African trypanosomiasis pathophysiology: Difference between revisions

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__NOTOC__
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{{African trypanosomiasis}}
{{African trypanosomiasis}}
{{CMG}}; {{AOEIC}} Pilar Almonacid; {{ADG}}
{{CMG}}; {{AOEIC}} Pilar Almonacid, {{ADG}}
==Overview==
==Overview==
African trypanosomiasis is a human tropical [[parasitic]] [[disease]] usually caused by [[Protozoa|protozoan]] hemoflagellates belonging to the complex ''[[Trypanosoma brucei]]''. A trypanosomal [[chancre]] develops on the site of [[inoculation]]. This is followed by a hemolymphatic stage with symptoms that include [[fever]], [[lymphadenopathy]], and [[pruritus]]. In the [[Meningoencephalitis|meningoencephalitic]] stage, invasion of the [[central nervous system]] can cause [[headache]]s, [[somnolence]], abnormal behavior, and lead to [[loss of consciousness]] and [[coma]]. The course of [[infection]] is much more acute with [[Trypanosoma brucei rhodesiense|''Trypanosoma brucei rhodesiense'']] than [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']]. Clinical manifestations generally appear within 1–3 weeks of the [[Infection|infective]] bite for ''[[Trypanosoma brucei rhodesiense]]'' and months to years for ''[[Trypanosoma brucei gambiense]]''.<ref name="pmid16673459">{{cite journal |vauthors= |title=Human African trypanosomiasis (sleeping sickness): epidemiological update |journal=Wkly. Epidemiol. Rec. |volume=81 |issue=8 |pages=71–80 |year=2006 |pmid=16673459 |doi= |url=}}</ref><ref name="pmid26807135">{{cite journal |vauthors=Kato CD, Matovu E, Mugasa CM, Nanteza A, Alibu VP |title=The role of cytokines in the pathogenesis and staging of Trypanosoma brucei rhodesiense sleeping sickness |journal=Allergy Asthma Clin Immunol |volume=12 |issue= |pages=4 |year=2016 |pmid=26807135 |pmc=4722787 |doi=10.1186/s13223-016-0113-5 |url=}}</ref><ref name="pmid18546153">{{cite journal |vauthors=Ferella M, Nilsson D, Darban H, Rodrigues C, Bontempi EJ, Docampo R, Andersson B |title=Proteomics in Trypanosoma cruzi--localization of novel proteins to various organelles |journal=Proteomics |volume=8 |issue=13 |pages=2735–49 |year=2008 |pmid=18546153 |pmc=2706665 |doi=10.1002/pmic.200700940 |url=}}</ref><ref name="pmid15771682">{{cite journal |vauthors=Sternberg JM |title=Human African trypanosomiasis: clinical presentation and immune response |journal=Parasite Immunol. |volume=26 |issue=11-12 |pages=469–76 |year=2004 |pmid=15771682 |doi=10.1111/j.0141-9838.2004.00731.x |url=}}</ref><ref name="urlCDC - African Trypanosomiasis - Biology">{{cite web |url=https://www.cdc.gov/parasites/sleepingsickness/biology.html |title=CDC - African Trypanosomiasis - Biology |format= |work= |accessdate=}}</ref><ref name="pmid17318257">{{cite journal |vauthors=Macleod ET, Darby AC, Maudlin I, Welburn SC |title=Factors affecting trypanosome maturation in tsetse flies |journal=PLoS ONE |volume=2 |issue=2 |pages=e239 |year=2007 |pmid=17318257 |pmc=1797825 |doi=10.1371/journal.pone.0000239 |url=}}</ref>
African trypanosomiasis is a human tropical [[parasitic]] [[disease]] usually caused by [[Protozoa|protozoan]] hemoflagellates belonging to the complex ''[[Trypanosoma brucei]]''. A trypanosomal [[chancre]] develops on the site of [[inoculation]]. This is followed by a hemolymphatic stage with [[symptoms]] that include [[fever]], [[lymphadenopathy]], and [[pruritus]]. In the [[Meningoencephalitis|meningoencephalitic]] stage, invasion of the [[central nervous system]] can cause [[headache]]s, [[somnolence]], abnormal behavior, [[loss of consciousness]] and [[coma]]. The course of [[infection]] is much more acute with [[Trypanosoma brucei rhodesiense|''Trypanosoma brucei rhodesiense'']] than with [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']]. Clinical manifestations generally appear within 1–3 weeks of the [[Infection|infective]] bite for ''[[Trypanosoma brucei rhodesiense]]'' and months to years for ''[[Trypanosoma brucei gambiense]]''.


