Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes
- Oxford University Clinical Research Unit, Viet Nam
- Imperial College London, United Kingdom
- The Hospital for Tropical Diseases, Viet Nam
- Angkor Hospital for Children, Cambodia
- University of Malaya Medical Centre, Malaysia
- Hospital Nacional de Niños Benjamin Bloom, El Salvador
- Monash University, Australia
- Heidelberg University Hospital, Germany
- Independent consultant, United States
- Global Good Fund, United States
- World Health Organization, Switzerland
- University of Oxford, United Kingdom
Abstract
Background: Early identification of severe dengue patients is important regarding patient management and resource allocation. We investigated the association of ten biomarkers (VCAM-1, SDC-1, Ang-2, IL-8, IP-10, IL-1RA, sCD163, sTREM-1, ferritin, CRP) with the development of severe/moderate dengue (S/MD).
Methods: We performed a nested case-control study from a multi-country study. A total of 281 S/MD and 556 uncomplicated dengue cases were included.
Results: On days 1-3 from symptom onset, higher levels of any biomarker increased the risk of developing S/MD. When assessing together, SDC-1 and IL-1RA were stable, while IP-10 changed the association from positive to negative; others showed weaker associations. The best combinations associated with S/MD comprised IL-1RA, Ang-2, IL-8, ferritin, IP-10, and SDC-1 for children, and SDC-1, IL-8, ferritin, sTREM-1, IL-1RA, IP-10, and sCD163 for adults.
Conclusions: Our findings assist the development of biomarker panels for clinical use and could improve triage and risk prediction in dengue patients.
Data availability
All data generated or analysed during this study have been deposited in the Oxford Research Archive (ORA) at https://doi.org/10.5287/bodleian:JN2wXDpjq
Article and author information
Author details
Nguyet Minh Nguyen
Funding
European Union's Seventh Framework Programme for research, technological development and demonstration (FP7-281803 IDAMS)
- Thomas Jaenisch
World Health Organization (UNICEF/UNDP/ World Bank/WHO Special Programme for Research and Training in Tropical Diseases)
- Sophie Yacoub
Bill and Melinda Gates Foundation Trust (The Global Good Fund I,LLC at Intellectual Ventures)
- Sophie Yacoub
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Balram Bhargava, Indian Council of Medical Research, India
Ethics
Human subjects: The study and the blood sample analysis were approved by the Scientific and Ethics Committees of all study sites (Hospital for Tropical Diseases [Ho Chi Minh City, Vietnam] Ref No 03/HDDD-05/01/2018; Angkor Hospital for Children [Siem Reap, Cambodia] Ref No 0146/18-AHC; University of Malaya Medical Centre [Kuala Lumpur, Malaysia] Ref No 201865-6361) and by the Oxford Tropical Research Ethics Committee (OxTREC Ref No 502-18).
Version history
- Received: February 11, 2021
- Accepted: June 11, 2021
- Accepted Manuscript published: June 22, 2021 (version 1)
- Version of Record published: August 3, 2021 (version 2)
Copyright
© 2021, Vuong et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,832
- views
-
- 377
- downloads
-
- 13
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes
eLife 10:e67460.
https://doi.org/10.7554/eLife.67460
Further reading
-
- Medicine
- Microbiology and Infectious Disease
- Epidemiology and Global Health
- Immunology and Inflammation
eLife has published articles on a wide range of infectious diseases, including COVID-19, influenza, tuberculosis, HIV/AIDS, malaria and typhoid fever.
-
- Medicine
- Neuroscience
Retinitis pigmentosa (RP) is an inherited retinal disease in which there is a loss of cone-mediated daylight vision. As there are >100 disease genes, our goal is to preserve cone vision in a disease gene-agnostic manner. Previously we showed that overexpressing TXNIP, an α-arrestin protein, prolonged cone vision in RP mouse models, using an AAV to express it only in cones. Here, we expressed different alleles of Txnip in the retinal pigmented epithelium (RPE), a support layer for cones. Our goal was to learn more of TXNIP’s structure-function relationships for cone survival, as well as determine the optimal cell type expression pattern for cone survival. The C-terminal half of TXNIP was found to be sufficient to remove GLUT1 from the cell surface, and improved RP cone survival, when expressed in the RPE, but not in cones. Knock-down of HSP90AB1, a TXNIP-interactor which regulates metabolism, improved the survival of cones alone and was additive for cone survival when combined with TXNIP. From these and other results, it is likely that TXNIP interacts with several proteins in the RPE to indirectly support cone survival, with some of these interactions different from those that lead to cone survival when expressed only in cones.
