Prolonged Fever in Pediatric Dengue is Associated With Clinical Severity and Immune Dysregulation

BACKGROUND: Prolonged fever occurs in some adults with dengue and is linked to greater severity. However, its frequency, characteristics and clinical outcomes in pediatric dengue remain unclear.

METHODS: We performed a prospective study in a dengue hyperendemic region of Colombia, including hospitalized children with confirmed dengue presenting warning signs or severe dengue (SD). Prolonged fever was defined as persistent temperature >38.3°C beyond day 7 of illness. We evaluated prolonged fever frequency, clinical features, immunologic status and outcomes.

RESULTS: Among 253 children (204 dengue warning signs, 49 SD), prolonged fever was identified in 11.06%. Median duration of fever >38.3°C in prolonged fever cases was 8 days. Children with prolonged fever had a higher proportion of SD compared with those without prolonged fever, and longer hospital stay. Rates of community-acquired secondary bacterial infections did not differ significantly, but children with prolonged fever had a higher occurrence of healthcare-associated secondary bacterial infections. Children with prolonged fever showed elevated inflammatory markers (C-reactive protein, interleukin-6, interleukin-10 and interferon-g), as well as ex vivo dysfunction of monocytes. All patients experienced spontaneous clinical and laboratory resolution without the need for steroids, immunoglobulin or antibiotics, except in confirmed secondary infections.

CONCLUSIONS: Prolonged fever is relatively frequent in pediatric patients hospitalized with dengue and is associated with clinical severity, immune dysregulation and an increased risk of healthcare-associated secondary bacterial infections. These findings highlight the importance of close monitoring of children with prolonged fever for secondary complications and the microbiologic confirmation of suspected bacterial infections to guide timely and rational antimicrobial therapy.