Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections |
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Authors: | Libraty Daniel H Endy Timothy P Houng Huo-Shu H Green Sharone Kalayanarooj Siripen Suntayakorn Saroj Chansiriwongs Wanya Vaughn David W Nisalak Ananda Ennis Francis A Rothman Alan L |
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Institution: | Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA. dlibraty@mozart.inet.co.th |
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Abstract: | 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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