Why is dengue more severe during secondary infections?

Dengue is often more severe during secondary infections due to a phenomenon called antibody-dependent enhancement (ADE). In ADE, non-neutralizing antibodies produced during a previous dengue infection facilitate the entry of the virus into immune cells during a subsequent infection with a different dengue serotype. This leads to increased viral replication, a more intense immune response, and a higher risk of severe disease, such as dengue hemorrhagic fever and dengue shock syndrome. Secondary infections can result in more severe symptoms, increased vascular permeability, bleeding, and organ damage. Understanding the risk of severe disease in secondary infections highlights the importance of early diagnosis and careful management in individuals with a history of dengue.