==Pathophysiology==
==Pathophysiology==
African trypanosomiasis is a human tropical [[parasitic]] [[disease]] usually caused by [[Protozoa|protozoan]] hemoflagellates belonging to the complex ''[[Trypanosoma brucei]]''. A trypanosomal [[chancre]] develops on the site of [[inoculation]]. This is followed by a hemolymphatic stage with symptoms that include [[fever]], [[lymphadenopathy]], and [[pruritus]]. In the [[Meningoencephalitis|meningoencephalitic]] stage, invasion of the [[central nervous system]] can cause [[headache]]s, [[somnolence]], abnormal behavior, and lead to [[loss of consciousness]] and [[coma]]. The course of [[infection]] is much more acute with [[Trypanosoma brucei rhodesiense|''Trypanosoma brucei rhodesiense'']] than [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']]. Clinical manifestations generally appear within 1–3 weeks of the [[Infection|infective]] bite for ''[[Trypanosoma brucei rhodesiense]]'' and months to years for ''[[Trypanosoma brucei gambiense]]''.<ref name="pmid16673459">{{cite journal |vauthors= |title=Human African trypanosomiasis (sleeping sickness): epidemiological update |journal=Wkly. Epidemiol. Rec. |volume=81 |issue=8 |pages=71–80 |year=2006 |pmid=16673459 |doi= |url=}}</ref><ref name="pmid26807135">{{cite journal |vauthors=Kato CD, Matovu E, Mugasa CM, Nanteza A, Alibu VP |title=The role of cytokines in the pathogenesis and staging of Trypanosoma brucei rhodesiense sleeping sickness |journal=Allergy Asthma Clin Immunol |volume=12 |issue= |pages=4 |year=2016 |pmid=26807135 |pmc=4722787 |doi=10.1186/s13223-016-0113-5 |url=}}</ref><ref name="pmid18546153">{{cite journal |vauthors=Ferella M, Nilsson D, Darban H, Rodrigues C, Bontempi EJ, Docampo R, Andersson B |title=Proteomics in Trypanosoma cruzi--localization of novel proteins to various organelles |journal=Proteomics |volume=8 |issue=13 |pages=2735–49 |year=2008 |pmid=18546153 |pmc=2706665 |doi=10.1002/pmic.200700940 |url=}}</ref><ref name="pmid15771682">{{cite journal |vauthors=Sternberg JM |title=Human African trypanosomiasis: clinical presentation and immune response |journal=Parasite Immunol. |volume=26 |issue=11-12 |pages=469–76 |year=2004 |pmid=15771682 |doi=10.1111/j.0141-9838.2004.00731.x |url=}}</ref><ref name="urlCDC - African Trypanosomiasis - Biology">{{cite web |url=https://www.cdc.gov/parasites/sleepingsickness/biology.html |title=CDC - African Trypanosomiasis - Biology |format= |work= |accessdate=}}</ref><ref name="pmid17318257">{{cite journal |vauthors=Macleod ET, Darby AC, Maudlin I, Welburn SC |title=Factors affecting trypanosome maturation in tsetse flies |journal=PLoS ONE |volume=2 |issue=2 |pages=e239 |year=2007 |pmid=17318257 |pmc=1797825 |doi=10.1371/journal.pone.0000239 |url=}}</ref>
