African trypanosomiasis pathophysiology

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]

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.

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]}

• Infection is usually transmitted via the tsetse fly bite to the human host.

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

• Humans are the main reservoir for Trypanosoma brucei gambiense.
• Wild animals are the main reservoir for Trypanosoma brucei rhodesiense.

• 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 consists of extracellular stages.

• 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.

• Metacyclic trypomastigotes

• Bloodstream trypomastigotes

• 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.

• 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 tumor necrosis factor α (TNF-α) and IFN-gamma.
• Cytokines such as interleukin (IL) 12, promote 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.