Mechanistic constraints in dengue severity: a systematic review with evidence stratification and agent-based evaluation of logical sufficiency

Category	Detail
Condition	Severe Dengue
Key Mechanisms	NS1-mediated endothelial injury, glycocalyx disruption, inflammatory myeloid activation, coagulation/platelet abnormalities
Target Population	Pediatric and immunocompromised populations
Care Setting	Clinical research and systematic review

Severe dengue is characterized by plasma leakage, thrombocytopenia, and hemorrhage.
Three mechanism families reached C1_conditional evidence: NS1-linked vascular permeability, endothelial glycocalyx/barrier disruption, and myeloid effector activation.
No mechanism family was eligible for quantitative pooling due to insufficient outcome harmonization.
The ABM demonstrated that NS1, barrier, and myeloid components can generate a connected endothelial-barrier failure analog.
Claim escalation requires longitudinal cohorts and functional perturbation assays.

Monitor for signs of severe dengue including plasma leakage and thrombocytopenia.

Track NS1 levels, endothelial barrier injury markers, and myeloid effector proxies.

Individuals infected with dengue virus, particularly those at risk for severe disease.

Current evidence does not support the efficacy of rupatadine or oseltamivir in reducing severe dengue symptoms.

Utilize a stratified evidence framework for mechanistic claims in dengue research.
Incorporate longitudinal studies to better understand the transition from uncomplicated to severe dengue.

Clinical Scorecard: Understanding Mechanisms Influencing Dengue Severity: A Systematic Review with Evidence Stratification and Agent-Based Assessment of Logical Coherence