Differing Influences of Virus Burden and Immune Activation on Disease Severity in Secondary Dengue‐3 Virus Infections

TLDR

Dengue hemorrhagic fever is a severe dengue manifestation marked by plasma leakage, thrombocytopenia, and hepatic inflammation, and its severity is influenced by virus burden, immune activation timing, and cytokine responses. The study aimed to examine how virus burden and immune activation interrelate with the development of DHF in children with secondary dengue‑3 infections. Researchers conducted a prospective, hospital‑based study of 54 children, measuring plasma viremia, cytokine levels (IFN‑γ, IL‑10, sTNF‑RII, sIL‑2R), and liver enzymes to assess their temporal dynamics. Higher early viremia and earlier IFN‑γ peaks were linked to DHF, while peak viremia correlated with plasma leakage and thrombocytopenia; IL‑10 and sTNF‑RII levels also correlated with thrombocytopenia independently of viremia, and elevated liver enzymes were associated with sIL‑2R rather than viremia.

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-γ 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.