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Macrophage Migration Inhibitory Factor as a Biomarker of Severe Dengue and Shock in Children: A Cross-Sectional Study in Indonesia

Agustin Iskandar ORCID
Department of Clinical Pathology, Faculty of Medicine, Brawijaya University/ Saiful Anwar General Hospital, Malang, East Java 65145, Indonesia
Iswanto Korompot ORCID
Clinical Pathology Study Program, Faculty of Medicine, Brawijaya University/ Saiful Anwar General Hospital, Malang, East Java 65145, Indonesia
Andrea Aprilia ORCID
Department of Clinical Pathology, School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta 12930, Indonesia
Irene Ratri Dewi ORCID
Department of Child Health, Faculty of Medicine, Brawijaya University/ Saiful Anwar General Hospital, Malang, East Java 65145, Indonesia

Received: 4 July 2025; Revised: 15 July 2025; Accepted: 30 July 2025; Published: 5 January 2026

Abstract

Dengue remains a leading cause of child mortality in Indonesia. Identifying reliable biomarkers to predict disease severity is essential for early intervention. Macrophage Migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine involved in the pathogenesis of dengue. This study aimed to assess the relationship between MIF levels and dengue severity in children, and to compare  the predictive value of MIF levels with C-Reactive Protein (CRP) and serum albumin levels. A cross-sectional study was conducted on 104 pediatric dengue patients hospitalized at Saiful Anwar General Hospital. Serum levels of MIF (ELISA), CRP, and albumin were measured upon admission. Patients were categorized into four severity grades (Grade 1–4) and also stratified into shock and non-shock groups. Statistical analyses included ANOVA, correlation analysis, and receiver operating characteristic (ROC) curve evaluation. MIF levels showed a significant stepwise increase with disease severity and were significantly higher in patients with shock (p < 0.001). CRP levels were also elevated in severe dengue, but the correlation with severity was moderate (r = 0.61, p < 0.05). In contrast, serum albumin levels were inversely associated with severity (r = –0.67, p < 0.05), with lower values observed in the shock group. ROC analysis demonstrated that MIF had the highest predictive accuracy for shock (AUC = 0.94), compared to CRP (AUC = 0.78) and albumin (AUC = 0.81). MIF is a robust biomarker for predicting dengue severity and shock in children, outperforming CRP and albumin in diagnostic performance. The integration of MIF with conventional markers may improve early risk stratification and clinical decision-making in pediatric dengue.

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