Open Access Highly Accessed Research article

Host biomarkers distinguish dengue from leptospirosis in Colombia: a case–control study

Andrea L Conroy12, Margarita Gélvez3, Michael Hawkes1, Nimerta Rajwans1, W Conrad Liles145, Luis Angel Villar-Centeno3 and Kevin C Kain1246*

Author Affiliations

1 Sandra A. Rotman Laboratories, Sandra Rotman Centre, University Health Network-Toronto General Hospital, University of Toronto, Toronto M5G 1 L7, Canada

2 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto M5S 1A8, Canada

3 Centro de Investigaciones Epidemiológicas, Facultad de Salud, Universidad Industrial de Santander, Bucaramanga Dept 680002, Colombia

4 Tropical Disease Unit, Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto M5G 2C4, Canada

5 Department of Medicine, University of Washington, Seattle, WA 98195, USA

6 Sandra Rotman Centre, Suite 10–351, Toronto Medical Discovery Tower, MaRS Centre, 101 College St., M5G1L7 Toronto, Canada

For all author emails, please log on.

BMC Infectious Diseases 2014, 14:35  doi:10.1186/1471-2334-14-35

Published: 20 January 2014

Abstract

Background

Dengue fever and leptospirosis have partially overlapping geographic distributions, similar clinical presentations and potentially life-threatening complications but require different treatments. Distinguishing between these cosmopolitan emerging pathogens represents a diagnostic dilemma of global importance. We hypothesized that perturbations in host biomarkers can differentiate between individuals with dengue fever and leptospirosis during the acute phase of illness.

Methods

We randomly selected subjects from a prospective cohort study of acute febrile illness in Bucaramanga, Colombia and tested 19 serum biomarkers by ELISA in dengue fever (DF, n = 113) compared to subjects with leptospirosis (n = 47). Biomarkers were selected for further analysis if they had good discriminatory ability (area under the ROC curve (AUC) >0.80) and were beyond a reference range (assessed using local healthy controls).

Results

Nine biomarkers differed significantly between dengue fever and leptospirosis, with higher levels of Angptl3, IL-18BP, IP-10/CXCL10, Platelet Factor 4, sICAM-1, Factor D, sEng and sKDR in dengue and higher levels of sTie-2 in leptospirosis (p < 0.001 for all comparisons). Two biomarkers, sEng and IL18BP, showed excellent discriminatory ability (AUROC >0.90). When incorporated into multivariable models, sEng and IL18BP improved the diagnostic accuracy of clinical information alone.

Conclusions

These results suggest that host biomarkers may have utility in differentiating between dengue and leptospirosis, clinically similar conditions of different etiology.

Keywords:
Dengue fever; Leptospirosis; Acute febrile illness; Host biomarkers; Clinical discrimination; Combinatorial models