Differing Influences of Virus Burden and Immune Activation on Disease Severity in Secondary Dengue-3 Virus Infections.
Libraty, Daniel H. 1,3; Endy, Timothy P. 2,3,a; Houng, Huo-Shu H. 2; Green, Sharone 1; Kalayanarooj, Siripen 4; Suntayakorn, Saroj 5; Chansiriwongs, Wanya 4; Vaughn, David W. 2; Nisalak, Ananda 3; Ennis, Francis A. 1; Rothman, Alan L. 1
[Miscellaneous Article] Journal of Infectious Diseases. 185(9):1213-1221, May 1, 2002.

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: 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.

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