Evidence map›Paper›PMID 41408303›Full record

ArticleJournal of translational medicine2025

Evaluation of immune-endothelial activation markers for the differentiation of severe dengue.

Yi-Sheng Khor, Sing-Sin Sam, Kind-Leng Tong, Sazaly AbuBakar, Suzana Misbah, Azureen Azmel, Puteri Nasyitah Aina Binti Kamal Faizul, Anusha Shunmugarajoo, Eashwary Mageswaren, Yih-Harng Soh and 2 more

Abstract readMulticenter Study
In one paragraph

Article in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Yi-Sheng KhorDepartment of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia.
Sing-Sin SamTropical Infectious Diseases Research and Educational Centre (TIDREC), Universiti Malaya, Kuala Lumpur, 50603, Malaysia.
Kind-Leng TongDepartment of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia.
Sazaly AbuBakarTropical Infectious Diseases Research and Educational Centre (TIDREC), Universiti Malaya, Kuala Lumpur, 50603, Malaysia.
Suzana MisbahBiological Security and Sustainability Research Group (BIOSES), Faculty of Science and Marine Environment, Universiti Malaysia Terengganu, Terengganu, Kuala Nerus, 21030, Malaysia.
Azureen AzmelMedical Department, Tengku Ampuan Rahimah Hospital, Klang, 41200, Malaysia.
Puteri Nasyitah Aina Binti Kamal FaizulMedical Department, Tengku Ampuan Rahimah Hospital, Klang, 41200, Malaysia.
Anusha ShunmugarajooMedical Department, Tengku Ampuan Rahimah Hospital, Klang, 41200, Malaysia.
Eashwary MageswarenMedical Department, Tengku Ampuan Rahimah Hospital, Klang, 41200, Malaysia.
Yih-Harng SohCenters for Disease Control and Prevention Unit, Central Melaka District Health Office, Jalan Bukit Baru, Melaka, 75150, Malaysia.
Ahmad Kashfi Ab RahmanDepartment of Medicine (Infectious Disease Unit), Sultanah Nur Zahirah Hospital, Jalan Sultan Mahmud, Kuala Terengganu, Terengganu, 20400, Malaysia.
Pooi-Fong WongDepartment of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia. wongpf@um.edu.my.ORCID 0000-0002-6705-2521

Funding

Development of Research Institute for Excellent Enterprises (ATC+) Project Grant IF001-2021
6 · The paper itself

Abstract

backgroundSevere dengue (SD) or dengue hemorrhagic fever is characterized by immune hyperactivation, endothelial dysfunction and vascular leakage. Early detection of the onset of SD, particularly during the febrile phase or before the onset of the critical phase is highly desirable. However, most dengue patients present late (≥ 5 days of illness) to the hospital, which coincides with the beginning of the critical phase. Biomarkers associated with these pathological processes may therefore serve as severity-associated markers. This study investigated the clinical utility of the immune-endothelial activation panel as a potential indicator for differentiating SD from dengue fever (DF).

methodsA multicenter cross-sectional study was conducted using sera of clinically- and laboratory-confirmed SD and DF patients, non-dengue febrile illness patients (NDFI) and healthy individuals. Serum levels of monocyte/macrophage activation markers CD163, CD14 and ferritin; endothelial activation and vascular permeability markers SDC-1 and VCAM-1; and cytokines CCL2, CCL3, CXCL9, CXCL10 and IL-10 were measured by ELISA or immunoplex assays. The ability to distinguish SD from DF was measured using Receiver Operating Characteristic (ROC) analysis.

resultsCD163, ferritin, SDC-1, VCAM-1 and CCL2 levels were significantly different between SD and DF, as well as between DF and NDFI. CD163, SDC-1 and VCAM-1 levels differed significantly between primary and secondary dengue. These indicators performed moderately as standalones in distinguishing SD from DF. However, a combination of SDC-1, CD163 and VCAM-1 improved diagnostic performance (AUC = 0.784, 95% Cl:0.725–0.835). Notably, combining AST, a hepatic injury marker with all four indicators (SDC-1, CD163, VCAM-1 and ferritin) significantly enhanced the diagnostic performance of this panel (AUC = 0.850, 95% Cl: 0.781–0.904).

conclusionA multi-marker panel consisting of immune-endothelial activation and hepatic injury can increase the accuracy of identifying SD during the critical phase of the illness. Given the absence of a specific test for the detection of impending SD, the strength of this multi-marker panel may support timely decision-making for high-risk patient management while safely discharging others to optimise the usage of hospital resources.

Indexed as

BiomarkersEndothelial CellsSevere DengueAdultAntigens, CDCytokinesDiagnosis, DifferentialFemaleHumansMaleMiddle AgedROC CurveAntigens, CDBiomarkersCytokinesBiomarkerClinicalDiagnosticImmunopathogenesisPrognosis

Identifiers

PMID41408303
PMCPMC12822092

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.