Advances in understanding and treatment of human African trypanosomiasis: divergent diseases caused by distinct parasites

Giordani, F. , Mwenechanya, R. and Barrett, M. (2014) Advances in understanding and treatment of human African trypanosomiasis: divergent diseases caused by distinct parasites. In: Padmanabhan, S. (ed.) Handbook of Pharmacogenomics and Stratified Medicine. Academic Press, pp. 901-917. ISBN 9780123868824 (doi: 10.1016/B978-0-12-386882-4.00039-6)

Abstract

Human African trypanosomiasis (HAT), often called sleeping sickness in its second, central nervous system–involved stage, is a disease of Sub-Saharan Africa. It is caused by subspecies of the protozoan parasite Trypanosoma brucei, which is transmitted by tsetse flies. Two distinctive conditions, classically discriminated by diverging clinical progression, are caused by different trypanosome subspecies. In East and Southern Africa, Trypanosoma brucei rhodesiense causes a rapidly advancing form that within weeks passes from the hemolymphatic first stage to the neurological second stage. In West and Central Africa, Trypanosoma brucei gambiense takes many months to progress to its second-stage form. Other trypanosome subspecies infect animals but not humans, in whom they are killed by several trypanosome-lytic factors. Rare genetic polymorphisms in which one such factor, apolipoprotein L1 (APOL1), is absent can lead to human infection by other trypanosome species (e.g., Trypanosoma evansi). Genetic variants of APOL1, common in African Americans suffering chronic kidney disease, originate in West Africa, where their prevalence is high. These alleles might have been selected during human evolution because of their ability to lyse trypanosomes (e.g., Trypanosoma rhodesiense) that would otherwise bypass the lytic effects of other APOL1 variants. Sleeping sickness treatment is stratified depending on the causative subspecies and whether the disease is diagnosed in the first or the second stage. For a variety of reasons, current drugs are unsatisfactory in the treatment of HAT.

• Item Type: Book Sections
• Status: Published
• Glasgow Author(s) Enlighten ID: Mwenechanya, Mr Roy and Giordani, Dr Federica and Barrett, Professor Michael
• Authors: Giordani, F., Mwenechanya, R., and Barrett, M.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Publisher: Academic Press
• ISBN: 9780123868824