DNDi and our partners are working to tackle the urgent need for treatments that can prevent progression to severe disease. Collaborating with leading public health institutes in the Dengue Alliance, our goal is to accelerate innovation to deliver an affordable and accessible dengue treatment solution, complete our assessment of the burden of dengue in Africa, and identify biomarkers that can accurately predict progression to severe disease.
Our progress in 2024 includes:
Discovery
AI-guided discovery: Studies to determine the protective effects on vascular integrity confirmed that selected compounds acting through the sphingosine 1-phosphate receptor provided protective effects on membrane integrity. This effect was confirmed in in vivo dengue infection models. Additional studies are underway to understand this mode of action for potential use in people with dengue virus infection.
Translation
Pre-clinical profiling: Dengue Alliance partners continued studying potential candidates for entry into clinical studies with three host-directed therapy (HDT) targets undergoing further in vivo and in vitro assays to validate their effects and provide the basis for dose selection. In addition, a number of repurposed antiviral treatments were selected for potential progression into first-in-human studies, pending dose selection and safety evaluations.
Implementation
Dengue seroprevalence in Africa and the impact of new control interventions on the global burden: Confirmation of ELISA (enzyme-linked immunosorbent assay) and multiplex immunoassay results were performed for selected samples from Senegal, Ghana, and the DRC with virus neutralization (plaque reduction neutralization tests, or PRNT). These analyses were performed in collaboration with the referral laboratory at Institut Pasteur Dakar, Senegal – with samples tested for dengue antibodies, as well as antibodies of several other arboviruses circulating in the region.
Following these results, mathematical modelling to estimate age-stratified dengue seroprevalence was performed with the support of Imperial College for all the countries’ sites (Senegal: 14 regions; Ghana: 3 cities; DRC: 2 cities). Final results were presented at the ASTMH (New Orleans, US) and ICID (Cape Town, South Africa) conferences.
An update of the global dengue age-stratified seroprevalence was performed with the review of dengue seroprevalence and case-notification studies published up to 2023. These estimates were published in a scientific article in eBiomedicine.
Photo credit: Fábio Nascimento-DNDi