African trypanosomiasis is a human tropical [[parasitic]] [[disease]] usually caused by [[Protozoa|protozoan]] hemoflagellates belonging to the complex ''[[Trypanosoma brucei]]''. A trypanosomal [[chancre]] develops on the site of [[inoculation]]. This is followed by a hemolymphatic stage with symptoms that include [[fever]], [[lymphadenopathy]] and [[pruritus]]. In the [[Meningoencephalitis|meningoencephalitic]] stage, invasion of the [[central nervous system]] can cause [[headache]]s, [[somnolence]], abnormal behavior, and lead to [[loss of consciousness]] and [[coma]]. The course of [[infection]] is much more acute with [[Trypanosoma brucei rhodesiense|''Trypanosoma brucei rhodesiense'']] than [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']]. Clinical manifestations generally appear within 1–3 weeks of the [[Infection|infective]] bite for ''[[Trypanosoma brucei rhodesiense]]'' and months to years for ''[[Trypanosoma brucei gambiense]]''.<ref name="pmid16673459">{{cite journal |vauthors= |title=Human African trypanosomiasis (sleeping sickness): epidemiological update |journal=Wkly. Epidemiol. Rec. |volume=81 |issue=8 |pages=71–80 |year=2006 |pmid=16673459 |doi= |url=}}</ref><ref name="pmid26807135">{{cite journal |vauthors=Kato CD, Matovu E, Mugasa CM, Nanteza A, Alibu VP |title=The role of cytokines in the pathogenesis and staging of Trypanosoma brucei rhodesiense sleeping sickness |journal=Allergy Asthma Clin Immunol |volume=12 |issue= |pages=4 |year=2016 |pmid=26807135 |pmc=4722787 |doi=10.1186/s13223-016-0113-5 |url=}}</ref><ref name="pmid18546153">{{cite journal |vauthors=Ferella M, Nilsson D, Darban H, Rodrigues C, Bontempi EJ, Docampo R, Andersson B |title=Proteomics in Trypanosoma cruzi--localization of novel proteins to various organelles |journal=Proteomics |volume=8 |issue=13 |pages=2735–49 |year=2008 |pmid=18546153 |pmc=2706665 |doi=10.1002/pmic.200700940 |url=}}</ref><ref name="pmid15771682">{{cite journal |vauthors=Sternberg JM |title=Human African trypanosomiasis: clinical presentation and immune response |journal=Parasite Immunol. |volume=26 |issue=11-12 |pages=469–76 |year=2004 |pmid=15771682 |doi=10.1111/j.0141-9838.2004.00731.x |url=}}</ref><ref name="urlCDC - African Trypanosomiasis - Biology">{{cite web |url=https://www.cdc.gov/parasites/sleepingsickness/biology.html |title=CDC - African Trypanosomiasis - Biology |format= |work= |accessdate=}}</ref><ref name="pmid17318257">{{cite journal |vauthors=Macleod ET, Darby AC, Maudlin I, Welburn SC |title=Factors affecting trypanosome maturation in tsetse flies |journal=PLoS ONE |volume=2 |issue=2 |pages=e239 |year=2007 |pmid=17318257 |pmc=1797825 |doi=10.1371/journal.pone.0000239 |url=}}</ref>
===Stages of infection===
*A trypanosomal [[chancre]] develops on the site of [[inoculation]]. 
*This is followed by a hemolymphatic stage with symptoms that include [[fever]], [[lymphadenopathy]], and [[pruritus]].
*In the [[Meningoencephalitis|meningoencephalitic]] stage, invasion of the [[central nervous system]] can cause [[headache]]s, [[somnolence]], abnormal behavior, and lead to [[loss of consciousness]] and [[coma]].
*The course of infection is much more acute with [[Trypanosoma brucei rhodesiense|''Trypanosoma brucei rhodesiense'']] than [[Trypanosoma brucei gambiense|''Trypanosoma brucei gambiense'']].
 
