A Three-Component Biomarker Panel for Prediction of Dengue Hemorrhagic Fever

Allan R. Brasier Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Hyunsu Ju Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Josefina Garcia Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Heidi M. Spratt Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Sundar S. Victor Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Brett M. Forshey Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Eric S. Halsey Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Guillermo Comach Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Gloria Sierra Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Patrick J. Blair Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Claudio Rocha Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Amy C. Morrison Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Thomas W. Scott Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Isabel Bazan Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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Tadeusz J. Kochel Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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the Venezuelan Dengue Fever Working Group Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas; Sealy Center for Molecular Medicine, UTMB, Institute for Translational Sciences, UTMB, the United States Naval Medical Research Unit-6, Lima, Peru; Department Preventive Medicine and Community Health, UTMB, Laboratorio Regional de Diagnostico e Investigacion del Dengue y otras Enfermedades Virales (LARDIDEV), Instituto de Investigaciones Biomedicas de la Universidad de Carabobo (BIOMED-UC), Maracay, Venezuela; Department of Entomology, University of California, Davis, California

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DOI:
https://doi.org/10.4269/ajtmh.2012.11-0469
Volume/Issue:
Volume 86: Issue 2
Page(s):
341–348
Restricted access
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Dengue virus infections are a major cause of morbidity in tropical countries. Early detection of dengue hemorrhagic fever (DHF) may help identify individuals that would benefit from intensive therapy. Predictive modeling was performed using 11 laboratory values of 51 individuals (38 DF and 13 DHF) obtained on initial presentation using logistic regression. We produced a robust model with an area under the curve of 0.9615 that retained IL-10 levels, platelets, and lymphocytes as the major predictive features. A classification and regression tree was developed on these features that were 86% accurate on cross-validation. The IL-10 levels and platelet counts were also identified as the most informative features associated with DHF using a Random Forest classifier. In the presence of polymerase chain reaction-proven acute dengue infections, we suggest a complete blood count and rapid measurement of IL-10 can assist in the triage of potential DHF cases for close follow-up or clinical intervention improving clinical outcome.

Author Notes

*Address correspondence to Allan R. Brasier, MRB 8.128, 301 University Blvd, UTMB, Galveston, TX 77555-1060. E-mail: arbrasie@utmb.edu
†Other members of the Venezuelan Dengue Fever Working Group are Iris Villalobos and Carlos Espino.

Financial support: This work was supported by the NIH/NIAID Clinical Proteomics Center, HHSN272200800048C (ARB), 1U54RR02614 UTMB CTSA (ARB) and the Military Infectious Diseases Research Program work unit 6000RAD1.S.B0302.

Disclosure: Josefina Garcia, Eric S. Halsey, Patrick J. Blair, Claudio Rocha, Isabel Bazan, and Tadeusz J. Kochel are military service members or employees of the U.S. Government. This work was prepared as part of their official duties. Title 17 U.S.C. §105 provides that ‘Copyright protection under this title is not available for any work of the United States Government.’ Title 17 U.S.C. §101 defines U.S. Government work as a work prepared by a military service member or employee of the U.S. Government as part of that person's official duties.

Authors' addresses: Allan R. Brasier, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, E-mail: arbrasie@utmb.edu. Hyunsu Ju and Heidi M. Spratt, Department of Preventive Medicine and Community Health, University of Texas Medical Branch, Galveston, TX, E-mails: hyju@utmb.edu and hespratt@utmb.edu. Josefina Garcia, Brett M. Forshey, Eric S. Halsey, and Claudio Rocha, U.S. Naval Medical Research Unit Six Unit 3230, DPO AA, FL, E-mails: Josefina.Garcia@med.navy.mil, brett.forshey@gmail.com, claudio.rocha@med.navy.mil, and Eric.halsey@med.navy.mil. Sundar S. Victor, Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, E-mail: ssvictor@utmb.edu. Guillermo Comach, Gloria Sierra, and Isabel Bazan, Instituto de Investigaciones Biomedicas de la Universidad de Carabobo, Estado Aragua, Venezuela, E-mails: gcomach@cantv.net, gmsierrac@yahoo.com, and isabelbazana@gmail.com. Patrick J. Blair, Naval Health Research Center, Respiratory Diseases, San Diego, CA, E-mail: Patrick.Blair@med.navy.mil. Amy C. Morrison and Thomas W. Scott, Department of Entomology, University of California, Davis, CA, E-mails: amy.aegypti@gmail.com and twscott@ucdavis.edu. Tadeusz J. Kochel, Viral and Rickettsial Diseases Department, Naval Medical Research Center, Silver Spring, MD, E-mail: Tad.kochel@med.navy.mil.

Copyright:
©The American Society of Tropical Medicine and Hygiene 2012
Received:
19 Jul 2011
|
Accepted:
18 Nov 2011
|
Published Online:
01 Feb 2012
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
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