African trypanosomiasis pathophysiology: Difference between revisions

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{{CMG}}; {{AOEIC}} Pilar Almonacid; {{ADG}}
{{CMG}}; {{AOEIC}} Pilar Almonacid; {{ADG}}
==Overview==
==Overview==
African trypanosomiasis is a human tropical [[parasitic]] [[disease]] usually caused by a [[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 ''T. b. rhodesiense'' than ''T. b. gambiense''. Clinical manifestations generally appear within 1–3 weeks of the [[Infection|infective]] bite for T. b. rhodesiense and months to years for T. b. 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="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><ref>{{cite journal|doi=10.1016/S0140- 6736(09)60829-1}}</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>
African trypanosomiasis is a human tropical [[parasitic]] [[disease]] usually caused by a [[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 ''T. b. rhodesiense'' than ''T. b. gambiense''. Clinical manifestations generally appear within 1–3 weeks of the [[Infection|infective]] bite for T. b. rhodesiense and months to years for T. b. 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="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><ref>{{cite journal|doi=10.1016/S0140- 6736(09)60829-1}}</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>


==Pathophysiology==
==Pathophysiology==
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* 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 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 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 the replication by [[binary fission]]
* They are carried to other sites throughout the body, reach other blood fluids (e.g. [[lymph]], [[spinal fluid]]), and continue the replication by [[binary fission]].
* The entire life cycle of African Trypanosomes is represented by [[extracellular]] stages.   
* The entire life cycle of African Trypanosomes is represented by [[extracellular]] stages.   
===Tsetse fly cycle===
===Tsetse fly 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, multiply by [[binary fission]]
* In the fly’s [[midgut]], the [[parasites]] transform into procyclic trypomastigotes, multiply by [[binary fission]].
* Procyclic trypomastigotes leave the [[midgut]], and transform into epimastigotes
* Procyclic trypomastigotes leave the [[midgut]] and transform into epimastigotes.
* The epimastigotes reach the fly’s [[salivary glands]] and continue multiplication by [[binary fission]]
* The epimastigotes reach the fly’s [[salivary glands]] and continue multiplication by [[binary fission]].
* The cycle in the fly takes approximately 3 weeks.   
* The cycle in the fly takes approximately 3 weeks.   
[[Image:Life cycle--trypanosomiasis.gif|frame|center|Life cycle of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense]]
[[Image:Life cycle--trypanosomiasis.gif|frame|center|Life cycle of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense]]
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*Trypomastigotes have [[proteins]] on their surface known as major variant surface [[glycoprotein]] (VSG). Approximately 10 million copies of a single VSG present on each trypomastigotes.
*Trypomastigotes have [[proteins]] on their surface known as major variant surface [[glycoprotein]] (VSG). Approximately 10 million copies of a single VSG present on each trypomastigotes.
*Once inside the host they undergo [[antigenic variation]].
*Once inside the host they undergo [[antigenic variation]].
*This VSG [[antigenic variation]] leads to nonspecific polyclonal B cell activation
*This VSG [[antigenic variation]] leads to nonspecific 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]], stimulates [[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]]) produces on activation of [[cell mediated immunity]], stimulates [[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 production of [[Interferon]] γ ([[Interferon|IFN-γ]]) responses. [[Interferon-gamma|IFN-γ,]] which drives [[TH1]]-type responses and stimulates [[macrophage]] activation. [[Cytokines]], which include , [[IL-6]], [[IL-4]]<nowiki/>and [[IL-10]], down-regulate the protective response.
*[[Cytokines]] such as [[Interleukin 12|interleukin (IL) 12]] promote the production of [[Interferon]] γ ([[Interferon|IFN-γ]]) responses. [[Interferon-gamma|IFN-γ,]] which drives [[TH1]]-type responses and stimulates [[macrophage]] activation. [[Cytokines]], which include, [[IL-6]], [[IL-4]]<nowiki/>and [[IL-10]], down-regulate the protective response.


==References==
==References==

Revision as of 16:22, 25 July 2017

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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 a 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 T. b. rhodesiense than T. b. gambiense. Clinical manifestations generally appear within 1–3 weeks of the infective bite for T. b. rhodesiense and months to years for T. b. gambiense.[1][2][3][4][5][6][7]

Pathophysiology

African trypanosomiasis is a human tropical parasitic disease usually caused by a 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 T. b. rhodesiense than T. b. gambiense. Clinical manifestations generally appear within 1–3 weeks of the infective bite for T. b. rhodesiense and months to years for T. b. gambiense.[1][2][3][4][5][8][7]

Stages of infection

Transmission

Incubation period

  • Clinical manifestations generally appear within 1–3 weeks of the infective bite for T. b. rhodesiense and months to years for T. b. gambiense.

Reservoir

Human cycle

Tsetse fly cycle

  • 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, multiply by binary fission.
  • Procyclic trypomastigotes leave the midgut and transform into epimastigotes.
  • The epimastigotes reach the fly’s salivary glands and continue multiplication by binary fission.
  • The cycle in the fly takes approximately 3 weeks.
Life cycle of Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense

Infective stage of the parasite

  • Metacyclic trypomastigotes

Diagnostic stage of the parasite

Pathogenesis

Immune response

References

  1. 1.0 1.1 "Human African trypanosomiasis (sleeping sickness): epidemiological update". Wkly. Epidemiol. Rec. 81 (8): 71–80. 2006. PMID 16673459.
  2. 2.0 2.1 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. 3.0 3.1 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. 4.0 4.1 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. 5.0 5.1 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.
  6. . doi:10.1016/S0140- 6736(09)60829-1 Check |doi= value (help). Missing or empty |title= (help)
  7. 7.0 7.1 "CDC - African Trypanosomiasis - Biology".
  8. . doi:10.1016/S0140- 6736(09)60829-1 Check |doi= value (help). Missing or empty |title= (help)