DiTECT-HAT: Diagnostic Tools for Human African Trypanosomiasis Elimination and Clinical Trials

How to diagnose HAT in basic health centres? How to monitor elimination of HAT? And how to asses cure after treatment of HAT? The DiTECT-HAT project develops cost-effective diagnostic algorithms for passive case detection and for monitoring of eliminated foci, and assesses the accuracy of RNA and neopterin as tests of cure.

Project start date

01/02/2016

Project end date

31/01/2021

Objectives

  • Determine the diagnostic and economic performance of HAT passive case detection based on rapid diagnostic tests, on combinations of rapid diagnostic tests and on algorithms of rapid diagnostic tests with serological or molecular reference tests.
  • Examine if certain diagnostic algorithms for HAT have sufficient positive predictive value to allow test and treat scenarios without need of parasitological confirmation.
  • To determine the feasibility and cost of a HAT post-elimination monitoring system based on serological and/or molecular testing of dried blood spots with or without preselection by rapid diagnostics tests.
  • To propose an appropriate threshold to trigger active case finding and avoid re-emergence of HAT, without false alarm.
  • To determine accuracy of SL-RNA and neopterin detection for assessing treatment outcome in therapeutic trials.

Location

Belgium, Burkina Faso, Côte d’Ivoire, DR Congo, France, Guinea, United Kingdom

Description

In the last decade, the prevalence of Trypanosoma brucei gambiense (Tbg) human African trypanosomiasis (HAT) has drastically decreased and HAT has been targeted for elimination. Integration of HAT diagnosis and treatment in peripheral health centres and sustainable monitoring of eliminated foci are vital for Tbg HAT elimination. Development of safe and efficacious drugs applicable in an elimination context would be accelerated by the availability of an early test-of-cure. The DiTECT-HAT project consists of 3 diagnostic trials, validating the performance of diagnostic tools and algorithms for early and rapid diagnosis of Tbg HAT for passive case detection, for post-elimination monitoring and for assessing the therapeutic response. 

Firstly, for passive case detection, DiTECT-HAT determines the diagnostic performance and cost-efficiency of RDTs performed in peripheral health centres, and of diagnostic algorithms combining RDTs with serological and/or molecular tests on filter paper performed at regional reference centres. Diagnostic algorithms with high positive predictive values will improve cost-effectiveness of passive case detection and might, in the near future, allow scenarios of testing and treating without the need for parasitological confirmation.

Secondly, for post-elimination monitoring, DiTECT-HAT proposes to determine the feasibility and cost-efficiency of different diagnostic algorithms with serological and molecular high-throughput tests. General health workers performing house to house visits in eliminated HAT foci can easily collect blood on filter paper and send it to regional HAT reference centers for analysis. This trial should allow for defining thresholds for a "transmission alarm" that should trigger reactive case finding to avoid re-emergence of HAT.

Finally, the accuracy of neopterin and trypanosomal spliced leader RNA detection as early test-of-cure are determined in a therapeutic trial. Early treatment outcome assessment will speed up the development and implementation of new drugs for HAT, and improve management of relapsing patients in routine patient care.

These 3 diagnostic trials take place in low and zero prevalence areas in DR Congo, Guinea, Côte d’Ivoire and Burkina Faso with additional testing in regional HAT reference centres in DR Congo and Burkina Faso. Results of DitECT-HAT will impact on clinical decision and health outcomes, and will contribute to successful and sustainable HAT elimination.

Partners

• IRD (coordinateur)
• Institute of Tropical Medicine Antwerp (ITM), Belgium, https://www.itg.be/
• Centre International de Recherche-Développement sur l’Elevage en zone Sub-humide (CIRDES), Burkina Faso, https://www.cirdes.org/
• Institut Pierre Richet-Institut National de Santé Publique (IPR-INSP), Côte d’Ivoire, https://iprci.org/
• Institut National de Recherche Biomédicale (INRB), Democratic Republic of Congo, http://inrb.net/
• Programme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Democratic Republic of Congo
• Programme National de Lutte contre la Trypanosomiase Humaine Africaine (PNLTHA), Ministère de Santé, Guinea
• University of Liverpool (ULIV), http://www.zoonotic-diseases.org/
• Drugs for Neglected Disease Initiative (DNDi), Switzerland, https://www.dndi.org/

Funding

European & Developing Countries Clinical Trial Partnership (EDCTP2, Horizon 2020, European Union Funding for Research and Innovation), grant DRIA2014-306-DiTECT-HAT: 2 999 006 €.

The DITECT-HAT, HAT-r-ACC, ACOZIKIDS and FEX-g-HAT projects as well as the research activities carried out within the framework of the Intertryp unit project are part of the EDCTP2 program supported by the "European Union”.