===Transmission===
===Transmission===
*[[Infection]] is usually transmitted via the [[tsetse fly]] bite to the human host.
*[[Infection]] is usually transmitted via the [[tsetse fly]] bite to the human host.


===Incubation period===
===Incubation period===
*Clinical manifestations generally appear within 1–3 weeks of the [[Infection|infective]] bite for ''[[Trypanosoma brucei rhodesiense]]'' and months to years for ''[[Trypanosoma brucei gambiense]]''.
*[[Clinical]] manifestations generally appear within 1–3 weeks of the [[Infection|infective]] bite for ''[[Trypanosoma brucei rhodesiense]]'' and months to years for ''[[Trypanosoma brucei gambiense]]''.


===Reservoir===
===Reservoir===
*[[Humans]] are the main [[reservoir]] for ''[[Trypanosoma brucei gambiense]]''.
*[[Humans]] are the main reservoir for ''[[Trypanosoma brucei gambiense]]''.
*Wild [[animals]] are the main reservoir of ''[[Trypanosoma brucei rhodesiense]]''.
*Wild [[animals]] are the main reservoir for ''[[Trypanosoma brucei rhodesiense]]''.


===Human cycle===
===Human cycle===
* During a [[blood]] meal on the [[mammalian]] host, an infected [[tsetse fly]] ([[genus]] ''Glossina'') injects metacyclic trypomastigotes into skin tissue.  
* During a [[blood]] meal on the [[mammalian]] host, an infected [[tsetse fly]] ([[genus]] ''Glossina'') injects metacyclic trypomastigotes into [[Skin|skin tissue]].  
* The [[parasites]] enter the [[lymphatic system]] and pass into the [[bloodstream]].
* The [[parasites]] enter the [[lymphatic system]] and pass into the [[bloodstream]].
* Inside the host, the microbe transforms into [[bloodstream]] trypomastigotes.
* Inside the host, the [[Microorganism|microbe]] transforms into [[bloodstream]] trypomastigotes.
* They are carried to other sites throughout the body, reach other blood fluids (e.g. [[lymph]], [[spinal fluid]]), and continue replication by [[binary fission]].
* They are carried to other sites throughout the body, reach other blood fluids (e.g., [[lymph]], [[spinal fluid]]), and continue replication by [[binary fission]].
* The entire life cycle of African trypanosomes is represented by [[extracellular]] stages.
* The entire life cycle of African [[trypanosomes]] consists of [[extracellular]] stages.
 
===Tsetse fly life-cycle===
===Tsetse fly life-cycle===
* The [[tsetse fly]] becomes infected with [[bloodstream]] trypomastigotes when taking a blood meal on an infected mammalian host.
* The [[tsetse fly]] becomes [[infected]] with [[bloodstream]] trypomastigotes when taking a blood meal on an infected mammalian host.
* In the fly’s [[midgut]], the [[parasites]] transform into procyclic trypomastigotes and multiply by [[binary fission]].
* In the fly’s [[midgut]], the [[parasites]] transform into procyclic trypomastigotes and multiply by [[binary fission]].
* Procyclic trypomastigotes leave the [[midgut]] and transform into epimastigotes.
* Procyclic trypomastigotes leave the [[midgut]] and transform into epimastigotes.
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===Diagnostic stage of the parasite===
===Diagnostic stage of the parasite===
*[[Bloodstream]] trypomastigotes
*[[Bloodstream]] trypomastigotes
===Pathogenesis===
==Pathogenesis==
*Trypomastigotes have [[proteins]] on their surface known as major variant surface [[glycoprotein]] (VSG). Approximately 10 million copies of a single VSG are present on each trypomastigote.
*Trypomastigotes have [[proteins]] on their surface known as major variant surface [[glycoprotein]] (VSG). Approximately 10 million copies of a single VSG are present on each trypomastigote.
*Once inside the host, they undergo [[antigenic variation]].
*Once inside the host, they undergo [[antigenic variation]].
*This VSG [[antigenic variation]] leads to non-specific polyclonal [[B cell]] activation.
*This VSG [[antigenic variation]] leads to non-specific [[Polyclonal response|polyclonal]] [[B cell]] activation.
*[[Immunoglobulin M]] is produced in large quantities in response to [[B cell]] activation.
*[[Immunoglobulin M]] is produced in large quantities in response to [[B cell]] activation.
*[[Immune complexes]] form and secondary [[hyperplasia]] of the [[reticuloendothelial system]] occurs.  
*[[Immune complexes]] form and secondary [[hyperplasia]] of the [[reticuloendothelial system]] occurs.  
*This process may lead to [[downregulation]] of the [[Immune system|immune system.]]
*This process may lead to [[downregulation]] of the [[Immune system|immune system.]]
===Immune response===
===Immune response===
*[[Tumour necrosis factor|Tumor necrosis factor α]] ([[TNF-α]]) produces on activation of [[cell mediated immunity]], stimulating [[T lymphocytes]] and [[macrophages]]. Virulent trypanomastigotes tend to suppress the activity of [[Tumour necrosis factor|tumor necrosis factor]] α ([[TNF-α]]) and [[IFN|IFN-gamma]].
*[[Tumour necrosis factor|Tumor necrosis factor α]] ([[TNF-α]]) is produced upon activation of [[cell mediated immunity]], stimulating [[T lymphocytes]] and [[macrophages]]. Virulent trypanomastigotes tend to suppress the activity of [[Tumour necrosis factor|tumor necrosis factor]] α ([[TNF-α]]) and [[IFN|IFN-gamma]].
*[[Cytokines]] such as [[Interleukin 12|interleukin (IL) 12]] promote the production of [[Interferon]] γ ([[Interferon|IFN-γ]]) responses. [[Interferon-gamma|IFN-γ]] drives [[TH1]]-type responses and stimulates [[macrophage]] activation. [[Cytokines]] including [[IL-6]], [[IL-4]], <nowiki/>and [[IL-10]] downregulate the protective response.
*[[Cytokines]] such as [[Interleukin 12|interleukin (IL) 12]], promote [[Interferon]] γ ([[Interferon|IFN-γ]]) responses.  
*[[Interferon-gamma|IFN-γ]] drives [[TH1]]-type responses and stimulates [[macrophage]] activation.  
*[[Cytokines]] including [[IL-6]], [[IL-4]], <nowiki/>and [[IL-10]] [[downregulate]] the protective response.


