Development and Validation of a Rapid and Inexpensive Sequence-Based Colorimetric Assay for Dengue Diagnosis and Serotype Determination

Principal Investigator: Kate McElroy Horne, PhD

blood laden mosquito in flightDengue is the most important arthropod-borne disease today, with a wide circulation that puts approximately 2.5 billion people at risk of infection with one of four related viruses (DENV-1 to 4). More than one serotype often co-circulates in a given area, and this hyperendemicity increases the risk of development of dengue hemorrhagic fever or dengue shock syndrome during secondary infection due to antibody-dependent enhancement. In addition, some serotypes and some genotypes of each serotype may be more likely to produce severe disease than others.

Because there is no vaccine against or treatment for dengue and vector control programs have been largely ineffective, rapid diagnosis of a DENV infection followed by effective patient management remains the only way to manage dengue disease.

Current DENV diagnostic tests are either inexpensive but slow and non-specific (antibody-based tests such as the ELISA) or relatively fast but expensive and complex (molecular tests such as multiplex, quantitative RT-PCR). Experiments outlined in this proposal will adapt a previously described genotyping assay, the oligonucleotide ligation assay, to identify and type DENV and validate this assay using contemporary DENV of all four serotypes collected in the Americas.

The long-term goal of this work is to improve DENV diagnostics through the development and implementation of a rapid and inexpensive DENV diagnostic assay. Use of such a test would alert clinicians to the possibility that a patient may progress to severe disease even when he or she presents with relatively non-specific symptoms. Improved early diagnosis and effective patient management would substantially reduce the burden of dengue disease.