African trypanosomiasis pathophysiology
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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, 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]
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]
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 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.
Transmission
- Infection is usually transmitted via the tsetse fly bite to the human host.
Incubation period
- Clinical manifestations generally appear within 1–3 weeks of the infective bite for Trypanosoma brucei rhodesiense and months to years for Trypanosoma brucei gambiense.
Reservoir
- Humans are the main reservoir for Trypanosoma brucei gambiense.
- Wild animals are the main reservoir of Trypanosoma brucei rhodesiense.
Human cycle
- 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.
- 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 replication by binary fission.
- The entire life cycle of African trypanosomes is represented by extracellular stages.
Tsetse fly life-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 and 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.
Infective stage of the parasite
- Metacyclic trypomastigotes
Diagnostic stage of the parasite
- Bloodstream trypomastigotes
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.
- Once inside the host, they undergo antigenic variation.
- This VSG antigenic variation leads to non-specific polyclonal 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.
- This process may lead to downregulation of the immune system.
Immune response
- 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 tumor necrosis factor α (TNF-α) and IFN-gamma.
- Cytokines such as interleukin (IL) 12 promote the production of Interferon γ (IFN-γ) responses. IFN-γ drives TH1-type responses and stimulates macrophage activation. Cytokines including IL-6, IL-4, and IL-10 downregulate the protective response.
References
- ↑ 1.0 1.1 "Human African trypanosomiasis (sleeping sickness): epidemiological update". Wkly. Epidemiol. Rec. 81 (8): 71–80. 2006. PMID 16673459.
- ↑ 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.
- ↑ 3.0 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.
- ↑ 4.0 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.
- ↑ 5.0 5.1 "CDC - African Trypanosomiasis - Biology".
- ↑ 6.0 6.1 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.