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 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]

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.

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 T. b. rhodesiense than T. b. 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 T. b. rhodesiense and months to years for T. b. gambiense.

Reservoir

  • Humans are the main reservoir for Trypanosoma brucei gambiense, but this species can also be found in animals.
  • Wild animals are the main reservoir of T. b. 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 the replication by binary fission
  • The entire life cycle of African Trypanosomes is represented by extracellular stages.

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

  • Bloodstream trypomastigotes

Pathogenesis

  • 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.
  • This VSG antigenic variation leads to nonspecific 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

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.