Beschrijving

With an estimated 20 million typhoid cases and an even higher number of non-typhoid cases the health burden caused by invasive salmonellosis is huge. Currently no single diagnostic test for invasive salmonellosis is available that has satisfactory accuracy. The diagnostic reference method is blood culture and subsequent serotyping, a procedure that takes several days, is labor intensive, complicated and suffers from low sensitivity (40%-80%). In many resource poor settings neither know-how nor the infrastructure and sufficient funding for this procedure are available. Consequently, in most cases empirical treatment is applied without any diagnostic testing, resulting in increased morbidity and mortality in affected populations and the emergent spreading of antibiotic resistance. The development of a sensitive and rapid diagnostic test applicable at the point of care will be groundbreaking.
The methodological approach of the IDIS project is divided into several work packages (WP). WP1 will be a project management work package that will support the IDIS consortium by drafting the consortium agreement and periodic reports and the organisation of plenary consortium meetings as well as intermediate meetings by the steering committee. In WP2 we will build a “fever” biobank at ITM. This large biobank will be syndrome-based rather than pathogen-based. WP3 will conduct a comparative full-scan Salmonella proteome study (“bottom-up” approach). Salmonella proteins will be ranked for their diagnostic potential and the top-30 proteins will be shortlisted. The targeted proteomics approach applied in WP4 will use selected reaction monitoring (SRM) to quantify the target proteins in urine and blood of invasive salmonellosis patients from the “fever” biobank. Targeted proteomics is much more sensitive than the frequently applied discovery proteomics approach and has the additional advantage that it accurately quantifies the proteins of interest in clinical specimens. In WP5, the proteins with the highest diagnostic potential will be purified and validated in the “fever” biobank using ELISA. WP6 will translate this output into antigen-based rapid diagnostic tests (RDT) using lateral flow principles. Since the bacterial load in urine and blood of invasive salmonellosis patients can be very low, WP7 will develop a field-applicable targeted protein enrichment approach. In WP8, the enrichment procedure coupled to the Ag RDT will be validated in phase I, II and III diagnostic evaluation studies.
The IDIS research question and methodology is highly innovative for several reasons: (i) the first antigen based RDT for invasive salmonellosis will be a major breakthrough; (ii) the “fever” biobank will be the first syndrome-based large-scale specimen repository at ITM and unique in its kind; (iii) the targeted proteomics approach has been selected as “method of the year 2012” by Nature Methods, confirming that the methodology used by the IDIS project is indeed cutting-edge; (iv) the IDIS research actors will be highly complementary with experts in basic research (pathogen), translational research (patient), methodology  (proteomics) and tool development and evaluation (RDT). This unique consortium will combine basic discovery research and translational research. The diagnostic tools developed in the IDIS project will be made available to the public at the end of the project and thus provide direct benefit to the patients.

AcroniemIDIS
StatusVoltooid
Effectieve start/einddatum1/09/1331/12/18

Financiering

  • Flemish Government - Department of Economy, Science & Innovation: 999.572,00 €

ID: 1094272