in different geographical areas where the species of the vector sandfly are also different. However none of the parasites are morphologically indistinguishable, except by molecular analysis. Molecular data show that genotype is strongly correlated with geographical origin. DNA sequencing of different geographical strains indicate that the protozoan complex can be classified into two valid taxons, L. donovani and L. infantum. The genus Leishmania most likely originated in South America, from where it migrated to Asia. L. donovani and L. infantum diverged ~1 Mya, with further divergence of infraspecific genetic groups between 0.4 and 0.8 Mya.[20]
References
- ^ van Griensven, Johan (2012). "Visceral Leishmaniasis". Infectious Disease Clinics of North America. 26 (2): 309–322. doi:10.1016/j.idc.2012.03.005. PMID 22632641.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help); Unknown parameter|month=ignored (help) - ^ Evans, TG (1993 Sep). "Leishmaniasis". Infectious Disease Clinics of North America. 7 (3): 527–46. PMID 8254158.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: date and year (link) - ^ Herwaldt, BL (1999). "Leishmaniasis". Lancet. 354 (9185): 1191–9. PMID 10513726.
- ^ a b Desjeux, P (2004). "Leishmaniasis: current situation and new perspectives". Comparative Immunology, Microbiology and Infectious Diseases. 27 (5): 305–18. PMID 15225981.
- ^ Engwerda, CR (2004). "Macrophages, pathology and parasite persistence in experimental visceral leishmaniasis". Trends in Parasitology. 20 (11): 524–30. PMID 15471704.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Lodge, R (2008). "Leishmania invasion and phagosome biogenesis". Sub-cellular biochemistry. 47: 174–81. PMID 18512351.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help)CS1 maint: date and year (link) - ^ Downing, T (2011). "Whole genome sequencing of multiple Leishmania donovani clinical isolates provides insights into population structure and mechanisms of drug resistance". Genome research. 21 (12): 2143–56. doi:10.1101/gr.123430.111. PMID 22038251.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ a b "Morphology and Life Cycle". UCLA. Retrieved 24 January 2014.
- ^ Pulvertaft, RJ (1960). "Stages in the life-cycle of Leishmania donovani". Transactions of the Royal Society of Tropical Medicine and Hygiene. 54 (2): 191–6. doi:10.1016/0035-9203(60)90057-2. PMID 14435316.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ a b c Chatterjee, K.D. (2009). Parasitology (protozoology and helminthology) in relation to clinical medicine (13th ed. ed.). New Delhi: CBC Publishers. pp. 67–72. ISBN 9788123918105.
{{cite book}}:|edition=has extra text (help) - ^ Hassan, Mo'awia M (2009). "Role of the domestic dog as a reservoir host of Leishmania donovani in eastern Sudan". Parasites & Vectors. 2 (1): 26. doi:10.1186/1756-3305-2-26. PMC 2706818. PMID 19534802.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help)CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ Ashford, RW (1996). "Leishmaniasis reservoirs and their significance in control". Clinics in Dermatology. 14 (5): 523–32. PMID 8889331.
- ^ Shaw, JJ (1988). "Animal reservoirs of Leishmania in different ecological situations and their importance in the epidemiology of the disease". Memorias do Instituto Oswaldo Cruz. 83 (Suppl 1): 486–90. PMID 3253511.
- ^ Lainson, R (2005). "Lutzomyia longipalpis and the eco-epidemiology of American visceral leishmaniasis, with particular reference to Brazil: a review". Memorias do Instituto Oswaldo Cruz. 100 (8): 811–27. PMID 16444411.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Desjeux, P (2001 May-Jun). "The increase in risk factors for leishmaniasis worldwide". Transactions of the Royal Society of Tropical Medicine and Hygiene. 95 (3): 239–43. PMID 11490989.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: date and year (link) - ^ Seaman, J (1996). "The epidemic of visceral leishmaniasis in western Upper Nile, southern Sudan: course and impact from 1984 to 1994". International Journal of Epidemiology. 25 (4): 862–71. PMID 8921468.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ "Cure for Fatal Tropical Disease - Oral Treatment of Leishmaniasis". Max Planck Institute for Biophysical Chemistry. 18 February 2000. Retrieved 25 January 2014.
- ^ Okwor, I (2013 May). "The immunology of Leishmania/HIV co-infection". Immunologic Research. 56 (1): 163–71. doi:10.1007/s12026-013-8389-8. PMID 23504228.
{{cite journal}}: Check date values in:|date=(help); Unknown parameter|coauthors=ignored (|author=suggested) (help)CS1 maint: date and year (link) - ^ Olivier, M (2003). "The pathogenesis of Leishmania/HIV co-infection: cellular and immunological mechanisms". Annals of tropical medicine and parasitology. 97 (Suppl 1): 79–98. PMID 14678636.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help) - ^ Lukes, J. (2007). "Evolutionary and geographical history of the Leishmania donovani complex with a revision of current taxonomy". Proceedings of the National Academy of Sciences. 104 (22): 9375–9380. doi:10.1073/pnas.0703678104. PMC 1890502. PMID 17517634.
{{cite journal}}: Unknown parameter|coauthors=ignored (|author=suggested) (help)CS1 maint: PMC format (link)