Dengue is an acute febrile illness caused by any of four related flaviviruses (dengue virus [DENV] serotypes 1-4). DENV infection is acquired through a transmission cycle between humans and mosquitoes of the genus Aedes, principally A. aegypti.

There is a wide spectrum of clinical manifestations of dengue in humans. This ranges from an uncomplicated and self-limited febrile illness (dengue fever, DF) to a plasma leakage syndrome accompanied by bleeding (dengue hemorrhagic fever, DHF). Although DHF is observed in only a small percentage of DENV infections, it plays a large role in the public health problem of dengue because it can lead to shock and death.

Many factors contribute to the risk for DHF, but one of the most important factors is pre-existing immunity from an earlier DENV infection. Infection with one DENV only provides long-lasting protection against that serotype; infection with other DENV serotypes remains possible, and, because of the increasing global circulation of DENV, is occurring with increasing frequency in tropical areas of the world.

The reason for the increased risk for DHF in a second DENV infection is a major focus of our research. We hypothesize that both the quality and timing of DENV-specific antibody and T lymphocyte responses influence whether their overall effect is beneficial (controlling viral replication and reducing the severity of illness) or harmful (creating a ‘cytokine storm’ leading to plasma leakage). Our research will be applied to the management of patients with suspected dengue and the development of vaccines and therapeutics against dengue.