Abstract
BackgroundDengue 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.MethodsWe 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).ResultsNine 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.ConclusionsThese results suggest that host biomarkers may have utility in differentiating between dengue and leptospirosis, clinically similar conditions of different etiology.
Highlights
Dengue fever and leptospirosis have partially overlapping geographic distributions, similar clinical presentations and potentially life-threatening complications but require different treatments
Clinical and laboratory factors that discriminate between dengue fever and leptospirosis To identify clinical signs and laboratory parameters that could aid in differentiating dengue fever from leptospirosis, we generated adjusted odds ratios for variables with p < 0.10 by bivariate analysis
Following adjustment for age, sex, height, and duration of illness, thrombocytopenia and leukopenia were independently associated as risk factors for dengue fever with adjusted odds ratios of 10.0, p = 0.003 and 9.3, p < 0.001 respectively
Summary
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. Dengue virus infection and leptospirosis represent important causes of acute febrile illness whose diagnosis and management in resource-poor settings remains challenging. Both diseases are potentially fatal, and represent important causes of morbidity and mortality globally. Clinical manifestations range from: (1) asymptomatic infection; to (2) a non-specific febrile illness (dengue fever); to (3) a life-threatening complication, severe dengue, often characterized by plasma leakage and coagulopathy. Specific anti-viral therapy is not available, but intensive supportive care may reduce mortality in severe dengue from 20% to less than 1% [6]
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