Trypanosomes & African Sleeping Sickness PDF

Trypanosomes and African Sleeping Sickness Samuel Dean. Assistant Professor  Learning objectives By the end of this session you will be able to: African sleeping sickness - epidemiology and control  Trypanosoma brucei causes disease in humans and...

Trypanosomes and African Sleeping Sickness Samuel Dean. Assistant Professor  Learning objectives By the end of this session you will be able to: African sleeping sickness - epidemiology and control  Trypanosoma brucei causes disease in humans and animals Trypanosoma brucei Trypanosoma brucei is a unicellular and extracellular parasite. Transmission via Tsetse flies. MSF HUMANS. Sleeping sickness is a fatal disease. 1,000 cases/year (historically has been much higher) No vaccine. Treatments can be highly toxic. ANIMALS (wild animals and cattle). Nagana is a major contributor to poverty. Economic impact US$4.5 billion per year in Africa. WHO report, 2016  Vector defines disease distribution African Sleeping Trypanosomiasis (HAT) only occurs in the 36 sub-Sharan countries where there are tsetse Yellow: T. b. gambiense The people most exposed to the tsetse fly and therefore the disease are in rural populations dependent on agriculture, fishing, animal husbandry or hunting There are major disease foci in the Democratic Republic of the Congo (DRC) HAT is caused by two different sub-species of African trypanosome: T. b. rhodesiense cases (severe, 1000) +1000 VSGs  Antigenic variation 3 – mosaic formation Sub-telomeric VSGs can recombine with the expression site VSG VSG This makes entirely new VSG “mosaics” Therefore, the potential VSG repertoire is unlimited y y y y y y y + unlimited VSGs  Each wave represents a different set of VSGs being expressed Slender à stumpy differentiation Immune Slender form clearance proliferation parasitemia weeks New VSG expressed  Summary: Trypanosome immune evasion 1. Variant surface glycoprotein (VSG) protects trypanosomes by providing a physical barrier: I. VSG shields other proteins from detection from antibodies II. VSG prevents complement from accessing the plasma membrane 2. Hydrodynamic-flow mediated endocytosis facilitates removal of antibodies that bind to VSG 3. Antigenic variation allows the cell to change the VSG isotype that is expressed: i. Expression site switching ii. Inserting a different VSG into the expression site iii. Making entirely new, mosaic VSGs 4. This means that a vaccine against trypanosomes is unlikely  Summary 1 1. Trypanosome cause the neglected tropical disease African Sleeping Sickness 2. Trypanosome infect mammals and are transmitted by tsetse in sub-Saharan Africa 3. Despite being extracellular parasites, trypanosome can survive for YEARS in the bloodstream 4. Trypanosomes have evolved mechanisms to overcome the host immune system  Summary 2 1. The characteristic ‘waves of parasitaemia’ observed in a chronic infection is explained by key features of the parasite’s biology: i. Slender form proliferation ii. Slender to stumpy differentiation iii. Parasite death caused by anti-VSG antibodies (when hydrodynamic flow is over- whelmed) iv. Antigenic variation Slender à stumpy differentiation Immune clearance Slender form proliferation parasitemia weeks New VSG expressed  Questions? [email protected]