Development and validation of next-generation serodiagnostics for the elimination of Trypanosoma brucei gambiense human African trypanosomiasis.

Project Details

Layman's description

Human African trypanosomiasis (HAT) is a neglected tropical disease, mainly caused by the parasite Trypanosoma brucei gambiense (referred to as gHAT). It has been targeted by the World Health Organization (WHO) for its interruption of transmission by the year 2030. The trypanosomes are covered by a dense layer of glycoproteins, called variant surface glycoproteins (VSGs), to protect themselves from the host’s immune response. Through antigenic variation, they change the VSG expressed to evade the antibody response and avoid elimination. Each VSG coat is called a Variant Antigen Type (VAT).

The diagnostic algorithm of gHAT starts off with a serological screening step. Different tests are available, from the Card Agglutination Test for Trypanosomiasis (CATT, used in active screening campaigns) to different rapid diagnostic tests (RDTs, more fit for passive case-detection). Other serological tests are available in reference laboratories: the immune trypanolysis test is considered the reference test, but it needs advanced skills and technical requirements for its performance. Two formats of ELISA are available for gHAT diagnosis: an indirect ELISA and an inhibition ELISA (iELISA). The latter might eventually replace the trypanolysis test, since it detects the same species-specific epitopes. An important drawback of the current RDTs and iELISA is their use of native antigens, that are produced through the massive infection of laboratory animals with highly infective T. b. gambiense clones. Investments in the recombinant expression of the same VSGs as used in the native tests (LiTat 1.3 and LiTat 1.5) in procaryote or eukaryote systems have been successful but have not yet yielded new versions of antibody detection tests with equal or better performance than the tests with native antigens.

The hypothesis of this project is that recombinant antigens can replace native antigens in a new generation of diagnostic tests for gHAT. The objectives are i) to develop a recombinant iELISA (r-iELISA) using recombinant fragments of VSGs LiTat 1.3 and LiTat 1.5 and ii) to validate the third generation recombinant RDTs that are currently being developed by the company Coris BioConcept (Gembloux, Belgium). For the first objective, recombinant antigens produced by Coris BioConcept for their RDTs will be provided for the development of the r-iELISA. The resulting test will be validated with both stored plasma samples in the laboratory and in a prospective field study in the Democratic Republic of the Congo. The 3rd generation RDTs will also be validated in both a retrospective and prospective study.
Effective start/end date8/06/23 → …

IWETO expertise domain

  • B680-public-health
  • B780-tropical-medicine


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