1. Medicine
  2. Microbiology and Infectious Disease
Download icon

Combination of inflammatory and vascular markers in the febrile phase of dengue is associated with more severe outcomes

  1. Nguyen Lam Vuong  Is a corresponding author
  2. Phung Khanh Lam
  3. Damien Keng Yen Ming
  4. Huynh Thi Le Duyen
  5. Nguyet Minh Nguyen
  6. Dong Thi Hoai Tam
  7. Kien Duong Thi Hue
  8. Nguyen VV Chau
  9. Ngoun Chanpheaktra
  10. Lucy Chai See Lum
  11. Ernesto Pleités
  12. Cameron P Simmons
  13. Kerstin D Rosenberger
  14. Thomas Jaenisch
  15. David Bell
  16. Nathalie Acestor
  17. Christine Halleux
  18. Piero Luigi Olliaro
  19. Bridget A Wills
  20. Ronald Geskus
  21. Sophie Yacoub  Is a corresponding author
  1. Oxford University Clinical Research Unit, Viet Nam
  2. Imperial College London, United Kingdom
  3. The Hospital for Tropical Diseases, Viet Nam
  4. Angkor Hospital for Children, Cambodia
  5. University of Malaya Medical Centre, Malaysia
  6. Hospital Nacional de Niños Benjamin Bloom, El Salvador
  7. Monash University, Australia
  8. Heidelberg University Hospital, Germany
  9. Independent consultant, United States
  10. Global Good Fund, United States
  11. World Health Organization, Switzerland
  12. University of Oxford, United Kingdom
Research Article
  • Cited 0
  • Views 582
  • Annotations
Cite this article as: eLife 2021;10:e67460 doi: 10.7554/eLife.67460

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

  1. Nguyen Lam Vuong

    Biostatistics group, Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam
    For correspondence
    vuongnl@oucru.org
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2684-3041
  2. Phung Khanh Lam

    Biostatistics group, Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam
    Competing interests
    No competing interests declared.
  3. Damien Keng Yen Ming

    Department of Infectious Diseases, Imperial College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  4. Huynh Thi Le Duyen

    Dengue group, Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam
    Competing interests
    No competing interests declared.
  5. Nguyet Minh Nguyen

    Dengue group, Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5960-7849
  6. Dong Thi Hoai Tam

    Oxford University Clinical Research Unit, The Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam
    Competing interests
    No competing interests declared.
  7. Kien Duong Thi Hue

    Dengue, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam
    Competing interests
    No competing interests declared.
  8. Nguyen VV Chau

    Dengue, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam
    Competing interests
    No competing interests declared.
  9. Ngoun Chanpheaktra

    -, Angkor Hospital for Children, Siem Reap, Cambodia
    Competing interests
    No competing interests declared.
  10. Lucy Chai See Lum

    -, University of Malaya Medical Centre, Kuala Lumpur, Malaysia
    Competing interests
    No competing interests declared.
  11. Ernesto Pleités

    -, Hospital Nacional de Niños Benjamin Bloom, San Salvador, El Salvador
    Competing interests
    No competing interests declared.
  12. Cameron P Simmons

    Institute for Vector-Borne Disease, Monash University, Clayton, Australia
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9039-7392
  13. Kerstin D Rosenberger

    Department for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany
    Competing interests
    No competing interests declared.
  14. Thomas Jaenisch

    Department for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany
    Competing interests
    Thomas Jaenisch, Dr. Jaenisch reports personal fees from Roche Diagnostics, outside the submitted work..
  15. David Bell

    -, Independent consultant, WA, United States
    Competing interests
    No competing interests declared.
  16. Nathalie Acestor

    Intellectual Ventures, Global Good Fund, WA, United States
    Competing interests
    No competing interests declared.
  17. Christine Halleux

    UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, World Health Organization, Geneva, Switzerland
    Competing interests
    No competing interests declared.
  18. Piero Luigi Olliaro

