Beyond supportive care in pediatric dengue: Emerging therapeutics and the WHO PADO 2026 priorities–A narrative review

Pediatric dengue remains an important cause of hospitalization and shock in endemic settings, while treatment continues to rely on supportive care. This narrative review critically evaluates investigational direct-acting antivirals, neutralizing monoclonal antibodies, and host-directed agents alongside the World Health Organization (WHO) Paediatric Drug Optimization (PADO) 2026 priorities. PubMed-indexed clinical and mechanistic literature and WHO guidance available through October 2026 informed a selective synthesis. NS4B and NS5 inhibitors provide convincing mechanistic signals, but early viral suppression has not been shown to prevent severe dengue in children. Mosnodenvir reduced viral RNA in a controlled human infection study conducted as prophylaxis in healthy adults; this does not establish efficacy in symptomatic pediatric infection, and resistance is a concern. In a randomized trial involving 250 adults, dengue-mAb (formerly VIS513) accelerated infectious-virus and fever clearance, but prevention of shock, organ dysfunction, and hospitalization was not established. Pediatric translation also depends on immune history, abrupt defervescence-associated vascular leakage, age-dependent physiology, the feasibility of very early treatment, and the safety of antibody-based interventions, not merely dose adjustment. PADO prioritizes SII dengue-mAb and places AV-1, EYU-688, fenretinide, and mosnodenvir on its watch list. Virological endpoints remain useful for early development; pediatric trials must ultimately demonstrate sustained clinical recovery or prevention of deterioration with acceptable safety and deployable regimens. No investigational agent reviewed is currently established for routine pediatric dengue treatment.