Objective:

To identify and evaluate the mechanisms influencing severe dengue and assess their logical coherence in explaining vascular decompensation.

Approach:

Key Findings:

• Three mechanism families reached C1_conditional evidence: NS1-linked vascular permeability, endothelial glycocalyx/barrier disruption, and myeloid effector activation.
• Two null randomized trials indicated that rupatadine did not significantly reduce plasma leakage (RR = 0.68, 95% CI 0.41–1.12) and oseltamivir did not improve time to defervescence (MD = +0.1 days, p=0.055).
• The ABM demonstrated that the NS1–barrier–myeloid set could generate a spatially connected endothelial-barrier failure analog under specific conditions.

Interpretation:

The evidence supports a minimum-range organizational account of severe dengue vascular decompensation centered on the NS1–barrier–myeloid unit, indicating competing constraints during progression toward vascular leakage.

Limitations:

• No mechanism family was eligible for quantitative pooling due to sparse CI-bearing estimates and insufficiently harmonized outcome definitions.
• The ABM does not establish causal mechanistic validation, molecular equivalence, or patient-level prediction.

Conclusion:

Future research should focus on longitudinal cohorts measuring NS1/viraemia and endothelial barrier injury markers, along with functional perturbation assays.

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This content is an AI-generated, fully rewritten summary based on a published scholarly article. It does not reproduce the original text and is not a substitute for the original publication. Readers are encouraged to consult the source for full context, data, and methodology.