The mosquito-transmitted Dengue virus (DV) is the causative agent of dengue fever (DF), the most prevalent arthropod-borne viral illness in humans with ~100 million symptomatically afflicted individuals.
DF is characterized by high fever, chills, body aches and skin rash and ranges from mild, flu-like symptoms to severe forms, the so called dengue hemorrhagic fever (DHF), and the dengue shock syndrome (DSS). About 250,000 individuals per year manifest these severe forms, which have a mortality rate of about 10 percent. DV infection has been described in more than 100 countries, with 2.5 billion people living in dengue endemic areas. Given the dramatic geographic expansion of epidemic DF and DHF, the World Health Organization has classified this disease as a major international public health concern.
Four serologically distinct serotypes that are distinguishable by neutralization and complement fixation tests have been described. Infection with one serotype confers a long-lasting immunity to re-infection with the same DV serotype but increases the risk of severe dengue manifestation upon infection with a heterologous serotype. This is most likely due to antibody-dependent enhancement (ADE) of infection substantially contributing to accelerated virus spread, replication and viremia. Other mechanisms that are under debate are reactivation of an inadequate T-cell immune response during secondary infection, viral factors of pathogenesis such as NS1 and host genetics.
Current therapy is symptomatic and primarily based on fluid replacement. So far there is no selective antiviral therapy available. A tetravalent vaccine has been developed, but owing to the possibility to increase the risk of severe dengue in people who did not have prior infection, it is only recommended for people who had previously DF or populations in which most people have been previously infected.