Neglected Diseases
Dengue is a viral infection transmitted to humans by the female Aedes mosquito – most often Aedes aegypti and Aedes albopictus.
The dengue virus has four serotypes, each with multiple genotypes. First-time infection results mostly in a flu-like illness; subsequent infections with a different serotype (or even genotype) can result in severe disease, and are more likely to lead to dengue haemorrhagic fever. In analogy, Dengue naïve persons vaccinated with Dengvaxia, the only currently licensed Dengue vaccine, risk developing severe dengue disease through antibody-dependent enhancement. Dengue outbreaks often occur in Asia, Central America and South America, while the first autochthonous cases of Dengue were registered in southern Europe in recent years; the disease is now present in more than 100 countries, up from only nine in 1970.
Currently, no curative therapy is available for managing dengue fever. Effective therapeutic options are needed, including direct-acting antivirals and mAbs. Several such candidates are currently in early-stage clinical development, including Novartis’ EYU 688 and Atea’s AT-752. Point-of-care serological tests are already available but have many drawbacks. There is a pressing need for diagnostics that can function across the entire disease spectrum, distinguish dengue from other febrile illnesses, and for RDTs for serostatus screening. New and improved vector control products targeting the Aedes mosquito, including adulticidal oviposition traps and space spray insecticides, are needed, as well as biological control tools such as Wolbachia and genetic manipulation (with field experiments currently ongoing across Asia and Latin America). Dengue’s prevalence in high- and upper-middle-income countries has attracted commercially focused industry investment in vaccine R&D; this category has therefore been excluded from the G-FINDER scope.
Early results from a Phase IIa human challenge study on Janssen’s novel oral antiviral, JNJ-1802, demonstrated its preventive antiviral action against dengue. The compound is now advancing to a community-based field study, evaluating its effectiveness against multiple circulating dengue serotypes in over 30 countries. Results from the World Mosquito Program’s deployment of Wolbachia-infected mosquitoes in Colombia demonstrated a resulting 94-97% reduction in dengue incidence. Oxitec’s large-scale field trials in Brazil using male-only, female-lethal Friendly Aedes aegypti intervention also achieved up to a 96% suppression of the local Aedes aegypti mosquito population. Note that much of the funding for mosquito control R&D is captured under our multidisease vector control categories, since it intended to target other mosquito-borne diseases alongside dengue.