==References==
==References==
{{reflist|2}}
{{reflist|2}}
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Latest revision as of 20:19, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Pilar Almonacid, Aditya Ganti M.B.B.S. [2]

Overview

African trypanosomiasis is a human tropical parasitic disease usually caused by protozoan hemoflagellates belonging to the complex Trypanosoma brucei. A trypanosomal chancre develops on the site of inoculation. This is followed by a hemolymphatic stage with symptoms that include fever, lymphadenopathy, and pruritus. In the meningoencephalitic stage, invasion of the central nervous system can cause headaches, somnolence, abnormal behavior, loss of consciousness and coma. The course of infection is much more acute with Trypanosoma brucei rhodesiense than with Trypanosoma brucei gambiense. Clinical manifestations generally appear within 1–3 weeks of the infective bite for Trypanosoma brucei rhodesiense and months to years for Trypanosoma brucei gambiense.

Pathophysiology

African trypanosomiasis is a human tropical parasitic disease usually caused by protozoan hemoflagellates belonging to the complex Trypanosoma brucei. A trypanosomal chancre develops on the site of inoculation. This is followed by a hemolymphatic stage with symptoms that include fever, lymphadenopathy and pruritus. In the meningoencephalitic stage, invasion of the central nervous system can cause headaches, somnolence, abnormal behavior, and lead to loss of consciousness and coma. The course of infection is much more acute with Trypanosoma brucei rhodesiense than Trypanosoma brucei gambiense. Clinical manifestations generally appear within 1–3 weeks of the infective bite for Trypanosoma brucei rhodesiense and months to years for Trypanosoma brucei gambiense.[1][2][3][4][5][6]

Transmission

Incubation period

Reservoir

Human cycle

Tsetse fly life-cycle

Life cycle of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense - Source: https://www.cdc.gov/

Infective stage of the parasite

  • Metacyclic trypomastigotes

Diagnostic stage of the parasite

Pathogenesis

Immune response

References

  1. "Human African trypanosomiasis (sleeping sickness): epidemiological update". Wkly. Epidemiol. Rec. 81 (8): 71–80. 2006. PMID 16673459.
  2. Kato CD, Matovu E, Mugasa CM, Nanteza A, Alibu VP (2016). "The role of cytokines in the pathogenesis and staging of Trypanosoma brucei rhodesiense sleeping sickness". Allergy Asthma Clin Immunol. 12: 4. doi:10.1186/s13223-016-0113-5. PMC 4722787. PMID 26807135.
  3. Ferella M, Nilsson D, Darban H, Rodrigues C, Bontempi EJ, Docampo R, Andersson B (2008). "Proteomics in Trypanosoma cruzi--localization of novel proteins to various organelles". Proteomics. 8 (13): 2735–49. doi:10.1002/pmic.200700940. PMC 2706665. PMID 18546153.
  4. Sternberg JM (2004). "Human African trypanosomiasis: clinical presentation and immune response". Parasite Immunol. 26 (11–12): 469–76. doi:10.1111/j.0141-9838.2004.00731.x. PMID 15771682.
  5. "CDC - African Trypanosomiasis - Biology".
  6. Macleod ET, Darby AC, Maudlin I, Welburn SC (2007). "Factors affecting trypanosome maturation in tsetse flies". PLoS ONE. 2 (2): e239. doi:10.1371/journal.pone.0000239. PMC 1797825. PMID 17318257.