Differing influences of virus burden and immune activation on disease severity in secondary dengue-3 virus infections.
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.
Libraty
Daniel H
DH
Center for Infectious Disease and Vaccine Research, University of Massachusetts Medical School, Worcester, MA 01655, USA. dlibraty@mozart.inet.co.th
Endy
Timothy P
TP
Houng
Huo-Shu H
HS
Green
Sharone
S
Kalayanarooj
Siripen
S
Suntayakorn
Saroj
S
Chansiriwongs
Wanya
W
Vaughn
David W
DW
Nisalak
Ananda
A
Ennis
Francis A
FA
Rothman
Alan L
AL
D015703:Antigens, CD / Q000097:blood; D002648:Child; D018076:DNA, Complementary / Q000032:analysis; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D015999:Multivariate Analysis; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019595:Severe Dengue / Q000276:immunology* / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000175:diagnosis / Q000276:immunology*
D015703:Antigens, CD; D018076:DNA, Complementary; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D016753:Interleukin-10; D007371:Interferon-gamma