Differing Influences of Virus Burden and Immune Activation on Disease Severity in Secondary dengue-3 Virus Infections

J Infect Dis. 2002 May 1;185(9):1213-21. doi: 10.1086/340365. Epub 2002 Apr 16.


Dengue hemorrhagic fever (DHF), the most severe form of illness following infection with a dengue virus, is characterized by plasma leakage, thrombocytopenia, and hepatic inflammation. The interrelationships among virus burden, immune activation, and development of DHF were examined in 54 children with secondary dengue-3 virus infections participating in a prospective, hospital-based study. DHF was associated with higher mean plasma viremia early in illness and earlier peak plasma interferon-gamma levels. Maximum plasma viremia levels correlated with the degree of plasma leakage and thrombocytopenia. Maximum plasma levels of interleukin (IL)-10 and soluble tumor necrosis factor receptor-II correlated with the degree of thrombocytopenia, independently of viremia levels. Hepatic transaminase elevation correlated with plasma soluble IL-2 receptor levels and not with viremia levels. Quantitative differences in virus burden and host immune responses, and the timing of type 1 cytokine responses, have differing influences on the severity of disease manifestations during secondary dengue-3 virus infections.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, CD / blood
  • Child
  • DNA, Complementary / analysis
  • Female
  • Humans
  • Interferon-gamma / blood
  • Interleukin-10 / blood
  • Male
  • Multivariate Analysis
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor / blood
  • Receptors, Tumor Necrosis Factor, Type II
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severe Dengue / immunology*
  • Severe Dengue / virology
  • Viral Load*
  • Viremia / diagnosis
  • Viremia / immunology*


  • Antigens, CD
  • DNA, Complementary
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type II
  • Interleukin-10
  • Interferon-gamma