    Nuffield Department of Clinical Medicine, University of Oxford, London, United Kingdom
    Competing interests
    No competing interests declared.
  19. Bridget A Wills

    Oxford Centre for Global Health Research, University of Oxford, Oxford, United Kingdom
    Competing interests
    Bridget A Wills, reports personal fees for contributions to the Roche Severe Dengue Advisory Board, and personal fees from Takeda for membership of the Data Monitoring Committee for their dengue vaccine trials, outside the submitted work..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9086-8804
  20. Ronald Geskus

    Dengue, Oxford University Clinical Research Unit, Ho Chi Minh City, Viet Nam
    Competing interests
    Ronald Geskus, Dr. Geskus reports grants from Wellcome Trust, during the conduct of the study..
  21. Sophie Yacoub

    Dengue group, Oxford University Clinical Research Unit, Ho Chi Minh, Viet Nam
    For correspondence
    syacoub@oucru.org
    Competing interests
    Sophie Yacoub, Dr. Yacoub reports personal fees from Roche Diagnostics, outside the submitted work..

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.

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).

Reviewing Editor

  1. Balram Bhargava, Indian Council of Medical Research, India

Publication history

  1. Received: February 11, 2021
  2. Accepted: June 11, 2021
  3. Accepted Manuscript published: June 22, 2021 (version 1)

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

  • 582
    Page views
  • 86
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

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)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Cancer Biology
    2. Medicine
    Xinbo Qiao et al.
    Research Article

    Tumor metastasis remains the main cause of breast cancer-related deaths, especially delayed breast cancer distant metastasis. The current study assessed the frequency of CD44-/CD24- breast cancer cells in 576 tissue specimens for associations with clinicopathological features and metastasis and investigated the underlying molecular mechanisms. The results indicated that higher frequency (≥19.5%) of CD44-/CD24- cells was associated with delayed postoperative breast cancer metastasis. Furthermore, CD44-/CD24- triple negative breast cancer (TNBC) cells spontaneously converted into CD44+/CD24- cancer stem cells (CSCs) with properties similar to CD44+/CD24- CSCs from primary human breast cancer cells and parental TNBC cells in terms of stemness marker expression, self-renewal, differentiation, tumorigenicity and lung metastasis in vitro and in NOD/SCID mice. RNA sequencing identified several differentially expressed genes (DEGs) in newly converted CSCs and RHBDL2, one of the DEGs, expression was up-regulated. More importantly, RHBDL2 silencing inhibited the YAP1/USP31/NF-κB signaling and attenuated spontaneous CD44-/CD24- cell conversion into CSCs and their mammosphere formation. These findings suggest that the frequency of CD44-/CD24- tumor cells and RHBDL2 may be valuable for prognosis of delayed breast cancer metastasis, particularly for TNBC.

    1. Medicine
    Julia Stokes et al.
    Research Article Updated

    Volatile anesthetics (VAs) are widely used in medicine, but the mechanisms underlying their effects remain ill-defined. Though routine anesthesia is safe in healthy individuals, instances of sensitivity are well documented, and there has been significant concern regarding the impact of VAs on neonatal brain development. Evidence indicates that VAs have multiple targets, with anesthetic and non-anesthetic effects mediated by neuroreceptors, ion channels, and the mitochondrial electron transport chain. Here, we characterize an unexpected metabolic effect of VAs in neonatal mice. Neonatal blood β-hydroxybutarate (β-HB) is rapidly depleted by VAs at concentrations well below those necessary for anesthesia. β-HB in adults, including animals in dietary ketosis, is unaffected. Depletion of β-HB is mediated by citrate accumulation, malonyl-CoA production by acetyl-CoA carboxylase, and inhibition of fatty acid oxidation. Adults show similar significant changes to citrate and malonyl-CoA, but are insensitive to malonyl-CoA, displaying reduced metabolic flexibility compared to younger animals.