Development and integration of serological and molecular diagnostics in view of interruption of transmission of gambiense-HAT

Project Details


Sleeping sickness, or human African trypanosomiasis (HAT), is an infectious disease that leads to death if the patient is not treated. The vast majority of infections are due to the parasite Trypanosoma brucei gambiense and are referred to as gHAT, humans are assumed to be the only reservoir. So far, treatment options for gHAT were limited and toxic, forcing control programs to avoid overtreatment through complex diagnostic procedures, including screening with a serological test, laborious microscopic confirmation of sero-positives and lumbar puncture for disease stage determination. The current epidemiological context and the availability of new diagnostic tools and treatments led to the development of a new gHAT strategy in DRC (Grant INV-031337) to better adapt the screening approaches to the new context. Improved diagnosis and quality assurance by integrating ELISA and molecular tests in the national control strategy are key elements of this new strategy and should accelerate progress to interruption of transmission of the disease. The integration of these tests will also be a prerequisite for effective and affordable post elimination surveillance. Currently treatment of gHAT is limited to individuals with infection confirmed by microscopy on the spot. However due to relatively low sensitivity and high complexity of microscopic tests, not all infected individuals tested are actually started on treatment. The availability of new oral drugs, in particular the non-toxic single-dose acoziborole expected by 2025, should allow to switch from a Screen, confirm & treat to a Screen & treat strategy, whereby serological suspects are treated without microscopic confirmation. However, this implies the need for post-hoc confirmation of infected individuals after treatment and an adapted gHAT case definition. We foresee a gradual shift from on the spot confirmation by microscopy to post-hoc confirmation in remote laboratories. The current grant should ensure that the diagnostic part of the new gHAT strategy can be applied in the following years, and also pave the way to implement a future Screen & treat strategy. A subnational laboratory will be provided with equipment and personnel, and capacity will be developed to run (i)ELISA tests and PCR. Combined with the already existing laboratory capacity in DRC, this should ensure that all demands for remote serological and molecular testing can be met within a reasonable delay in the next 3 years. A system will be set up to assemble and distribute sample collection kits that will provide viable samples for ELISA and molecular tests. The integration of iELISA will replace the Immune Trypanolysis as serological gold standard for post-hoc confirmation of contact with the infective agent and become an asset in post elimination surveillance. Within the grant, a molecular gold standard test for gHAT diagnosis will be delivered with higher sensitivity and specificity than any other currently available gHAT test, by refining an existing multiplex qPCR. This test will allow post-hoc confirmation of infection and facilitate a new gHAT case definition. Another multiplex PCR will be developed suitable for confirmation of T.b.gambiense infection in vertebrate animals, humans and tsetse flies. This test will be used to tackle research questions such as the potential role of an animal reservoir in gHAT transmission.
Short titleHAT Diagnostics to support EoT
Effective start/end date1/12/2230/11/25