The Pathogenesis of African Trypanosomiasis

Annu Rev Pathol. 2023 Jan 24:18:19-45. doi: 10.1146/annurev-pathmechdis-031621-025153. Epub 2022 Sep 2.

Abstract

African trypanosomes are bloodstream protozoan parasites that infect mammals including humans, where they cause sleeping sickness. Long-lasting infection is required to favor parasite transmission between hosts. Therefore, trypanosomes have developed strategies to continuously escape innate and adaptive responses of the immune system, while also preventing premature death of the host. The pathology linked to infection mainly results from inflammation and includes anemia and brain dysfunction in addition to loss of specificity and memory of the antibody response. The serum of humans contains an efficient trypanolytic factor, the membrane pore-forming protein apolipoprotein L1 (APOL1). In the two human-infective trypanosomes, specific parasite resistance factors inhibit APOL1 activity. In turn, many African individuals express APOL1 variants that counteract these resistance factors, enabling them to avoid sleeping sickness. However, these variants are associated with chronic kidney disease, particularly in the context of virus-induced inflammation such as coronavirus disease 2019. Vaccination perspectives are discussed.

Keywords: APOL1; African trypanosomes; VSG; antigenic variation; apolipoprotein L1; kidney disease; sleeping sickness; variant surface glycoprotein.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein L1 / genetics
  • COVID-19*
  • Humans
  • Inflammation
  • Trypanosoma brucei rhodesiense / physiology
  • Trypanosomiasis, African* / genetics
  • Trypanosomiasis, African* / parasitology

Substances

  • APOL1 protein, human
  • Apolipoprotein L1